Merkel cell carcinoma (MCC), or neuroendocrine carcinoma of the skin, is an uncommon and often aggressive malignancy that has a poor prognosis. More than 400 new cases of MCC occur in the United States each year, and the mortality rate is approximately 25%. [1] MCC is predominantly a tumor of the elderly, and most reported cases have occurred in white subjects. [2] [3] [4] [5] [6] It occurs most frequently in the head and neck region and the extremities and has a predilection for the periocular region. [2] [3] [5] [6] People treated with methoxsalen and ultraviolet A for psoriasis and people who are immunocompromised have an increased incidence of developing MCC. [7]

The Merkel cell is located in or near the basal layer of the epidermis and is closely associated with terminal axons. [2] [3] [8] While MCC may be difficult to diagnose, it usually presents as a painless, indurated, solitary dermal nodule with a slightly erythematous to deeply violaceous color. MCC frequently involves regional lymph nodes (10%–45% at initial presentation), [2] [3] [4] [5] [9] and between 50% and 75% of patients will develop regional lymph node metastases at some time during the course of their disease. [2] [3] [4] Distant metastases eventually occur in as many as 50% of patients, with lymph nodes, the liver, bone, brain, lung, and skin the most common sites of distant involvement. [2] [3] [5] [6] [10] MCC may progress rapidly, similar to aggressive melanoma. After primary tumor excision, local recurrence develops in 25% to 44% of patients; this has been attributed to inadequate surgical margins. [2] [4] [5]

Cellular Classification

Merkel cell carcinoma (MCC) is usually found within the dermis but may extend into the subcutaneous tissue. The combination of vesicular nuclei with small nucleoli, abundant mitoses, and apoptosis is characteristic of this tumor when evaluated within the context of certain architectural features. Histologically, MCC has been classified into 3 distinct subtypes: [1] [2] [3]

Trabecular

—      Cells are arranged in distinctly organoid clusters and trabeculae with occasional ribbons.

—      Individual cells are round to polygonal in shape and are compactly arranged.

—      Cell cytoplasm is comparatively abundant and often well defined.

—      Mitoses are few to moderate in number.

—      The tumor is usually found adjacent to adnexal structures, particularly hair follicles.

—      Trabecular is the least frequent histologic pattern identified.

Intermediate

—      The tumor exhibits a solid and diffuse growth pattern.

—      Cells are less compactly arranged, and the cytoplasm is less abundant than in the trabecular type.

—      Mitoses and focal areas of necrosis are frequently seen.

—      Intermediate tumors arise adjacent to adnexa but may also invade the epidermis.

—      Intermediate tumors may behave in a clinically more aggressive manner than trabecular tumors.

—      Intermediate is the most frequent histologic subtype identified.

Small cell

—      The tumor closely mimics small cell tumors of other sites.

—      The tumors arise in the dermis and appear as solid sheets and clusters of cells.

—      Areas of necrosis and crushing artifact are frequently seen.

—      The clinical behavior of small cell tumors appears to be as aggressive as that of intermediate tumors.

References:

1.        Haag ML, Glass LF, Fenske NA: Merkel cell carcinoma. Diagnosis and treatment. Dermatol Surg 21 (8): 669-83, 1995.

2.        Ratner D, Nelson BR, Brown MD, et al.: Merkel cell carcinoma. J Am Acad Dermatol 29 (2 Pt 1): 143-56, 1993.

3.        Gould VE, Moll R, Moll I, et al.: Neuroendocrine (Merkel) cells of the skin: hyperplasias, dysplasias, and neoplasms. Lab Invest 52 (4): 334-53, 1985.