Pulmonary carcinomas with mucinous and neuroendocrine differentiation: Expanding the spectrum of amphicrine carcinomas

Amphicrine carcinoma is a distinct type of carcinoma characterized by synchronous exocrine and endocrine differentiation within the same tumor cell. Such tumors are exceedingly rare and most commonly recognized in the gastrointestinal tract. In the lung, sporadic descriptions of such lesions exist. This report presents 3 more such tumors, expanding the spectrum of amphicrine carcinomas in this organ. The patients were 3 men, 53 to 78 years of age (mean: 63 y) and all were current or former smokers. In one patient the tumor was an incidental finding, the others presented with lower respiratory symptoms. Microscopically, the lesions had an organoid pattern, consisting of nests of large tumor cells with peripheral palisading, vesicular nuclei and prominent nucleoli reminiscent of large cell neuroendocrine carcinoma. In addition, the tumor nests also showed glandular features, characterized by gland-like lumina filled with mucin and intracytoplasmic mucin droplets. Immunohistochemical studies showed diffuse reactivity of the tumor cells with synaptophysin and chromogranin and variable reactivity with TTF-1. Mucin stains highlighted extracellular and intracellular mucin deposition. Clinical follow-up demonstrated that one patient had died of his disease 12 months after surgery while another was alive and free of disease 21 months after surgery. The third patient was alive with widespread metastatic disease 8 months after diagnosis. This series highlights a rare variant of pulmonary carcinoma showing synchronous exocrine and endocrine differentiation. Recognition of this type of tumor is important in terms of tumor classification and to identify an entity with potential aggressive behavior.