Next Generation Sequencing of Renal Medullary Carcinoma Diagnosed Concurrently with Sickle Cell Trait: A Case Report and Literature Review

Abstract

Abstract Casestudy We present a 33-year-old African American male with 4 months of intermittent right flank pain and gross hematuria with hypermetabolic retroperitoneal lymphadenopathy, persistent right-sided hydronephrosis, perinephric fat stranding and a 5.5-cm hypermetabolic right lower pole mass demonstrated on imaging. Results Core needle biopsies of the mass contained atypical glands composed of epithelioid cells with pleomorphic nuclei, prominent nucleoli, eosinophilic cytoplasm and abundant mitoses infiltrating through desmoplastic stroma. Immunohistochemical staining demonstrated CK7 and PAX8 reactivity of the tumor cells, and negative staining for CK20, WT1, PSA, PLAP and CD10. The patient underwent a radical right nephrectomy; microscopic examination illustrated invasion of the renal sinus, perirenal fat, and lymphovascular space by the neoplastic glands and sickling erythrocytes in the vasculature. Further IHC staining revealed intact mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) and a loss in expression of INI1 (SMARCB1), leading to the concurrent diagnoses of renal medullary carcinoma and sickle cell trait (confirmed with hemoglobin fractionation). Next generation sequencing of 144 clinically significant genes detected no mutations. Conclusion Renal medullary carcinoma is a rare, aggressive neoplasm that accounts for less than 0.5% of all renal cell carcinomas and presents at an advanced stage. Patients are usually young males who are of African or Mediterranean descent with comorbid sickling disease. Although loss of SMARCB1/INI-1 gene expression is associated with this neoplasm, no effective therapeutic targets have yet been established. Renal medullary carcinomas are usually resistant to chemotherapy and radiotherapy, making the identification of an immunotherapy target paramount. With a median survival of four months from diagnosis, additional genetic studies of these malignancies may identify an effective treatment option for renal medullary carcinoma.