Morphological and immunohistochemical study of typical and atypical carcinoids of the lung with clinico-pathological correlation

Abstract

ABSTRACT Typical and atypical carcinoids are neuroendocrine epithelial lung tumours which are difficult to distinguish. Confusion has been introduced by designating atypical carcinoids as well differentiated neuroendocrine carcinomas and including some tumours which are large cell neuroendocrine carcinomas. We therefore investigated 32 typical and 23 atypical carcinoids of the lung, and 9 combined forms of atypical carcinoid and small cell carcinoma. The following parameters were each independently correlated in a multivariate analysis with 10-year survival data: nuclear and nucleolar polymorphism, mitotic counts, vascular invasion, lymph node metastasis, structural pattern, location of the tumours, immunohistochemistry, age and sex of the patients. Typical carcinoids were characterized by an absence of vascular invasion and lymph node metastases, and a mean mitotic rate of 0.75/10 high power fields (HPFs), while atypical carcinoids were characterized by vascular invasion and/or metastases, a mean mitotic rate of 4.25/10 HPFs and nuclear pleomorphism. Combined forms of atypical carcinoid and small cell carcinoma were characterized by vascular invasion, metastases and a mean mitotic rate of 20.7/10 HPFs. Vascular invasion, lymph node metastases, mitotic counts and nuclear pleomorphism significantly correlated with 10-year survival data, whereas location, size and structural pattern of the tumour, age and sex did not correlate with survival. All tumours were positive for cytokeratins and at least two out of three general neuroendocrine markers. However, positive reactivity for different peptides, hormones, and neurotransmitters did not correlate with one of the structural subtypes of carcinoid or with patient survival.