The Cytopathological Diagnosis of Fumarate Hydratase (FH)-Deficient Renal Cell Carcinoma in Two Patients With FH Gene Mutation.

Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a high-grade renal cell carcinoma characterised by mutations in the FH gene. FH-dRCC is highly aggressive and has a poor prognosis, underscoring the importance of accurate diagnosis. Although the histopathological features of this neoplasm have been reported in previous studies, descriptions of its cytopathological features are limited. Here, we report the cytopathological morphologies of two cases of metastatic FH-dRCC in male patients aged 48 and 35 years. Case 1 presented with a cystic solid mass in the right retroperitoneal lumbar rib triangle region after the excision of a cystic tumour in the right kidney. Cytopathological examination of the fine-needle aspiration sample revealed papillary and tubular tumour cells. Case 2 developed abdominal ascites after bilateral nephrectomy, and cytopathological examination of ascitic fluid-characterised tumour cells with a high nuclear grade arranged in papillary and glandular patterns. In both cases, large tumour cells were observed with abundant eosinophilic cytoplasm, coarse chromatin and irregular nuclear shapes. Some cells exhibited characteristic eosinophilic macronucleoli and perinucleolar halos. Tumour cell clusters with a high nuclear grade, papillary structures, prominent eosinophilic macronucleoli and perinucleolar halos are the major cytopathological traits of FH-dRCC. CK7-negative/CA9-negative and PAX8-positive immunophenotypes may serve as important diagnostic markers. Moreover, the AKR1B10-positive/2SC-positive/FH-deficient immunophenotype contributes to the diagnosis of this tumour. Consequently, if the tumour cells have these characteristics, the diagnosis of FH-dRCC should be considered in cytology.