Pathology Flashcards

A 45-year-old woman presents with a neck mass. Histology reveals follicular structures filled with colloid surrounded by a fibrous capsule with focal capsular penetration but no vascular invasion. Which finding would definitively upgrade this lesion to malignant?

Answer: Tumor cells penetrating through the entire capsule thickness

Complete capsular penetration (full-thickness breach of the fibrous capsule) is required to classify a follicular thyroid neoplasm as follicular carcinoma rather than follicular adenoma. Partial penetration without full breakthrough is insufficient. Vascular invasion (tumor within vascular channels lined by endothelium) is the other criterion. Psammoma bodies, Hurthle cell change, and follicle size variation are not diagnostic of malignancy in follicular lesions.

An autopsy of a 62-year-old man with a history of alcoholic cirrhosis reveals a hepatocellular carcinoma with a distinctive histologic pattern: tumor cells arranged around a central fibrous scar with radiating fibrous bands. This morphology is most characteristic of which variant, and what is its associated prognosis compared to conventional HCC?

Answer: Fibrolamellar HCC; better prognosis due to resectability but same 5-year survival when matched for stage

Fibrolamellar HCC is characterized by large polygonal cells with abundant eosinophilic cytoplasm embedded in parallel lamellar fibrous bands, often with a central fibrous scar. It occurs in young patients WITHOUT cirrhosis, making surgical resection more often feasible. However, when stage-matched, the 5-year survival is similar to conventional HCC. This nuanced point — better apparent prognosis due to resectability rather than intrinsic biologic difference — distinguishes this variant.

A renal biopsy from a 38-year-old with nephrotic syndrome shows segmental sclerosis on light microscopy with IgM and C3 deposits on immunofluorescence in the sclerotic segments. Electron microscopy reveals foot process effacement predominantly in the non-sclerotic segments. Which mechanism best explains why this lesion is more resistant to steroid therapy than minimal change disease?

Answer: Permanent architectural destruction of the glomerular tuft in sclerotic segments prevents reversal even if podocyte dysfunction resolves

In FSGS, the sclerotic segments represent irreversible glomerular scarring — collapse of the capillary tuft with matrix deposition and podocyte loss. Even if the underlying injury (podocyte dysfunction) is halted by steroids, the destroyed architecture cannot regenerate. This is mechanistically distinct from MCD, where foot process effacement is fully reversible because no structural destruction has occurred. The IgM and C3 in FSGS sclerotic segments are non-specific 'trapped' proteins, not primary immune deposits driving the lesion.

A 55-year-old smoker develops hemoptysis. Bronchoscopy reveals a central endobronchial mass. Histology shows small cells with nuclear molding, finely granular 'salt-and-pepper' chromatin, absent nucleoli, and a high mitotic rate with abundant necrosis. IHC is positive for synaptophysin, chromogranin A, and TTF-1, but negative for CK7. Which additional finding would most strongly support a diagnosis of small cell lung carcinoma over atypical carcinoid?

Answer: Ki-67 proliferation index greater than 50%

The WHO classification distinguishes pulmonary neuroendocrine tumors by mitotic rate and Ki-67: typical carcinoid 50–80%. A Ki-67 >50% definitively places the tumor in the high-grade category. Crush artifact and Azzopardi effect are characteristic morphologic features of SCLC but are also seen in atypical carcinoid in small biopsies. CD56 is expressed across the neuroendocrine spectrum and does not discriminate grade.

A 28-year-old woman presents with painless cervical lymphadenopathy. Excisional biopsy shows effaced nodal architecture with Reed-Sternberg cells in a background of lymphocytes, plasma cells, and eosinophils with broad bands of fibrosis. EBV-encoded RNA (EBER) in situ hybridization is NEGATIVE. This EBV-negative status is most characteristically associated with which subtype?

Answer: Nodular sclerosis classic Hodgkin lymphoma

EBV association varies significantly among Hodgkin lymphoma subtypes. Nodular sclerosis (NS-CHL) is the most common subtype in developed countries and is EBV-positive in only ~10–25% of cases. In contrast, mixed cellularity CHL is EBV-positive in ~75% of cases, lymphocyte-depleted CHL is EBV-positive in ~75–96%, and lymphocyte-rich CHL in ~40%. The clinical scenario — young woman, cervical nodes, fibrous bands, lacunar Reed-Sternberg cells — is classic NS-CHL, which is also the subtype LEAST associated with EBV.

A researcher studying tumorigenesis identifies a gene whose protein product forms a complex with MDM2, preventing MDM2-mediated ubiquitination of p53 in response to oncogenic stress. Loss-of-function mutations in this gene would most likely result in:

Answer: Impaired ARF-MDM2 interaction, leading to unrestrained MDM2-mediated p53 degradation and failure of oncogene-induced senescence

The gene described is CDKN2A (ARF/p14ARF in humans, p19ARF in mice). ARF binds MDM2 and sequesters it in the nucleolus, preventing MDM2 from targeting p53 for proteasomal degradation. This is the primary mechanism by which oncogenic signals (e.g., Ras activation, Myc overexpression) stabilize p53 to trigger senescence or apoptosis. Loss-of-function mutations in ARF remove this brake — MDM2 freely degrades p53, and oncogene-induced senescence fails, permitting tumor progression. This is distinct from direct p53 mutation; the p53 protein is intact but functionally suppressed by excess MDM2 activity.