Large‐cell neuroendocrine carcinoma of the skin: ultrastructural and immunohistochemical findings

Abstract

Large-cell neuroendocrine carcinoma (LCNEC) is an uncommon and aggressive neuroendocrine tumor, found mainly in the lung. Although LCNEC has been reported in various organs, LCNEC of the skin is extremely rare, poorly recognized and probably underestimated. Here we report a case of LCNEC of the skin, focusing on the histopathological and ultrastructural findings in detail. The patient was an 85-year-old Japanese woman presented with a mass on her right upper eyelid. Biopsy specimen showed an infiltrative mass with extension into the subcutis. Tumor cells were arranged in organoid and trabecular patterns with sheets, nests and trabecular cords. Extensive necrotic areas were observed. Most of the tumor cells were characterized by large cell size, polygonal shape, low nuclear-cytoplasmic ratio, coarse nuclear chromatin and frequent nucleoli. They were positive for CD56, NSE, AE1/AE3, CK7, and negative for CK20, TTF-1, synaptophysin and chromogranin A. A systematic radiographic examination revealed no additional neoplastic lesions other than the right upper eyelid mass. These findings suggest that the present case is a LCNEC of the skin. The existence of LCNEC in the skin should be recognized, as it is a rare variant of carcinoma that can potentially be misconstrued as a metastasis or as Merkel cell carcinoma.

Primary large cell neuroendocrine carcinoma of the skin: An under‐recognized entity and a mimic of metastatic disease

“…Another entry to the group came in the form of EMPSGC, first described in 1997 and later found to be the likely precursor of mucinous carcinoma of the skin . The most recently described and least recognized subset of primary cutaneous neuroendocrine tumors, and the focus of this communication, is that of LCNCS …”

“…The characteristics of primary cutaneous neuroendocrine tumors have been summarized in Table and distinction between LCNCS and other members of the group is generally feasible on morphological and immunohistochemical grounds . Particular attention should be directed to discriminating between a large cell lymphoepithelioma‐like MCC and LCNCS.…”

“…5 The most recently described and least recognized subset of primary cutaneous neuroendocrine tumors, and the focus of this communication, is that of LCNCS. 6,7 The scant data on this entity are summarized, along with details of the current case, in Table 1. Briefly, the tumors occurred as nodules on the head of 3 patients and as a papule on the chest of 1.…”

“…8 The characteristics of primary cutaneous neuroendocrine tumors have been summarized in Table 2 and distinction between LCNCS and other members of the group is generally feasible on morphological and immunohistochemical grounds. [5][6][7]9,10 Particular attention should be directed to discriminating between a large cell lymphoepithelioma-like MCC 11 and LCNCS. This diagnostic issue has a bearing on the cases reported by Kasami et al 6 Ordinarily morphological features and a comprehensive panel of immunohistochemistry including the expression patterns of CK20, CK7 and neurofilament are helpful in this context.…”

Ectopic ACTH-producing large cell neuroendocrine Pancoast tumour presenting as Horner syndrome

“…LCNEC is a type of neuroendocrine tumour that can affect lungs, gall bladder,7 urinary bladder,8 head and neck,9 prostate,10 ovary,11 uterine cervix,12 vagina,13 endometrium,14 breast,15 colon,16 ileum,17 rectum,18 bile ducts,19 stomach,20 renal pelvis,21 skin,22 thymus,23 etc. Pulmonary neuroendocrine tumours make up to 20% of all lung cancers of which LCNEC are 10% (ie, 2–3% of all lung cancers).…”