Large cell neuroendocrine [corrected] carcinoma of the uterine cervix: a clinicopathologic study of 12 cases

Twelve cervical tumors showing morphologic evidence of neuroendocrine differentiation and lesional cells larger than those of typical small cell carcinoma are reported in women 21 to 62 (mean 34) years of age. The patients presented with an abnormal Papanicolaou smear or vaginal bleeding. Two tumors were stage Ia2, nine were stage Ib, and one was stage IIa. All patients were treated by radical hysterectomy, and most received adjuvant chemotherapy. Seven of 10 patients with > 1 year of follow-up died of tumor 6 to 24 months after hysterectomy. The tumors had insular, trabecular, glandular, and solid growth patterns and contained medium to large cells with moderate to abundant cytoplasm; eosinophilic cytoplasmic granules were present in nine cases. The tumors were mitotically active, and necrosis was present in 10 of them. Nine of 10 tumors were argyrophilic, and all 12 were immunoreactive for chromogranin. Individual cells containing somatostatin, serotonin, or glucagon were identified in four of eight cases. Adenocarcinoma in situ was present adjacent to the tumor in eight cases; invasive adenocarcinoma of non-neuroendocrine type was present in three of these tumors. Using diagnostic criteria established for pulmonary neuroendocrine tumors, the 12 tumors were classified as large cell neuroendocrine carcinomas. Cervical large cell neuroendocrine carcinomas are distinctive cervical carcinomas that are frequently misdiagnosed and have an unfavorable outcome, similar to that of small cell carcinoma.