Contributed by Dimitrios Korentzelos, MD and Gabriela M Quiroga-Garza, MD
The patient is a man in his fifties with an incidental finding of a 5 cm enhancing renal mass on the right upper pole during low-dose screening CT scan performed for history of tobacco use. He denies flank pain, gross hematuria, fever, chills, nausea, vomiting, night sweats, and change in appetite or weight loss. He is not aware of any family history of renal cancer. The patient's CT scan of the abdomen/pelvis exhibits a lesion in the upper pole of the right kidney highly concerning for a hypo-enhancing solid renal tumor/carcinoma, an additional simple cortical cyst in the right kidney, and one cortical cystic lesion in the lower pole of the left kidney, too small to further characterize. There is no evidence of adenopathy or metastatic disease.
Gross examination revealed a disrupted 3.7 x 3.7 x 3.2 cm partial nephrectomy specimen, with a 2.7 x 2.0 cm capsular defect with exposed friable, tan-yellow mass, and a 9.2 x 5.2 x 2.2 cm irregular portion of fragmented yellow and focally hemorrhagic lobulated adipose tissue with attached renal capsule and friable mass (Figure 1). The deep (parenchymal) margin was inked black, the capsular margin was inked blue, and the capsular defect was inked green. The distance of the mass from the parenchymal resection margin was 0.3 cm.
Histologic examination demonstrates a lesion with solid to focally papillary architecture, composed of eosinophilic to pale polygonal cells with voluminous cytoplasm and round nuclei with prominent nucleoli (Figure 2A). In areas the neoplastic cells display varying degrees of cytoplasmic vacuolization. Prominent granular cytoplasmic stippling is also identified. Scattered microcalcifications are noted throughout the tumor. No definite necrosis or increased mitoses are identified. Morphologic evaluation, in particular regarding the possibility of the tumor having cystic areas, is limited due to specimen fragmentation. Of note, the carcinoma focally extends into the perirenal adipose tissue (pT3a). Lymphovascular invasion is not identified.
Immunohistochemical stains performed show the neoplastic cells to be positive for Cytokeratin AE1/3, PAX8, CD10, Vimentin , P504S, CK20 (patchy) and cathepsin K with rare only positivity for CK7 (Figure 2B-F). SDHB and Fumarate Hydratase are retained. The tumor cells are negative for CAIX, c-kit, Melan A and HMB45. TFE3 and TFEB FISH studies are negative for translocation.
Next generation sequencing (NGS) studies performed on the formalin-fixed paraffin-embedded tissue demonstrate a TSC1 frameshift mutation with a variant allelic frequency (VAF) of 33%. No gene fusions or copy number alterations were detected, and the tumor was microsatellite stable (MSS) with a low tumor mutational burden (TMB) of 2 mutations/Mb.