[Clinicopathological features of low-grade eosinophilic renal tumor associated with FLCN mutation: an analysis of eighteen cases].

Objective

To investigate the clinicopathological characteristics, immunophenotype, molecular features, and differential diagnosis of low-grade eosinophilic renal tumors associated with FLCN mutations.

Methods

Clinical and pathological data from 18 cases of FLCN-mutation-associated low-grade eosinophilic renal tumors were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histological morphology and immunophenotyping were performed, and high-throughput targeted gene mutation sequencing was performed on all 18 cases.

Results

Among the 18 patients, 13 were male and 5 were female, aged 55 (43, 62) years. Twelve cases were diagnosed with hereditary Birt-Hogg-Dubé (BHD) syndrome. Among patients with BHD syndrome, 10 had multifocal tumors and 7 had bilateral tumors. Of the 18 patients, 10 had typical hybrid eosinophilic/chromophobe tumors (HOCT), and 8 had unclassified eosinophilic tumors. Histologically, 10 cases of typical HOCT showed a characteristic "mosaic" pattern. The 8 cases of unclassified eosinophilic cell tumors were morphologically heterogeneous, including 4 cases resembling chromophobe renal cell carcinoma (ChRCC), 1 case resembling succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), 2 cases rich in "histiocytic lakes," and 1 case with eosinophilic cell; all lacked the hybrid cell components and "mosaic" morphological features typical of HOCT. Immunophenotypically, in the 10 typical HOCT cases, L1CAM, E-cadherin, CD117, and CK7 predominantly showed "mosaic" -like immunohistochemical features, consistent with the histological morphology; Cathepsin K was diffusely moderate positive in 2 cases and focally positive in 3 cases; CD10 was positive in 2 cases. Eight cases of unclassified eosinophilic tumors partially lacked typical immunohistochemical features, and their immunophenotypes were inconsistent. Other commonly used immunohistochemical markers vimentin, CK20, Melan A, TFE3, and TFEB were all negative. Despite their heterogeneity, non-metastatic glycoprotein B (GPNMB) showed diffusely, strongly positive in both typical HOCT and unclassified eosinophilic cell tumors (18/18). Next-generation sequencing (NGS) confirmed the presence of pathogenic or likely pathogenic FLCN mutations in all 18 cases.

Conclusions

FLCN-mutation-associated low-grade eosinophilic renal tumors show distinct histological morphology, immunophenotype, and molecular genetic characteristics. It is necessary to make differential diagnosis from morphologically similar renal tumors in clinical practice. GPNMB serves as an important auxiliary marker for diagnosis of FLCN-mutation-associated low-grade eosinophilic renal tumors. Clinical, molecular, and genetic testing should be integrated to assess potential association with BHD syndrome, for making a precise diagnosis.