Renal cell carcinoma with fibromyomatous stroma (RCC FMS) and with hemangioblastoma-like areas is part of the RCC FMS spectrum in patients with tuberous sclerosis complex

Abstract

Aims: Sporadic renal cell carcinomas with fibromyomatous stroma (RCC FMS) with coexistent haemangioblastoma (HB)-like morphology have been previously reported. Such morphology has not, however, been documented in patients with tuberous sclerosis complex (TSC). We evaluated clinicopathologic, immunohistochemical and molecular findings of RCC FMS with HB-like features in three TSC patients. Methods and results: All three patients were females with confirmed germline mutations in TSC1 in the absence of VHL or other alterations. One patient had bilateral nephrectomy with six separate tumours (three in each kidney), and two patients had one tumour each, resected by partial nephrectomy. Prominent fibromuscular stroma was present at the tumoral periphery and surrounding clear cell nests forming tubules and papillary formations (RCC FMS areas), admixed with solid, clear to eosinophilic and spindle cell areas (HB-like areas). HB-like areas were variably represented in individual tumours, but in some, HB-like features were almost exclusive. HB-like areas were negative for CK7 and showed inhibin-α and S100 reactivity, in contrast to typical RCC FMS areas, which were CK7 positive, while negative for inhibin-α and S100. GPNMB, which is consistently expressed in TSC/mTOR altered tumours, was positive in both components. On follow-up (10 months–21 years), all patients had an indolent course. Conclusions: HB-like morphology found in RCC FMS in TSC patients represents part of the morphologic spectrum of RCC FMS, which is a previously underreported and underrecognized feature. RCC FMS with HB-like areas show uniform GPNMB reactivity and are associated with TSC/MTOR alterations, but not with VHL alterations.