Clinicopathologic, Immunohistochemical, and Molecular Analysis of Primary Ovarian Carcinoid Tumors With Correlation of Ki67 Proliferation Index With Patient Outcomes

Primary ovarian carcinoid tumors (pOCTs) are a rare subset of ovarian neoplasms resembling well-differentiated neuroendocrine tumors (NETs) arising in the gastrointestinal tract. Unlike NETs at other anatomic sites, the use of proliferation markers, such as mitotic count and Ki67 proliferation index, is not well established in the classification of these tumors. In this study, we describe the clinicopathologic, immunohistochemical, and molecular characteristics of pOCTs and correlate mitotic count and Ki67 index with patient outcomes. In our series of 23 pOCTs, most cases were associated with at least 1 other ovarian neoplasm (19/23; 82.6%), most often a mature teratoma or struma ovarii (each 43.5%; 10/23). All 23 cases (100%) expressed synaptophysin, whereas 87.0% (20/23) expressed chromogranin. Frequent staining with TTF-1 and CDX2 (33.3% and 83.3%, respectively) was also observed. Targeted exome sequencing was performed in 14 cases, which identified no recurrent NET-associated mutations or novel mutations in pOCTs. Most pOCTs presented as stage IA disease (13/23; 56.5%), of which 6 had Ki67 indices >3% (46.2%; 6/13). There were 6 cases of stage IC disease (26.0%), which exhibited a variable Ki67 index (range: 1.2%-35.6%). Extraovarian spread was noted in 4 cases (17.4%), with 3 cases having Ki67 indices >3% (range: 1.0%-58.8%). Local recurrence occurred in 1 case (4.3%) with pelvic sidewall involvement at diagnosis and a Ki67 index of 58.8%. Follow-up, ranging from 3 to 153 months (median: 55.5 months), showed no disease-related deaths. We combined our findings with 16 previously published cases of pOCTs and found that cases with >20 mitoses per 2 mm² had the highest rate of recurrence. Cases with Ki67 indices ≥ 7.5% were associated with worse overall and disease-free survival. Overall, our findings reaffirm the indolent nature of most pOCTs, although disease recurrence and aggressive behavior can occur, particularly in cases with elevated proliferation indices.