A novel pathogenic variant of the FH gene in a family with hereditary leiomyomatosis and renal cell carcinoma.

Hereditary leiomyomatosis and renal cell carcinoma caused by loss-of-function germline variants of the FH gene can develop into aggressive renal cell carcinoma (RCC). We report the case of a 27-year-old man who died of RCC. Genetic testing revealed a novel pathogenic variant of FH, NM_000143.3:c.1013_1014del (p.Ile338Serfs*3), that was also identified in healthy siblings. Identification of genetic causes in the proband helped us to provide relatives with precise genetic counseling and appropriate surveillance programs.

Gross mucinous multinodular appearance aids in the identification of ovarian metastases in low-grade appendiceal mucinous neoplasms during intraoperative consultation.

Ovarian metastases of low-grade appendiceal mucinous neoplasms (LAMNs) show grossly abundant nodular mucous cells, with a gross mucinous multinodular appearance and a histological resemblance to primary ovarian mucinous tumors (POMTs). This study aimed to elucidate the utility of gross features including the gross mucinous multinodular appearance and available clinical information at the time of intraoperative consultation, in distinguishing the ovarian metastases of LAMNs from POMTs or the ovarian metastases of colorectal cancer (CRC). In total, 776 patients with primary ovarian tumor and 68 patients with ovarian metastases underwent intraoperative consultation during 1998-2018. Of the total cases, 4 ovarian metastases of LAMNs, 19 ovarian metastases of CRC, and 50 POMTs (36 borderline tumors and 14 carcinomas) were identified. The gross features including the gross mucinous multinodular appearance were analyzed based on the gross photographs obtained before formalin fixation and the available clinical information collected during intraoperative consultation. The analysis indicated that the ovarian metastases of LAMNs significantly presented with gross mucinous multinodular appearance (4/4 vs. 0/50, P < 0.0001), extraovarian disease (4/4 vs. 2/50, P < 0.0001), ovarian surface involvement (3/4 vs. 2/50, P = 0.0016), and abnormal appendix (4/4 vs. 0/50, P < 0.0001) as compared to POMT. Moreover, the gross mucinous multinodular appearance was a distinguishable feature between the ovarian metastases of LAMNs and ovarian metastases of CRC (4/4 vs. 0/19, P = 0.0001). Based on these results, we proposed an algorithm to diagnose ovarian tumors using the gross mucinous multinodular appearance. Thus, recognizing unique gross features including the gross mucinous multinodular appearance would be useful for both pathologists and surgeons to accurately diagnose ovarian metastases of LAMNs during intraoperative consultation.

Diagnostic Discordance in Intraoperative Frozen Section Diagnosis of Ovarian Tumors: A Literature Review and Analysis of 871 Cases Treated at a Japanese Cancer Center.

BACKGROUND: This study examined the accuracy and pitfalls associated with frozen section diagnosis of primary ovarian tumors and ovarian metastases based on the 2014 World Health Organization classification (WHO) criteria and proposed improvements from a pathologist's perspective. METHODS: We microscopically reviewed 871 cases of primary ovarian tumor (N = 802) and ovarian metastasis (N = 69) and compared the results of frozen sections with the final diagnosis. Malignant potential concordance (benign, borderline, or malignant) and specific discordant diagnosis rates were analyzed. Finally, we conducted a unique literature review of specific diagnostic errors in the frozen section diagnosis of primary ovarian tumors. RESULTS: Of 802 primary ovarian tumors, 50 (6.2%) cases showed discordant diagnoses in which mucinous carcinoma (40.5%), low-grade serous carcinoma (LGSC; 31.3%), and mucinous borderline tumor (18.4%) were frequently misinterpreted. Of 69 ovarian metastases, all 4 cases of low-grade appendiceal mucinous neoplasm (LAMN) were misdiagnosed as primary ovarian mucinous tumor. A literature review revealed that mucinous/serous borderline tumor or carcinoma accounted for approximately 70% of 217 reported discordant diagnoses. CONCLUSION: In the present study, the concordance rate of malignant potential of the tumor was comparable to that previously reported. Even in the 2014 WHO classification, primary ovarian mucinous borderline tumor/carcinoma and LGSC still comprised the majority of discordant cases. Grossing methods that reduce sampling error are required. LAMN was frequently misinterpreted as a benign or borderline ovarian mucinous tumor. To prevent this error, a differential algorithm integrating clinical information and gross findings should be developed.