Cutaneous metastases as an initial manifestation of visceral well‐differentiated neuroendocrine tumor: a report of four cases and a review of literature

Abstract

Well-differentiated neuroendocrine tumors metastasize to the skin uncommonly, and only 35 cases are reported in the literature. In only five of these patients, cutaneous metastases were the presenting symptom of malignancy; herein we report four such cases. Two patients were female and two male, aged 50 to 74 years (mean: 64.5 years), each with a solitary painless, slowly-enlarging, non-ulcerated cutaneous nodule of 3 to 12 months duration (mean: 9 months). The lesions were on the scalp (n=3) and trunk (n=1), and ranged in greatest dimension from 0.5 to 2.5 cm. The distinction from other microscopically similar entities, and the interpretation of origination from gastrointestinal, pancreatic or respiratory system primaries, was made clinically, or was based on the morphologic features and the immunohistochemical profile. One patient died of the disease progression after 36 months while two patients are alive with significant disease progression after 24 and 60 months. Metastatic neuroendocrine tumor should be considered in the differential diagnosis of cutaneous tumors with neuroendocrine morphology even in patients with no known history of visceral malignancy.

Low-Grade Neuroendocrine Carcinoma of the Skin (Primary Cutaneous Carcinoid Tumor) as a Distinctive Entity of Cutaneous Neuroendocrine Tumors: A Clinicopathologic Study of 3 Cases With Literature Review

“…29 Only on histomorphologic analysis, LGNECS might be indistinguishable from other organ neuroendocrine tumors including those of gastrointestinal tract, pancreas, and lung origin. 36,37 Although it remains unknown whether they belong to the same group as LGNECS, the 8 literature cases were primarily elderly patients with a median age of 66 years and a mean age of 64.1 years (range, 40-79 years), as well as a 4:4 male:female ratio. 30 However, it would not be difficult to rule out other organ tumors by detecting histological in situ components and performing clinical systemic examinations and immunohistochemical studies for markers such as ER, PgR, AR, GCDFP-15, mammaglobin, GATA3, CDX2, and thyroid transcription factor-1.…”

Well‐differentiated neuroendocrine tumors in skin: Terminology and diagnostic utility of cytokeratin 5/6 and p63

“…Carcinoid tumors in visceral sites can behave indolently with occult tumors being diagnosed in 0.5%‐1% of all autopsies performed . In addition, initial presentation of cutaneous metastatic disease followed by the detection of visceral primary tumor after months or years has been reported and half of metastatic carcinoid tumors may have unknown primary sites . Thus, even in cases of presumed primary cutaneous carcinoid tumor, in the setting of a negative clinical and imaging work‐up, the possibility of an occult primary visceral tumor cannot be entirely excluded.…”

“…Ten cases of cutaneous WDNETs, including 6 (cases 1‐6) from the Yale Dermatopathology Service and 4 (cases 7‐10) from Memorial Sloan Kettering Cancer Center were reviewed retrospectively. Five of these cases (6‐10) have been previously reported . This study was approved by the appropriate Institutional Review Boards.…”

“…WDNETs have been rarely described in the skin. These tumors usually represent metastatic disease from the bronchopulmonary or gastroenteropancreatic tracts . The clinical presentation is typically non‐informative—a firm purple‐red papule or nodule that may have associated pain or pruritus .…”

“…The past medical history is infrequently provided to the dermatopathologist, making the diagnosis more challenging. In addition, there are documented case reports of cutaneous metastasis presenting before the visceral primary . As metastatic carcinoid tumor to the skin and primary cutaneous adnexal tumors can have similar histopathologic features, immunohistochemistry might be a helpful diagnostic adjunct, particularly in cases with an unknown/occult primary.…”