Answer: C. Large cell neuroendocrine carcinoma-adenocarcinoma

Histology Description: The lesion is biphasic. One component is predominantly lepidic, and characterized by glandular cells which have hyperchromatic nuclei and line alveolar spaces. The apical cytoplasm is clear, suggestive of mucin formation. These are features of adenocarcinoma. The second component is nested, and associated with a high mitotic rate. These cells have vesicular chromatin and prominent nucleoli. By immunohistochemistry, the nested component labels for neuroendocrine markers like chromogranin and synaptophysin, while the glandular component labels for napsin A. TTF1 labels both components. The solid nested component demonstrates a high mitotic rate (>10 per high power fields). These features are diagnostic of mixed large cell neuroendocrine carcinoma-adenocarcinoma.

Differential Diagnosis: Adenocarcinoma with solid areas is the main differential diagnosis. The highly nested architecture of the solid component, along with its high mitotic rate, suggests the possibility of neuroendocrine differentiation, which much be confirmed by immunohistochemistry to support the diagnosis of a large cell neuroendocrine carcinoma component. Of note, the large cell neuroendocrine carcinoma component should label for TTF1 but not for napsin A, whereas a solid adenocarcinoma should label for both. Small cell carcinoma can be excluded by the absence of the typical diffuse hyperchromatic chromatin and nuclear molding of that lesion. Adenocarcinoma mixed with carcinoid tumor is a consideration, but it is easily excluded by recognition of the non-salt and pepper chromatin of the solid component along with its high mitotic rate.