Clinicopathologic and DNA cytometric analysis of carcinoid tumors of the thymus

Abstract

Twelve cases of carcinoid tumors of the thymus were reviewed in terms of clinicopathologic, histo-chemical, and immunohistochemical features and DNA ploidy patterns. The collective consisted of nine male and three female patients, aged 34 to 74 years, of whom five (42%) had symptoms. Eleven patients underwent surgical resection, and one with systemic metastases was autopsied. In the 11 resected patients, tumors had invaded surrounding structures in four cases, and mediastinal lymph node metastases were detected in six. Recurrence occurred in two of the resected patients (18%), and the 5-year survival rate was 82%. Histologically, all tumors showed an organoid growth pattern with delicate fibrovascular stroma. In addition, three tumors had unusual morphologic features such as combined features of carcinoid tumor and thymoma and solid growth pattern with occasional large tumor cells. Mitotic counts ranged from 1 to 14 per 10 high-power fields with a mean count of 4.9. Central necrosis within solid nests was observed in nine tumors. Classification of this series using the WHO histologic classification system resulted in categorization of all 12 tumors as atypical carcinoids. All tumors were positive for Grimelius staining and for cytokeratin. Immunohistochemical staining documented the presence of moderately to strongly positive neuroendocrine markers such as neuron-specific enolase, chromogranin A, synaptophysin, and neural cell adhesion molecule. No correlation between proliferative activity based on the Ki67 labeling index and prognosis or lymph node metastasis was found. Concerning DNA ploidy patterns, only one tumor with multiple lymph node metastases was considered to be aneuploid. In conclusion, although all of our cases were histologically classified as atypical carcinoid tumors of the thymus, most were diploid, and the patients enjoyed a relatively good prognosis.