Pathology Flashcards

A 45-year-old woman presents with progressive dysphagia and a mediastinal mass on imaging. Biopsy reveals cells with abundant pale cytoplasm, prominent nucleoli, and a 'chicken-wire' vascular pattern. Immunohistochemistry shows positivity for CD138 and negativity for CD45. Which translocation is most characteristically associated with this neoplasm?

Answer: t(11;14)(q13;q32)

The histologic and immunohistochemical features describe a plasmacytoma/plasma cell myeloma. The t(11;14)(q13;q32) translocation, which juxtaposes CCND1 (cyclin D1) to the IGH locus, is the hallmark translocation in plasma cell neoplasms (multiple myeloma variant) and also mantle cell lymphoma. The 'chicken-wire' vascularity and CD138+/CD45- profile confirm plasma cell lineage. t(14;18) is characteristic of follicular lymphoma; t(8;14) of Burkitt lymphoma; t(15;17) of acute promyelocytic leukemia.

A renal biopsy from a 32-year-old man with hematuria and proteinuria shows mesangial hypercellularity with IgA and C3 deposits on immunofluorescence. Electron microscopy reveals predominantly mesangial electron-dense deposits. Three months after an upper respiratory infection, his serum complement levels are checked: C3 is normal, C4 is normal. Which mechanism best explains preserved complement levels in this disease?

Answer: Activation of the lectin complement pathway with sparing of C4 consumption

IgA nephropathy (Berger disease) activates primarily the lectin pathway (via mannose-binding lectin recognizing galactose-deficient IgA1) and the alternative pathway. Both bypass C1q and C4, meaning C4 is not consumed. C3 can also remain normal in many patients because the complement activation is focal or adequately regulated. The classical pathway (C1q→C4→C2→C3) would reduce both C3 and C4, as seen in lupus nephritis or membranoproliferative GN type I. Preserved C4 with normal or near-normal C3 is a key distinguishing feature of IgA nephropathy.

A 58-year-old male smoker undergoes lung resection. Pathology shows a peripheral tumor with a lepidic growth pattern along intact alveolar walls, no stromal, vascular, or pleural invasion, and a size of 1.8 cm. No lymph node involvement is identified. According to the current WHO classification, what is the correct diagnosis and expected 5-year disease-specific survival?

Answer: Adenocarcinoma in situ; ~100% 5-year disease-specific survival

Adenocarcinoma in situ (AIS) is defined as a ≤3 cm solitary adenocarcinoma with pure lepidic growth and NO invasion (no stromal, vascular, or pleural invasion). When completely resected, AIS carries ~100% disease-specific survival. Minimally invasive adenocarcinoma (MIA) also has ~100% survival but requires ≤5 mm of invasion. Since this tumor shows NO invasion at all, it is AIS, not MIA. Lepidic predominant invasive adenocarcinoma has >5 mm invasion and lower (though still favorable) survival. Atypical adenomatous hyperplasia is ≤5 mm.

A 67-year-old woman with a history of Barrett esophagus undergoes surveillance endoscopy. Biopsy shows glands lined by cells with stratified nuclei reaching the surface, nuclear pleomorphism, and loss of polarity without submucosal invasion. A second pathologist confirms the findings. CDX2 and MUC2 are positive. What is the most precise pathologic diagnosis and the most appropriate next management step?

Answer: High-grade dysplasia; endoscopic eradication therapy (EMR or RFA)

The described histology—stratified, pleomorphic nuclei reaching the luminal surface with loss of polarity, confirmed by two pathologists, without submucosal invasion—meets criteria for high-grade dysplasia (HGD) in Barrett esophagus. Current guidelines (ACG/AGA) recommend endoscopic eradication therapy (endoscopic mucosal resection and/or radiofrequency ablation) rather than esophagectomy for HGD confined to the mucosa, as outcomes are equivalent with far less morbidity. CDX2/MUC2 positivity confirms intestinal metaplasia lineage. Intramucosal adenocarcinoma would show lamina propria invasion but still generally managed endoscopically.

An autopsy of a 71-year-old man with dementia reveals abundant neocortical neuritic plaques and neurofibrillary tangles (NFTs) meeting NIA-AA criteria for high Alzheimer disease neuropathologic change (ADNC). Additionally, alpha-synuclein-positive Lewy bodies are present in the amygdala only. TDP-43 inclusions are absent. Which statement best characterizes this neuropathologic combination?

Answer: Alzheimer disease with limbic-predominant Lewy body co-pathology, a common mixed dementia pattern

Alpha-synuclein Lewy bodies confined to the amygdala represent a Braak Lewy body stage of amygdala-predominant (sometimes called limbic-predominant) distribution—not neocortical stage. This is a well-recognized co-pathology in Alzheimer disease, occurring in up to 50% of autopsy-confirmed AD cases. It does NOT upgrade the Braak LB staging to neocortical (that requires neocortical involvement). The primary diagnosis remains high ADNC Alzheimer disease with limbic-predominant Lewy body co-pathology. LATE requires TDP-43 inclusions, which are absent here. Parkinson disease dementia requires substantia nigra and brainstem Lewy body involvement as the dominant pathology.

A 24-year-old woman presents with episodic hypertension, headache, and diaphoresis. Urine metanephrines are markedly elevated. Adrenal resection is performed. Histology shows the 'Zellballen' pattern with sustentacular cells at the periphery of cell nests, confirmed by S100 positivity. The tumor is 5.5 cm with no capsular invasion, but Ki-67 is 4% and there is focal vascular invasion. According to the PASS (Pheochromocytoma of the Adrenal Gland Scaled Score) system, which histologic feature most strongly predicts malignant behavior?

Answer: Vascular invasion

In the PASS scoring system, vascular invasion carries a score of 1 point and is one of the most clinically significant individual features because it represents direct evidence of aggressive tumor behavior. While large tumor size (>5 cm) contributes to the score, it is less specific for malignancy. A Ki-67 of 4% is borderline but not as weighted in PASS as invasion. The absence of sustentacular cells (loss of S100+ cells) does contribute to PASS, but vascular invasion is the most definitive indicator of malignant potential in pheochromocytoma since benign appearance cannot be guaranteed by histology alone—only metastasis confirms malignancy, making vascular invasion the strongest surrogate marker.