Mesothelioma Diagnosis Clinical Knowledge Assessment — Questions and Answers

Question 1: The combination of nivolumab and ipilimumab has been approved for first-line treatment of mesothelioma based on which trial?

KEYNOTE-158
CheckMate 743 (Correct answer)
MAPS2
EMPHACIS

Correct answer: CheckMate 743

The CheckMate 743 trial demonstrated improved overall survival with nivolumab plus ipilimumab versus chemotherapy, leading to FDA approval for first-line mesothelioma.

Question 2: Paraganglioma occurring in the posterior mediastinum may mimic mesothelioma on imaging; it is distinguished by positive staining for:

Synaptophysin and chromogranin A (Correct answer)
Calretinin and WT1
CK5/6 and D2-40
TTF-1 and Napsin A

Correct answer: Synaptophysin and chromogranin A

Paragangliomas are neuroendocrine tumors that express synaptophysin and chromogranin A, neuroendocrine markers completely absent in mesothelioma.

Question 3: Which imaging finding would most likely prompt a change from surgical to palliative management in pleural mesothelioma?

Small ipsilateral pleural effusion
Mediastinal lymph node involvement on PET/CT (Correct answer)
Pleural thickening less than 5 mm
Single pleural nodule without invasion

Correct answer: Mediastinal lymph node involvement on PET/CT

Mediastinal nodal involvement (N2 disease) indicates unresectable disease in most staging systems, often redirecting management toward palliative intent.

Question 4: In mesothelioma imaging, contralateral pleural disease or pericardial extension indicates which TNM stage?

Stage I
Stage IV (Correct answer)
Stage III
Stage II

Correct answer: Stage IV

Extension to contralateral pleura or pericardium indicates advanced T4 disease, placing the patient in Stage IV of the IMIG staging system.

Question 5: Which complete blood count (CBC) finding is associated with advanced mesothelioma and poor prognosis?

Eosinophilia
Thrombocytosis (Correct answer)
Lymphocytosis
Neutropenia

Correct answer: Thrombocytosis

Paraneoplastic thrombocytosis (elevated platelet count) is common in advanced mesothelioma and is associated with poor survival outcomes.

Question 6: Which occupational group historically has the highest risk of developing mesothelioma?

Office workers
Shipyard workers (Correct answer)
Retail workers
Farmers

Correct answer: Shipyard workers

Shipyard workers historically faced heavy asbestos exposure from pipe insulation, boilers, and ship components, placing them at the highest risk.

Question 7: Which combination of IHC markers is commonly used as a positive panel for epithelioid mesothelioma?

GATA3, ER, PR, GCDFP-15
Calretinin, WT1, CK5/6, D2-40 (Correct answer)
TTF-1, Napsin A, CEA, MOC-31
CDX2, CK20, villin, CEA

Correct answer: Calretinin, WT1, CK5/6, D2-40

Calretinin, WT1, CK5/6, and D2-40 form a standard positive mesothelial IHC panel used to support a diagnosis of epithelioid mesothelioma.

Question 8: Which characteristic morphological feature differentiates epithelioid mesothelioma from reactive mesothelial hyperplasia on histology?

Mitotic rate alone
Stromal invasion (Correct answer)
Nuclear pleomorphism alone
Cell size

Correct answer: Stromal invasion

Stromal invasion is the definitive histological feature of malignancy; reactive mesothelial cells may appear atypical but do not invade underlying stroma.

Question 9: Which IHC marker strongly supports synovial sarcoma over sarcomatoid mesothelioma in a chest wall/pleural spindle cell tumor?

TLE1 positivity with SYT-SSX fusion on FISH (Correct answer)
D2-40 positivity
Pancytokeratin positivity alone
BAP1 loss

Correct answer: TLE1 positivity with SYT-SSX fusion on FISH

TLE1 is a sensitive marker for synovial sarcoma, and the SYT-SSX translocation confirmed by FISH definitively distinguishes it from sarcomatoid mesothelioma.

Question 10: Which imaging study is most useful for assessing the extent of chest wall invasion in mesothelioma?

PET scan
Chest X-ray
MRI (Correct answer)
Ultrasound

Correct answer: MRI

MRI provides superior soft tissue contrast and is the best modality for evaluating chest wall, diaphragm, and mediastinal invasion in mesothelioma staging.

Question 11: On CT imaging, which feature is most suggestive of peritoneal mesothelioma?

Diffuse peritoneal thickening with ascites (Correct answer)
Retroperitoneal lymphadenopathy alone
Isolated hepatic lesion
Single large abdominal mass

Correct answer: Diffuse peritoneal thickening with ascites

Peritoneal mesothelioma typically appears on CT as diffuse peritoneal thickening or nodularity accompanied by ascites.

Question 12: What is the significance of finger clubbing in a patient being evaluated for mesothelioma?

It rules out mesothelioma and suggests primary lung cancer instead
It is pathognomonic for mesothelioma
It indicates successful response to treatment
It suggests underlying chronic hypoxia and pulmonary disease, raising suspicion for advanced thoracic malignancy (Correct answer)

Correct answer: It suggests underlying chronic hypoxia and pulmonary disease, raising suspicion for advanced thoracic malignancy

Finger clubbing indicates chronic hypoxia or pulmonary disease and, combined with other findings, raises suspicion for advanced thoracic malignancy including mesothelioma.

Question 13: Elevated serum SMRP is most specific for which mesothelioma cell type?

Biphasic
Sarcomatoid
Desmoplastic
Epithelioid (Correct answer)

Correct answer: Epithelioid

SMRP is primarily expressed by epithelioid mesothelioma cells; sarcomatoid tumors express little to no mesothelin, reducing biomarker sensitivity in those cases.

Question 14: Pleural involvement by breast carcinoma can be excluded in favor of mesothelioma by the absence of which markers?

D2-40 and CK5/6
TTF-1 and Napsin A
Calretinin and WT1
ER, GATA3, and mammaglobin (Correct answer)

Correct answer: ER, GATA3, and mammaglobin

ER, GATA3, and mammaglobin are breast carcinoma markers; their absence, combined with positive mesothelial markers, supports mesothelioma over metastatic breast cancer.

Question 15: TTF-1 (thyroid transcription factor-1) positivity in a pleural biopsy would support a diagnosis of:

Epithelioid mesothelioma
Sarcomatoid mesothelioma
Pleural fibroma
Metastatic lung adenocarcinoma (Correct answer)

Correct answer: Metastatic lung adenocarcinoma

TTF-1 is a marker of lung and thyroid epithelial origin; its positivity in pleural disease supports metastatic lung adenocarcinoma rather than mesothelioma.

Question 16: At what stage is mesothelioma most often diagnosed due to the non-specific nature of early symptoms?

Stage III or IV with advanced disease (Correct answer)
Incidentally at Stage I during routine screening
Stage II with minimal spread
Stage I with localized disease

Correct answer: Stage III or IV with advanced disease

Because early symptoms like dyspnea and fatigue are non-specific, most mesothelioma cases are diagnosed at Stage III or IV when disease is already advanced.

Question 17: A pleural biopsy showing diffuse large B-cell lymphoma cells would be differentiated from mesothelioma by which finding?

BAP1 loss
CDKN2A deletion
Calretinin positivity
CD20 positivity and cytokeratin negativity (Correct answer)

Correct answer: CD20 positivity and cytokeratin negativity

DLBCL expresses B-cell marker CD20 and lacks cytokeratin expression, which is the opposite of mesothelioma's keratin-positive, CD20-negative profile.

Question 18: CT scan of the chest in pleural mesothelioma most characteristically shows which finding?

Ground-glass opacities
Bilateral hilar adenopathy
Circumferential pleural thickening (Correct answer)
Central lung mass

Correct answer: Circumferential pleural thickening

CT imaging typically reveals circumferential or nodular pleural thickening, often encasing the lung, which is highly characteristic of malignant pleural mesothelioma.

Question 19: Which serum biomarker is most widely used to support a diagnosis of malignant pleural mesothelioma?

AFP
CEA
CA 19-9
Mesothelin (SMRP) (Correct answer)

Correct answer: Mesothelin (SMRP)

Soluble mesothelin-related peptide (SMRP) in serum is the most validated blood biomarker for malignant mesothelioma, approved by the FDA as an adjunct diagnostic tool.

Question 20: Which IHC profile helps distinguish pleural mesothelioma (positive) from metastatic adenocarcinoma (negative)?

TTF-1 positive, calretinin negative
Calretinin positive, CEA negative (Correct answer)
MOC-31 positive, D2-40 negative
CEA positive, WT1 negative

Correct answer: Calretinin positive, CEA negative

Mesothelioma characteristically stains positive for calretinin and negative for CEA, while the reverse pattern is seen in metastatic adenocarcinoma.

Question 21: What is the role of next-generation sequencing (NGS) in mesothelioma diagnosis?

Measuring mesothelin expression
Replacing IHC for routine diagnosis
Identifying actionable mutations and confirming malignancy (Correct answer)
Assessing asbestos burden in tissue

Correct answer: Identifying actionable mutations and confirming malignancy

NGS identifies somatic mutations (e.g., BAP1, NF2, CDKN2A) that confirm malignancy and may reveal targetable alterations for clinical trials.

Question 22: Which gender is more commonly diagnosed with mesothelioma in the US?

Women
Depends on the subtype
Men (Correct answer)
Both equally

Correct answer: Men

Men are diagnosed with mesothelioma far more often than women due to historical occupational asbestos exposure in male-dominated industries.

Question 23: VEGF (vascular endothelial growth factor) serum levels in mesothelioma are elevated and correlate with:

Response to surgery
Pleural effusion volume and tumor angiogenesis (Correct answer)
BAP1 mutation status
Sarcomatoid cell type only

Correct answer: Pleural effusion volume and tumor angiogenesis

Elevated VEGF promotes tumor angiogenesis and is associated with larger pleural effusions; it has been explored as a therapeutic target in mesothelioma.

Question 24: Which type of mesothelioma affects the lining of the lungs?

Testicular mesothelioma
Pericardial mesothelioma
Peritoneal mesothelioma
Pleural mesothelioma (Correct answer)

Correct answer: Pleural mesothelioma

Pleural mesothelioma arises from the pleura, the thin membrane surrounding the lungs, and is the most common form.

Question 25: Serum osteopontin has been proposed as a mesothelioma screening biomarker in asbestos-exposed individuals because:

It is specific for peritoneal disease
It is only elevated after symptoms begin
It replaces imaging in annual surveillance
It is elevated in asbestos-exposed individuals who develop mesothelioma compared to exposed but disease-free individuals (Correct answer)

Correct answer: It is elevated in asbestos-exposed individuals who develop mesothelioma compared to exposed but disease-free individuals

Serum osteopontin is significantly elevated in asbestos-exposed individuals who develop mesothelioma, suggesting a role in surveillance of high-risk populations.

Question 26: Which imaging modality is typically the first used when mesothelioma is suspected based on symptoms?

Chest X-ray (Correct answer)
Ultrasound
PET scan
MRI

Correct answer: Chest X-ray

A chest X-ray is the initial imaging tool used when pleural mesothelioma is suspected, often revealing pleural effusion or pleural thickening.

Question 27: Which imaging finding on CT is used to calculate the peritoneal cancer index (PCI) in peritoneal mesothelioma?

Distribution and size of peritoneal tumor deposits (Correct answer)
Diameter of the largest lymph node
Thickness of the bowel wall
Volume of ascites

Correct answer: Distribution and size of peritoneal tumor deposits

The PCI is calculated by scoring the size and distribution of tumor deposits across 13 abdominal regions on CT to guide surgical planning.

Question 28: MicroRNA-625-3p in pleural effusion has been studied as a mesothelioma biomarker because:

It measures asbestos-induced DNA damage
It indicates BAP1 loss
It predicts surgical margins
It is elevated in malignant effusions and may improve cytological diagnosis (Correct answer)

Correct answer: It is elevated in malignant effusions and may improve cytological diagnosis

MicroRNA-625-3p levels are elevated in pleural fluid from mesothelioma patients and may augment cytological diagnosis in indeterminate cases.

Question 29: Solitary fibrous tumor of the pleura (SFTP) is distinguished from mesothelioma by which key feature?

It is always malignant
It is usually localized and has a pedunculated attachment to the pleura (Correct answer)
It always occurs in asbestos-exposed workers
It is diffuse and bilateral

Correct answer: It is usually localized and has a pedunculated attachment to the pleura

SFTP is typically a well-circumscribed, pedunculated, localized mass attached to the pleura by a stalk, in contrast to the diffuse pleural involvement of mesothelioma.

Question 30: Which symptom, when present in a patient with a history of asbestos exposure, should prompt immediate evaluation for mesothelioma?

Bilateral ankle edema
Dry nonproductive cough without fever
Unilateral pleural effusion (Correct answer)
Mild seasonal allergies

Correct answer: Unilateral pleural effusion

A unilateral pleural effusion in a patient with asbestos exposure history is a red-flag symptom that warrants urgent evaluation for pleural mesothelioma.

Mesothelioma Diagnosis Clinical Knowledge Assessment

Assesses clinical competency in diagnosing malignant mesothelioma, covering diagnostic imaging, biopsy and pathology, biomarker interpretation, and differential diagnosis from adenocarcinoma and benign conditions.

Questions

35 min

Time Limit

70%

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