Renal Cell Carcinoma With Fibromyomatous Stroma-The Whole Story.

Renal cell carcinoma (RCC) with fibromyomatous stroma (FMS) was included as an "emerging/provisional" entity in the 2016 World Health Organization (WHO) classification as a "RCC with (angio) leiomyomatous stroma." It has been debated whether RCCFMS represents a separate entity or a group of RCCs with overlapping morphologies. Accordingly, various names have been used to refer to the RCCs that exhibited clear cells and prominent smooth muscle and fibromatous stroma. Recent studies have demonstrated that RCCFMS indeed represents a distinct entity with subtle but distinguishable features that can be separated from other RCCs that exhibit clear cells, as well as tubulopapillary morphology and smooth muscle/fibromatous stroma, such as clear cell RCC and clear cell papillary RCC. Microscopically, the epithelial component forms tumor nodules composed of elongated and frequently branching tubules, lined by clear or mildly eosinophilic cells containing voluminous cytoplasm. Focal papillary morphology is also frequently present. Diffuse CK7 positivity is typical and is required for the diagnosis. Molecular analysis of these tumors demonstrated recurrent mutations involving the TSC/mTOR pathway. A subset of tumors with similar morphology has shown mutations involving ELOC (previously referred to as TCEB1), typically associated with monosomy 8. Finally, in addition to the more common RCCFMS that are sporadic, essentially identical tumors have been found in patients with tuberous sclerosis complex, suggesting the existence of hereditary and sporadic counterparts of this tumor. It is currently debated whether TSC/mTOR and ELOC mutated RCCFMS should be grouped together, based on their shared and overlapping morphology and common CK7 reactivity, despite the differing molecular alterations. This review outlines evidence supporting the recognition of RCCFMS as a novel subtype of RCC with morphologic, immunohistochemical, and molecular characteristics distinct from clear cell RCC and clear cell papillary RCC.