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Q1: What is the differential diagnosis on clinical examination?
The possible differential diagnosis on clinical examination is:
Metastatic oat cell carcinoma.
Q2: What does the histology reveal (see p 249) and what histological techniques are used to establish the diagnosis?
The histology reveals malignant round cells consistent with a Merkel cell carcinoma or trabecular carcinoma. This is a rare primary cutaneous neuroendocrine tumour arising from Merkel cells.
The Merkel cell is a round cell in the basal layer of the epidermis named after Fredrick Sigmund Merkel who discovered it in 1875. These round cells may be isolated or arranged in clusters around hair follicles, which are innervated and function as touch receptors. The tumour was first described by Toker in 1972 who, along with Tang in 1978, described the intracytoplasmic dense core granules similar to those seen in neuroendocrine cells.1
Q3: Discuss the clinical features and management of this lesion
The Merkel cell carcinoma is a rare but aggressive tumour presenting as a dark red to dark blue papule. It usually arises on the head, neck, and the extremities of the elderly.2 It is often associated with other neoplasms, most commonly with a squamous cell carcinoma previously resected from the same anatomical site. The two may also coexist. It is also associated with Bowen's disease and basal cell carcinoma. The most important differential diagnosis is metastatic oat cell carcinoma as there are no specific histological differentiating features between the two. It is, therefore, important to undertake a careful history and examination followed by chest radiography to rule out a primary lung lesion. The tumour has a high incidence of local recurrence (39%) and regional recurrence (46%). Distant metastasis occur to bones, liver, and lung.
The cellular pattern ranges from trabecular to an insular or to a diffuse growth but all may coexist in a single tumour. The lesion tends to occupy the whole of the dermis with sparing of epidermis by a thin zone of Grenz. Cytologically the cells are monomorphic with scanty cytoplasm and homogenous nuclei with a central nucleolus (arrowed fig 1A). They may show a moulding effect as seen in small cell carcinomas.
Silver stains are negative, indicating the small number of neurosecretory granules.
This is helpful in differentiating Merkel cell carcinoma from other tumours such as lymphoma, melanoma, and metastatic oat cell carcinoma.
The useful markers studies are:
Positive for low molecular weight keratins such as AE1 or CAM 5.2, epithelial membrane antigen, neuron specific enolase (fig 1B), and chromagranin.3
Negative for S-100 protein, carcinoembryonic antigen, and lymphocytic markers.
Some Merkel cell carcinomas have been reported to regress spontaneously.4 The optimal treatment is not well defined due to its rarity and the limitations of retrospective data.5 Early lesions can be managed by surgical resection alone. Moh's microsurgery, which involves immediate histological assessment of resection margins, has a role in ensuring tumour clearance at the lateral and deep margins.6 It is not known whether prophylactic lymph node dissection and/or adjuvant radiotherapy increases the survival. Merkel cell carcinoma is a radiosensitive tumour and the field of treatment should include both the primary and the regional lymphatics.7 The role of chemotherapy is still controversial and should be considered in patients with advanced disease who are unfit for surgery.8
Merkel cell carcinoma.