Cystic Neoplasms of Kidney in Adults

1. Cystic Neoplasms of Kidney in Adults L. Priya Kunju, M.D. Assistant Professor Department of Pathology The University of Michigan

2. Case 11Patient history 47 Y Male patient with a complex cystic renal mass noted on CT who underwent partial nephrectomy A 2 cm complex cystic renal mass was noted

4. DiagnosisAngiomyolipoma with Epithelial Cysts (AMLEC)

5. Angiomyolipoma Sporadic or in association with Tuberous Sclerosis Arise from perivascular epitheliod cells (HMB-45 positive) Solid tumors, well demarcated from adjacent kidney Composed of varying mixtures of blood-vessels, smooth muscle and fat

6. Angiomyoplioma with Epithelial Cysts Gross Complex cystic mass Microscopic features Multiple cysts lined by epithelium: columnar, cuboidal. Abundant eosinophilic cytoplasm with hob-nail appearance

7. Angiomyoplioma with Epithelial Cysts Microscopic features Sub-epithelial “cambium-like” condensation of stromal cells. Stroma with prominent capillary vascularity.

8. AMLEC • Microscopic features • Smooth muscle arranged in poorly formed fascicles • Intimately association with thick-walled blood vessels • Entrapped renal tubules

9. HMB-45 Melan-A AMLEC Immunohistochemistry HMB-45+, Melan-A +

10. PR Desmin AMLEC Immunohistochemistry HMB-45+, Melan-A + ER/PR + Desmin/SMA+

11. Cystic Renal Mass

12. Cystic Neoplasms of KidneysDifferential Diagnosis Renal Cell Carcinoma • Multilocular cystic RCC • Tubulocystic RCC (GU Break-out session) Mixed epithelial and stromal tumor Cystic nephroma (multilocular cyst) Angiomyolipoma with epithelial cysts Cystic partially differentiated nephroblastoma

14. Multilocular Cystic Renal Cell Carcinoma Expansile cystic mass with fibrous pseudocapsule Composed entirely of cysts and septa NO solid expansile nodules Cysts lined by epithelial cells with low Fuhrman grade nuclei Fibrous septa that contain clusters of epithelial cells with clear cytoplasm Uncommon tumor of adults Male predominance (3:1) No documented progression/recurrence

15. Multilocular Cystic Renal Cell CarcinomaCritical Issues Distinct subtype of conventional clear cell RCC Volume of carcinoma cells may be small. Potential mis-diagnosis as a benign multilocular cyst Sampling is key, IHC ( CK+, EMA+ )useful Reporting as “ Clear cell type RCC, with prominent cystic changes” Prognostic Implications Multiloculated Cystic RCC has excellent prognosis

16. Mixed Epithelial & Stromal Tumor of Kidney • Multiple terminology “cystic hamartoma of renal pelvis”, “mesoblastic nephroma of adults” • Strong female predominance, often perimenopausal • No recurrence reported • GROSS Variable amounts of solid areas and multiple cysts Solid areas may be extensive Septa of cysts thick

17. Mixed Epithelial & Stromal Tumor of Kidney • Variably sized cysts and tubules • Simple microcysts with abundant stroma to densely packed microcysts/complex branching tubules • Columnar/cuboidal epithelium with clear/pale/vaccuolated/ eosinophilic cytoplasm • Stroma composed of variably cellular spindle cells

18. Mixed Epithelial & Stromal Tumor of Kidney Complex tumors with large cysts Cysts may be lined by hob-nail cells Smooth muscle bundles in stroma Urothelium (hyperplastic) may line cysts

19. Mixed Epithelial & Stromal Tumor of Kidney • Stroma composed of variably cellular spindle cells • Myxoid stroma and smooth muscle bundles may be prominent • Blood vessels with thick walls may be present • NO cytologic atypia and/or mitosis

20. PR Desmin Mixed Epithelial & Stromal Tumor of Kidney Immunohistochemistry Desmin+ SMA+ ER/PR+ HMB-45 Negative

21. Cystic Nephroma(Multilocular Benign Cyst) • Benign neoplasm occurring predominantly in adults • Strong female predominance (8:1) • Usually found incidentally, rarely present with pain, palpable mass • Entirely cystic mass, NO solid nodules • Excision is curative

22. Cystic Nephroma • Mass composed exclusively of cysts covered by fibrous pseudocapsule • Cysts lined by flattened cuboidal or hobnail epithelium • Nuclei are low-grade with no prominent nucleoli • Nosolid nodules Noclusters of clear epithelial cells

23. Cystic Nephroma • Septa show myxoid to collagenous stroma • Cellular spindle cell stroma resembling ovarian stroma may be seen (Strongly positive for ER and PR) • Septa may contain entrapped renal tubules • No smooth or skeletal muscle

24. Are Cystic Nephromas and Mixed Epithelial & Stromal Tumors of Kidney A Single Entity?

25. Points in Favor Overlapping gross and microscopic features Overlapping immunohistochemical features Both tumors are predominant in females Points Against Similar gross and microscopic areas may be seen in CPDN, MCRCC Some (? crucial) differences Several unrelated tumors (MA, Mucinous tubular spindle RCC, AML) are predominant in females Are Cystic Nephromas and Mixed Epithelial & Stromal tumors of Kidney A Single Entity?

26. Immunohistochemical Profile

27. Cystic Neoplasms of KidneysTake-Home Message • Angiomyolipoma with epithelial cysts (AMLEC) should be included in the differential diagnosis of adult cystic renal neoplasms. • Differential diagnosis of adult cystic renal neoplams also include multilocular cystic RCC, tubulocystic RCC, cystic nephroma (CN) and mixed epithelial & stromal tumor of kidney (MEST) • Cystic partially differentiated nephroblastoma (CPDN) are cystic renal neoplasms common in children (unusual after 2Y), - Blastemal cells and undifferentiated mesenchyma elements - Commonly shows skeletal muscle in septa

28. Cystic Neoplasms of KidneysTake- Home Message • AMLEC and MEST may have overlapping morphologic features, however the most distinctive immunohistochemicalfeature distinguishing the two entities is the fact that MEST, unlike AMLEC, does not label with melanocytic markers (HMB-45 and/or Melan A)

29. Thank You