Anatomic and Clinical Pathology Flashcards

A 58-year-old man with a history of ulcerative colitis undergoes surveillance colonoscopy. Biopsy shows low-grade dysplasia with crypt architectural distortion, loss of mucin, and nuclear stratification not reaching the luminal surface. Which feature, if present, would most strongly prompt consideration of colectomy even in the absence of high-grade dysplasia?

Answer: Flat, invisible dysplasia confirmed on two sequential surveillance biopsies

Flat, endoscopically invisible low-grade dysplasia confirmed on two separate surveillance colonoscopies carries a substantial risk of harboring synchronous or metachronous colorectal carcinoma and is a recognized indication for colectomy discussion. DALM lesions are managed differently depending on whether they are adenoma-like vs. non-adenoma-like, but the question specifies no DALM. Pancolonic distribution and pseudopolyps raise overall risk but are not the strongest single trigger for surgical escalation absent high-grade change.

A 34-year-old woman presents with a thyroid nodule. FNA cytology demonstrates a follicular patterned lesion with nuclear features including irregular nuclear contours, nuclear grooves, and occasional intranuclear pseudoinclusions in approximately 30% of cells; the remainder show bland follicular cells. The lesion is encapsulated with a thick fibrous capsule and no capsular or vascular invasion on excision. What is the most appropriate classification?

Answer: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

NIFTP requires: (1) encapsulation or clear demarcation, (2) follicular growth pattern (≤1% papillae, no psammoma bodies, no well-formed papillae), (3) papillary-like nuclear features (nuclear score ≥2), and (4) NO capsular or vascular invasion. This lesion meets all criteria. Papillary carcinoma requires invasion or unambiguous papillary architecture. Follicular adenoma lacks the nuclear features. Minimally invasive follicular carcinoma requires capsular/vascular invasion.

In evaluating renal biopsy material for a patient with nephrotic syndrome, light microscopy shows segmental sclerosis and hyalinosis with collapse of the glomerular tuft involving the hilum, with foam cells and overlying podocyte hypertrophy. Electron microscopy reveals diffuse foot process effacement and no electron-dense deposits. Which FSGS variant does this pattern represent, and what is its prognostic implication compared to the classic variant?

Answer: Perihilar FSGS variant; better response to steroids and lower risk of ESRD than classic FSGS

The described lesion — hilum-centered segmental sclerosis with foam cells and hyalinosis — is the perihilar FSGS variant, typically associated with secondary FSGS (obesity, hyperfiltration states) rather than primary immune-mediated injury. It carries a relatively favorable prognosis compared to classic FSGS, with lower rates of steroid responsiveness (since it is often secondary) but slower progression to ESRD. Collapsing FSGS (wrinkling/collapse of GBM) and tip variant (lesion at the tubular pole) are distinct patterns with different clinical correlates.

A 72-year-old man with a longstanding monoclonal gammopathy undergoes kidney biopsy for worsening proteinuria and renal insufficiency. Congo red stain is negative. Light microscopy shows mesangial expansion with PAS-positive, non-fibrillary deposits. Electron microscopy reveals granular (non-fibrillary) electron-dense deposits in the mesangium and along the inner aspect of glomerular basement membranes. Immunofluorescence shows strong staining for IgG (kappa light chain restricted) but negative for lambda. What is the most likely diagnosis?

Answer: Monoclonal immunoglobulin deposition disease (MIDD), specifically light chain deposition disease (LCDD)

MIDD (light chain or heavy chain deposition disease) presents with Congo red-negative, non-fibrillary granular deposits on EM — distinguishing it from amyloidosis (fibrils, Congo red positive) and fibrillary GN (larger, randomly arranged fibrils, ~20nm). Kappa light chain restriction is characteristic of LCDD (kappa >> lambda in LCDD). The subendothelial/mesangial granular deposits with mesangial expansion and IF showing monotypic kappa are hallmarks. MPGN/cryoglobulinemia would show organized deposits and typically polyclonal or different IF patterns.

A surgical pathologist receives a radical prostatectomy specimen. On H&E, a focus shows small acini with prominent nucleoli, amphophilic cytoplasm, and lack of a basal cell layer confirmed by p63/HMCK immunostains. The architectural pattern shows cribriform glands with intraluminal necrosis (comedonecrosis). Per the current 2019 WHO/ISUP grading system, what Gleason grade and Grade Group does this pattern represent?

Answer: Gleason pattern 5; Grade Group 5 regardless of other patterns present

Cribriform glands with comedonecrosis are graded as Gleason pattern 5 per the 2014 ISUP/2019 WHO revised criteria. Comedonecrosis within cribriform glands was upgraded from pattern 4 to pattern 5 in the 2014 consensus. Grade Group 5 corresponds to Gleason score 9–10 (pattern 4+5 or 5+anything). A pure pattern 5 specimen would be Gleason 5+5=10, Grade Group 5. Cribriform glands WITHOUT necrosis are pattern 4.

A clinical laboratory receives a specimen from a 45-year-old immunocompromised patient with pulmonary infiltrates. Bronchoalveolar lavage Grocott methenamine silver (GMS) stain reveals thin-walled, narrow-angle (acute-angle) branching septate hyphae measuring 3–6 μm in diameter with parallel walls. The organism does not produce conidia in tissue. Culture at 25°C reveals hyaline hyphae with conidiophores bearing biseriate phialides covering the entire vesicle surface (radiate head). What is the most likely organism, and what additional finding would specifically distinguish Aspergillus fumigatus from Aspergillus flavus in this context?

Answer: Aspergillus fumigatus; A. fumigatus produces uniseriate phialides covering only the upper two-thirds of the vesicle (columnar head), while A. flavus has biseriate phialides covering the entire vesicle with a radiate head

The histologic features (narrow-angle, septate, thin-walled hyphae 3–6 μm) are characteristic of Aspergillus species. The biseriate radiate conidial head covering the entire vesicle is characteristic of A. flavus (and A. niger, which also produces black conidia). A. fumigatus produces a columnar head with phialides on the upper half to two-thirds of the vesicle only (uniseriate, columnar). A. flavus typically has biseriate phialides and a radiate head with full vesicle coverage. Fusarium hyphae can appear similar in tissue but produce curved macroconidia in culture and often invade blood vessels similarly; the culture here clearly shows Aspergillus morphology. Sclerotia can be produced by some A. flavus strains but are not a reliable distinguishing criterion.