Atypical Lung Carcinoid with GFAP Immunoreactive Cells

Abstract

A case of atypical carcinoid with peculiar histological and ultrastructural pattern and immunohistochemical phenotype is presented. The neoplasm is composed of three types of cells. Type 1 cells are small to medium sized, fusiform, with scarce cytoplasm and are arranged in fascicles. Type 2 cells are cuboidal and line acinar structures. Type 3 cells have more abundant eosinophilic cytoplasm, larger nuclei and are arranged in fascicles intersecting with fascicles of type 1 cells, and sometimes surround acinar structures. The three cell types are present both in the primary lesion and in its lymph node metastases. Immunohistochemistry demonstrates immunoreactivity of all cell types for general neuroendocrine markers. Cytokeratin immunoreactivity is more prominent in type 1 and 2 cells, and is only focally expressed in type 3 cells. Type 3 cells are also immunoreactive for glial fibrillary acidic protein (GFAP), alpha-actin, S-100 protein, vimentin. Electron microscopic examination confirms the neuroendocrine nature of the cells, and show that type 3 cells have prominent bundles of intermediate filaments, electron-dense granules and junctional complexes. To our knowledge, this is the first case of atypical lung carcinoid with GFAP immunoreactivity. The nature of type 3 GFAP positive cells is unclear. There are some clues pointing to their sustentacular nature, and other ones pointing to a myoepithelial origin, but the data are inconclusive. Type 3 cells may be the malignant counterpart of sustentacular cells seen in typical carcinoids, but their GFAP positivity and the presence of electron-dense granules are very unique features, which differentiates them from sustentacular cells. Alternatively, their unusual GFAP + immunohistochemical phenotype may be due to aberrant expression of cytoskeletal proteins.