slide 17-Papilla Renal Cell CaType2.pptx

Papillary Renal Cell Carcinoma

1. SLIDE NO-17 60 YEARS MALE PARTIAL Nephrectomy

2. Low power view showing renal perenchyma and papillary fronds

3. High power Section shows papillary structures with delicate fibrovascular cores . The lining epithelial cells are cuboidal to columnar with moderate amount of cytoplasm and round to oval nuclei. Occasional areas show overlapping nuclei.

4. Section shows papillae with tall columnar tumor cells having eosinophilic cytoplasm. Tumor cells show mild nuclear pleomorphism. The fibrovascular cores are evident and contain congested vessels.

5. Section shows complex branching papillae lined by tumor cells. The lining cells show vesicular nuclei with prominent nucleoli. Some papillae show foamy macrophages within the cores, a characteristic feature of papillary RCC.

6. Section shows tumor cells arranged in papillary projections with fibrovascular cores infiltrating into stroma . Tumor cells are cuboidal with moderate eosinophilic cytoplasm. Perivascular inflammatory infiltrate is seen in some areas.

7. Papillary Renal Cell Carcinoma (Type 2)

8. Introduction Epidemiology: Second most common subtype of RCC (~10–15% of all RCCs). Age/Sex: Middle-aged to older adults; slight male predominance. Type 2 shows higher nuclear grade and worse prognosis than Type 1. Associated with MET mutations and hereditary leiomyomatosis RCC syndrome.

9. Gross Features Tumor often appears as a well-circumscribed mass. Frequently shows hemorrhage, necrosis, and cystic changes. Usually tan-brown to yellow in color.

10. Microscopic Features Papillary/ tubulopapillary architecture. Cells with abundant eosinophilic cytoplasm. High nuclear grade with prominent nucleoli. Foamy macrophages and psammoma bodies may be present.

11. Etiology & Pathogenesis Genetic alterations : Type 1 PRCC → MET proto-oncogene alterations (chromosome 7). Type 2 PRCC → More heterogeneous : CDKN2A silencing , SETD2 , FH (fumarate hydratase) mutations (especially in hereditary leiomyomatosis and RCC syndrome, HLRCC). Chromosome abnormalities: loss of 9p, gain of 8q, trisomy 7 & 17 sometimes seen. Sporadic vs. Hereditary : Sporadic : most common. Hereditary : associated with HLRCC syndrome (germline FH mutations → defective Krebs cycle → fumarate accumulation → oncogenic signaling). Pathogenesis : Accumulation of fumarate → stabilization of HIF (hypoxia-inducible factor) → upregulation of angiogenesis and glycolysis → tumor progression. Explains the more aggressive clinical behavior compared to type 1.

12. Differential Diagnosis Type 1 PRCC Basophilic cytoplasm, low-grade nuclei, foamy macrophages & psammoma bodies more common. Type 2: eosinophilic cytoplasm, high-grade nuclei, worse prognosis. Clear Cell RCC Clear cytoplasm, rich vascular network, associated with VHL mutations. PRCC type 2: papillary/ tubulopapillary pattern and eosinophilic cells. Chromophobe RCC Pale/eosinophilic cytoplasm, perinuclear halos, "plant cell" appearance. Hale’s colloidal iron positive (diffuse cytoplasmic). Type 2 PRCC lacks these features. Oncocytoma Purely eosinophilic cytoplasm, nested architecture, no true papillae. Benign behavior; distinguishable with immunohistochemistry. Translocation RCC (Xp11) Seen in young patients, papillary-like features but with TFE3 gene fusions (immunohistochemistry or FISH required).