Neuroendocrine tumor with an atypical clinical course: a description of 2 cases.

We report 2 cases of cytokeratin-20 negative neuroendocrine tumors with skin involvement that were not Merkel cell carcinoma. Patient 1. Patient 1 was a 72-year-old man with 3 asymptomatic papular, erythematous lesions measuring 2 to 3 mm in the right paranasal region (Fig. 1). The lesions had appeared 20 days earlier. One of the lesions was excised to reveal a diffuse epithelial tumor consisting of solid nests of irregular, atypical polygonal cells with abundant mitotic figures. There was no sign of morphologic differentiation and the epidermis was not involved. The tumor was composed of keratin cells positive for AE1-AE3, synaptophysin, chromogranin, and neuron-specific enolase and negative for cytokeratin 20, thyroid transcription factor 1, CD30, S100, and human melanoma marker (HMB45) (Fig. 2). The tumor was diagnosed as intradermal carcinoma with neuroendocrine differentiation. Plasma levels of chromogranin A were elevated (124.2 ng/mL; normal range, 19.4-98.1 mg/mL). Other hormones were normal in both blood and urine. Chest radiography, abdominal magnetic resonance imaging, In-labeled octreotide scintigraphy and positron electron imaging findings were normal. There were no significant findings in gastroscopy and colonoscopy revealed an adenomatous polyp. The 3 lesions were excised without any adjuvant therapy and chromogranin A levels returned to normal. The patient has remained asymptomatic during 5 years of follow-up. Patient 2. Patient 2 was a 62-year-old woman with a progressively growing sternal lesion that had appeared 2 years earlier. Examination revealed an erythematous-violaceous plaque measuring 3 × 2 cm (Fig. 3). In the biopsy, a tumor was detected in the dermis in the form of disperse nests of monomorphic cells of epithelial appearance and few atypical cells. They had a poorly defined cytoplasm with occasional microcalcifications and limited mitotic activity. These cells were positive for AE1-AE3 keratins, cytokeratin 8, synaptophysin, chromogranin, and neuron-specific enolase and negative for S100, MELAN-A, HMB45, and cytokeratin 20. Histologic diagnosis was of cutaneous metastasis of a well-differentiated neuroendocrine tumor. Elevated levels of plasma somatostatin were found (27.3 pmol/L; normal range, <16 pmol/L). Other hormones were normal in both blood and urine. In view of a suspected diagnosis of cutaneous metastasis of a somatostatin-secreting neuroendocrine tumor, octreotide scintigraphy was performed. Uptake was detected in the sternal region and the left axilla. In the other imaging tests, the only finding of note was biliary lithiasis and a hepatic lesion suggestive of hemangioma.