New insights in the new WHO classification of adult renal tumors.

Abstract

The 5th edition of WHO classification of adult renal tumors introduced a couple of changes in existing, well established entities, as well as some new distinct renal tumors. Papillary renal cell carcinoma (RCC) is no longer divided into type 1 and type 2. Type 1 is now called “classic” variant and type 2 doesn´t exist anymore. There were long discussion about problematic type 2. According to WHO 2022 the correct name is papillary RCC (and subtype/variant should be mentioned in the description). Another important change came for clear cell papillary RCC. Because there is no convincing evidence that genuine clear cell papillary RCC can produce recurrences or metastases, it is now termed as clear cell papillary tumor. All previously reported aggressive cases are now considered misclassified clear cell RCC (mostly) or other entities. In less typical cases, genetic support of diagnosis with complex analysis of VHL gene should be added. New category “other oncocytic tumors” emerged for tumors from gray zone between renal oncocytoma and chromophobe RCC. Term hybrid oncocytic tumor should be reserved for those with hereditary Birth-Hogg-Dubé syndrome. Emerging entities, like eosinophilic vacuolated tumor (EVT) and oncocytic low-grade tumor (LOT) are mentioned, however, more work is needed for better establishment of the criteria. There is a new category of “molecularly defined renal carcinomas”, where MITf translocation RCCs are divided into TFE3 rearranged RCC with fusion partner dependent morphologic variability, and to TFEB rearranged RCC. In this group, indolent TFEB translocated RCCs are recognized, as well as potentionally aggressive RCC with TFEB gene amplification. In WHO 2016, ALK rearranged RCC was considered as emerging entity. In WHO 2022 it is listed among “molecularly defined RCC” as a distinct renal tumor with broad morphologic spectrum dependent partly on fusion partners. ELOC (TCEB1) mutated RCC is renal tumor composed of clear cell elements and huge fibromyomatous stroma. Diagnostic approach should be complex with support of immunohistochemistry (including CK7) and molecular genetic approach. However, there is overlap with MTOR pathway genes mutated RCC with fibromyomatous stroma. SMARCB1 deficient renal medullary carcinoma is high-grade invasive adenocarcinoma in patients with clinically proved sickle-cell trait and SMARCB1 deficiency.