American Board of Pathology (ABPath) Clinical Pathology Certification Exam — Questions and Answers

Question 1: A patient with chronic gastroesophageal reflux develops columnar epithelium with goblet cells in the distal esophagus. This is termed?

Squamous metaplasia
Esophageal varices
Barrett esophagus (Correct answer)
Achalasia

Correct answer: Barrett esophagus

Barrett esophagus is intestinal metaplasia of the esophageal lining, a risk factor for adenocarcinoma.

Question 2: The direct antiglobulin test (DAT) detects which of the following?

Fibrin degradation products
Antibody or complement bound to red cells in vivo (Correct answer)
Free antibody in the patient's serum
Platelet antibodies

Correct answer: Antibody or complement bound to red cells in vivo

The DAT detects immunoglobulin or complement already coating red cells in vivo.

Question 3: Apoptosis differs from necrosis primarily in that apoptosis:

Only occurs in pathologic states
Is energy-dependent and does not incite inflammation (Correct answer)
Triggers a strong inflammatory response
Involves cell swelling and membrane rupture

Correct answer: Is energy-dependent and does not incite inflammation

Apoptosis is an ATP-dependent, programmed cell death that leaves the membrane intact and does not provoke inflammation.

Question 4: Which finding is most characteristic of a 12-hour-old myocardial infarct on microscopy?

Granulation tissue with fibroblasts
Dense collagenous scar
Wavy fibers and contraction band necrosis only
Coagulative necrosis with early neutrophil infiltration (Correct answer)

Correct answer: Coagulative necrosis with early neutrophil infiltration

By 12–24 hours, coagulative necrosis with early neutrophilic infiltration begins to appear.

Question 5: A 68-year-old male with a history of myelodysplastic syndrome receives a transfusion of 2 units of packed red blood cells. Five days later, he presents with a low-grade fever, mild jaundice, and a greater than expected drop in his hemoglobin level. A direct antiglobulin test (DAT) is now positive. Which of the following is the most likely cause of this presentation?

Acute hemolytic transfusion reaction
Transfusion-associated graft-versus-host disease (TA-GVHD)
Febrile non-hemolytic transfusion reaction
Delayed hemolytic transfusion reaction (Correct answer)

Correct answer: Delayed hemolytic transfusion reaction

The patient's presentation of symptoms such as fever and jaundice several days after a transfusion, along with a positive DAT and unexpected anemia, is characteristic of a delayed hemolytic transfusion reaction (DHTR). [8, 15] This reaction occurs when a patient has been previously sensitized to a red blood cell antigen and has an anamnestic antibody response upon re-exposure through transfusion. [26] Acute reactions occur within 24 hours, TA-GVHD has different primary symptoms, and febrile reactions typically do not involve hemolysis or a positive DAT.

Question 6: Passive hyperemia (congestion) of the liver in right heart failure classically produces a:

Cirrhotic micronodular pattern immediately
Caseous necrosis
Nutmeg liver appearance (Correct answer)
Fatty liver only

Correct answer: Nutmeg liver appearance

Chronic hepatic congestion produces a mottled 'nutmeg liver' from centrilobular congestion and periportal fatty change.

Question 7: The main cell responsible for collagen synthesis during wound repair is the:

Endothelial cell
Neutrophil
Osteoclast
Fibroblast (Correct answer)

Correct answer: Fibroblast

Fibroblasts produce the collagen and extracellular matrix that form the scar during repair.

Question 8: What is the most common presenting symptom of acute leukemia?

Abdominal pain
Fever and infections (Correct answer)
Severe anemia
Weight loss

Correct answer: Fever and infections

Acute leukemia is characterized by the rapid proliferation of immature white blood cells (blasts) in the bone marrow, which suppresses the production of normal blood cells. This leads to pancytopenia, including neutropenia (low neutrophils). Consequently, patients often present with fever and recurrent infections due to a compromised immune system, as their body cannot effectively fight pathogens.

Question 9: Auer rods on a peripheral blood smear are most characteristic of which condition?

Multiple myeloma
Chronic lymphocytic leukemia
Acute myeloid leukemia (Correct answer)
Hairy cell leukemia

Correct answer: Acute myeloid leukemia

Auer rods are azurophilic cytoplasmic inclusions of fused primary granules seen in myeloblasts of AML.

Question 10: A urine cytology specimen shows cells with high N/C ratio, hyperchromatic irregular nuclei, and coarse chromatin. This best fits which Paris System category?

Low-grade urothelial neoplasm
Atypical urothelial cells
Negative for high-grade urothelial carcinoma
High-grade urothelial carcinoma (Correct answer)

Correct answer: High-grade urothelial carcinoma

High N/C ratio with hyperchromasia and coarse chromatin defines high-grade urothelial carcinoma in the Paris System.

Question 11: Which finding indicates high-grade dysplasia rather than invasive carcinoma in the colon?

Invasion into the muscularis propria
Distant metastasis
Cells confined above the basement membrane (Correct answer)
Lymphovascular invasion

Correct answer: Cells confined above the basement membrane

High-grade dysplasia lacks invasion beyond the basement membrane, unlike invasive carcinoma.

Question 12: What is the most common cause of iron deficiency anemia worldwide?

Malabsorption
Vitamin B12 deficiency
Chronic inflammation
Blood loss (Correct answer)

Correct answer: Blood loss

Iron deficiency anemia occurs when the body lacks sufficient iron to produce hemoglobin. Globally, chronic blood loss, particularly from the gastrointestinal tract (e.g., peptic ulcers, colon cancer, hookworm infection) or gynecological sources (e.g., menorrhagia), is the predominant cause. This consistent depletion of iron stores through blood loss is the leading factor worldwide.

Question 13: A febrile nonhemolytic transfusion reaction is most commonly caused by which mechanism?

Bacterial contamination
IgA deficiency
ABO incompatibility
Cytokines from donor leukocytes and recipient antibodies to leukocytes (Correct answer)

Correct answer: Cytokines from donor leukocytes and recipient antibodies to leukocytes

FNHTRs result from accumulated cytokines and recipient anti-leukocyte antibodies.

Question 14: Aschoff bodies are pathognomonic of which condition?

Infective endocarditis
Cardiac amyloidosis
Dilated cardiomyopathy
Acute rheumatic fever (Correct answer)

Correct answer: Acute rheumatic fever

Aschoff bodies with Anitschkow cells are diagnostic of rheumatic myocarditis.

Question 15: Flow cytometry showing surface light-chain restriction confirms that a B-cell population is:

Of T-cell origin
Reactive and polyclonal
Clonal (neoplastic) (Correct answer)
Composed of plasma cells only

Correct answer: Clonal (neoplastic)

Restriction to a single kappa or lambda light chain indicates a clonal B-cell proliferation.

Question 16: Which feature of appendiceal carcinoid (well-differentiated neuroendocrine tumor) is MOST strongly associated with metastatic potential?

Tumor size >2 cm (Correct answer)
Presence of mucin
Location at the appendiceal tip
Mitotic rate <2 per 10 HPF

Correct answer: Tumor size >2 cm

Appendiceal carcinoids >2 cm have a significantly higher risk of metastasis (up to 30%), while tumors <2 cm rarely metastasize (<2%).

Question 17: A patient's tumor shows microsatellite instability (MSI-high). Which pathway defect is most directly responsible?

DNA mismatch repair deficiency (Correct answer)
Nucleotide excision repair defect
Homologous recombination deficiency
Base excision repair defect

Correct answer: DNA mismatch repair deficiency

MSI results from loss of DNA mismatch repair function, commonly involving MLH1, MSH2, MSH6, or PMS2.

Question 18: A biopsy of a mitral valve from a patient with a history of recurrent pharyngitis in childhood and subsequent development of mitral stenosis shows a focal collection of plump macrophages, some of which are multinucleated, admixed with lymphocytes and plasma cells surrounding a central area of fibrinoid necrosis. Some of the macrophages have abundant cytoplasm and central nuclei with wavy, ribbon-like chromatin. What is the pathognomonic term for this inflammatory lesion?

Libman-Sacks endocarditis
Granuloma with caseous necrosis
Aschoff body (Correct answer)
Infective endocarditis vegetation

Correct answer: Aschoff body

The lesion described is an Aschoff body, which is the pathognomonic finding of acute rheumatic carditis. The characteristic plump macrophages with wavy, 'caterpillar-like' nuclei are known as Anitschkow cells. These lesions are found in the hearts of individuals with rheumatic fever, which is a complication of a group A streptococcal infection.

Question 19: Leukocyte rolling along the endothelium during inflammation is mediated primarily by:

Integrins
Cadherins
Immunoglobulins
Selectins (Correct answer)

Correct answer: Selectins

Selectins mediate the initial loose, rolling adhesion of leukocytes to activated endothelium.

Question 20: Hairy cell leukemia is characteristically positive for which mutation?

NPM1
JAK2 V617F
FLT3-ITD
BRAF V600E (Correct answer)

Correct answer: BRAF V600E

BRAF V600E is present in essentially all hairy cell leukemia cases.

Question 21: Which of the following cellular infiltrates is most characteristic of chronic inflammation?

Erythrocytes and platelets
Basophils and mast cells
Lymphocytes and macrophages (Correct answer)
Neutrophils and eosinophils

Correct answer: Lymphocytes and macrophages

Chronic inflammation is characterized by the infiltration of mononuclear cells, primarily lymphocytes, macrophages, and plasma cells. [4, 21, 29] This is in contrast to acute inflammation, which is dominated by neutrophils. [4, 29] Macrophages play a central role in chronic inflammation through phagocytosis, antigen presentation, and secretion of cytokines and growth factors that perpetuate the inflammatory response and promote tissue remodeling. [21]

Question 22: A 45-year-old female presents with fatigue, easy bruising, and bleeding gums. Her CBC shows pancytopenia with Auer rods seen in numerous promyelocytes. Coagulation studies indicate disseminated intravascular coagulation (DIC). A bone marrow biopsy confirms the diagnosis of acute promyelocytic leukemia (APL). Which genetic translocation is specifically targeted by all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) therapy in this condition?

PML-RARA (Correct answer)
BCR-ABL1
RUNX1-RUNX1T1
CBFB-MYH11

Correct answer: PML-RARA

Acute promyelocytic leukemia (APL) is defined by the presence of the t(15;17)(q22;q21) translocation, which creates the PML-RARA fusion gene. The resulting fusion protein blocks myeloid differentiation at the promyelocyte stage. All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are targeted therapies that specifically act on the PML-RARA protein to induce degradation and promote differentiation of the leukemic cells, leading to high rates of remission.

Question 23: The interval between specimen receipt and result reporting is called:

Reference interval
Turnaround time (Correct answer)
Analytical sensitivity
Lot-to-lot variation

Correct answer: Turnaround time

Turnaround time (TAT) measures elapsed time from specimen receipt to result availability.

Question 24: A low TSH with elevated free T4 is most consistent with which condition?

Euthyroid sick syndrome
Primary hypothyroidism
Primary hyperthyroidism (Correct answer)
Secondary hypothyroidism

Correct answer: Primary hyperthyroidism

Excess thyroid hormone from the gland suppresses pituitary TSH via negative feedback.

Question 25: Which safety standard governs bloodborne pathogen exposure control in U.S. labs?

EMTALA
HIPAA Privacy Rule
OSHA Bloodborne Pathogens Standard (Correct answer)
Stark Law

Correct answer: OSHA Bloodborne Pathogens Standard

The OSHA Bloodborne Pathogens Standard mandates exposure control plans, PPE, and training.

Question 26: A proficiency testing (PT) sample must be handled in what manner under CLIA?

Analyzed only by the director personally
Tested in the same manner as patient specimens without inter-lab communication (Correct answer)
Referred to another lab for confirmation
Repeated until the expected answer is obtained

Correct answer: Tested in the same manner as patient specimens without inter-lab communication

CLIA prohibits referral or communication about PT samples; they must be tested like routine patient specimens.

Question 27: Which syndrome links multiple sebaceous adenomas/carcinomas to internal malignancies (especially colorectal cancer) through mismatch repair gene mutations?

Birt-Hogg-Dubé syndrome
Muir-Torre syndrome (Correct answer)
Cowden syndrome
Gardner syndrome

Correct answer: Muir-Torre syndrome

Muir-Torre syndrome is a variant of Lynch syndrome caused by mismatch repair gene mutations (MLH1, MSH2), characterized by sebaceous neoplasms and an increased risk of visceral malignancies.

Question 28: When lot-to-lot reagent verification shows a significant bias, the appropriate action is to:

Discard all patient samples
Investigate, re-verify, and not place the new lot into service until acceptable (Correct answer)
Use the new lot immediately without checks
Change the reference range arbitrarily

Correct answer: Investigate, re-verify, and not place the new lot into service until acceptable

A new reagent lot showing bias must be investigated and verified acceptable before use in patient testing.

Question 29: In a non-ulcerated melanoma, Breslow thickness is measured from:

The base of the epidermis to the base of the tumor
The granular layer to the deepest tumor cell (Correct answer)
The dermal-epidermal junction to the deepest tumor cell
The skin surface to the deepest tumor cell

Correct answer: The granular layer to the deepest tumor cell

Breslow thickness is measured from the top of the granular layer (or the base of an ulcer if ulcerated) to the deepest invasive tumor cell.

Question 30: A compound melanocytic lesion shows large epithelioid cells with abundant cytoplasm containing fine 'dusty' melanin pigment arranged in nests, with a pushing border into the deep dermis but no significant atypia or mitoses. This best describes:

Nodular melanoma
Reed (pigmented spindle cell) nevus
Deep penetrating nevus (Correct answer)
Cellular blue nevus

Correct answer: Deep penetrating nevus

Deep penetrating nevus is characterized by large epithelioid-to-spindle melanocytes with abundant dusty melanin pigment arranged in nests and fascicles, extending deeply into the dermis with a pushing border but without significant atypia.

Question 31: A 68-year-old female is admitted with chest pain. Serial high-sensitivity cardiac troponin I (hs-cTnI) levels are measured. The first result is 45 ng/L (99th percentile URL: 26 ng/L). A second result 3 hours later is 250 ng/L. According to the universal definition of myocardial infarction, what does this pattern represent?

Analytic interference in the assay
A clinically insignificant fluctuation
A significant rise and fall pattern indicative of acute myocardial infarction (Correct answer)
Chronic myocardial injury

Correct answer: A significant rise and fall pattern indicative of acute myocardial infarction

The universal definition of myocardial infarction requires a rise and/or fall of cardiac troponin values with at least one value above the 99th percentile upper reference limit. The significant increase from 45 ng/L to 250 ng/L over 3 hours, with the initial value already being elevated, is characteristic of an acute event like a myocardial infarction, differentiating it from chronic, stable elevations.

Question 32: Which immunohistochemical staining pattern is most characteristic of Merkel cell carcinoma and helps distinguish it from metastatic small cell carcinoma of the lung?

Dot-like CK20 positivity with TTF-1 negativity (Correct answer)
Membranous CD20 positivity with CK20 negativity
Diffuse S100 positivity with synaptophysin negativity
Diffuse CK7 positivity with CK20 negativity

Correct answer: Dot-like CK20 positivity with TTF-1 negativity

Merkel cell carcinoma shows a characteristic dot-like (perinuclear) CK20 staining pattern and is TTF-1 negative, distinguishing it from metastatic pulmonary small cell carcinoma which is TTF-1 positive and CK20 negative.

Question 33: Elevated conjugated (direct) bilirubin with elevated alkaline phosphatase most suggests which process?

Cholestasis/biliary obstruction (Correct answer)
Hemolysis
Gilbert syndrome
Crigler-Najjar syndrome

Correct answer: Cholestasis/biliary obstruction

Obstruction to bile flow raises conjugated bilirubin and ALP, the hallmark of a cholestatic pattern.

Question 34: Which pre-analytical error most commonly causes falsely elevated serum lactate?

Rapid centrifugation
Using a fluoride tube
Delayed separation of plasma from cells (Correct answer)
Refrigerating the sample immediately

Correct answer: Delayed separation of plasma from cells

Red and white cells continue glycolysis in the tube, generating lactate if plasma is not separated promptly.

Question 35: A catalase-positive, coagulase-positive gram-positive cocci in clusters is isolated from a wound. Which organism is most likely?

Staphylococcus epidermidis
Streptococcus pyogenes
Staphylococcus aureus (Correct answer)
Enterococcus faecalis

Correct answer: Staphylococcus aureus

S. aureus is catalase-positive and coagulase-positive, distinguishing it from other staphylococci.

Question 36: In the ABO system, which individual is the universal plasma donor?

Group B
Group AB (Correct answer)
Group A
Group O

Correct answer: Group AB

Group AB plasma lacks anti-A and anti-B, making it the universal plasma donor.

Question 37: Celiac disease (gluten-sensitive enteropathy) is characterized by which histologic triad?

Mucosal erosions, pseudopolyps, crypt abscesses
Transmural inflammation, skip lesions, fissuring ulcers
Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (Correct answer)
Granulomas, crypt hyperplasia, goblet cell loss

Correct answer: Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis

The classic triad of celiac disease is villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis (>25 IELs per 100 enterocytes) on duodenal biopsy.

Question 38: Before issuing RBCs, the antihuman globulin (AHG) crossmatch primarily ensures:

The recipient is RhD positive
Platelet function is adequate
The donor has no infectious disease
Donor cells are compatible with recipient antibodies (Correct answer)

Correct answer: Donor cells are compatible with recipient antibodies

The AHG crossmatch confirms donor red cells are compatible with clinically significant recipient antibodies.

Question 39: A patient's peripheral smear shows schistocytes, thrombocytopenia, and elevated LDH with normal coagulation studies. Which condition is most consistent?

Immune thrombocytopenic purpura
Vitamin K deficiency
Disseminated intravascular coagulation
Thrombotic thrombocytopenic purpura (Correct answer)

Correct answer: Thrombotic thrombocytopenic purpura

TTP causes microangiopathic hemolytic anemia with schistocytes and thrombocytopenia while PT/PTT remain normal.

Question 40: Transfusion-associated circulatory overload (TACO) is best distinguished from TRALI by which feature?

Positive DAT
Normal blood pressure
Absence of respiratory symptoms
Elevated BNP and response to diuretics (Correct answer)

Correct answer: Elevated BNP and response to diuretics

TACO shows cardiogenic edema with elevated BNP and improves with diuresis, unlike TRALI.

Question 41: Which of the following immunophenotypic profiles, as determined by flow cytometry, is most characteristic of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)?

CD19+, CD5+, CD23+, dim CD20 (Correct answer)
CD19+, CD103+, CD25+, CD11c+
CD19+, CD5-, CD10+, CD23-
CD19+, CD5+, CD10+, Cyclin D1+

Correct answer: CD19+, CD5+, CD23+, dim CD20

The classic immunophenotype for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) is the co-expression of the B-cell marker CD19 with the T-cell associated marker CD5. Additionally, CLL/SLL cells are typically positive for CD23 and show characteristically dim expression of CD20 and surface immunoglobulin. This pattern helps distinguish it from other B-cell lymphomas, such as mantle cell lymphoma (CD5+, CD23-, bright CD20, Cyclin D1+) and follicular lymphoma (CD5-, CD10+).

Question 42: An organized thrombus that becomes recanalized indicates:

Conversion to an infarct
Immediate embolization
Complete permanent occlusion
New vascular channels forming through the thrombus (Correct answer)

Correct answer: New vascular channels forming through the thrombus

Recanalization is the formation of new endothelial-lined channels through an organizing thrombus, partially restoring flow.

Question 43: Neurofibrillary tangles seen in Alzheimer disease are composed primarily of which protein?

Alpha-synuclein
Hyperphosphorylated tau (Correct answer)
Prion protein
Ubiquitin

Correct answer: Hyperphosphorylated tau

Neurofibrillary tangles consist of paired helical filaments made of hyperphosphorylated tau protein that accumulates intraneuronally in Alzheimer disease.

Question 44: At what temperature must red blood cell units be stored during refrigerated storage?

10 to 15°C
1 to 6°C (Correct answer)
-18°C or colder
20 to 24°C

Correct answer: 1 to 6°C

RBC units are stored refrigerated at 1 to 6°C.

Question 45: Which histologic feature defines squamous cell carcinoma?

Keratin pearls and intercellular bridges (Correct answer)
Gland formation and mucin
Rosette formation
Signet ring cells

Correct answer: Keratin pearls and intercellular bridges

Keratinization (keratin pearls) and intercellular bridges characterize squamous cell carcinoma.

Question 46: Which cells are the primary phagocytic immune cells of the central nervous system?

Ependymal cells
Microglia (Correct answer)
Oligodendrocytes
Astrocytes

Correct answer: Microglia

Microglia are the resident macrophage-like immune cells of the CNS, derived from yolk sac progenitors, and serve as the primary CNS phagocytes.

Question 47: A keloid represents which abnormality of wound healing?

Wound dehiscence
Failure of epithelialization
Deficient collagen deposition
Excessive collagen deposition beyond the wound margins (Correct answer)

Correct answer: Excessive collagen deposition beyond the wound margins

A keloid is an exuberant scar with excess collagen that extends beyond the original wound boundaries.

Question 48: What is the most common genetic mutation in colorectal cancer?

TP53 mutation
BRCA1 mutation
KRAS mutation (Correct answer)
BRAF mutation

Correct answer: KRAS mutation

Colorectal cancer development is often driven by a series of genetic mutations. Among these, mutations in the KRAS gene are one of the most common, occurring in approximately 30-50% of colorectal cancers. KRAS mutations are significant as they activate downstream signaling pathways that promote cell growth and proliferation, and they also have implications for targeted therapy selection.

Question 49: Which finding best supports a diagnosis of paroxysmal cold hemoglobinuria?

Warm IgG autoantibody
A biphasic Donath-Landsteiner antibody with anti-P specificity (Correct answer)
Anti-I cold agglutinin
Anti-D alloantibody

Correct answer: A biphasic Donath-Landsteiner antibody with anti-P specificity

PCH is caused by a biphasic Donath-Landsteiner IgG antibody with anti-P specificity.

Question 50: Rapid accumulation of blood in the pericardial sac causing impaired filling defines:

Right heart failure
Cardiac tamponade (Correct answer)
Constrictive pericarditis
Restrictive cardiomyopathy

Correct answer: Cardiac tamponade

Cardiac tamponade occurs when pericardial fluid compresses the heart, limiting diastolic filling.

Question 51: A 'dry tap' on bone marrow aspiration with fibrosis and teardrop cells suggests:

Chronic lymphocytic leukemia
Primary myelofibrosis (Correct answer)
Polycythemia vera
Multiple myeloma

Correct answer: Primary myelofibrosis

Marrow fibrosis in PMF yields a dry tap and dacrocytes (teardrop cells) on smear.

Question 52: Which oncogene is most classically amplified in HER2-positive breast carcinoma and targeted by trastuzumab?

APC
TP53
ERBB2 (HER2/neu) (Correct answer)
RB1

Correct answer: ERBB2 (HER2/neu)

ERBB2 (HER2/neu) amplification defines HER2-positive breast cancer treated with trastuzumab.

Question 53: A patient with a history of anaphylactic transfusion reactions and undetectable IgA most likely needs which product?

Fresh frozen plasma
Leukoreduced plasma only
Washed or IgA-deficient components (Correct answer)
Irradiated platelets

Correct answer: Washed or IgA-deficient components

IgA-deficient patients with anti-IgA require washed or IgA-deficient components.

Question 54: Which tumor marker is most useful for monitoring colorectal cancer recurrence?

PSA
CA-125
AFP
CEA (Correct answer)

Correct answer: CEA

Carcinoembryonic antigen is the standard marker for surveillance of colorectal carcinoma after treatment.

Question 55: Which of the following cell types is the primary constituent of the fatty streak, the earliest grossly visible lesion of atherosclerosis?

Adherent platelets
Lipid-laden macrophages (foam cells) (Correct answer)
Proliferating smooth muscle cells
Neutrophils

Correct answer: Lipid-laden macrophages (foam cells)

The fatty streak is the initial lesion of atherosclerosis and is composed primarily of lipid-laden macrophages, also known as foam cells. These cells form when circulating monocytes adhere to the endothelium, migrate into the intima, differentiate into macrophages, and then engulf modified lipoproteins (like oxidized LDL). While smooth muscle cells and lymphocytes are also involved in the progression of the plaque, foam cells define the fatty streak.

Question 56: Which of the following conditions is associated with a high erythrocyte sedimentation rate (ESR)?

Rheumatoid arthritis (Correct answer)
Iron-deficiency anemia
Chronic dehydration
Sickle cell anemia

Correct answer: Rheumatoid arthritis

The erythrocyte sedimentation rate (ESR) is a non-specific marker of inflammation. It measures the rate at which red blood cells settle in a tube of blood over a specific time. In inflammatory conditions like rheumatoid arthritis, increased levels of acute phase proteins (e.g., fibrinogen) cause red blood cells to aggregate and settle faster, resulting in an elevated ESR.

Question 57: Ring sideroblasts seen with Prussian blue staining are a feature of which category of disease?

Acute lymphoblastic leukemia
Myelodysplastic syndrome (Correct answer)
Immune thrombocytopenia
Hodgkin lymphoma

Correct answer: Myelodysplastic syndrome

Ring sideroblasts reflect abnormal iron accumulation in mitochondria seen in certain MDS subtypes.

Question 58: Which stain best demonstrates iron (hemosiderin) in tissue?

Congo red
Silver stain
Prussian blue (Correct answer)
Oil red O

Correct answer: Prussian blue

Prussian blue (Perls) stain highlights iron deposits as blue.

Question 59: A salivary gland FNA shows a biphasic pattern of epithelial cells and metachromatic fibrillary stroma on Diff-Quik. Which diagnosis is favored?

Mucoepidermoid carcinoma
Acinic cell carcinoma
Warthin tumor
Pleomorphic adenoma (Correct answer)

Correct answer: Pleomorphic adenoma

The magenta fibrillary myxochondroid stroma with epithelial cells is classic for pleomorphic adenoma.

Question 60: Large, friable vegetations that can embolize and destroy the valve suggest which type of endocarditis?

Rheumatic verrucae
Nonbacterial thrombotic (marantic)
Libman-Sacks
Acute infective endocarditis (Correct answer)

Correct answer: Acute infective endocarditis

Acute infective endocarditis, often from S. aureus, produces large destructive vegetations.

Question 61: A positive direct antiglobulin test (DAT) with C3d only and cold agglutinins is most consistent with:

Warm autoimmune hemolytic anemia
Paroxysmal nocturnal hemoglobinuria
Cold agglutinin disease (Correct answer)
Drug-induced hemolysis

Correct answer: Cold agglutinin disease

Cold agglutinin disease typically shows complement (C3d) coating without IgG on the DAT.

Question 62: A laboratory is considering purchasing a new instrument that has a fixed cost of $120,000. The variable cost per test (e.g., reagents, consumables) is $8, and the reimbursement per test is $20. Disregarding other fixed costs like labor and overhead, how many tests must be performed to reach the break-even point for the instrument?

5,000
15,000
10,000 (Correct answer)
6,000

Correct answer: 10,000

The break-even point in units is calculated by dividing the total fixed costs by the contribution margin per unit. First, calculate the contribution margin: Reimbursement ($20) - Variable Cost ($8) = $12 per test. Then, divide the fixed cost by the contribution margin: $120,000 / $12 = 10,000 tests.

Question 63: Granulomatous inflammation of the temporal artery with giant cells and skip lesions defines which vasculitis?

Kawasaki disease
Giant cell (temporal) arteritis (Correct answer)
Buerger disease
Polyarteritis nodosa

Correct answer: Giant cell (temporal) arteritis

Giant cell arteritis affects large-to-medium vessels with granulomas, giant cells, and segmental skip lesions.

Question 64: The t(9;22) BCR-ABL1 fusion is the defining genetic lesion of which chronic myeloproliferative neoplasm?

Polycythemia vera
Primary myelofibrosis
Chronic myeloid leukemia (Correct answer)
Essential thrombocythemia

Correct answer: Chronic myeloid leukemia

The Philadelphia chromosome t(9;22) producing BCR-ABL1 defines CML.

Question 65: Spongiform encephalopathy with PrP-positive plaques and rapid progressive dementia is MOST consistent with which condition?

Multi-infarct dementia
Huntington disease
Creutzfeldt-Jakob disease (Correct answer)
ALS

Correct answer: Creutzfeldt-Jakob disease

Creutzfeldt-Jakob disease (CJD) is a prion disease characterized by spongiform change, astrogliosis, neuronal loss, and PrP-positive amyloid plaques.

Question 66: Apple-green birefringence under polarized light after Congo red staining indicates deposition of what?

Calcium
Glycogen
Amyloid (Correct answer)
Hemosiderin

Correct answer: Amyloid

Amyloid shows apple-green birefringence with Congo red and causes restrictive cardiomyopathy.

Question 67: Which parasite is transmitted by ingesting undercooked pork and forms cysts in muscle?

Giardia lamblia
Taenia saginata
Trichinella spiralis (Correct answer)
Entamoeba histolytica

Correct answer: Trichinella spiralis

Trichinella spiralis larvae encyst in striated muscle after ingesting undercooked pork.

Question 68: Healing by primary intention (first intention) is characteristic of:

A chronic diabetic ulcer
An abscess cavity
A clean surgical incision with approximated edges (Correct answer)
A large open wound with tissue loss

Correct answer: A clean surgical incision with approximated edges

Primary intention healing occurs in clean wounds with closely apposed edges, requiring minimal granulation tissue.

Question 69: Which bacterium is the most common cause of hospital-acquired Clostridioides difficile risk after broad-spectrum antibiotics?

Enterococcus faecium
Clostridioides difficile (Correct answer)
Bacteroides fragilis
Clostridium perfringens

Correct answer: Clostridioides difficile

C. difficile overgrows after antibiotic disruption of normal flora, causing pseudomembranous colitis.

Question 70: A 17-year-old athlete suddenly collapses and dies during a basketball game. Autopsy reveals a heart weight of 550 grams (normal <350g) with marked, asymmetric thickening of the interventricular septum. Microscopic examination of the septum shows extensive, haphazardly arranged cardiomyocytes with interstitial fibrosis. Which of the following is the most likely diagnosis?

Hypertrophic cardiomyopathy (Correct answer)
Arrhythmogenic right ventricular cardiomyopathy
Restrictive cardiomyopathy due to amyloidosis
Dilated cardiomyopathy

Correct answer: Hypertrophic cardiomyopathy

The clinical scenario of a young athlete with sudden cardiac death, combined with the gross finding of asymmetric septal hypertrophy and the key microscopic feature of myofiber disarray, is classic for hypertrophic cardiomyopathy (HCM). HCM is the most common cause of sudden cardiac death in young athletes. The histopathologic hallmarks are myocyte hypertrophy, myofiber disarray, and interstitial fibrosis.

Question 71: Necrotizing vasculitis of medium arteries with lesions of varying ages, sparing the lungs, and associated with hepatitis B is characteristic of?

Granulomatosis with polyangiitis
Microscopic polyangiitis
Churg-Strauss syndrome
Polyarteritis nodosa (Correct answer)

Correct answer: Polyarteritis nodosa

Polyarteritis nodosa shows segmental transmural necrotizing inflammation of medium vessels of differing ages and links to HBV.

Question 72: A CD5-positive, CD23-positive small B-cell lymphoma with smudge cells on smear is most consistent with:

Follicular lymphoma
Mantle cell lymphoma
Burkitt lymphoma
Chronic lymphocytic leukemia/small lymphocytic lymphoma (Correct answer)

Correct answer: Chronic lymphocytic leukemia/small lymphocytic lymphoma

CLL/SLL is CD5+/CD23+ and classically shows smudge cells on the peripheral smear.

Question 73: Which histologic feature best supports a diagnosis of Spitz nevus over melanoma in a pediatric patient?

High mitotic rate at the base
Nuclear pleomorphism
Presence of Kamino bodies (Correct answer)
Pagetoid spread throughout epidermis

Correct answer: Presence of Kamino bodies

Kamino bodies — eosinophilic PAS-positive globules at the dermal-epidermal junction — are characteristic of Spitz nevi and are a helpful benign feature distinguishing them from melanoma.

Question 74: A comatose patient is brought to the emergency room with suspected toxic ingestion. Labs show: measured osmolality 350 mOsm/kg, Na+ 140 mmol/L, BUN 28 mg/dL, Glucose 90 mg/dL. The calculated osmolality is 295 mOsm/kg. Anion gap is 25 mEq/L. What is the most likely cause of the elevated osmolal gap and anion gap?

Diabetic ketoacidosis
Ethylene glycol poisoning (Correct answer)
Isopropanol ingestion
Ethanol intoxication

Correct answer: Ethylene glycol poisoning

The osmolal gap is the difference between the measured and calculated osmolality (350 - 295 = 55 mOsm/kg). An elevated osmolal gap (>10-15) indicates the presence of unmeasured osmoles. Ethylene glycol is an osmotically active parent compound that causes an initial elevation in the osmolal gap. As it is metabolized by alcohol dehydrogenase to acidic metabolites (e.g., glycolic acid, oxalic acid), the osmolal gap decreases while the anion gap increases. The presence of both a significantly elevated osmolal gap and a high anion gap is highly characteristic of ethylene glycol (or methanol) poisoning. Isopropanol causes an elevated osmolal gap but typically not a significant anion gap.

Question 75: Direct immunofluorescence (DIF) in dermatitis herpetiformis characteristically shows:

Linear IgG along the basement membrane zone
Intercellular IgG in a fish-net pattern
Granular IgA deposits in the dermal papillae (Correct answer)
IgM deposits around superficial blood vessels

Correct answer: Granular IgA deposits in the dermal papillae

Dermatitis herpetiformis shows granular IgA deposits in the tips of the dermal papillae on DIF, reflecting tissue transglutaminase autoantibody deposition in this gluten-sensitive dermatosis.

Question 76: A febrile patient returning from sub-Saharan Africa has ring forms and banana-shaped gametocytes on blood smear. Diagnosis?

Trypanosoma brucei
Plasmodium vivax
Plasmodium falciparum (Correct answer)
Babesia microti

Correct answer: Plasmodium falciparum

Crescent/banana-shaped gametocytes are characteristic of P. falciparum.

Question 77: A patient with uncontrolled Type 1 diabetes presents with nausea, vomiting, and altered mental status. Laboratory results are: Na+ 132 mmol/L, K+ 5.1 mmol/L, Cl- 95 mmol/L, HCO3- 10 mmol/L, Glucose 550 mg/dL. What is the calculated serum anion gap, and what is its significance?

27 mmol/L, indicating a high anion gap metabolic acidosis (Correct answer)
12 mmol/L, which is a normal anion gap
17 mmol/L, which is borderline high and requires further investigation
5 mmol/L, indicating a low anion gap

Correct answer: 27 mmol/L, indicating a high anion gap metabolic acidosis

The anion gap is calculated as [Na+] – ([Cl-] + [HCO3-]). Using the patient's values: 132 – (95 + 10) = 27 mmol/L. A normal anion gap is typically between 8-12 mEq/L. An anion gap of 27 is significantly elevated, indicating a high anion gap metabolic acidosis. In this clinical context, it is due to the accumulation of unmeasured ketoacids (beta-hydroxybutyrate and acetoacetate) characteristic of diabetic ketoacidosis (DKA).

Question 78: Which analyte is most affected by prolonged tourniquet application during venipuncture?

Chloride
Glucose
Sodium
Potassium (Correct answer)

Correct answer: Potassium

Venous stasis and hemoconcentration falsely elevate potassium due to leakage from cells and muscle activity.

Question 79: Labile cells that continuously divide throughout life include:

Neurons
Hepatocytes
Cardiac myocytes
Surface epithelium of the gut and skin (Correct answer)

Correct answer: Surface epithelium of the gut and skin

Labile cells such as gut and skin epithelium proliferate continuously to replace lost cells.

Question 80: Which protozoan causes profuse watery diarrhea in AIDS patients and stains acid-fast in stool?

Entamoeba histolytica
Giardia lamblia
Trichomonas vaginalis
Cryptosporidium parvum (Correct answer)

Correct answer: Cryptosporidium parvum

Cryptosporidium oocysts are acid-fast and cause chronic diarrhea in immunocompromised patients.

Question 81: Cost per reportable result is calculated by dividing total costs by:

Number of instruments
Number of staff
Square footage of the lab
Number of reportable patient results (Correct answer)

Correct answer: Number of reportable patient results

Cost per reportable result divides total operating costs by the number of billable/reportable results produced.

Question 82: Which accreditation body offers the deemed-status inspection program most commonly used by U.S. pathology laboratories?

OSHA
CDC
FDA
College of American Pathologists (CAP) (Correct answer)

Correct answer: College of American Pathologists (CAP)

CAP holds CMS deemed status and inspects labs for CLIA compliance through its accreditation program.

Question 83: Which metric best describes the fraction of time an analyzer is available and functioning for testing?

Instrument uptime (Correct answer)
Turnaround time
Specimen rejection rate
Critical value rate

Correct answer: Instrument uptime

Instrument uptime measures the percentage of time equipment is operational and available for use.

Question 84: The CD30-positive, ALK-positive large cell lymphoma with t(2;5) is:

Burkitt lymphoma
Follicular lymphoma
Classic Hodgkin lymphoma
Anaplastic large cell lymphoma (Correct answer)

Correct answer: Anaplastic large cell lymphoma

ALK-positive ALCL carries t(2;5) NPM-ALK fusion and expresses CD30.

Question 85: Caseating granulomas with central 'cheese-like' necrosis are most characteristic of?

Sarcoidosis
Crohn disease
Rheumatoid arthritis
Tuberculosis (Correct answer)

Correct answer: Tuberculosis

Caseous (cheese-like) necrosis within granulomas is the hallmark of tuberculosis.

Question 86: Competency assessment of testing personnel under CLIA must occur at minimum:

Every month
Once every five years
Only at hiring
Semiannually in the first year, then annually (Correct answer)

Correct answer: Semiannually in the first year, then annually

CLIA requires competency assessment at six months and twelve months during the first year, then annually thereafter.

Question 87: A weak D phenotype is best explained by which molecular mechanism?

Reduced quantity of complete D antigen on the red cell (Correct answer)
Presence of anti-D
Complete absence of the RHD gene
An acquired B antigen

Correct answer: Reduced quantity of complete D antigen on the red cell

Weak D results from a reduced number of otherwise complete D antigen sites.

Question 88: Which stain is used to highlight fungal organisms and Pneumocystis in tissue?

Trichrome
Congo red
Prussian blue
GMS (Grocott methenamine silver) (Correct answer)

Correct answer: GMS (Grocott methenamine silver)

GMS silver stain highlights fungi and Pneumocystis jirovecii as black organisms.

Question 89: Which finding on the CBC differential defines a leukemoid reaction rather than chronic myeloid leukemia?

Presence of BCR-ABL fusion
Low LAP score
Basophilia
High leukocyte alkaline phosphatase score (Correct answer)

Correct answer: High leukocyte alkaline phosphatase score

A leukemoid reaction shows a high LAP score, whereas CML characteristically shows a low LAP score.

Question 90: What is the primary function of platelets in the blood?

Oxygen transport
Immune response
Nutrient transport
Blood clotting (Correct answer)

Correct answer: Blood clotting

Platelets, also known as thrombocytes, are small, anucleated cell fragments crucial for hemostasis, the process of stopping bleeding. Their primary function is to form a platelet plug at sites of vascular injury and to provide a surface for the activation of coagulation factors, ultimately leading to the formation of a stable fibrin clot.

Question 91: A lymphoma of the stomach associated with Helicobacter pylori that may regress with antibiotics is:

Burkitt lymphoma
Follicular lymphoma
Extranodal marginal zone (MALT) lymphoma (Correct answer)
Mantle cell lymphoma

Correct answer: Extranodal marginal zone (MALT) lymphoma

Gastric MALT lymphoma is driven by chronic H. pylori infection and can regress after eradication.

Question 92: Which marker is a sensitive indicator of vascular/endothelial differentiation?

CK7
CDX2
GFAP
CD31 (Correct answer)

Correct answer: CD31

CD31 is a highly specific and sensitive endothelial marker used in vascular tumors.

Question 93: A variant found in a healthy population at 5% allele frequency in gnomAD is best classified using which ACMG criterion?

Pathogenic very strong (PVS1)
Pathogenic moderate (PM2)
Stand-alone benign (BA1) for high population frequency (Correct answer)
Supporting pathogenic (PP3)

Correct answer: Stand-alone benign (BA1) for high population frequency

BA1 applies when allele frequency exceeds a threshold (commonly 5%) too high for a pathogenic Mendelian variant.

Question 94: The predominant cell type in acute inflammation during the first 24 hours is the:

Plasma cell
Lymphocyte
Eosinophil
Neutrophil (Correct answer)

Correct answer: Neutrophil

Neutrophils are the first responders and dominate the early acute inflammatory infiltrate.

Question 95: Westgard rule 1-3s violation on quality control indicates that a single result exceeded:

The reportable range
Two standard deviations from the mean
One standard deviation from the mean
Three standard deviations from the mean (Correct answer)

Correct answer: Three standard deviations from the mean

The 1-3s rule flags a run when one control value falls outside three standard deviations of the mean.

Question 96: Which condition produces a spuriously low measured sodium due to hyperlipidemia or hyperproteinemia when using indirect ISE?

SIADH
True hypovolemic hyponatremia
Pseudohyponatremia (Correct answer)
Cerebral salt wasting

Correct answer: Pseudohyponatremia

Pseudohyponatremia occurs when excess lipids or proteins displace plasma water, lowering indirect ISE sodium readings.

Question 97: The t(X;18)(p11;q11) translocation producing an SS18-SSX fusion gene is the defining molecular alteration of:

Clear cell sarcoma of soft tissue
Epithelioid sarcoma
Kaposi sarcoma
Synovial sarcoma (Correct answer)

Correct answer: Synovial sarcoma

Synovial sarcoma is defined by the t(X;18)(p11;q11) translocation creating SS18-SSX1 or SS18-SSX2 fusion genes, which is diagnostic and found in virtually all cases regardless of morphology.

Question 98: Which of the following best defines analytical specificity?

The ability of an assay to measure only the intended analyte without interference (Correct answer)
The smallest amount detectable
The total time to result
The cost per test

Correct answer: The ability of an assay to measure only the intended analyte without interference

Analytical specificity is the assay's ability to measure the target analyte without cross-reacting substances.

Question 99: Clonality assessment of a suspected B-cell lymphoma is best performed by evaluating:

T-cell receptor gamma rearrangement
Immunoglobulin heavy chain (IGH) gene rearrangement (Correct answer)
KRAS mutation
JAK2 mutation

Correct answer: Immunoglobulin heavy chain (IGH) gene rearrangement

PCR-based IGH rearrangement analysis detects clonal B-cell populations supporting a lymphoma diagnosis.

Question 100: A 30-year-old male presents with recurrent episodes of dark urine, particularly in the morning, along with fatigue and abdominal pain. Laboratory studies show evidence of intravascular hemolysis (elevated LDH, low haptoglobin) and a CBC reveals pancytopenia. Which test is considered the gold standard for confirming a diagnosis of Paroxysmal Nocturnal Hemoglobinuria (PNH)?

Acidified serum lysis (Ham) test
Osmotic fragility test
Direct antiglobulin (Coombs) test
High-sensitivity flow cytometry for GPI-anchored proteins (Correct answer)

Correct answer: High-sensitivity flow cytometry for GPI-anchored proteins

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, acquired disorder caused by a mutation in the PIGA gene, leading to a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on the surface of blood cells. This makes them susceptible to complement-mediated destruction. High-sensitivity flow cytometry is the current gold standard diagnostic test, as it can accurately detect and quantify the percentage of cells (e.g., granulocytes and erythrocytes) that lack GPI-anchored proteins like CD55 and CD59. The Ham test is historical and has been replaced by flow cytometry.

Question 101: Which glomerular disease shows a 'wire-loop' appearance and is strongly associated with systemic lupus erythematosus?

Minimal change disease
IgA nephropathy
Diffuse proliferative glomerulonephritis (Correct answer)
Membranous nephropathy

Correct answer: Diffuse proliferative glomerulonephritis

Wire-loop lesions from subendothelial immune deposits characterize lupus diffuse proliferative GN.

Question 102: Which bacterium causes whooping cough and is cultured on Bordet-Gengou or Regan-Lowe media?

Corynebacterium diphtheriae
Haemophilus influenzae
Bordetella pertussis (Correct answer)
Legionella pneumophila

Correct answer: Bordetella pertussis

B. pertussis requires specialized Bordet-Gengou or Regan-Lowe media for isolation.

Question 103: In which condition would you most likely find hyperkalemia?

Acute myocardial infarction
Addison’s disease
Chronic kidney disease (Correct answer)
Hyperparathyroidism

Correct answer: Chronic kidney disease

Hyperkalemia, an elevated potassium level in the blood, is commonly seen in chronic kidney disease (CKD). The kidneys are primarily responsible for excreting excess potassium from the body. As kidney function declines in CKD, the ability to excrete potassium is impaired, leading to its accumulation in the bloodstream.

Question 104: Which of the following is a pre-analytical error?

Transcription error in the report
Incorrect instrument calibration
Wrong reference range applied
Patient misidentification during collection (Correct answer)

Correct answer: Patient misidentification during collection

Patient misidentification occurs before analysis and is a classic pre-analytical error.

Question 105: The Rh antigen most commonly implicated in hemolytic disease of the fetus and newborn is:

c
Cw
E
D (Correct answer)

Correct answer: D

Anti-D remains the most clinically significant cause of severe HDFN.

Question 106: Which type of shock results from a massive systemic vasodilation due to sepsis?

Obstructive shock
Distributive (septic) shock (Correct answer)
Cardiogenic shock
Hypovolemic shock

Correct answer: Distributive (septic) shock

Septic shock is a form of distributive shock caused by widespread vasodilation and increased vascular permeability.

Question 107: Which agar selectively isolates Neisseria gonorrhoeae from genital specimens?

Thayer-Martin agar (Correct answer)
Mannitol salt agar
Sabouraud agar
MacConkey agar

Correct answer: Thayer-Martin agar

Modified Thayer-Martin agar contains antibiotics that select for pathogenic Neisseria.

Question 108: Which anticoagulant-preservative allows RBC storage for up to 42 days?

CPD alone
Heparin
CPDA-1 with additive solution (AS) (Correct answer)
ACD-A

Correct answer: CPDA-1 with additive solution (AS)

Additive solutions extend RBC storage to 42 days.

Question 109: A patient with an anion gap of 24 and positive serum ketones most likely has which condition?

Lactic acidosis
Renal tubular acidosis
Diabetic ketoacidosis (Correct answer)
Chronic diarrhea

Correct answer: Diabetic ketoacidosis

High anion gap with ketonemia points to diabetic ketoacidosis from insulin deficiency.

Question 110: Schwannomas characteristically occur at which location in the central nervous system?

Cerebellum
Third ventricle
Cerebellopontine angle (CN VIII) (Correct answer)
Frontal lobe

Correct answer: Cerebellopontine angle (CN VIII)

Vestibular schwannomas (acoustic neuromas) arise from the vestibulocochlear nerve sheath at the cerebellopontine angle and are the most common schwannoma location.

Question 111: Which fasting requirement is essential before measuring a lipid panel's triglycerides accurately?

2 hours fasting
No fasting needed
9 to 12 hours fasting (Correct answer)
24 hours fasting

Correct answer: 9 to 12 hours fasting

Triglycerides rise after meals, so a 9-12 hour fast is standard for reliable measurement.

Question 112: Which test is used to quantify fetomaternal hemorrhage to calculate the RhIG dose?

Kleihauer-Betke test (Correct answer)
Coombs cross-match
Direct antiglobulin test
Osmotic fragility test

Correct answer: Kleihauer-Betke test

The Kleihauer-Betke test quantifies fetal cells in maternal blood to determine RhIG dosing.

Question 113: A low serum osmolality with high urine osmolality and hyponatremia suggests which diagnosis?

SIADH (Correct answer)
Diabetes insipidus
Psychogenic polydipsia with dilute urine
Dehydration

Correct answer: SIADH

SIADH causes inappropriate water retention with concentrated urine despite low plasma osmolality.

Question 114: A peripheral blood smear from a patient who recently returned from a trip to sub-Saharan Africa shows multiple small, ring-form trophozoites within some erythrocytes. Additionally, several distinct crescent-shaped gametocytes are observed. These findings are diagnostic for an infection with which of the following species?

Babesia microti
Plasmodium ovale
Plasmodium falciparum (Correct answer)
Plasmodium vivax

Correct answer: Plasmodium falciparum

The presence of crescent-shaped (or banana-shaped) gametocytes is a pathognomonic feature of Plasmodium falciparum. The observation of multiple ring forms within a single red blood cell and high levels of parasitemia are also characteristic of this species. Plasmodium vivax and ovale have amoeboid trophozoites and round gametocytes, while Babesia microti appears as ring forms but does not produce gametocytes in human blood and may form tetrads ('Maltese cross').

Question 115: Sensitivity of an assay to detect a mutation present at low tumor fraction is best described as its:

Positive predictive value
Reproducibility
Specificity
Limit of detection (Correct answer)

Correct answer: Limit of detection

The limit of detection defines the lowest variant allele fraction the assay can reliably identify.

Question 116: Which alteration is the primary target of EGFR tyrosine kinase inhibitor therapy in non-small cell lung cancer?

TP53 missense mutation
MYC amplification
KRAS G12C alone
EGFR exon 19 deletion (Correct answer)

Correct answer: EGFR exon 19 deletion

Exon 19 deletions and the L858R mutation are the classic activating EGFR alterations predicting TKI response.

Question 117: A 60-year-old patient presents with erythrocytosis, leukocytosis, and splenomegaly. A bone marrow biopsy is consistent with a myeloproliferative neoplasm (MPN). Molecular testing for the JAK2 V617F mutation is ordered. This mutation is most prevalent, occurring in over 95% of cases, in which of the following MPNs?

Polycythemia vera (PV) (Correct answer)
Essential thrombocythemia (ET)
Primary myelofibrosis (PMF)
Chronic myeloid leukemia (CML)

Correct answer: Polycythemia vera (PV)

The JAK2 V617F mutation is a hallmark of Philadelphia-negative MPNs. While it is found in approximately 50-60% of patients with ET and PMF, it is present in over 95% of patients with polycythemia vera (PV) and is a major diagnostic criterion for this disorder. CML is characterized by the BCR-ABL1 fusion gene.

Question 118: Which type of necrosis is most characteristically associated with ischemic injury to the myocardium?

Caseous necrosis
Fat necrosis
Liquefactive necrosis
Coagulative necrosis (Correct answer)

Correct answer: Coagulative necrosis

Ischemic injury to solid organs except the brain produces coagulative necrosis, where tissue architecture is preserved.

Question 119: A ruptured ventricular free wall after MI most commonly occurs at what time point?

Within 1 hour
3 to 7 days (Correct answer)
6 to 8 weeks
6 months or later

Correct answer: 3 to 7 days

Free wall rupture peaks at 3–7 days when the wall is maximally softened by macrophage-mediated debris removal.

Question 120: Which of the following is an appropriate corrective action after a QC failure?

Halt reporting, investigate, correct the problem, and re-run QC before resuming (Correct answer)
Ignore the failure if only one level failed
Change the mean to match the result
Release patient results immediately

Correct answer: Halt reporting, investigate, correct the problem, and re-run QC before resuming

A QC failure requires stopping reporting, investigating the cause, correcting it, and confirming acceptable QC before releasing results.

Question 121: A biopsy shows suprabasilar acantholysis with basal cells remaining attached to the basement membrane ('tombstoning'). This pattern is diagnostic of:

Epidermolysis bullosa simplex
Pemphigus vulgaris (Correct answer)
Bullous pemphigoid
Dermatitis herpetiformis

Correct answer: Pemphigus vulgaris

Pemphigus vulgaris shows suprabasilar acantholysis with 'tombstoning' of single basal cells still attached to the basement membrane, forming intraepidermal blisters due to anti-desmoglein 3 autoantibodies.

Question 122: On a Pap smear, koilocytes with perinuclear halos and raisinoid nuclei are the cytologic signature of which infection?

Human papillomavirus (LSIL) (Correct answer)
Actinomyces
Chlamydia
Candida

Correct answer: Human papillomavirus (LSIL)

Koilocytosis with perinuclear halos and wrinkled raisinoid nuclei is the hallmark of HPV cytopathic effect.

Question 123: Ki-67 immunostaining is used primarily to assess:

Hormone receptor status
Apoptosis rate
Vascular density
Proliferative index (Correct answer)

Correct answer: Proliferative index

Ki-67 labels proliferating cells and estimates the tumor proliferation index.

Question 124: Orphan Annie eye nuclei and nuclear grooves are cytologic features of which thyroid malignancy?

Follicular carcinoma
Papillary thyroid carcinoma (Correct answer)
Medullary thyroid carcinoma
Anaplastic carcinoma

Correct answer: Papillary thyroid carcinoma

Empty-appearing 'Orphan Annie' nuclei and grooves are diagnostic of papillary thyroid carcinoma.

Question 125: Which fungus shows a mold at 25°C and yeast at 37°C, causing pulmonary disease in the Ohio River Valley?

Sporothrix schenckii
Aspergillus fumigatus
Cryptococcus neoformans
Histoplasma capsulatum (Correct answer)

Correct answer: Histoplasma capsulatum

Histoplasma is a dimorphic fungus endemic to the Ohio and Mississippi River Valleys.

Question 126: Which stain is used to identify Mycobacterium tuberculosis in sputum?

Giemsa
India ink
Gram stain
Ziehl-Neelsen (acid-fast) (Correct answer)

Correct answer: Ziehl-Neelsen (acid-fast)

Acid-fast staining detects mycolic acid in the mycobacterial cell wall.

Question 127: The Westgard rule 1-3s is violated when a single control result falls:

Beyond 3 SD from the mean (Correct answer)
Exactly at the mean
Beyond 1 SD from the mean
Beyond 2 SD from the mean

Correct answer: Beyond 3 SD from the mean

The 1-3s rule flags a run when one control exceeds three standard deviations from the mean.

Question 128: Which fungus is identified by broad, ribbon-like, aseptate hyphae with wide-angle branching?

Candida albicans
Mucor (Zygomycetes) (Correct answer)
Cryptococcus neoformans
Aspergillus

Correct answer: Mucor (Zygomycetes)

Mucormycosis shows broad aseptate hyphae branching at wide (~90°) angles.

Question 129: Donovan bodies (Klebsiella granulomatis within macrophages) in granuloma inguinale are best demonstrated with:

Ziehl-Neelsen stain
Giemsa stain (Correct answer)
Grocott methenamine silver (GMS)
Periodic acid-Schiff (PAS)

Correct answer: Giemsa stain

Donovan bodies appear as bipolar-staining intracytoplasmic rod-shaped organisms with a 'safety pin' appearance, best demonstrated with Giemsa stain on tissue smears or biopsies.

Question 130: Depositions of monosodium urate crystals with negative birefringence are diagnostic of?

Rheumatoid arthritis
Gout (Correct answer)
Pseudogout
Osteoarthritis

Correct answer: Gout

Needle-shaped, negatively birefringent monosodium urate crystals confirm gout.

Question 131: A 55-year-old male presents to the emergency department with severe headache, palpitations, and sweating. His blood pressure is 210/120 mmHg. A 24-hour urine collection is ordered to screen for a suspected pheochromocytoma. Which of the following analytes provides the highest diagnostic sensitivity for this condition?

Fractionated metanephrines (Correct answer)
Total catecholamines
Vanillylmandelic acid (VMA)
Homovanillic acid (HVA)

Correct answer: Fractionated metanephrines

Fractionated metanephrines (metanephrine and normetanephrine) in urine or plasma are the metabolites of epinephrine and norepinephrine. Their measurement is recommended for the initial biochemical testing for pheochromocytomas and paragangliomas due to their superior diagnostic sensitivity compared to catecholamines or VMA. Tumors secrete these metabolites continuously, making them less susceptible to fluctuations seen with catecholamine secretion.

Question 132: Granulomatous inflammation is characterized by aggregates of activated macrophages known as:

Foam cells
Epithelioid cells (Correct answer)
Reed-Sternberg cells
Mast cells

Correct answer: Epithelioid cells

Granulomas contain epithelioid histiocytes, which are activated macrophages with abundant cytoplasm.

Question 133: Free radical injury to cells is mediated most directly by:

Increased ATP synthesis
Enhanced protein folding
Lipid peroxidation of membranes (Correct answer)
Antioxidant enzymes

Correct answer: Lipid peroxidation of membranes

Reactive oxygen species damage cells largely through peroxidation of membrane lipids.

Question 134: The t(8;14) translocation involving MYC is the classic cytogenetic finding in:

Chronic lymphocytic leukemia
Burkitt lymphoma (Correct answer)
Follicular lymphoma
Mantle cell lymphoma

Correct answer: Burkitt lymphoma

Burkitt lymphoma harbors MYC translocation, most commonly t(8;14).

Question 135: Transfusion-related acute lung injury (TRALI) is characterized by which finding?

Isolated urticaria
Delayed hemolysis at 7 days
Volume overload with elevated BNP
Non-cardiogenic pulmonary edema within 6 hours of transfusion (Correct answer)

Correct answer: Non-cardiogenic pulmonary edema within 6 hours of transfusion

TRALI presents as acute non-cardiogenic pulmonary edema within 6 hours of transfusion.

Question 136: Which HPV genotypes are most strongly associated with cervical squamous carcinoma detected on Pap testing?

HPV 16 and 18 (Correct answer)
HPV 40 and 54
HPV 42 and 44
HPV 6 and 11

Correct answer: HPV 16 and 18

HPV 16 and 18 are the high-risk genotypes responsible for most cervical cancers.

Question 137: Which analyte requires collection on ice and rapid processing to avoid falsely low results?

Ammonia (Correct answer)
Cholesterol
Uric acid
Total protein

Correct answer: Ammonia

Ammonia rises rapidly at room temperature from deamination, so chilled tubes and quick processing are required.

Question 138: In a Fragile X (FMR1) analysis, which molecular feature defines a full mutation?

A balanced translocation at Xq27
A point mutation in exon 1
More than 200 CGG repeats with hypermethylation (Correct answer)
Deletion of the entire gene

Correct answer: More than 200 CGG repeats with hypermethylation

A full mutation is >200 CGG repeats, typically accompanied by promoter hypermethylation and gene silencing.

Question 139: Which of the following infectious agents is NOT universally tested for on all allogeneic blood donations in the United States?

Hepatitis B Virus (HBV)
Cytomegalovirus (CMV) (Correct answer)
Human Immunodeficiency Virus (HIV)
Hepatitis C Virus (HCV)

Correct answer: Cytomegalovirus (CMV)

While all blood donations in the U.S. are tested for a panel of infectious agents including HIV, HCV, HBV, and others, Cytomegalovirus (CMV) testing is not performed on every unit. [9, 12, 23] CMV testing is typically performed on a subset of donations to provide CMV-seronegative products for specific at-risk patient populations, such as premature infants and transplant recipients.

Question 140: A patient with hemolyzed serum will show a falsely increased value for which analyte?

Potassium (Correct answer)
Albumin
Bicarbonate
Sodium

Correct answer: Potassium

Red cells are rich in potassium, so hemolysis releases it into serum and elevates the measured value.

Question 141: Which of the following is a benign tumor of smooth muscle commonly arising in the uterus?

Leiomyoma (Correct answer)
Lipoma
Leiomyosarcoma
Rhabdomyoma

Correct answer: Leiomyoma

A leiomyoma (fibroid) is a benign smooth-muscle tumor of the myometrium.

Question 142: Caseating granulomas are most characteristic of infection with:

Candida albicans
Escherichia coli
Mycobacterium tuberculosis (Correct answer)
Staphylococcus aureus

Correct answer: Mycobacterium tuberculosis

Caseating (necrotizing) granulomas are the hallmark of tuberculosis.

Question 143: What is the maximum room-temperature storage duration for platelet concentrates with continuous agitation?

42 days
21 days
5 to 7 days (Correct answer)
24 hours

Correct answer: 5 to 7 days

Platelets are stored 5 days (up to 7 with approved testing) at 20-24°C with agitation.

Question 144: Which vitamin deficiency most directly impairs collagen synthesis and wound healing?

Vitamin K
Vitamin C (Correct answer)
Vitamin B12
Vitamin D

Correct answer: Vitamin C

Vitamin C is required for hydroxylation of proline and lysine in collagen synthesis, so its deficiency impairs healing.

Question 145: Which pattern of inflammation is characterized by lymphocytes lined up along the dermal-epidermal junction with associated vacuolar change and dyskeratotic keratinocytes?

Psoriasiform
Granulomatous
Interface (Correct answer)
Perivascular

Correct answer: Interface

Interface dermatitis is defined by lymphocytes at the dermal-epidermal junction with vacuolar alteration and dyskeratotic (necrotic) keratinocytes, as seen in lichen planus and lupus.

Question 146: A lung biopsy from a severely immunocompromised patient with a pulmonary nodule is examined. Microscopic evaluation reveals fungal elements consisting of septate hyphae that branch at acute, 45-degree angles. This morphological finding is most characteristic of which of the following organisms?

Mucor species
Candida albicans
Cryptococcus neoformans
Aspergillus fumigatus (Correct answer)

Correct answer: Aspergillus fumigatus

The presence of septate hyphae with acute-angle (approximately 45-degree) branching is a classic histopathologic feature of Aspergillus species. In contrast, Mucor species (Zygomycetes) are characterized by broad, pauciseptate or non-septate hyphae with right-angle branching. Cryptococcus neoformans is an encapsulated yeast, and Candida albicans typically appears as budding yeasts and pseudohyphae.

Question 147: Which iron study pattern is most consistent with anemia of chronic disease?

Normal iron, normal ferritin
High serum iron, high ferritin, high transferrin saturation
Low serum iron, high TIBC, low ferritin
Low serum iron, low TIBC, high ferritin (Correct answer)

Correct answer: Low serum iron, low TIBC, high ferritin

Anemia of chronic disease shows low iron, low TIBC, and elevated ferritin as an acute-phase reactant.

Question 148: In a mixing study, a prolonged PTT that fails to correct after mixing with normal plasma indicates the presence of a(n):

Heparin contamination only
Vitamin K deficiency
Inhibitor (Correct answer)
Factor deficiency

Correct answer: Inhibitor

Failure to correct on mixing indicates an inhibitor rather than a simple factor deficiency, which would correct.

Question 149: Which stain is BEST used to highlight amyloid plaques in Alzheimer disease on formalin-fixed paraffin-embedded brain sections?

Prussian blue
PAS stain
Congo red (Correct answer)
Luxol fast blue

Correct answer: Congo red

Congo red stain reveals amyloid deposits as red-orange material with apple-green birefringence under polarized light, used to identify amyloid plaques.

Question 150: Digital droplet PCR offers an advantage over qPCR primarily because it provides:

Direct protein detection
Absolute quantification without a standard curve (Correct answer)
Whole-genome coverage
Longer read lengths

Correct answer: Absolute quantification without a standard curve

By partitioning the sample into thousands of droplets, ddPCR counts target molecules absolutely without needing a standard curve.

Question 151: A urease-positive, curved gram-negative rod is found in a gastric biopsy. Which organism?

Vibrio vulnificus
Campylobacter jejuni
Helicobacter pylori (Correct answer)
Bacteroides fragilis

Correct answer: Helicobacter pylori

H. pylori is urease-positive and colonizes gastric mucosa, causing ulcers.

Question 152: A patient presents with a high white blood cell count. Which condition is most likely?

Chronic myelogenous leukemia (Correct answer)
Lymphoma
Acute viral infection
Acute leukemia

Correct answer: Chronic myelogenous leukemia

While acute leukemia can present with a high WBC count, chronic myelogenous leukemia (CML) is classically associated with extremely high, often markedly elevated, white blood cell counts, sometimes exceeding 100,000 cells/µL. This is due to the uncontrolled proliferation of mature and immature myeloid cells, particularly neutrophils, in the bone marrow and peripheral blood.

Question 153: TRAP (tartrate-resistant acid phosphatase) positivity and cytoplasmic projections point to which leukemia?

Adult T-cell leukemia
Hairy cell leukemia (Correct answer)
Prolymphocytic leukemia
Chronic myeloid leukemia

Correct answer: Hairy cell leukemia

Hairy cell leukemia classically shows TRAP positivity and hairy cytoplasmic projections.

Question 154: Which test detects carbapenemase-producing Enterobacteriaceae?

Bile solubility test
Modified Hodge test / Carba-NP (Correct answer)
Optochin test
Coagulase test

Correct answer: Modified Hodge test / Carba-NP

The modified Hodge test and Carba-NP detect carbapenemase activity in resistant Enterobacteriaceae.

Question 155: Which of the following is a key feature that distinguishes apoptosis from necrosis?

Caspase activation and formation of apoptotic bodies (Correct answer)
Uncontrolled release of cellular contents
Cell swelling and membrane rupture
Significant inflammatory response

Correct answer: Caspase activation and formation of apoptotic bodies

Apoptosis, or programmed cell death, is a tightly regulated process characterized by the activation of a cascade of enzymes called caspases. This leads to the orderly dismantling of the cell and formation of membrane-bound apoptotic bodies, which are phagocytosed without eliciting an inflammatory response. [22] In contrast, necrosis is characterized by cell swelling, loss of membrane integrity, uncontrolled release of cellular contents, and a significant inflammatory response. [15, 24]

Question 156: In acute inflammation, which leukocyte is typically the FIRST to arrive at the site of injury?

Lymphocyte
Neutrophil (Correct answer)
Eosinophil
Plasma cell

Correct answer: Neutrophil

Neutrophils are the predominant early responders in acute inflammation.

Question 157: Which stain is most commonly used to demonstrate acid-fast bacilli such as Mycobacterium tuberculosis in tissue sections?

Periodic acid-Schiff
Ziehl-Neelsen (Correct answer)
Congo red
Prussian blue

Correct answer: Ziehl-Neelsen

Ziehl-Neelsen stain highlights the mycolic-acid-rich cell walls of acid-fast organisms.

Question 158: Which bacterium requires cysteine and iron (BCYE agar) and is diagnosed by urine antigen test?

Legionella pneumophila (Correct answer)
Chlamydia pneumoniae
Mycoplasma pneumoniae
Francisella tularensis

Correct answer: Legionella pneumophila

Legionella grows on charcoal yeast extract (BCYE) agar and is detected by urinary antigen.

Question 159: A delayed hemolytic transfusion reaction most often results from an anamnestic response to which antibody type?

Kidd (anti-Jka) antibodies (Correct answer)
Anti-A
Anti-P1
Anti-Lewis

Correct answer: Kidd (anti-Jka) antibodies

Kidd antibodies notoriously drop below detection and cause delayed reactions on re-exposure.

Question 160: A boggy, dilated heart with a mixed inflammatory infiltrate and myocyte necrosis on biopsy most suggests which diagnosis?

Lymphocytic myocarditis (Correct answer)
Chronic ischemic scarring
Amyloidosis
Hemochromatosis

Correct answer: Lymphocytic myocarditis

Lymphocytic (often viral) myocarditis shows interstitial lymphocytic infiltrate with adjacent myocyte necrosis.

Question 161: The gel column agglutination method detects antigen-antibody reactions based on:

Enzyme-linked fluorescence
Color change of a substrate
Trapping of agglutinated cells in a dextran gel matrix (Correct answer)
Precipitation of DNA

Correct answer: Trapping of agglutinated cells in a dextran gel matrix

In gel technology, agglutinated cells are trapped in the gel while unagglutinated cells settle to the bottom.

Question 162: What is the purpose of Rh immune globulin (RhIG) administration in an RhD-negative pregnant woman?

To prevent maternal anti-D alloimmunization from fetal RhD-positive cells (Correct answer)
To prevent ABO incompatibility
To treat existing anti-D antibodies
To raise the mother's hemoglobin

Correct answer: To prevent maternal anti-D alloimmunization from fetal RhD-positive cells

RhIG prevents active immunization by clearing fetal RhD-positive cells before sensitization.

Question 163: An explanted heart from a 50-year-old patient with progressive dyspnea and signs of right-sided heart failure shows normal-sized, non-dilated ventricles with marked atrial enlargement. The myocardium is firm and rubbery on sectioning. Endomyocardial biopsy with Congo red staining reveals salmon-pink deposits within the interstitium that exhibit apple-green birefringence under polarized light. These findings are most consistent with which type of cardiomyopathy?

Hypertrophic cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Restrictive cardiomyopathy (Correct answer)
Dilated cardiomyopathy

Correct answer: Restrictive cardiomyopathy

The clinical and gross findings of non-dilated, stiff ventricles with biatrial enlargement are characteristic of restrictive cardiomyopathy (RCM). The histologic finding of amyloid deposits, confirmed by Congo red staining with apple-green birefringence, identifies cardiac amyloidosis as the specific cause of the RCM. Amyloid deposition in the myocardial interstitium increases ventricular stiffness, impairs diastolic filling, and leads to heart failure.

Question 164: Which enzyme is most useful for distinguishing hepatocellular from cholestatic liver injury when elevated predominantly?

ALT (hepatocellular) versus ALP (cholestatic) (Correct answer)
Amylase
Creatine kinase
Lactate dehydrogenase

Correct answer: ALT (hepatocellular) versus ALP (cholestatic)

Predominant ALT elevation indicates hepatocellular injury while predominant ALP elevation indicates cholestasis.

Question 165: A skin biopsy shows parakeratosis, regular acanthosis with elongated rete ridges, and collections of neutrophils in the stratum corneum (Munro microabscesses). This is most consistent with:

Lichen planus
Pityriasis rosea
Psoriasis (Correct answer)
Seborrheic dermatitis

Correct answer: Psoriasis

Psoriasis classically shows Munro microabscesses (neutrophil collections in the stratum corneum), regular acanthosis with elongated rete ridges, and parakeratosis with suprapapillary plate thinning.

Question 166: Which organism produces a green pigment (pyocyanin) and a grape-like odor in culture?

Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa (Correct answer)
Escherichia coli

Correct answer: Pseudomonas aeruginosa

P. aeruginosa produces pyocyanin and a fruity/grape-like odor.

Question 167: Which vascular change is responsible for the redness and warmth (rubor and calor) of acute inflammation?

Vasoconstriction
Vasodilation and increased blood flow (Correct answer)
Thrombosis of arterioles
Decreased vascular permeability

Correct answer: Vasodilation and increased blood flow

Vasodilation increases local blood flow, producing the warmth and redness of inflammation.

Question 168: Bisulfite conversion is a required step for which type of analysis?

DNA methylation detection (Correct answer)
RNA fusion detection
Protein expression
Copy number quantification

Correct answer: DNA methylation detection

Bisulfite converts unmethylated cytosines to uracil while methylated cytosines are protected, enabling methylation analysis.

Question 169: Cardiac hemochromatosis leads to which functional pattern, and iron is best demonstrated by which stain?

Constrictive pattern; trichrome
Dilated pattern; PAS stain
Restrictive/dilated pattern; Prussian blue stain (Correct answer)
Hypertrophic pattern; Congo red

Correct answer: Restrictive/dilated pattern; Prussian blue stain

Iron overload causes a restrictive-then-dilated cardiomyopathy, and Prussian blue highlights myocyte iron.

Question 170: Verrucous, sterile vegetations on both surfaces of the valve leaflets in a lupus patient describe:

Infective endocarditis
Rheumatic endocarditis
Libman-Sacks endocarditis (Correct answer)
Marantic endocarditis

Correct answer: Libman-Sacks endocarditis

Libman-Sacks endocarditis of SLE produces small sterile vegetations on either or both leaflet surfaces.

Question 171: Primary sclerosing cholangitis (PSC) is MOST strongly associated with which bowel disease?

Microscopic colitis
Ulcerative colitis (Correct answer)
Celiac disease
Crohn disease (small bowel)

Correct answer: Ulcerative colitis

PSC is associated with ulcerative colitis in approximately 70–80% of cases; patients with both conditions have elevated risk for cholangiocarcinoma and colorectal cancer.

Question 172: A KRAS mutation in metastatic colorectal cancer predicts:

Sensitivity to imatinib
Resistance to anti-EGFR monoclonal antibody therapy (Correct answer)
Response to tamoxifen
Sensitivity to trastuzumab

Correct answer: Resistance to anti-EGFR monoclonal antibody therapy

Activating KRAS mutations downstream of EGFR confer resistance to cetuximab and panitumumab.

Question 173: Which of the following is the most common cause of acquired hemolytic anemia?

Autoimmune hemolytic anemia (Correct answer)
Thalassemia
Sickle cell disease
Hereditary spherocytosis

Correct answer: Autoimmune hemolytic anemia

Acquired hemolytic anemias are conditions where red blood cells are prematurely destroyed due to factors outside of inherited defects. Autoimmune hemolytic anemia (AIHA) is the most common acquired form, where the body's immune system mistakenly produces antibodies that target and destroy its own red blood cells. This immune-mediated destruction can be primary or secondary to other diseases.

Question 174: Which analyte is best measured in a first-morning urine sample for microalbuminuria screening?

Albumin-to-creatinine ratio (Correct answer)
Serum albumin
Urine specific gravity
Total protein by dipstick

Correct answer: Albumin-to-creatinine ratio

The albumin-to-creatinine ratio corrects for urine concentration and detects early diabetic nephropathy.

Question 175: A blood bank technologist is resolving an ABO discrepancy. The forward typing shows A positive, while the reverse typing is consistent with group O (anti-A and anti-B are reactive). The patient is a 75-year-old male with multiple myeloma. What is the most likely cause of this discrepancy?

Rouleaux formation (Correct answer)
Cold agglutinins
Recent transfusion with group O red cells
A weak subgroup of A

Correct answer: Rouleaux formation

The discrepancy described (forward type A, reverse type O) is a classic example of a Group III ABO discrepancy. [2] In patients with conditions causing hyperproteinemia, such as multiple myeloma, red blood cells can non-specifically aggregate in a 'stack of coins' appearance known as rouleaux formation. [14] This can cause false agglutination in the forward typing. Saline replacement or dilution techniques can typically resolve this type of discrepancy. [14]

Question 176: A monoclonal spike in the gamma region on serum protein electrophoresis with Bence Jones proteinuria is most characteristic of:

Chronic inflammation
Multiple myeloma (Correct answer)
Alpha-1 antitrypsin deficiency
Nephrotic syndrome

Correct answer: Multiple myeloma

A monoclonal M-spike with free light chains in urine (Bence Jones protein) is the hallmark of multiple myeloma.

Question 177: Six Sigma quality at the '6 sigma' level corresponds to approximately how many defects per million opportunities?

3.4 (Correct answer)
66,800
6800
340

Correct answer: 3.4

Six Sigma performance equates to roughly 3.4 defects per million opportunities.

Question 178: Concentric left ventricular hypertrophy without dilation is most typical of which cardiomyopathy pattern?

Dilated cardiomyopathy
Restrictive cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy
Hypertensive/pressure-overload hypertrophy (Correct answer)

Correct answer: Hypertensive/pressure-overload hypertrophy

Pressure overload (e.g., hypertension, aortic stenosis) causes concentric hypertrophy with parallel sarcomere addition.

Question 179: A markedly elevated hCG with a uterine mass and 'snowstorm' ultrasound suggests which condition?

Normal early pregnancy
Hydatidiform mole (Correct answer)
Ectopic pregnancy
Choriocarcinoma of the lung

Correct answer: Hydatidiform mole

Molar pregnancy produces very high hCG levels with characteristic vesicular sonographic appearance.

Question 180: The JAK2 V617F mutation is a key diagnostic marker for which group of disorders?

Hodgkin lymphoma
Myeloproliferative neoplasms (Correct answer)
Acute lymphoblastic leukemia
Multiple myeloma

Correct answer: Myeloproliferative neoplasms

JAK2 V617F is present in most polycythemia vera cases and many essential thrombocythemia and primary myelofibrosis cases.

Question 181: Which sampling error most commonly causes a false-negative FNA result?

Using liquid-based preparation
Missing the lesion and aspirating adjacent benign tissue (Correct answer)
Overstaining the slide
Adding an immunostain panel

Correct answer: Missing the lesion and aspirating adjacent benign tissue

Geographic miss of the target lesion is a leading cause of false-negative aspirates.

Question 182: Peripheral palisading of basaloid nuclei and retraction artifact (clefting) between tumor nests and stroma are hallmarks of:

Trichoepithelioma
Basal cell carcinoma (Correct answer)
Pilomatricoma
Syringoma

Correct answer: Basal cell carcinoma

Peripheral nuclear palisading and stromal retraction artifact (clefting) between tumor nests and the surrounding stroma are defining histological features of basal cell carcinoma.

Question 183: Which of the following is the most common site of metastasis for prostate cancer?

Lungs
Brain
Bone (Correct answer)
Liver

Correct answer: Bone

Prostate cancer frequently metastasizes, and the most common site for its spread is the bone, particularly the axial skeleton (spine, pelvis, ribs). These bone metastases are typically osteoblastic, meaning they stimulate new bone formation, and can cause significant pain and complications. Early detection and treatment are crucial to prevent such spread.

Question 184: Which condition classically produces a decreased haptoglobin level?

Iron deficiency
Intravascular hemolysis (Correct answer)
Acute infection
Dehydration

Correct answer: Intravascular hemolysis

Free hemoglobin from hemolysis binds and consumes haptoglobin, lowering its serum concentration.

Question 185: Which immunostain is the most widely used marker for gastrointestinal stromal tumors (GIST)?

S100
CD117 (c-KIT) (Correct answer)
TTF-1
Desmin

Correct answer: CD117 (c-KIT)

Most GISTs express CD117 (c-KIT), reflecting activating KIT mutations.

Question 186: Contraction band necrosis is most characteristically associated with which mechanism?

Chronic ischemia
Reperfusion injury and catecholamine excess (Correct answer)
Viral infection
Amyloid deposition

Correct answer: Reperfusion injury and catecholamine excess

Reperfusion and high catecholamine states cause hypercontracted myofibers with eosinophilic transverse bands.

Question 187: Which of the following laboratory findings is most consistent with hypercalcemia of malignancy?

Low serum calcium, elevated PTH
Elevated serum calcium, low PTH, elevated PTHrP (Correct answer)
Elevated serum calcium, low PTH, low PTHrP
Elevated serum calcium, elevated PTH

Correct answer: Elevated serum calcium, low PTH, elevated PTHrP

Hypercalcemia of malignancy is a common cause of nonparathyroid hypercalcemia. It is often mediated by the secretion of parathyroid hormone-related peptide (PTHrP) by tumors. PTHrP mimics the action of PTH on bone and kidney, leading to increased calcium levels. However, the high calcium level provides negative feedback to the parathyroid glands, suppressing the secretion of endogenous PTH. Therefore, the characteristic pattern is high calcium, low PTH, and high PTHrP.

Question 188: A red (hemorrhagic) infarct is most likely to occur in an organ with:

A single end-arterial supply
No venous drainage
Dual blood supply such as the lung (Correct answer)
Dense connective tissue

Correct answer: Dual blood supply such as the lung

Red infarcts occur in organs with dual circulation or collateral flow, like the lung, allowing blood to re-enter necrotic tissue.

Question 189: A 45-year-old woman presents with bilateral lower extremity swelling that has worsened over several months. She has a history of severe congestive heart failure. Physical examination reveals pitting edema to the mid-shin. The primary mechanism responsible for this patient's edema is an increase in which of the following?

Lymphatic drainage
Interstitial oncotic pressure
Capillary hydrostatic pressure (Correct answer)
Plasma oncotic pressure

Correct answer: Capillary hydrostatic pressure

Edema in congestive heart failure is primarily caused by an increase in capillary hydrostatic pressure. [19] The failing heart cannot pump blood effectively, leading to venous congestion and increased pressure in the capillaries, which forces fluid into the interstitial space. Decreased plasma oncotic pressure, as seen in nephrotic syndrome or liver failure, can also cause edema, but increased hydrostatic pressure is the dominant mechanism in heart failure. [3, 11, 19]

Question 190: Which enzyme elevation is most specific for acute pancreatitis?

Alkaline phosphatase
ALT
Lipase (Correct answer)
Amylase

Correct answer: Lipase

Lipase is more specific and stays elevated longer than amylase in acute pancreatitis.

Question 191: Which of the following is a common histologic feature of chronic inflammation?

Neutrophil infiltration
Granuloma formation (Correct answer)
Hyperemia
Eosinophil infiltration

Correct answer: Granuloma formation

Chronic inflammation is characterized by the prolonged presence of inflammatory cells, tissue destruction, and attempts at repair. Granuloma formation, a specific type of chronic inflammation, involves aggregates of activated macrophages (epithelioid cells) often surrounded by lymphocytes, and is a hallmark response to persistent irritants or certain microorganisms like Mycobacterium tuberculosis. While neutrophils are key in acute inflammation, granulomas are distinctive for chronic processes.

Question 192: What is the characteristic histologic feature of Crohn’s disease?

Villous atrophy
Granulomas (Correct answer)
Crypt abscesses
Goblet cell hyperplasia

Correct answer: Granulomas

Crohn's disease is a chronic inflammatory bowel disease that can affect any part of the gastrointestinal tract. A characteristic histologic feature, though not always present, is the presence of non-caseating granulomas in the bowel wall. These granulomas are aggregates of epithelioid macrophages and lymphocytes, distinguishing Crohn's disease from ulcerative colitis.

Question 193: A 75-year-old patient develops profuse watery diarrhea after a 10-day course of antibiotics for pneumonia. A stool sample is tested using a multi-step algorithm. The initial glutamate dehydrogenase (GDH) antigen test is positive, but the toxin A/B enzyme immunoassay (EIA) is negative. According to current guidelines, what is the most appropriate next step to resolve this discrepancy?

Perform a nucleic acid amplification test (NAAT) for toxin genes. (Correct answer)
Culture the stool for C. difficile and perform toxigenic culture.
Repeat the toxin A/B EIA test.
Report the result as negative for C. difficile infection.

Correct answer: Perform a nucleic acid amplification test (NAAT) for toxin genes.

When a sensitive screening test like GDH is positive but a less sensitive, specific test like the toxin EIA is negative, a third, highly sensitive and specific test is needed for resolution. A nucleic acid amplification test (NAAT) for the C. difficile toxin genes (e.g., tcdB) is the recommended reflex test in this scenario. GDH is a sensitive but non-specific marker, as it detects both toxigenic and non-toxigenic strains. The EIA for toxin is specific but can lack sensitivity. NAAT provides a definitive answer on whether a toxigenic strain is present.

Question 194: The reversible cellular change of hydropic swelling results primarily from:

Mitochondrial DNA mutation
Increased lysosomal enzyme activity
Failure of the Na+/K+ ATPase pump (Correct answer)
Excess collagen deposition

Correct answer: Failure of the Na+/K+ ATPase pump

Cellular swelling occurs when the Na+/K+ ATPase fails, causing sodium and water influx into the cell.

Question 195: Which test differentiates Streptococcus pneumoniae from viridans streptococci?

Coagulase test
Optochin sensitivity (Correct answer)
Bacitracin sensitivity
Oxidase test

Correct answer: Optochin sensitivity

S. pneumoniae is optochin-sensitive whereas viridans streptococci are resistant.

Question 196: A clinical laboratory is implementing a new, unmodified, FDA-approved assay. According to CLIA '88, which of the following sets of performance characteristics must the laboratory verify before using the test for patient reporting?

Analytical sensitivity, analytical specificity, and linearity.
Only the manufacturer's stated reportable range and reference interval.
Full method validation including interfering substance studies.
Accuracy, precision, reportable range, and reference interval. (Correct answer)

Correct answer: Accuracy, precision, reportable range, and reference interval.

For an unmodified, FDA-approved test, CLIA '88 requires the laboratory to *verify* the manufacturer's stated performance specifications. This verification process must include demonstrating performance for accuracy, precision, reportable range, and verifying that the manufacturer's reference interval is appropriate for the laboratory's patient population. A full, more extensive validation is required only for laboratory-developed tests or modified FDA-approved tests.

Question 197: What is the expected corrected count increment purpose when transfusing platelets?

To evaluate fibrinogen levels
To check for ABO antibodies
To measure red cell survival
To assess platelet transfusion response and detect refractoriness (Correct answer)

Correct answer: To assess platelet transfusion response and detect refractoriness

The corrected count increment evaluates the platelet response and identifies refractoriness.

Question 198: Peutz-Jeghers syndrome is caused by germline mutations in which gene and features which type of polyp?

APC; tubular adenoma
SMAD4; juvenile polyp
STK11/LKB1; hamartomatous polyp (Correct answer)
MUTYH; serrated polyp

Correct answer: STK11/LKB1; hamartomatous polyp

Peutz-Jeghers syndrome is caused by STK11/LKB1 mutations and is characterized by hamartomatous polyps with arborizing smooth muscle cores throughout the GI tract.

Question 199: The intestinal type of gastric adenocarcinoma is most strongly associated with which precursor condition?

H. pylori-associated chronic atrophic gastritis with intestinal metaplasia (Correct answer)
Zollinger-Ellison syndrome
Ménétrier disease
Autoimmune gastritis

Correct answer: H. pylori-associated chronic atrophic gastritis with intestinal metaplasia

The Correa cascade describes the progression: H. pylori gastritis → atrophic gastritis → intestinal metaplasia → dysplasia → intestinal-type gastric carcinoma.

Question 200: Which of the following is a hallmark of malignancy rather than benign reactive change?

Preserved polarity
Low nuclear-to-cytoplasmic ratio
Marked nuclear pleomorphism with atypical mitoses (Correct answer)
Uniform nuclei

Correct answer: Marked nuclear pleomorphism with atypical mitoses

Atypical mitoses and marked pleomorphism favor malignancy.

Question 201: Which stain is used to identify amyloid deposits, showing apple-green birefringence under polarized light?

Masson trichrome
PAS
Prussian blue
Congo red (Correct answer)

Correct answer: Congo red

Congo red stains amyloid and produces apple-green birefringence under polarized light.

Question 202: A blood culture growing gram-positive cocci in clusters that is coagulase-positive is most likely:

Streptococcus pyogenes
Staphylococcus aureus (Correct answer)
Staphylococcus epidermidis
Enterococcus faecalis

Correct answer: Staphylococcus aureus

Coagulase positivity distinguishes S. aureus from coagulase-negative staphylococci.

Question 203: A signet-ring cell carcinoma of the stomach with diffuse infiltration and marked desmoplasia creating a 'leather bottle' appearance is termed:

Borrmann type I
Mucinous carcinoma
Adenosquamous carcinoma
Scirrhous carcinoma (linitis plastica) (Correct answer)

Correct answer: Scirrhous carcinoma (linitis plastica)

Linitis plastica (scirrhous carcinoma) is a diffuse-type gastric adenocarcinoma characterized by signet-ring cells, desmoplastic stroma, and diffuse wall thickening without discrete mass.

Question 204: Which immunohistochemical marker is MOST useful for distinguishing meningioma from other CNS tumors?

GFAP
EMA (Correct answer)
S-100
Synaptophysin

Correct answer: EMA

EMA (epithelial membrane antigen) is characteristically expressed in meningiomas and helps differentiate them from glial tumors that express GFAP.

Question 205: A monoclonal IgM paraprotein with lymphoplasmacytic marrow infiltration and MYD88 L265P mutation defines:

Waldenstrom macroglobulinemia (Correct answer)
Chronic lymphocytic leukemia
Marginal zone lymphoma
Multiple myeloma

Correct answer: Waldenstrom macroglobulinemia

Waldenstrom (lymphoplasmacytic lymphoma) produces IgM and carries the MYD88 L265P mutation.

Question 206: Transudate differs from exudate in that a transudate has:

Low protein content and low specific gravity (Correct answer)
High protein and high specific gravity
Abundant inflammatory cells
High LDH levels

Correct answer: Low protein content and low specific gravity

A transudate is protein-poor with low specific gravity, resulting from hydrostatic or oncotic imbalance rather than inflammation.

Question 207: A cyst fluid FNA of the pancreas showing thin, watery fluid with glycogen-rich cuboidal cells and low CEA favors which diagnosis?

Intraductal papillary mucinous neoplasm
Pancreatic ductal adenocarcinoma
Serous cystadenoma (Correct answer)
Mucinous cystic neoplasm

Correct answer: Serous cystadenoma

Low CEA with glycogen-rich cuboidal cells indicates a benign serous cystadenoma.

Question 208: A blood culture from a patient with a catheter-related bloodstream infection grows Gram-positive cocci in clusters. The organism is catalase-positive. Which of the following biochemical tests is most critical for differentiating Staphylococcus aureus from coagulase-negative staphylococci (CoNS)?

Coagulase test (Correct answer)
Novobiocin susceptibility
Bacitracin susceptibility
PYR test

Correct answer: Coagulase test

The coagulase test is the principal laboratory test used to differentiate Staphylococcus aureus (positive) from coagulase-negative staphylococci (CoNS), such as S. epidermidis. The production of coagulase is a key virulence factor for S. aureus. Novobiocin susceptibility is used to differentiate S. saprophyticus (resistant) from other CoNS. Bacitracin is used for differentiating Streptococcus pyogenes, and PYR is used for identifying Enterococcus and S. pyogenes.

Question 209: Which marker is most specific for melanoma among the following?

TTF-1
CK20
CD45
HMB-45 (Correct answer)

Correct answer: HMB-45

HMB-45 is a specific melanocytic marker used to confirm melanoma.

Question 210: A new molecular diagnostics section is being established, which will perform high-complexity testing. According to CLIA '88 regulations, which of the following individuals meets the minimum qualifications to serve as the Technical Supervisor for this section?

A physician with a license to practice medicine and 1 year of experience overseeing a moderate complexity laboratory.
An individual with an associate's degree in medical laboratory technology and 4 years of experience in high-complexity testing.
An individual with a master's degree in biology and 6 months of training in the specific high-complexity assays being performed.
An individual with a bachelor's degree in clinical laboratory science and 2 years of experience in high-complexity testing. (Correct answer)

Correct answer: An individual with a bachelor's degree in clinical laboratory science and 2 years of experience in high-complexity testing.

CLIA '88 specifies several pathways to qualify as a Technical Supervisor for high-complexity testing. One of the most common pathways requires an individual to have earned a bachelor's degree in a relevant science (such as clinical laboratory science or medical technology) and have at least 2 years of pertinent laboratory experience in high-complexity testing. The other options are incorrect because they lack the required degree level, sufficient duration of experience, or experience specifically in high-complexity testing.

Question 211: What is the minimum hemoglobin concentration typically required for an allogeneic whole blood donor in the US?

13.0 g/dL
11.0 g/dL
10.0 g/dL
12.5 g/dL (Correct answer)

Correct answer: 12.5 g/dL

US regulations require a minimum hemoglobin of 12.5 g/dL for allogeneic donors.

Question 212: Helicobacter pylori preferentially colonizes which region of the stomach?

Antrum (Correct answer)
Greater curvature body
Cardia
Fundus

Correct answer: Antrum

H. pylori colonizes the gastric antrum preferentially, where it is detected by Giemsa, Warthin-Starry silver stain, or CLO (rapid urease) test.

Question 213: Pseudomembranous colitis caused by Clostridioides difficile is histologically characterized by:

Non-caseating granulomas
Volcanic eruption pattern with fibrinopurulent caps over crypts (Correct answer)
Transmural neutrophilic infiltrate
Intraepithelial lymphocytosis

Correct answer: Volcanic eruption pattern with fibrinopurulent caps over crypts

C. difficile colitis shows the classic 'volcano lesion' — a pseudomembrane of fibrin, mucin, and neutrophils erupting from damaged crypts like a volcanic plume.

Question 214: Whipple disease is caused by which organism and is confirmed by which stain?

Mycobacterium avium; AFB stain
Giardia lamblia; H&E
Yersinia enterocolitica; Gram stain
Tropheryma whipplei; PAS stain (Correct answer)

Correct answer: Tropheryma whipplei; PAS stain

Whipple disease is caused by Tropheryma whipplei; foamy macrophages containing the organism in the lamina propria stain positive with PAS (periodic acid-Schiff).

Question 215: The most common source of a pulmonary embolus is a thrombus in the:

Coronary arteries
Left atrium
Hepatic portal vein
Deep veins of the lower extremities (Correct answer)

Correct answer: Deep veins of the lower extremities

Most pulmonary emboli arise from deep vein thrombosis in the legs.

Question 216: A critical (panic) value should be:

Filed without notification
Reported at the end of the shift
Communicated immediately to a responsible caregiver with documented read-back (Correct answer)
Reported only if requested

Correct answer: Communicated immediately to a responsible caregiver with documented read-back

Critical values require immediate notification with documented read-back to ensure patient safety.

Question 217: A lymph node biopsy from a 62-year-old male with generalized lymphadenopathy shows a nodular proliferation of crowded follicles composed of centrocytes and centroblasts. Immunohistochemistry is strongly positive for BCL2 in the germinal centers, as well as CD10 and BCL6. Flow cytometry confirms a monoclonal B-cell population. Which of the following cytogenetic abnormalities is most characteristic of this diagnosis?

t(11;14)(q13;q32)
t(14;18)(q32;q21) (Correct answer)
t(9;22)(q34;q11)
t(8;14)(q24;q32)

Correct answer: t(14;18)(q32;q21)

The clinical presentation, morphology (nodular proliferation of centrocytes and centroblasts), and immunophenotype (CD10+, BCL6+, BCL2+) are classic for Follicular Lymphoma. The characteristic cytogenetic abnormality in the vast majority of follicular lymphomas is the t(14;18)(q32;q21), which juxtaposes the BCL2 gene on chromosome 18 with the immunoglobulin heavy chain (IGH) gene locus on chromosome 14, leading to overexpression of the anti-apoptotic protein BCL2.

Question 218: Gastrointestinal stromal tumors (GISTs) are MOST commonly driven by activating mutations in which gene?

KIT (CD117) (Correct answer)
HER2
KRAS
BRAF

Correct answer: KIT (CD117)

Approximately 80–85% of GISTs harbor activating mutations in KIT (CD117), with PDGFRA mutations in most KIT-wild-type cases; imatinib targets these kinases.

Question 219: Which histologic feature BEST distinguishes Crohn disease from ulcerative colitis?

Mucosal ulceration
Transmural inflammation with granulomas (Correct answer)
Goblet cell depletion
Crypt abscesses

Correct answer: Transmural inflammation with granulomas

Transmural inflammation with non-caseating granulomas is the hallmark of Crohn disease, whereas ulcerative colitis is limited to the mucosa and submucosa.

Question 220: Which tumor marker is most useful for monitoring hepatocellular carcinoma and certain germ-cell tumors?

Chromogranin A
Alpha-fetoprotein (AFP) (Correct answer)
CA-125
CEA

Correct answer: Alpha-fetoprotein (AFP)

AFP is elevated in hepatocellular carcinoma and yolk-sac (endodermal sinus) tumors.

Question 221: Which organism causes watery diarrhea via a toxin that activates adenylate cyclase, seen in rice-water stools?

Vibrio cholerae (Correct answer)
Campylobacter jejuni
Yersinia enterocolitica
Shigella sonnei

Correct answer: Vibrio cholerae

Cholera toxin permanently activates Gs, raising cAMP and causing massive fluid secretion.

Question 222: Which feature is used to distinguish invasive carcinoma from carcinoma in situ?

Breach of the basement membrane (Correct answer)
Presence of mitoses
Increased cell size
Nuclear pleomorphism

Correct answer: Breach of the basement membrane

Invasion requires penetration through the basement membrane into surrounding stroma.

Question 223: Which patients require irradiated cellular blood products to prevent transfusion-associated graft-versus-host disease?

Patients with sickle cell trait
All group O recipients
Severely immunocompromised and intrauterine transfusion recipients (Correct answer)
Healthy adult trauma patients

Correct answer: Severely immunocompromised and intrauterine transfusion recipients

Irradiation prevents TA-GVHD in immunocompromised and fetal/neonatal recipients.

Question 224: Signet-ring cells filled with mucin pushing the nucleus to the periphery are characteristic of which cancer?

Diffuse-type gastric adenocarcinoma (Correct answer)
Basal cell carcinoma
Small cell lung carcinoma
Renal cell carcinoma

Correct answer: Diffuse-type gastric adenocarcinoma

Signet-ring cells are typical of diffuse (linitis plastica) gastric carcinoma.

Question 225: A 32-year-old woman's liquid-based Pap test shows atypical squamous cells with a high nuclear-to-cytoplasmic ratio, irregular nuclear membranes, and hyperchromatic, coarse chromatin. The cells are arranged in sheets and as single cells with scant cytoplasm. According to the Bethesda System for Reporting Cervical Cytology, which of the following is the most likely diagnosis?

Atypical Squamous Cells of Undetermined Significance (ASC-US)
High-grade Squamous Intraepithelial Lesion (HSIL) (Correct answer)
Reactive cellular changes associated with inflammation
Low-grade Squamous Intraepithelial Lesion (LSIL)

Correct answer: High-grade Squamous Intraepithelial Lesion (HSIL)

The described cytomorphologic features—specifically the high nuclear-to-cytoplasmic ratio, significant nuclear hyperchromasia, and irregular nuclear contours—are the classic characteristics of a High-grade Squamous Intraepithelial Lesion (HSIL). LSIL typically presents with more cytoplasm and less severe nuclear atypia, often with koilocytic change. ASC-US is used when cellular changes are present but do not quantitatively or qualitatively meet the criteria for SIL. Reactive changes lack the marked nuclear atypia seen in HSIL.

Question 226: Which of the following is the primary reason for irradiating cellular blood components?

To prevent transfusion-associated graft-versus-host disease (TA-GVHD) (Correct answer)
To inactivate viruses such as CMV and HIV
To prevent bacterial contamination
To reduce the risk of febrile non-hemolytic transfusion reactions

Correct answer: To prevent transfusion-associated graft-versus-host disease (TA-GVHD)

The sole purpose of irradiating cellular blood products is to inactivate donor T-lymphocytes, thereby preventing their proliferation and engraftment in a susceptible recipient. [19, 36, 38] This action prevents transfusion-associated graft-versus-host disease (TA-GVHD), a rare but highly fatal complication of transfusion. [36, 39] Irradiation does not eliminate bacteria or viruses.

Question 227: Reed-Sternberg cells are the diagnostic hallmark of which malignancy?

Hodgkin lymphoma (Correct answer)
Chronic lymphocytic leukemia
Burkitt lymphoma
Multiple myeloma

Correct answer: Hodgkin lymphoma

Binucleate 'owl-eye' Reed-Sternberg cells define Hodgkin lymphoma.

Question 228: Which blood group system antigen is destroyed by treating red cells with proteolytic enzymes like ficin?

Jka (Kidd)
Fya (Duffy) (Correct answer)
E (Rh)
K (Kell)

Correct answer: Fya (Duffy)

Duffy antigens (Fya/Fyb) are denatured by proteolytic enzymes such as ficin and papain.

Question 229: A child has a barking cough and inspiratory stridor. Which virus is the most common cause?

Respiratory syncytial virus
Influenza A
Parainfluenza virus (Correct answer)
Adenovirus

Correct answer: Parainfluenza virus

Parainfluenza virus is the leading cause of croup (laryngotracheobronchitis).

Question 230: In liquid-based cytology, which advantage is most notable compared with conventional smears?

Increased air-drying artifact
Reduced obscuring blood and inflammation with even cell distribution (Correct answer)
Loss of ability to perform HPV testing
Thicker cell layers requiring more focus adjustment

Correct answer: Reduced obscuring blood and inflammation with even cell distribution

Liquid-based preparations clear obscuring material and distribute cells evenly in a thin layer.

Question 231: Which finding best confirms a diagnosis of diabetes mellitus in an asymptomatic patient?

Single HbA1c of 6.0%
Fasting glucose of 115 mg/dL
Random glucose of 150 mg/dL
HbA1c of 6.8% confirmed on repeat testing (Correct answer)

Correct answer: HbA1c of 6.8% confirmed on repeat testing

An HbA1c ≥6.5% confirmed on a separate occasion meets diagnostic criteria for diabetes.

Question 232: Which histologic pattern of hepatocellular carcinoma is associated with the BEST prognosis?

Solid pattern
Trabecular pattern
Scirrhous pattern
Fibrolamellar carcinoma (Correct answer)

Correct answer: Fibrolamellar carcinoma

Fibrolamellar carcinoma occurs in young patients without cirrhosis, has characteristic lamellar fibrous bands around tumor cells, and carries a significantly better prognosis than conventional HCC.

Question 233: Which viral inclusion body ('owl's eye') is characteristic of cytomegalovirus infection?

Negri bodies
Downey cells
Intranuclear owl's-eye inclusions (Correct answer)
Councilman bodies

Correct answer: Intranuclear owl's-eye inclusions

CMV produces large cells with intranuclear owl's-eye inclusions.

Question 234: Which of the following is a key histopathologic feature of Alzheimer's disease?

Lewy bodies
Neurofibrillary tangles (Correct answer)
Beta-amyloid plaques
Astrocytosis

Correct answer: Neurofibrillary tangles

Neurofibrillary tangles are a hallmark histopathological feature of Alzheimer's disease. These intracellular aggregates are composed of hyperphosphorylated tau protein, which disrupts neuronal transport and function, leading to neuronal dysfunction and death. While beta-amyloid plaques are also crucial, neurofibrillary tangles correlate more strongly with the degree of cognitive decline and neuronal loss observed in Alzheimer's patients.

Question 235: Barrett esophagus is defined histologically by the presence of which type of metaplasia?

Gastric fundic metaplasia
Squamous metaplasia
Pseudostratified columnar metaplasia
Intestinal metaplasia with goblet cells (Correct answer)

Correct answer: Intestinal metaplasia with goblet cells

Barrett esophagus requires intestinal metaplasia with goblet cells in the distal esophagus, confirmed by Alcian blue stain at pH 2.5.

Question 236: A patient develops acute respiratory distress, hypoxemia, and bilateral pulmonary infiltrates on chest X-ray within 2 hours of receiving a platelet transfusion. There are no signs of circulatory overload. Which of the following is the most likely diagnosis?

Septic transfusion reaction
Anaphylactic transfusion reaction
Transfusion-Related Acute Lung Injury (TRALI) (Correct answer)
Transfusion-Associated Circulatory Overload (TACO)

Correct answer: Transfusion-Related Acute Lung Injury (TRALI)

The clinical presentation of acute respiratory distress, non-cardiogenic pulmonary edema, and hypoxemia occurring within 6 hours of a transfusion is the classic definition of Transfusion-Related Acute Lung Injury (TRALI). [4, 18, 35] It is a leading cause of transfusion-related mortality. [4] The absence of signs of heart failure or volume overload helps distinguish it from TACO. [28]

Question 237: A 70-year-old man dies suddenly at home five days after being diagnosed with a large transmural anterior wall myocardial infarction. Autopsy is performed. Which of the following is the most likely cause of death?

Ventricular aneurysm formation
Ventricular arrhythmia
Dressler syndrome
Rupture of the ventricular free wall (Correct answer)

Correct answer: Rupture of the ventricular free wall

Rupture of the ventricular free wall is a catastrophic mechanical complication of MI that typically occurs 3 to 7 days after the event. This timing corresponds to the period of maximal inflammation, with a dense infiltrate of macrophages and neutrophils that release lytic enzymes, leading to significant weakening of the necrotic myocardial wall before sufficient granulation tissue and scarring can provide structural integrity. Ventricular arrhythmias are most common in the first 24-48 hours. Dressler syndrome is a delayed autoimmune pericarditis, usually occurring weeks to months post-MI. A true ventricular aneurysm is a late complication that develops weeks to months after an MI.

Question 238: The six elements of competency assessment include direct observation, monitoring records, and:

Reviewing the employee's salary
Assessment of problem-solving skills (Correct answer)
Counting vacation days
Checking parking assignments

Correct answer: Assessment of problem-solving skills

One of the six CLIA competency elements is evaluating problem-solving skills.

Question 239: A serous pericardial effusion with a 'bread-and-butter' fibrinous appearance is most characteristic of which process?

Chylopericardium
Purulent bacterial pericarditis
Hemopericardium
Fibrinous/uremic pericarditis (Correct answer)

Correct answer: Fibrinous/uremic pericarditis

Fibrinous pericarditis, seen in uremia or post-MI, produces a rough bread-and-butter surface with a friction rub.

Question 240: Berry (saccular) aneurysms most commonly occur at which location?

Posterior communicating artery
Middle cerebral artery bifurcation
Basilar tip
Anterior communicating artery (Correct answer)

Correct answer: Anterior communicating artery

The anterior communicating artery is the single most common site for berry aneurysm formation, accounting for approximately 30–35% of all intracranial aneurysms.

Question 241: Which molecular finding defines a favorable-risk category in acute myeloid leukemia when NPM1 is mutated?

NPM1 with high FLT3-ITD ratio
Complex karyotype
TP53 mutation
NPM1 mutation without FLT3-ITD (or low allelic ratio) (Correct answer)

Correct answer: NPM1 mutation without FLT3-ITD (or low allelic ratio)

NPM1 mutation in the absence of FLT3-ITD (or with a low ratio) confers favorable prognosis in AML.

Question 242: A patient with meningitis has CSF showing gram-negative diplococci. Which organism is most likely?

Neisseria meningitidis (Correct answer)
Haemophilus influenzae
Streptococcus pneumoniae
Listeria monocytogenes

Correct answer: Neisseria meningitidis

N. meningitidis appears as gram-negative diplococci and is a leading cause of bacterial meningitis.

Question 243: Which genetic alteration is PATHOGNOMONIC for oligodendroglioma per WHO 2021 CNS classification?

H3 K27M mutation
IDH mutation + 1p/19q codeletion (Correct answer)
EGFR amplification
BRAF V600E mutation

Correct answer: IDH mutation + 1p/19q codeletion

The combination of IDH mutation and 1p/19q codeletion is required for the diagnosis of oligodendroglioma by WHO 2021 molecular criteria.

Question 244: Myofiber disarray on histology is the hallmark of which condition?

Cardiac sarcoidosis
Dilated cardiomyopathy
Ischemic cardiomyopathy
Hypertrophic cardiomyopathy (Correct answer)

Correct answer: Hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy shows haphazard myofiber and myofibril disarray, often with sarcomeric gene mutations.

Question 245: Barrett esophagus is defined histologically by replacement of squamous epithelium with:

Intestinal-type columnar epithelium with goblet cells (Correct answer)
Ciliated respiratory epithelium
Keratinizing squamous cells
Transitional epithelium

Correct answer: Intestinal-type columnar epithelium with goblet cells

Barrett esophagus shows intestinal metaplasia with goblet cells in the distal esophagus.

Question 246: Which encapsulated yeast stains with India ink in CSF and causes meningitis in AIDS patients?

Cryptococcus neoformans (Correct answer)
Histoplasma capsulatum
Coccidioides immitis
Candida glabrata

Correct answer: Cryptococcus neoformans

Cryptococcus has a polysaccharide capsule visualized by India ink.

Question 247: An antibody that reacts more strongly with cells expressing a double dose of antigen demonstrates:

Panagglutination
Rouleaux
Dosage effect (Correct answer)
Prozone

Correct answer: Dosage effect

Dosage effect describes stronger reactivity with homozygous (double-dose) antigen expression.

Question 248: On CSF cytology, which finding is most concerning for leptomeningeal carcinomatosis?

Predominance of small mature lymphocytes
Clusters of atypical epithelial cells with high N/C ratio (Correct answer)
Occasional reactive monocytes
Numerous neutrophils and bacteria

Correct answer: Clusters of atypical epithelial cells with high N/C ratio

Malignant epithelial cell clusters in CSF indicate metastatic (leptomeningeal) spread.

Question 249: A fine-needle aspiration is performed on a 3.5 cm solid mass in the head of the pancreas in a 68-year-old male. The cytology shows crowded, three-dimensional clusters of ductal cells with significant nuclear size variation, irregular nuclear membranes, and prominent nucleoli, suspicious for malignancy. Which of the following molecular alterations is most frequently associated with pancreatic ductal adenocarcinoma?

ALK gene rearrangement
EGFR mutation
KRAS gene mutation (Correct answer)
BRAF V600E mutation

Correct answer: KRAS gene mutation

Activating mutations in the KRAS oncogene are the most common and earliest genetic alteration found in pancreatic ductal adenocarcinoma (PDAC), occurring in over 90% of cases. Therefore, detecting a KRAS mutation provides strong ancillary evidence for the diagnosis. BRAF V600E is associated with melanoma and some colon/thyroid cancers, while EGFR mutations and ALK rearrangements are most famously associated with lung adenocarcinoma.

Question 250: A urine culture from a patient with a complicated urinary tract infection grows a gram-negative rod identified as Klebsiella pneumoniae. Antimicrobial susceptibility testing reveals it is resistant to ceftriaxone and cefepime but susceptible to imipenem. A synergy test using a ceftazidime disk and a clavulanate-containing disk shows an enhanced zone of inhibition ('keyhole' effect). This phenotype is characteristic of what resistance mechanism?

Efflux pump overexpression
Carbapenemase (KPC) production
Extended-Spectrum Beta-Lactamase (ESBL) production (Correct answer)
AmpC beta-lactamase production

Correct answer: Extended-Spectrum Beta-Lactamase (ESBL) production

This pattern is classic for an Extended-Spectrum Beta-Lactamase (ESBL) producer. ESBLs are enzymes that hydrolyze extended-spectrum cephalosporins (like ceftriaxone and cefepime) but are inhibited by beta-lactamase inhibitors like clavulanate. The positive synergy test confirms this. Carbapenemase production would confer resistance to imipenem. AmpC beta-lactamases are typically not inhibited by clavulanate.

Question 251: What is the primary molecular alteration in the pathogenesis of chronic myelogenous leukemia (CML)?

EGFR amplification
TP53 mutation
MYC oncogene activation
BCR-ABL fusion gene (Correct answer)

Correct answer: BCR-ABL fusion gene

Chronic myelogenous leukemia (CML) is definitively characterized by a specific chromosomal translocation, t(9;22), which results in the formation of the Philadelphia chromosome. This translocation creates the BCR-ABL fusion gene, encoding a constitutively active tyrosine kinase. This abnormal kinase drives the uncontrolled proliferation of myeloid cells, which is the hallmark of CML.

Question 252: Which histologic feature is MOST characteristic of glioblastoma multiforme (GBM)?

Rosenthal fibers
Verocay bodies
Pseudopalisading necrosis (Correct answer)
Homer Wright rosettes

Correct answer: Pseudopalisading necrosis

Pseudopalisading necrosis, where tumor cells line up around areas of necrosis, is the hallmark histologic feature of GBM (WHO Grade IV astrocytoma).

Question 253: Signet ring cells are most classically associated with carcinoma of the:

Stomach (Correct answer)
Kidney
Lung
Prostate

Correct answer: Stomach

Diffuse gastric carcinoma characteristically contains mucin-filled signet ring cells.

Question 254: A saccular outpouching of the ascending aorta with tree-bark intimal wrinkling suggests which etiology?

Takayasu arteritis
Marfan syndrome
Atherosclerotic abdominal aneurysm
Tertiary syphilitic aortitis (Correct answer)

Correct answer: Tertiary syphilitic aortitis

Syphilitic aortitis causes obliterative endarteritis of the vasa vasorum, producing a tree-bark appearance of the ascending aorta.

Question 255: A newborn screen flags elevated 17-hydroxyprogesterone. This most strongly suggests:

Congenital hypothyroidism
Galactosemia
Congenital adrenal hyperplasia (Correct answer)
Phenylketonuria

Correct answer: Congenital adrenal hyperplasia

Elevated 17-hydroxyprogesterone is the marker for 21-hydroxylase deficiency causing congenital adrenal hyperplasia.

Question 256: A patient develops sudden hypotension, back pain, and hemoglobinuria minutes after starting a transfusion. What is the most likely reaction?

Acute hemolytic transfusion reaction (Correct answer)
Febrile nonhemolytic reaction
TRALI
Allergic reaction

Correct answer: Acute hemolytic transfusion reaction

These signs indicate an acute intravascular hemolytic reaction, usually from ABO incompatibility.

Question 257: Which type of skin cancer is associated with the highest mortality rate?

Actinic keratosis
Squamous cell carcinoma
Melanoma (Correct answer)
Basal cell carcinoma

Correct answer: Melanoma

While basal cell carcinoma and squamous cell carcinoma are more common, melanoma is the most aggressive and deadliest form of skin cancer. It has a high propensity for metastasis to distant organs if not detected and treated early, leading to a significantly higher mortality rate compared to other skin cancers. Early diagnosis is critical for improving prognosis.

Question 258: A stool culture on sorbitol-MacConkey shows sorbitol-nonfermenting colonies. Which pathogen is suspected?

Shigella dysenteriae
Salmonella typhi
Vibrio cholerae
E. coli O157:H7 (Correct answer)

Correct answer: E. coli O157:H7

E. coli O157:H7 does not ferment sorbitol, distinguishing it on SMAC agar.

Question 259: Granulation tissue in a healing wound is composed of:

New capillaries and proliferating fibroblasts (Correct answer)
Necrotic debris and neutrophils only
Mature dense collagen only
Adipose tissue

Correct answer: New capillaries and proliferating fibroblasts

Granulation tissue consists of new blood vessels (angiogenesis) and fibroblasts in a loose matrix.

Question 260: A 'fried egg' appearance of cells with perinuclear halos is characteristic of:

Glioblastoma
Meningioma
Ependymoma
Oligodendroglioma (Correct answer)

Correct answer: Oligodendroglioma

Oligodendrogliomas show clear perinuclear halos, giving a fried-egg appearance.

Question 261: Which infectious agent is a major concern for platelet units due to their room-temperature storage?

Bacterial contamination (Correct answer)
Malaria
Hepatitis C virus
Prions

Correct answer: Bacterial contamination

Room-temperature storage of platelets promotes bacterial growth, the leading infectious risk.

Question 262: A 70-year-old female with a history of ER-positive invasive ductal carcinoma of the breast develops a large pleural effusion. Cytologic evaluation shows cohesive clusters of malignant cells. A cell block is prepared for ancillary studies to confirm the origin. Which of the following immunohistochemical markers is most specific for supporting a diagnosis of metastatic breast carcinoma in this context?

TTF-1
Calretinin
GATA3 (Correct answer)
WT-1

Correct answer: GATA3

GATA3 is a transcription factor that is a highly sensitive and specific marker for carcinomas of breast and urothelial origin. In the differential diagnosis of a malignant pleural effusion in a woman, which includes mesothelioma (positive for WT-1, Calretinin) and lung adenocarcinoma (positive for TTF-1), strong positivity for GATA3 is excellent evidence for metastatic breast carcinoma.

Question 263: TdT positivity in a population of blasts is most typical of:

Lymphoblastic leukemia/lymphoma (Correct answer)
Plasma cell myeloma
Hairy cell leukemia
Acute promyelocytic leukemia

Correct answer: Lymphoblastic leukemia/lymphoma

Terminal deoxynucleotidyl transferase (TdT) marks immature lymphoblasts.

Question 264: The chemical mediator most responsible for pain in inflammation, along with prostaglandins, is:

Bradykinin (Correct answer)
Histamine
Selectin
Fibrinogen

Correct answer: Bradykinin

Bradykinin and prostaglandins are key mediators that sensitize nerve endings and produce pain.

Question 265: Which cytologic feature most distinguishes reactive urothelial cells (e.g., from instrumentation) from carcinoma?

Smooth nuclear membranes with even chromatin (Correct answer)
Markedly irregular nuclear contours
Coarse hyperchromatic chromatin
Very high N/C ratio

Correct answer: Smooth nuclear membranes with even chromatin

Reactive cells retain smooth nuclear membranes and even chromatin despite enlargement.

Question 266: On a cervical Pap smear, which cellular feature is most characteristic of a high-grade squamous intraepithelial lesion (HSIL)?

Abundant glycogenated cytoplasm
Increased nuclear-to-cytoplasmic ratio with hyperchromasia (Correct answer)
Perinuclear halos with mild nuclear enlargement
Prominent cytoplasmic keratinization only

Correct answer: Increased nuclear-to-cytoplasmic ratio with hyperchromasia

HSIL cells show markedly increased nuclear-to-cytoplasmic ratio, hyperchromasia, and irregular nuclear contours.

Question 267: Which document establishes standardized formatting and content for laboratory procedures in the U.S.?

A CLSI-formatted standard operating procedure (Correct answer)
A commercial marketing brochure
The instrument warranty card
A billing codebook

Correct answer: A CLSI-formatted standard operating procedure

CLSI provides consensus guidelines for writing standardized SOPs used in clinical laboratories.

Question 268: Reed-Sternberg cells are the hallmark of which disease?

Multiple myeloma
Burkitt lymphoma
Follicular lymphoma
Classic Hodgkin lymphoma (Correct answer)

Correct answer: Classic Hodgkin lymphoma

Binucleate Reed-Sternberg cells define classic Hodgkin lymphoma.

Question 269: The most common primary cardiac tumor in children is:

Lipoma
Myxoma
Fibroma
Rhabdomyoma (Correct answer)

Correct answer: Rhabdomyoma

Rhabdomyomas are the most common pediatric cardiac tumors and are associated with tuberous sclerosis.

Question 270: Lynch syndrome (hereditary non-polyposis colorectal cancer) is caused by germline mutations in which genes?

MLH1, MSH2, MSH6, PMS2 (MMR genes) (Correct answer)
APC and MUTYH
BRCA1 and BRCA2
SMAD4 and BMPR1A

Correct answer: MLH1, MSH2, MSH6, PMS2 (MMR genes)

Lynch syndrome results from germline mutations in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, PMS2), leading to microsatellite instability.

Question 271: A villous adenoma of the rectum is associated with highest risk for malignant transformation compared to other polyp types because it has:

Microsatellite instability
Largest surface area with maximal dysplasia exposure (Correct answer)
Highest density of goblet cells
Submucosal invasion at presentation

Correct answer: Largest surface area with maximal dysplasia exposure

Villous adenomas have the greatest malignant potential (up to 40%) due to their larger size, greater surface area, and higher degree of dysplasia at diagnosis.

Question 272: Lean methodology in the laboratory primarily aims to:

Add redundant testing steps
Eliminate waste and improve workflow efficiency (Correct answer)
Reduce the number of QC runs
Increase inventory stockpiles

Correct answer: Eliminate waste and improve workflow efficiency

Lean focuses on removing non-value-added steps (waste) to streamline laboratory processes.

Question 273: A gradual increase in consecutive QC values over several days most likely represents:

A shift
Random error
A trend (Correct answer)
Normal variation

Correct answer: A trend

A trend is a progressive drift in one direction, often indicating deteriorating reagent or calibration.

Question 274: Psammoma bodies (laminated calcifications) are characteristically seen in all of the following EXCEPT?

Hepatocellular carcinoma (Correct answer)
Serous ovarian carcinoma
Papillary thyroid carcinoma
Meningioma

Correct answer: Hepatocellular carcinoma

Hepatocellular carcinoma does not typically contain psammoma bodies, unlike the other three tumors.

Question 275: Hirschsprung disease results from absence of ganglion cells in which layer of the bowel wall?

Lamina propria
Muscularis mucosae
Serosa
Submucosal (Meissner) and myenteric (Auerbach) plexuses (Correct answer)

Correct answer: Submucosal (Meissner) and myenteric (Auerbach) plexuses

Hirschsprung disease results from failed neural crest cell migration, causing absence of ganglion cells in the submucosal and myenteric plexuses of the rectosigmoid.

Question 276: A liver FNA shows enlarged hepatocyte-like cells with increased N/C ratio and thickened trabeculae wrapped by endothelium. Which lesion is most likely?

Focal nodular hyperplasia
Regenerative nodule
Hepatic adenoma
Hepatocellular carcinoma (Correct answer)

Correct answer: Hepatocellular carcinoma

Thickened trabeculae with endothelial wrapping and increased N/C ratio favor hepatocellular carcinoma.

Question 277: Delta checks are used primarily to detect:

Instrument temperature drift
Significant changes in a patient's result compared to prior results, flagging possible errors (Correct answer)
Staff scheduling conflicts
Reagent expiration

Correct answer: Significant changes in a patient's result compared to prior results, flagging possible errors

A delta check compares a current result to the patient's previous value to catch specimen mix-ups or errors.

Question 278: The primary purpose of a Levey-Jennings chart is to:

Monitor quality control values over time to detect shifts and trends (Correct answer)
Calculate reimbursement rates
Schedule staff shifts
Track specimen turnaround time

Correct answer: Monitor quality control values over time to detect shifts and trends

Levey-Jennings charts plot QC values over time to visualize random error, shifts, and trends.

Question 279: A thyroid FNA shows follicular cells with nuclear grooves, powdery chromatin, and intranuclear pseudoinclusions. Which diagnosis is most likely?

Papillary thyroid carcinoma (Correct answer)
Medullary carcinoma
Hashimoto thyroiditis
Follicular adenoma

Correct answer: Papillary thyroid carcinoma

Nuclear grooves, pale powdery chromatin, and intranuclear pseudoinclusions are hallmarks of papillary thyroid carcinoma.

Question 280: Which mechanism explains vancomycin resistance in Enterococcus (VRE)?

Beta-lactamase production
Ribosomal methylation
Altered DNA gyrase
D-Ala-D-Ala changed to D-Ala-D-Lac (Correct answer)

Correct answer: D-Ala-D-Ala changed to D-Ala-D-Lac

VRE alters the peptidoglycan terminus to D-Ala-D-Lac, reducing vancomycin binding.

Question 281: Which value indicates the specimen was contaminated with intravenous fluid containing dextrose?

Elevated potassium only
Extremely high glucose with low potassium and sodium (Correct answer)
Low glucose with high protein
Normal all analytes

Correct answer: Extremely high glucose with low potassium and sodium

IV fluid contamination dilutes electrolytes while spiking glucose, a classic drawn-above-the-line artifact.

Question 282: Which of the following findings is most characteristic of a myocardial infarction on histology within the first 24 hours?

Fibrosis
Coagulative necrosis (Correct answer)
Granulation tissue
Neutrophil infiltration

Correct answer: Coagulative necrosis

Myocardial infarction involves ischemic cell death due to lack of blood flow. Within the first 24 hours of an acute myocardial infarction, the most characteristic histological finding is coagulative necrosis. This type of necrosis is typical of ischemia in solid organs like the heart, where the cell's architecture is preserved but nuclei are lost and cytoplasm becomes intensely eosinophilic, indicating irreversible cell injury before significant inflammatory response or repair processes begin.

Question 283: Chronic inflammation is distinguished from acute inflammation by the prominence of:

Neutrophils and edema
Margination of platelets
Immediate vasoconstriction
Mononuclear cells and tissue destruction with repair (Correct answer)

Correct answer: Mononuclear cells and tissue destruction with repair

Chronic inflammation features macrophages, lymphocytes, plasma cells, ongoing tissue damage, and attempts at repair.

Question 284: Which control is essential to confirm that a negative PCR result is not due to amplification failure?

An internal amplification (endogenous) control (Correct answer)
A reagent blank only
A no-template control only
A positive control only

Correct answer: An internal amplification (endogenous) control

An internal/endogenous control confirms amplifiable DNA is present, ruling out inhibition or failed extraction behind a true-negative call.

Question 285: A patient with disseminated intravascular coagulation (DIC) and significant hypofibrinogenemia requires factor replacement. Which blood component is the most concentrated source of fibrinogen?

Cryoprecipitate (Correct answer)
Packed Red Blood Cells (PRBCs)
Platelets
Fresh Frozen Plasma (FFP)

Correct answer: Cryoprecipitate

Cryoprecipitate is a plasma-derived product that is prepared by thawing Fresh Frozen Plasma and collecting the cold-insoluble precipitate. [5, 13] This process concentrates several clotting factors, most notably fibrinogen, as well as Factor VIII, Factor XIII, and von Willebrand factor. [10, 37] It is the most concentrated source of fibrinogen available for transfusion. [10]

Question 286: Which pattern of cell death is characterized by activation of caspases, cell shrinkage, and no surrounding inflammation?

Caseous necrosis
Apoptosis (Correct answer)
Coagulative necrosis
Liquefactive necrosis

Correct answer: Apoptosis

Apoptosis is programmed, caspase-mediated death without inflammatory response.

Question 287: A fine-needle aspiration of a 3 cm thyroid nodule from a 45-year-old female shows cellular smears with follicular cells arranged in syncytial-type clusters. The nuclei are enlarged and overlapping, with finely dispersed pale chromatin, prominent nuclear grooves, and occasional intranuclear cytoplasmic inclusions. These cytomorphologic features are most characteristic of which of the following?

Medullary Thyroid Carcinoma
Anaplastic Thyroid Carcinoma
Follicular Adenoma
Papillary Thyroid Carcinoma (Correct answer)

Correct answer: Papillary Thyroid Carcinoma

The combination of nuclear features including enlargement, overlapping, pale "Orphan Annie eye" chromatin, nuclear grooves, and intranuclear pseudoinclusions is the classic constellation of findings for Papillary Thyroid Carcinoma. Follicular neoplasms lack these specific nuclear changes, Medullary carcinoma typically shows plasmacytoid cells with salt-and-pepper chromatin, and Anaplastic carcinoma is characterized by marked pleomorphism and high-grade features.

Question 288: Which is the most common cause of a false-positive low-level variant call in FFPE-derived DNA?

Formalin-induced cytosine deamination artifacts (Correct answer)
Excess magnesium
Bacterial contamination
Primer dimers

Correct answer: Formalin-induced cytosine deamination artifacts

Formalin fixation causes cytosine deamination producing C>T/G>A artifacts that mimic low-VAF variants.

Question 289: Which anaerobic gram-positive rod produces a toxin causing flaccid paralysis in infants who ingest honey?

Clostridium botulinum (Correct answer)
Clostridium tetani
Clostridium perfringens
Listeria monocytogenes

Correct answer: Clostridium botulinum

C. botulinum toxin blocks acetylcholine release, causing flaccid paralysis (floppy baby).

Question 290: Which immunohistochemical marker is most useful for confirming a prostatic origin of an adenocarcinoma?

TTF-1
PSA (prostate-specific antigen) (Correct answer)
GFAP
CD20

Correct answer: PSA (prostate-specific antigen)

PSA and PSAP are highly specific markers for prostatic epithelial cells.

Question 291: Pseudohyponatremia is classically caused by which of the following?

Diuretic use
Adrenal insufficiency
Severe hyperlipidemia or hyperproteinemia (Correct answer)
SIADH

Correct answer: Severe hyperlipidemia or hyperproteinemia

High lipids or proteins displace plasma water, causing a spurious low sodium with indirect ion-selective electrodes.

Question 292: t(15;17) with PML-RARA fusion characterizes which subtype of acute myeloid leukemia?

Acute megakaryoblastic leukemia
Acute promyelocytic leukemia (Correct answer)
Acute erythroid leukemia
AML with t(8;21)

Correct answer: Acute promyelocytic leukemia

APL is defined by t(15;17)/PML-RARA and responds to ATRA therapy.

Question 293: A 68-year-old male with a long history of hypertension and coronary artery disease dies of a massive myocardial infarction. At autopsy, the heart is enlarged, and the left ventricular wall is notably thickened. Microscopically, the cardiac myocytes are increased in size, but not in number. This cellular alteration is best described as which of the following?

Atrophy
Metaplasia
Hyperplasia
Hypertrophy (Correct answer)

Correct answer: Hypertrophy

Hypertrophy is an increase in the size of cells, resulting in an increase in the size of the organ. [20] It occurs in cells with limited capacity to divide, such as cardiac myocytes, in response to increased workload. [28, 30] In this case, chronic hypertension increased the workload on the heart, leading to an adaptive increase in myocyte size. Hyperplasia is an increase in the number of cells. Atrophy is a decrease in cell size. [20] Metaplasia is the replacement of one mature cell type with another. [28]

Question 294: Which cardiac tumor is the most common overall, arising from spread of another malignancy?

Metastatic tumor to the heart (Correct answer)
Rhabdomyoma
Primary angiosarcoma
Myxoma

Correct answer: Metastatic tumor to the heart

Metastases to the heart and pericardium are far more common than any primary cardiac tumor.

Question 295: The purpose of an inventory par level is to:

Determine test pricing
Set staff salaries
Define the minimum stock that triggers reordering to avoid stockouts (Correct answer)
Maximize reagent expiration waste

Correct answer: Define the minimum stock that triggers reordering to avoid stockouts

Par level is the minimum inventory that prompts reordering to prevent running out of supplies.

Question 296: Which cellular adaptation refers to an increase in the SIZE of individual cells, as seen in cardiac muscle under hypertension?

Metaplasia
Atrophy
Hyperplasia
Hypertrophy (Correct answer)

Correct answer: Hypertrophy

Hypertrophy is enlargement of cells; cardiac myocytes cannot divide so they enlarge.

Question 297: Which immunostain panel best distinguishes lung adenocarcinoma from mesothelioma in an effusion?

Calretinin and WT-1 positive, BerEP4 negative
TTF-1 and MOC-31 positive, calretinin negative (Correct answer)
p40 and CK5/6 positive only
CK20 and CDX2 positive

Correct answer: TTF-1 and MOC-31 positive, calretinin negative

TTF-1 and MOC-31 positivity with calretinin negativity supports pulmonary adenocarcinoma over mesothelioma.

Question 298: The most common mutation causing cystic fibrosis is F508del in the CFTR gene. This genetic alteration leads to the production of a misfolded protein that is retained in the endoplasmic reticulum and targeted for degradation, preventing its transport to the cell membrane. According to the functional classification system, this type of defect is categorized as a:

Class IV mutation (defective chloride conductance)
Class III mutation (defective channel regulation or gating)
Class II mutation (defective protein processing and trafficking) (Correct answer)
Class I mutation (defective protein production)

Correct answer: Class II mutation (defective protein processing and trafficking)

CFTR mutations are classified based on their functional consequences. The F508del mutation is the archetypal Class II mutation, where the synthesized protein is misfolded and does not traffic correctly to the cell surface, leading to a severe loss of function. Class I mutations result in no protein production, Class III mutations result in a protein that reaches the membrane but has defective gating, and Class IV mutations result in a protein with reduced ion flow.

Question 299: A 68-year-old male is diagnosed with multiple myeloma. According to the International Myeloma Working Group (IMWG) criteria, which of the following findings would be classified as a CRAB feature, indicating myeloma-defining end-organ damage?

Serum creatinine of 2.5 mg/dL (Correct answer)
Serum M-protein of 2.5 g/dL
Involved/uninvolved free light chain ratio of 50
Bone marrow plasma cell percentage of 15%

Correct answer: Serum creatinine of 2.5 mg/dL

The CRAB criteria are used to define end-organ damage in multiple myeloma and are an indication for initiating therapy. CRAB stands for: C (Calcium elevation >11 mg/dL), R (Renal insufficiency, defined as serum creatinine >2 mg/dL or creatinine clearance <40 mL/min), A (Anemia, hemoglobin <10 g/dL or >2 g/dL below normal), and B (Bone lesions, one or more osteolytic lesions on imaging). A serum creatinine of 2.5 mg/dL clearly meets the 'R' criterion. The other options, while relevant to the diagnosis, do not by themselves constitute a CRAB feature.

Question 300: Massive transfusion can lead to which metabolic complication from citrate anticoagulant?

Hypocalcemia (Correct answer)
Hyperkalemia only
Metabolic alkalosis immediately
Hypernatremia

Correct answer: Hypocalcemia

Citrate chelates calcium, causing hypocalcemia during massive transfusion.

Question 301: Metaplasia of respiratory columnar epithelium to squamous epithelium in chronic smokers is best characterized as:

A reversible adaptive change to chronic irritation (Correct answer)
An example of atrophy
An irreversible malignant transformation
A form of dysplasia by definition

Correct answer: A reversible adaptive change to chronic irritation

Metaplasia is a reversible replacement of one differentiated cell type with another in response to chronic stress.

Question 302: Ferruginous bodies (asbestos bodies) in lung tissue indicate prior exposure to?

Silica
Asbestos (Correct answer)
Beryllium
Coal dust

Correct answer: Asbestos

Iron-coated asbestos fibers form dumbbell-shaped ferruginous bodies.

Question 303: A skin biopsy shows a perivascular lymphoplasmacytic infiltrate and spirochetes on Warthin-Starry stain. This is most consistent with:

Granuloma annulare
Tinea corporis
Erythema migrans (Lyme disease)
Secondary syphilis (Correct answer)

Correct answer: Secondary syphilis

Secondary syphilis shows lichenoid or superficial/deep perivascular infiltrate with prominent plasma cells; Treponema pallidum spirochetes can be demonstrated with Warthin-Starry or immunohistochemical stains.

Question 304: A positive nitroprusside urine test in a newborn with feeding difficulties suggests which metabolic disorder?

Phenylketonuria
Maple syrup urine disease
Cystinuria/homocystinuria (sulfur amino acids) (Correct answer)
Galactosemia

Correct answer: Cystinuria/homocystinuria (sulfur amino acids)

The nitroprusside (cyanide-nitroprusside) test detects sulfhydryl-containing amino acids like cystine and homocystine.

Question 305: A breast FNA shows cohesive sheets of bland ductal cells with numerous bipolar bare nuclei in the background. Which interpretation is favored?

Ductal carcinoma
Lobular carcinoma
Benign (fibrocystic changes) (Correct answer)
Mucinous carcinoma

Correct answer: Benign (fibrocystic changes)

Cohesive bland cells with abundant bipolar bare nuclei indicate a benign process.

Question 306: Cystic medial degeneration of the aorta predisposing to dissection is classically linked to which condition?

Giant cell arteritis
Marfan syndrome (Correct answer)
Diabetes mellitus
Hypertension only

Correct answer: Marfan syndrome

Marfan syndrome (fibrillin-1 defect) causes cystic medial degeneration, a major risk for aortic dissection.

Question 307: A blood culture grows lactose-fermenting, mucoid, string-test-negative gram-negative rods. Which organism?

Klebsiella pneumoniae (Correct answer)
Salmonella enterica
Pseudomonas aeruginosa
Serratia marcescens

Correct answer: Klebsiella pneumoniae

Klebsiella is a mucoid, lactose-fermenting gram-negative rod due to its prominent capsule.

Question 308: In immunohistochemistry, cytokeratin positivity supports an origin that is:

Lymphoid
Melanocytic
Epithelial (Correct answer)
Mesenchymal

Correct answer: Epithelial

Cytokeratins are intermediate filaments expressed by epithelial cells and carcinomas.

Question 309: Which serologic marker indicates immunity to hepatitis B after vaccination?

Anti-HBc IgM
HBeAg
HBsAg
Anti-HBs antibody (Correct answer)

Correct answer: Anti-HBs antibody

Anti-HBs is the protective antibody present after vaccination or recovery.

Question 310: Which stain is used to identify Pneumocystis jirovecii cysts in bronchoalveolar lavage specimens?

Gomori methenamine silver (GMS) (Correct answer)
Mucicarmine
Congo red
Prussian blue

Correct answer: Gomori methenamine silver (GMS)

GMS stains the cyst walls of Pneumocystis jirovecii black.

Question 311: Dystrophic calcification is best described as calcium deposition in:

Normal tissue with hypercalcemia
Damaged or necrotic tissue with normal serum calcium (Correct answer)
Bone matrix during remodeling
Only vascular walls

Correct answer: Damaged or necrotic tissue with normal serum calcium

Dystrophic calcification occurs in previously injured or necrotic tissue despite normal serum calcium levels.

Question 312: FAP (familial adenomatous polyposis) is caused by germline mutations in which gene, and what is the lifetime colorectal cancer risk without intervention?

PTEN; 50%
SMAD4; 60%
MLH1; 80%
APC; nearly 100% (Correct answer)

Correct answer: APC; nearly 100%

FAP is caused by APC gene mutations (chromosome 5q21) and carries nearly 100% lifetime risk of colorectal cancer without prophylactic colectomy.

Question 313: Reed-Sternberg cells are the diagnostic hallmark of which lymphoma?

Marginal zone lymphoma
Anaplastic large cell lymphoma
Classic Hodgkin lymphoma (Correct answer)
Diffuse large B-cell lymphoma

Correct answer: Classic Hodgkin lymphoma

Binucleate Reed-Sternberg cells (CD15+/CD30+) define classic Hodgkin lymphoma.

Question 314: Which virus is most commonly associated with cervical cancer?

Human papillomavirus (HPV) (Correct answer)
Herpes simplex virus type 2
Epstein-Barr virus
Cytomegalovirus

Correct answer: Human papillomavirus (HPV)

High-risk HPV types 16 and 18 are the primary cause of cervical carcinoma.

Question 315: Which cardiac enzyme/protein remains elevated longest after myocardial infarction?

Myoglobin
AST
CK-MB
Troponin I/T (Correct answer)

Correct answer: Troponin I/T

Troponins remain elevated for 7–10 days, longer than CK-MB or myoglobin.

Question 316: A perivascular pseudorosette pattern on histology is MOST characteristic of which brain tumor?

Oligodendroglioma
Choroid plexus papilloma
Ependymoma (Correct answer)
Craniopharyngioma

Correct answer: Ependymoma

Ependymomas characteristically display perivascular pseudorosettes (tumor cell processes tapering toward vessels) and true ependymal rosettes.

Question 317: A 48-year-old renal transplant recipient presents with fever, malaise, and leukopenia. A gastrointestinal biopsy performed to evaluate diarrhea reveals enlarged cells containing prominent basophilic intranuclear inclusions surrounded by a clear halo, creating an "owl's eye" appearance. Which of the following is the most likely causative agent?

Adenovirus
Herpes Simplex Virus (HSV)
Epstein-Barr Virus (EBV)
Cytomegalovirus (CMV) (Correct answer)

Correct answer: Cytomegalovirus (CMV)

The clinical scenario of an organ transplant recipient with systemic symptoms and the pathognomonic finding of large cells with "owl's eye" intranuclear inclusions is classic for Cytomegalovirus (CMV) infection. While HSV, EBV, and Adenovirus can also cause disease in this patient population, the specific cytopathic effect described is the hallmark of CMV.

Question 318: Which mechanism confers methicillin resistance in MRSA?

Efflux pump overexpression
Altered penicillin-binding protein (PBP2a) via mecA gene (Correct answer)
Beta-lactamase production
Porin channel loss

Correct answer: Altered penicillin-binding protein (PBP2a) via mecA gene

The mecA gene encodes PBP2a with low affinity for beta-lactams.

Question 319: An aortic dissection most commonly originates in which segment?

Aortic arch
Abdominal aorta
Ascending aorta within 10 cm of the valve (Correct answer)
Descending thoracic aorta

Correct answer: Ascending aorta within 10 cm of the valve

Most dissections begin in the ascending aorta within about 10 cm of the aortic valve.

Question 320: Hypersegmented neutrophils and macro-ovalocytes on a smear are classic for:

Aplastic anemia
Megaloblastic anemia (Correct answer)
Anemia of chronic disease
Sideroblastic anemia

Correct answer: Megaloblastic anemia

B12 or folate deficiency causes megaloblastic changes including hypersegmented neutrophils.

Question 321: Fibrofatty replacement of the right ventricular myocardium is characteristic of which disorder?

Arrhythmogenic right ventricular cardiomyopathy (Correct answer)
Restrictive cardiomyopathy
Hypertensive heart disease
Rheumatic heart disease

Correct answer: Arrhythmogenic right ventricular cardiomyopathy

ARVC features fibrofatty replacement of RV myocardium, predisposing to arrhythmias and sudden death.

Question 322: Which spirochete causes Lyme disease and is transmitted by Ixodes ticks?

Leptospira interrogans
Borrelia recurrentis
Treponema pallidum
Borrelia burgdorferi (Correct answer)

Correct answer: Borrelia burgdorferi

B. burgdorferi is transmitted by Ixodes ticks and causes erythema migrans.

Question 323: Collagenous colitis is distinguished from lymphocytic colitis by the presence of which histologic finding?

Granuloma formation
Increased intraepithelial lymphocytes
Thickened subepithelial collagen band (>10 µm) (Correct answer)
Crypt architectural distortion

Correct answer: Thickened subepithelial collagen band (>10 µm)

Collagenous colitis features a thickened subepithelial collagen band >10 µm (normal <5 µm) with entrapment of capillaries, in addition to surface epithelial damage and increased IELs.

Question 324: A patient's serum reacts with all reagent red cells in an antibody panel including the autocontrol. What is the most likely cause?

Rouleaux only
A warm autoantibody (Correct answer)
A single low-frequency antibody
Anti-K alloantibody

Correct answer: A warm autoantibody

Pan-reactivity with a positive autocontrol typically indicates a warm autoantibody.

Question 325: A 50-year-old woman undergoes a routine Papanicolaou (Pap) test. The report describes a reversible change in which the normal columnar epithelium of the endocervix has been replaced by stratified squamous epithelium. This cellular adaptation is known as:

Hyperplasia
Anaplasia
Metaplasia (Correct answer)
Dysplasia

Correct answer: Metaplasia

Metaplasia is a reversible change in which one differentiated cell type is replaced by another cell type, often in response to chronic irritation. [20, 28] In the cervix, the columnar epithelium of the endocervix can undergo squamous metaplasia in response to the acidic vaginal environment. While this is an adaptive response, it can be a precursor to dysplasia if the injurious stimulus persists. [28] Dysplasia refers to disordered growth, anaplasia to lack of differentiation in malignant tumors, and hyperplasia to an increase in cell number. [13, 30]

Question 326: An elevated anion gap metabolic acidosis with high osmolar gap suggests ingestion of which substance?

Ethylene glycol (Correct answer)
Ammonium chloride
Aspirin
Acetazolamide

Correct answer: Ethylene glycol

Ethylene glycol raises both the anion gap (from metabolic acids) and the osmolar gap (from the parent alcohol).

Question 327: A serum protein electrophoresis showing a monoclonal M-spike with marrow plasmacytosis and lytic bone lesions indicates:

Waldenstrom macroglobulinemia
Monoclonal gammopathy of undetermined significance
Reactive plasmacytosis
Multiple myeloma (Correct answer)

Correct answer: Multiple myeloma

M-spike with clonal plasma cells, lytic lesions, and end-organ damage defines multiple myeloma.

Question 328: Method validation for a new FDA-cleared assay used unmodified requires the lab to establish:

Only the reagent cost
Verification of accuracy, precision, reportable range, and reference intervals (Correct answer)
Nothing at all
A new CPT code

Correct answer: Verification of accuracy, precision, reportable range, and reference intervals

For unmodified FDA-cleared tests, the lab must verify performance characteristics like accuracy, precision, and reference intervals.

Question 329: A dexamethasone suppression test that fails to suppress cortisol suggests which disorder?

Hypothyroidism
Cushing syndrome (Correct answer)
Addison disease
Diabetes insipidus

Correct answer: Cushing syndrome

Autonomous cortisol production in Cushing syndrome resists suppression by exogenous glucocorticoid.

Question 330: Which component is the treatment of choice for fibrinogen replacement in a bleeding patient with hypofibrinogenemia?

Packed red blood cells
Platelets
Cryoprecipitate (Correct answer)
Albumin

Correct answer: Cryoprecipitate

Cryoprecipitate is rich in fibrinogen and is used to correct hypofibrinogenemia.

Question 331: A group O mother delivers a group A infant with a positive DAT and jaundice at birth. What is the most likely diagnosis?

ABO hemolytic disease of the newborn (Correct answer)
Hereditary spherocytosis
G6PD deficiency
Rh hemolytic disease

Correct answer: ABO hemolytic disease of the newborn

Group O mothers produce IgG anti-A,B that crosses the placenta causing ABO HDN.

American Board of Pathology (ABPath) Clinical Pathology Certification Exam

The ABPath Clinical Pathology exam certifies physicians in laboratory medicine, covering hematopathology, blood banking/transfusion medicine, medical microbiology, chemical pathology, and laboratory management across a full-day computer-based examination.

330

Questions

396 min

Time Limit

70%

To Pass

Checking for saved progress...

Exam Rules

You can skip questions and return to them later
Flag questions for review before submitting
No feedback shown until you submit the entire exam
Unanswered questions count as wrong — answer everything
10 pretest questions are mixed in and don't affect your score
Timer auto-submits when time runs out
Your progress is auto-saved every 30 seconds