Anatomic and Clinical Pathology Flashcards

A 58-year-old man undergoes resection of a pulmonary nodule. Histology shows nests of cells with abundant pink granular cytoplasm, round nuclei with prominent nucleoli, and positive staining for CD10, PAX8, and vimentin but negative for TTF-1 and napsin A. The tumor also shows loss of VHL expression by immunohistochemistry. What is the most likely diagnosis?

Answer: Metastatic clear cell renal cell carcinoma

The immunoprofile — CD10+, PAX8+, vimentin+, TTF-1−, napsin A− — combined with VHL loss is characteristic of clear cell renal cell carcinoma (ccRCC). Pulmonary carcinoid is synaptophysin/chromogranin+; large cell carcinoma lacks this specific IHC profile; sclerosing pneumocytoma is TTF-1+ and EMA+. A solitary pulmonary nodule with these markers should prompt clinical correlation for a renal primary.

On flow cytometry of a bone marrow aspirate, a population of cells is identified that is CD19+, CD5+, CD23+, CD20 dim, surface IgM dim, and FMC7−. The Matutes score is 4. A FISH panel reveals del(17p) and del(11q). Which prognostic statement is MOST accurate regarding this patient's disease course?

Answer: Del(17p) indicates TP53 dysfunction and poor response to most conventional therapies

Del(17p) disrupts TP53 and is the most adverse cytogenetic abnormality in CLL, conferring resistance to purine analogues and alkylating agents. These patients have the shortest time to treatment and overall survival. Del(11q) (ATM loss) is also high-risk but responds better to bendamustine-based regimens. BTK inhibitors (ibrutinib) are now preferred for del(17p) CLL. The combination of both deletions is not a favorable prognostic pairing.

A nephrectomy specimen from a 45-year-old woman reveals a tumor with papillary architecture, cells with abundant foamy cytoplasm, prominent macrophage infiltration, and a fibrovascular core. Immunohistochemistry shows CK7+, AMACR (racemase)+, and CD10−. Cytogenetics shows gains of chromosomes 7 and 17 with loss of chromosome Y. Which subtype of renal cell carcinoma does this BEST represent?

Answer: Type 1 papillary renal cell carcinoma

Type 1 papillary RCC is characterized by small cells with scant pale cytoplasm, foamy macrophages in the papillary cores, CK7 positivity, AMACR positivity, and trisomy 7 and 17 with loss of Y. Type 2 has more eosinophilic, pseudostratified cells with higher nuclear grade and a worse prognosis. Chromophobe RCC has characteristic 'raisinoid' nuclei and diffuse CK7 positivity without AMACR. Collecting duct carcinoma is aggressive with high-grade cells and desmoplastic stroma.

A 30-year-old woman presents with recurrent DVTs and a prolonged aPTT that does NOT correct on 1:1 mixing study. Anti-β2 glycoprotein I IgG and anti-cardiolipin IgM antibodies are both elevated on two occasions 12 weeks apart. Lupus anticoagulant is also positive. The platelet count is 95,000/μL. Which laboratory finding is the MOST specific for diagnosing the primary thrombotic mechanism in antiphospholipid syndrome?

Answer: Prolonged dilute Russell's viper venom time (dRVVT) that corrects with excess phospholipid

Lupus anticoagulant (LA) detection via dRVVT is the most specific test for antiphospholipid syndrome (APS). A prolonged dRVVT that corrects with excess phospholipid (but NOT with normal plasma) confirms phospholipid-dependent inhibition — the hallmark of LA. Anti-cardiolipin IgM alone has lower specificity; low complement and anti-dsDNA point toward systemic lupus erythematosus as an associated condition but are not specific for the APS thrombotic mechanism.

Autopsy of a 55-year-old man with a history of chronic alcohol use reveals a liver weighing 3,200 g. Histologic sections show bridging fibrosis, regenerative nodules of varying size (some >3 mm), and thick fibrous septa with few inflammatory cells. Portal tracts are almost completely replaced by fibrous tissue. What morphologic subtype of cirrhosis BEST describes this pattern, and what additional histologic feature distinguishes it from the early active phase?

Answer: Mixed cirrhosis with inactive pattern; distinguished by paucity of necroinflammatory activity and absence of interface hepatitis

The nodules >3 mm with variability in size indicate macronodular to mixed cirrhosis, commonly seen in burned-out alcoholic liver disease. The 'inactive' phase is characterized by a paucity of necroinflammatory activity and absence of interface hepatitis — features seen when the injurious stimulus (alcohol) has been removed. Active cirrhosis would show lobular inflammation, Mallory-Denk bodies, and interface activity. Congestive cirrhosis has a distinct pattern with dilated sinusoids and 'cardiac cirrhosis' features.

A transbronchial biopsy from a lung transplant recipient at 8 months post-transplant shows perivascular lymphocytic infiltrates grading A2, fibrous obliteration of small airways with eccentric submucosal fibrosis, and loss of bronchiolar epithelium. No viral cytopathic changes are identified. CMV PCR is undetectable. What pathologic process is MOST likely responsible for this biopsy pattern, and what is its significance?

Answer: Obliterative bronchiolitis (chronic lung allograft dysfunction); it represents the dominant cause of late post-transplant mortality

The combination of perivascular A2 rejection with fibrous obliteration of small airways and loss of bronchiolar epithelium — in the absence of viral infection — is consistent with obliterative bronchiolitis (OB), the histologic correlate of bronchiolitis obliterans syndrome (BOS), the leading cause of death in long-term lung transplant survivors. Unlike acute rejection, OB is poorly reversible with steroids and portends progressive allograft loss. PTLD would show atypical lymphoid proliferations, often EBV-driven, with mass-like lesions.