Abstract
Pulmonary carcinoid tumors occur in both central and peripheral locations, and some differences in clinico-pathological features have long been observed. We investigated a large number of resected carcinoid tumors with the aim to further define the characteristics of tumors from both locations. One hundred sixty-six resected carcinoid tumors of the lung were analyzed for a variety of clinical and pathologic features, including histology subtype, mitotic rate, Ki67 index, necrosis, invasive pattern, architectural pattern, cell morphology, sustentacular cells, neuroendocrine hyperplasia, and orthopedia homeobox protein (OTP) and TTF-1 immunohistochemical expressions. Unsupervised hierarchical cluster analysis suggested three clusters as the best solution using TTF-1 and OTP expression: TTF-1-positive and OTP-positive tumors as cluster 1, TTF-1-positive but OTP-negative as cluster 2, and TTF-1-negative and OTP-negative as cluster 3. Cluster 1 was characterized by peripheral location, presence of spindle cell component, presence of sustentacular cells, female predominance, and strong association with neuroendocrine hyperplasia. Cluster 2 was characterized by central location, polygonal cell morphology, acinar growth pattern in a subset of tumors, and only rare association with neuroendocrine hyperplasia. Cluster 3 consisted of more aggressive tumors with more heterogeneous pathologic features. Tumors showed polygonal cell morphology and acinar growth pattern. Occurrence of neuroendocrine hyperplasia was exceptional. Our study confirmed distinct characteristics of central and peripheral type carcinoid. An important difference was a strong association of the peripheral tumor with neuroendocrine hyperplasia while such an association in central tumors was negligible. The tumor location might be relevant for pathobiology of lung carcinoid tumors.
Highlights
Lung carcinoid tumor belongs to a neuroendocrine tumor group and is subdivided to typical carcinoid and atypical carcinoid, based on mitotic rate and presence or absence of necrosis
The carcinoid of gastrointestinal tract has demonstrated significant biologic differences depending on their anatomic location within the system [7], and given the variety of histopathological features seen in pulmonary carcinoid tumors, it would be reasonable to hypothesize that lung carcinoid tumor is not a pathobiologically homogeneous entity [8]
Neuroendocrine tumors of the lung are a unique group of tumors which share morphological, ultrastructural, and immunohistochemical features, and according to the current WHO classification, classification encompasses four major subtypes, including typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma [1]
Summary
Lung carcinoid tumor belongs to a neuroendocrine tumor group and is subdivided to typical carcinoid (low grade) and atypical carcinoid (intermediate grade), based on mitotic rate and presence or absence of necrosis. The carcinoid (neuroendocrine tumor/NET) of gastrointestinal tract has demonstrated significant biologic differences depending on their anatomic location within the system [7], and given the variety of histopathological features seen in pulmonary carcinoid tumors, it would be reasonable to hypothesize that lung carcinoid tumor is not a pathobiologically homogeneous entity [8]. It has long been known that there are some clinical and pathological differences between carcinoid tumors arising in the bronchus and those located in the periphery of the lung. We analyzed a variety of clinical, morphological, and immunohistochemical features in a large number of resected lung carcinoid tumors to investigate whether central and peripheral locations could signify biological relevance
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