Poorly differentiated neuroendocrine carcinoma of unknown primary site. A newly recognized clinicopathologic entity.

Twenty-nine patients with poorly differentiated neuroendocrine tumors of unknown primary site were seen at Vanderbilt Medical Center between May 1977 and February 1987. All patients had pathologic findings typical of neuroendocrine tumors by electron microscopy (22 patients), light microscopy (6 patients), or immunochemical staining (1 patient). Patient age ranged from 18 to 77 years; 21 were men and 8 were women; and 12 had no history of tobacco use. Seventeen patients had metastatic tumor at two or more locations. Common metastatic sites included the retroperitoneum, lymph nodes (particularly cervical), and mediastinum. In most patients, these neoplasms showed an aggressive biology, with rapid onset of symptoms and rapid growth of metastases. Major responses were seen in 18 of 25 patients who received combination chemotherapy; 6 patients achieved a complete response. Three patients remain disease-free more than 24 months after completing therapy. Four patients with single sites of disease received local therapy only; all remain disease-free 1 to 10 years after completion of therapy. In 4 patients, specific tumor types were eventually recognized: small cell lung cancer, 1; gastrointestinal carcinoid tumor, 2; and extragonadal germinal tumor with predominant neuroendocrine differentiation, 1. In the remaining 25 patients, no well-recognized type of neuroendocrine tumor was identified. Recognition of these tumors broadens the spectrum of neuroendocrine neoplasia, and also identifies a distinct subset of patients with poorly differentiated carcinoma of unknown primary site. Although optimal therapy remains undefined, these patients are usually responsive to combination chemotherapy, and long-term survival is attainable in a minority.