Original Contribution
Merkel cell carcinoma with eccrine differentiation: a clinicopathologic study of 7 cases

https://doi.org/10.1016/j.anndiagpath.2008.07.001Get rights and content

Abstract

We described 7 examples of Merkel cell carcinoma of the skin with eccrine and squamous differentiation. Five patients were men, and 2 were women; and their ages ranged from 63 to 81 years (mean age, 73 years). Six tumors arose in the head and neck; and one, on the sole of the right foot. Three tumors recurred locally, and 2 metastasized to the regional lymph nodes. No patient developed distant metastasis. Two patients died of unrelated causes. Five Merkel cell carcinomas showed classic cytology, and 2 were similar to small cell carcinomas of the lung. All 7 tumors showed small eccrine ducts, and 2 exhibited foci of squamous differentiation. The eccrine ducts label with cytokeratin 7 and carcinoembryonic antigen, whereas the predominant endocrine component displayed the characteristic paranuclear dot-like reactivity with cytokeratin 20 and was synaptophysin and chromogranin positive. The lymph node metastasis contained both eccrine ducts and squamous elements, suggesting that they are an integral component of the tumors. Eccrine differentiation in Merkel cell carcinomas similar to small cell carcinomas of the lung and extrapulmonary sites is an important feature in the differential diagnosis because eccrine differentiation has not been described in primary or metastatic small cell carcinomas. The prognosis of these Merkel cell carcinomas with divergent differentiation appears to be less aggressive than that of pure Merkel cell carcinomas. However, larger series of patients with longer follow-ups are needed to confirm this observation.

Introduction

Primary cutaneous endocrine carcinoma is characterized by a small cell population with a neuroendocrine phenotype. Toker [1] first described this tumor as trabecular carcinoma and suggested its sudoriferous origin. However, after the demonstration of dense-core neurosecretory granules and neuroendocrine markers in neoplastic cells, the term Merkel cell carcinoma was used and became popular [2], [3], [4], [5]. The neoplastic cells were thought to arise from the specialized Merkel cells of the epidermis, hair sheath, and sweat ducts [6], [7]. During the last 2 decades, however, several nonendocrine cell types as well as sarcomatous elements have also been recognized in some of the tumors [8], [9], [10], [11], [12], [13], [14], suggesting that Merkel cell carcinoma probably arises from a stem cell that is able to differentiate along different cell lines.

The purpose of this investigation is to report 7 examples of Merkel cell carcinoma that showed eccrine differentiation and determine whether or not this feature is present in metastatic deposits and alters the prognosis of the tumors.

Section snippets

Material and methods

Seven cases of Merkel cell carcinoma with eccrine differentiation were retrieved from the consultation files of one of the authors (J-AS). Hematoxylin-eosin–stained sections and immunostains for cytokeratin (CK) 7, CK20, carcinoembryonic antigen (CEA), chromogranin, synaptophysin, and neuron-specific enolase were available for review in all cases. Positive and negative control immunostains were also available and examined. Clinical information and follow-up were obtained from the surgical

Results

The patients, 5 men and 2 women, ranged in age from 63 to 81 years, with a mean age of 73 years. There was no history of immunosuppression in any of the patients. Six tumors were located on the head and neck: ear, 3; cheek, 1; forehead, 1; and eyebrow, 1. One tumor was located on the sole of the left foot. All tumors were surgically excised. One patient received postoperative radiotherapy. A modified radical neck dissection was performed in 2 patients. Three patients developed local recurrence,

Discussion

Merkel cell carcinoma is an aggressive neoplasm that commonly arises in the sun-exposed skin of elderly and often immunocompromised patients [5], [15], [16], [17], [18], [19]. It has also been reported in the vulva [20], on the oral mucosa [21], and in lymph nodes in patients with no primary cutaneous lesion [15]. Approximately 40% of the tumors recur locally, and 75% of these tumors eventually metastasize in lymph nodes or in distant organs. Several investigators have recently detected Merkel

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    This work was supported by La Fundación La Cruz Azul.

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