Renal mucinous tubular and spindle cell carcinoma: clinicopathological and whole exome sequencing analyses

Abstract

Objective: To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of renal mucinous tubular and spindle cell carcinoma (MTSCC), and to explore the all-exon mutations, microsatellite stability and tumor mutational burden (TMB) in MTSCC cases. Methods: The data of 5 patients with MTSCC that were submitted to the Department of Pathology, First Affiliated Hospital of Soochow University, China from January 2008 to May 2020, were reviewed and analyzed. The whole exome sequencing (WES) was conducted in all patients, while 3 of them were subject to the analyses of microsatellite stability and TMB. Results: Among the 5 patients, 3 were males and 2 were females. They were 37-76 years old. The maximum diameter of the tumor was 3.5-6.0 cm. The borders of the tumors were well defined. Microscopically, MTSCC was characterized by tubular structure, spindle cell and mucinous stroma, and the nuclear grade of tumor cells was overall low. The average follow-up was 15 months, and no recurrence or metastasis was found. Immunohistochemistry showed that all 5 cases were positive for broad-spectrum cytokeratin (CKpan), cytokeratin (CK)7, CK19, vimentin, PAX8, and P504s (varying expression levels), and the Ki-67 positive index was low. The WES of 5 cases showed that NF2 and PTPN14 exhibited higher mutation rates, which were 3/5 and 2/5, respectively. The microsatellite stability analysis indicated that the 3 cases were all microsatellite stable, and the TMB analysis showed that the TMB of the 3 cases were all <9 mut/Mb. Conclusions: MTSCC is a unique, low-grade pleomorphic kidney tumor. The WES analyses suggest that NF2 and PTPN14 have a higher mutation rate, indicating that the occurrence and development of MTSCC may be closely related to the Hippo pathway. The analysis of microsatellite stability indicates that there is no significant relationship between microsatellite stability and MTSCC, and the TMB analysis suggests that MTSCC patients may not benefit from immunotherapy.