SPLIT, Croatia AMR Slide Seminar Case # 29 Kidney tumor Ivan Damjanov, MD, PhD Department of Pathology The University of Kansas School of Medicine, Kansas City, Kansas

Case # 29 Clinical History 26-year-old African American woman complaining of lower abdominal and lumbar pain CT-scan –left kidney tumor and hepatic metastases Lab findings- mild anemia, LDH ↑and sickle cell trait Negative tumor markers (AFP, hCG, CEA)

Case # 38 Pathology Macro: Renal tumor measuring 12x 7 x 6.5 cm with 20% necrosis. Tumor extending into the surrounding perinephric fat tissue and into the peri-adrenal fat tissue and renal vein Enlarged regional lymph nodes, positive for malignancy Stage: pT3a Micro: Metastasis in the perirenal hilar lymph nodes Stage: p3a,N1,M1

Reticular the predominant pattern

Reticular and solid

Reticular with prominent mucoid stroma

Cribriform –sieve like and solid

Yolk sac like,loose stroma, inflammatory cells

Loosely structured permeated with blood

Solid, cord nests and cystic

Solid,invasive cords and ,nests

Cribriform and clear cell

Clear cell reticular and mucinous

Infiltrating with desmoplastic inflammatory reaction

Case # 29 Immunohistochemistry Positive: Pancytokeratin, CK7, vimentin, PAX8, OCT4 Negative: SMARCB1(INI1)

Diagnosis: Renal medullary carcinoma

Renal medullary carcinoma-quick review Rare, highly aggressive carcinoma of the kidney First described by Davis, Mostofi and Sesterhenn (AJSP,1995) as “seventh sickle cell nephropathy” Most patients are positive for sickle cell trait, but there are well documented exceptions Median survival 4-5 months, essentially all die by 3 years

Renal medullary carcinoma-microscopic Variety of patterns of which the most common are the following ( see Ohe C et al,AJSP 2018;42:279— multicenter study, AMR members participated: Abbas Agaimy and Ondra Hes) Solid, cord, nests (97%) Cribriform, sieve like (88%) Reticular (yolk sac tumor like) 85% (associated usually with cribriform) Stromal myxoid change (94%)—on gross examination appears mucoid!! ======================= Infiltrating glandular (55%) Tubular/papillary ( 35%) Sarcomatoid change (15%),rhabdoid cells,desmoplasia

Renal medullary carcinoma- immunohistochemistry Confirm that it is renal and not a metastasis or germ cell tumor (e.g., yolk sac carcinoma) Watch out: RMC is often positive for OCT4! Exclude other high grade distal nephron-related adenocarcinomas (collecting duct carcinoma and fumarate hydratase-deficient RCC) Confirm the diagnosis with antibodies to SMRCB1(INI1)

Renal medullary carcinoma- unresolved questions-take home message(if any!?) Clinical data are important—typically: aggressive carcinoma in a young person of African origin with sickle cell trait. SMARCB1 (INI1) loss by immunohistochemistry- diagnostic (Note: Rhabdoid kidney tumors also lack SMARCB1) Molecular questions: SMARCB1 rearrangement/fusion vs. loss? No consensus among uropathologists if sickle cell trait is an obligate criterion for diagnosis RMC or is it enough demonstrate a “SMARCB1-opathy”. Lets watch out for the proposed groups of tumors called Renal cell carcinoma, unclassified, with medullary phenotype (Sirohi et al.Hum Pathol 2017; 67:134)

The End

SPLIT,Croatia AMR Slide Seminar Case # 76 Ovarian tumor Ivan Damjanov, MD, PhD Department of Pathology The University of Kansas School of Medicine, Kansas City, Kansas

Case # 76 Clinical History 60-year-old woman complaining of lower abdominal and pelvic pain Past history: 30 years ago had “her uterus and tubes removed” Left ovarian mass measuring 15 cm was found partially attached to the loops of the large intestine. Several tumor nodules on the mesentery and several pelvic lymph nodes contained tumor on frozen section. Right ovary contained an adenofibroma. Radical removal of all the neoplastic tissue was attempted. She received chemotherapy. Two years after surgery she was found to have liver metastases. Lost to follow up, presumably died of spreading tumor.

Case # 38 Macroscopic and Intraoperative Pathology Macro: Tumor received in several parts .Tissue soft friable and partially necrotic. Partial colectomy with tumor attached to the intestine. Partial omentectomy and lymph node dissection with apparent tumor. Frozen sections: Malignant tumor, favor adenocarcinoma. Metastases in the submitted lymph nodes and omentum.