Renal Pathology Update. Sundus Hussein MD, FRCPC

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1 Renal Pathology Update Sundus Hussein MD, FRCPC

2 Case History A 45 year old male with incidentally discovered a 3.5 x 3.9 x 2.7 cm renal mass

3

4

5 Handling partial nephrectomy

6 Handling partial nephrectomy 1 1. Always look for irregular and ragged margin

7

8 Indication for Nephron Sparing Surgery

9 Absolute indications - anatomically or functionally solitary kidney - bilateral RCC

10 Relative Indications - the contralateral kidney has pre-existing renal disease, or its future function is threatened. Conditions: stone disease chronic pyelonephritis renal artery stenosis vesicoureteral reflux (with or without renal scarring), chronic renal obstruction from congenital or acquired causes. systemic diseases such as diabetes, hypertension and nephrosclerosis.

11

12 Classification The classification of renal neoplasms has evolved greatly over the past two decades Detailed morphological studies incorporating immunohistochemical and molecular techniques have resulted in the 2004 World Health Organization (WHO) monograph

13 WHO 2004 Classification

14 Renal cell carcinoma The common renal cell carcinomas i.e. clear cell, papillary and chromophobe types account for 85-90% The remaining 10-15% includes a variety of uncommon sporadic and familial carcinomas some of which have been recently described

15

16 Uncommon and recently described carcinomas Established New and emerging Collecting duct carcinoma Renal medullary carcinoma Mucinous tubular and spindle-cell carcinoma Translocation carcinoma Post-neuroblastoma renal carcinoma Tubulocystic carcinoma Carcinoma associated with end-stage renal disease Clear cell papillary renal cell carcinoma Follicular renal carcinoma Leiomyomatous renal cell carcinoma

17 Refinements to existing WHO (2004) Renal Cell Tumor Categories 5 entities recognized as new distinct epithelial tumors within the classification system Working Group 1

18

19 1. Tubulocystic RCC Low grade collecting duct carcinoma Mean age 60 years (range 18-94) M:F 7:1 Imaging: Complex cyst Low grade and amenable to partial or radical nephrectomy

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21 10

22

23 IHC, cytokeratins CK8, CK18, and CK19 and less frequently for CK7. A small % of cases stain positively HMWK (34bE12). Nearly all cases show positivity for CD10 and racemase (AMACR). Less than half of the cases will show positivity for PAX2 and carbonic anhydrase IX (CA-IX)

24 Molecular Diagnosis, Gains in chromosomes 7 and 17 and loss of the Y chromosome using FISH Some type 2 PRCCs have areas that are virtually indistinguishable from TC- RCC suggesting a possible relationship. separate TC-RCC and PRCC tumors may be found in the same kidney.

25 2. Acquired cystic disease-associated RCC ACD-RCC 46% of these are in end stage kidneys with acquired cystic diseases Nodules arising from cyst wall Multifocal >50% bilateral >20% Good prognosis (early)

26 2. Acquired cystic disease-associated RCC ACD-RCC composed mainly of large eosinophilic cells arranged in solid, cribriform, acinar, or papillary patterns. Tumor is characterized by intraluminal oxalate crystals (most but not all)

27

28

29 Carcinoma associated with endstage renal disease 10 X risk of developing RCCs RCCs associated with ESKD and ACKD are multicentric and bilateral younger patients (mostly male) less aggressive behavior

30 Carcinoma associated with endstage renal disease Acquired cystic disease-associated renal cell carcinoma Clear cell papillary RCC. Cystic degenerative changes (acquired cystic kidney disease [ACKD]) and RCC

31 3. Clear cell (tubulo) papillary RCC 1% of all RCC 60 years; (18-88) M:F Indolent clinical behavior

32

33 IHC, CK7/CA-IX/ high molecular weight cytokeratin positivity CD10 and AMACR negativity.

34 5. Hereditary leiomyomatosis RCC syndrome-associated RCC It was described in 2004 WHO classification of renal neoplasm in the section related to hereditary RCC Aggressive behavior with advance stage AD and associated with germline mutations in the fumarate hydratase gene (located at 1q42) Cutanous and uterine leiomyoma

35 5. Hereditary leiomyomatosis RCC syndrome-associated RCC 80% respondents by consensus believed that it was important to recognize HLRCC as a distinctive entity as the diagnosis carries significant implication for patient management and follow up for family members.

36 4. MITF/TFE family translocationassociated carcinoma) Different translocations involving chromosome Xp11.2, all resulting in gene fusions involving thetfe3 gene 1. Xp11 translocation RCC (2004 WHO classification)- TFE3 2. t(6;11) RCCs results in TFEB gene fusion

37 ? Distinct Histological Entity Sarcomatoid changes Rhabdoid features

38 Thank you

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