Ovarian mixed low- and high-grade serous carcinoma as a synchronous or metachronous phenomenon: A clinicopathologic study of 39 cases.

OBJECTIVE

Low-grade serous ovarian carcinoma (LGSOC) and high-grade serous ovarian carcinoma (HGSOC) are distinct entities. Although typically occurring in pure forms, some present as synchronous or metachronous mixed histotypes.

METHODS

This retrospective study examined patients with mixed LGSOC and HGSOC treated between 1994 and 2024 at MD Anderson Cancer Center (MDACC). Diagnoses were confirmed by MDACC gynecologic pathologists. Demographics, clinical characteristics, diagnosis rendered by referral institution, treatment, immunohistochemistry, somatic tumor testing, and survival outcomes were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, with log-rank tests to compare cohorts, p < 0.05 significant.

RESULTS

Among 39 cases, 85 % were synchronous, and 15 % were metachronous. Seven (25 %) of patients tested for germline mutations (n = 28) had germline BRCA mutations. Of the 35 cases diagnosed at referral institutions, only eight (23 %) were correctly identified as mixed. Sixteen (41 %) patients underwent somatic tumor testing, revealing three KRAS, one NRAS, and eight TP53 mutations. All patients underwent cytoreductive surgery, with 97 % receiving adjuvant therapy and 26 % maintenance therapy. Recurrence occurred in 90 % of cases. Median PFS was 17 months, and median OS was 56.7 months, with a 5-year survival rate of 48.5 %. There was no statistically significant difference when comparing PFS or OS by BRCA status, primary vs interval cytoreduction, residual disease, tumor presentation, or maintenance therapy.

CONCLUSION

Diagnosing mixed LGSOC and HGSOC remains challenging. Despite low TP53 mutation rates, survival outcomes resembled those of HGSOC. These findings advocate for further investigations to identify risk factors and biomarkers for low-grade to high-grade transformation and to improve treatment strategies.