Anatomic and Clinical Pathology Flashcards

A 58-year-old man undergoes resection of a colonic mass. Histology shows a serrated adenocarcinoma with loss of MLH1 and PMS2 by immunohistochemistry, but MSI-PCR shows microsatellite stability (MSS). Which of the following best explains this discordant finding?

Answer: Somatic BRAF V600E mutation causing MLH1 promoter hypermethylation with incomplete protein loss

BRAF V600E-driven MLH1 promoter hypermethylation can result in partial or heterogeneous MLH1/PMS2 protein loss on IHC while PCR-based MSI testing remains stable if sufficient mismatch repair capacity persists or if only a subclone is affected. This IHC/MSI discordance is a recognized pitfall in Lynch syndrome screening; BRAF mutation testing and MLH1 methylation analysis are the appropriate next steps.

A lymph node biopsy from a 34-year-old HIV-positive man shows paracortical expansion by large cells with prominent nucleoli, abundant pale cytoplasm, and interspersed small lymphocytes. EBER in-situ hybridization is positive. CD30 is positive; CD15 is negative; CD20 is dim positive; PAX5 is weakly positive; CD45 is positive. What is the most likely diagnosis?

Answer: EBV-positive diffuse large B-cell lymphoma, NOS

EBV-positive DLBCL, NOS (formerly EBV-positive DLBCL of the elderly, now recognized across age groups especially in immunocompromised patients) characteristically shows CD20 dim positivity, PAX5 weak positivity, CD45 positivity, and CD30 positivity with EBER+. CD15 negativity and retained B-cell markers distinguish it from classic Hodgkin lymphoma. Plasmablastic lymphoma typically loses CD20/PAX5 entirely and is EBER+ but shows plasmacytic differentiation markers.

In reporting a radical prostatectomy specimen, you encounter a focus where adenocarcinoma invades into the muscular wall of the seminal vesicle proper, but the ureteral segment and fat surrounding the seminal vesicle are uninvolved. According to the 2019 AJCC staging system, what pathologic T stage is assigned?

Answer: pT3b

Seminal vesicle invasion (SVI) is defined as tumor invading the muscular wall of the seminal vesicle. This qualifies as pT3b regardless of whether the surrounding fat or ureter is involved. pT3a covers extraprostatic extension or bladder neck invasion without SVI. pT4 requires invasion of adjacent structures such as the rectum, levator muscles, or pelvic wall—not the seminal vesicles.

A 45-year-old woman presents with recurrent hypoglycemia. Serum insulin is markedly elevated; C-peptide is elevated; proinsulin is elevated; insulin antibodies are absent. Intraoperative ultrasound localizes a 1.2 cm pancreatic tail lesion. Histology shows a well-differentiated neuroendocrine tumor (NET). Which Ki-67 proliferation index threshold, per WHO 2022, would upstage this lesion from Grade 1 to Grade 2?

Answer: Ki-67 > 2%

Per the WHO 2022 classification of pancreatic NETs, Grade 1 is defined as Ki-67 ≤ 2% (and mitotic count 2% (with mitotic count 2–20/2mm²) defines Grade 2. The > 3% cutoff applies to pulmonary carcinoid grading in a different classification system, and > 5% or > 10% are not the relevant pancreatic NET thresholds.

A 62-year-old woman undergoes liver biopsy for elevated liver enzymes. Histology shows portal tract inflammation with interface hepatitis, periportal rosette formation, hepatocyte swelling, and prominent plasma cells. Direct immunofluorescence on frozen liver shows IgG deposits in a 'chicken-wire' sinusoidal pattern. Which pattern of indirect immunofluorescence on HEp-2 cells would most specifically support the underlying diagnosis?

Answer: Cytoplasmic actin staining pattern

The clinical and histologic picture is classic for autoimmune hepatitis (AIH) Type 1. Anti-smooth muscle antibodies (ASMA) targeting F-actin produce a cytoplasmic actin-staining pattern on HEp-2 cells and are the most specific serologic marker for AIH Type 1. The homogeneous ANA pattern can be seen in AIH but is less specific. p-ANCA is associated with primary sclerosing cholangitis. Anti-Ro/SSA is characteristic of Sjögren syndrome and neonatal lupus.

During frozen section analysis of a sentinel lymph node from a breast cancer patient, you observe a 0.6 mm cluster of cytokeratin-positive epithelial cells within the subcapsular sinus. No other nodes are submitted. According to the AJCC 8th Edition, how should this finding be classified and what is the resulting nodal stage?

Answer: Micrometastasis; pN1mi

Per AJCC 8th Edition, micrometastases are defined as tumor deposits > 0.2 mm but ≤ 2.0 mm, staged as pN1mi. At 0.6 mm, this deposit exceeds the 0.2 mm threshold for isolated tumor cells (ITC, classified pN0(i+) when ≤ 0.2 mm or ≤ 200 cells) but is well below the 2.0 mm threshold for macrometastasis (pN1a). ITCs are specifically ≤ 0.2 mm clusters or single cells, so 0.6 mm qualifies as a micrometastasis regardless of method of detection.