Answer: C. Biphasic hyalinizing psammomatous renal cell carcinoma

Histologic Description: This is a lesion with a variety of unusual morphologic patterns. The lesion is both solid and papillary, and the papillae often have a branching “glomeruloid” pattern. The cytology is biphasic, with smaller epithelioid cells clustered around nodules of basement membrane material with larger epithelioid cells with more columnar shape at the edge. The stroma is generally fibrotic, and there are scattered psammoma bodies in the lesion. There is additionally a population of smaller primitive appearing spindled cells. These are the typical features of biphasic hyalinizing psammomatous renal cell carcinoma (BHP RCC), a recently described entity associated with mutations in the neurofibromatosis type 2 (NF2) gene.

Differential Diagnosis: Mucinous tubular spindle cell carcinoma (MTSC) may also be associated with NF2 mutations, may have non-mucinous areas with papillary growth, and is associated with spindling as in seen in the current case. However, MTSC does not have the biphasic morphology of the current lesion, lacks the distinctive glomeruloid architecture seen herein, and typically demonstrates fascicles of eosinophilic spindle cells which can mimic a smooth muscle tumor. TFEB rearranged renal cell carcinoma is suggested by the biphasic appearance and hyaline nodules, which are hallmark features of these tumors. However, BHP RCC does not demonstrate TFEB rearrangements, and does not label for melanocytic markers like Melan A and HMB45 as is characteristic of the TFEB rearranged renal cell carcinoma. Wilms tumor is a consideration given the primitive appearance of the smaller epithelioid cells and the spindled cells within the lesion. However, the more open chromatin of the larger cells in the lesion is not typical of Wilms, nor are the hyalinized nodules, fibrotic stroma, or advanced patient age.

Reference Am J Surg Pathol 2020; 44:901-916 (PMID: 32217839).