Cutaneous Merkel cell carcinoma of the left lower leg

ARTICLE

A reclusive, 77-year-old lady was admitted to hospital with shortness of breath and anorexia. Chest X-ray revealed extensive pulmonary metastases. Abdominal ultrasound was normal, but due to her poor general medical health with cardiac and renal failure, no invasive investigations were performed to hunt the hidden primary tumour. She was referred to dermatology to review her long standing "venous" leg ulcers which had become increasingly malodorous. Removal of the leg ulcer dressings revealed this pigmented "wound" affecting the left lower leg (Fig. 1).

Cutaneous Merkel cell carcinoma of the left lower leg

Our differential diagnosis included malignant melanoma, squamous cell carcinoma, basal cell carcinoma or a cutaneous metastasis. Histological examination revealed a poorly differentiated carcinoma consisting of small cells and larger pleomorphic cells. Immunoperoxidase stains were positive for cytokeratins and negative with melanoma specific antigen, S100, factor VIII, and leucocyte common antigen. Neuron-specific enolase stains were positive also, giving a diagnosis of Merkel cell carcinoma.

Our patient had extensive metastases and poor general medical health, so was treated conservatively. She died 3 weeks after admission.

Comments

Merkel cell carcinoma is an aggressively malignant neuroendocrine tumour with epithelial differentiation. It typically occurs in patients over the age of 65 years [1], but has been reported in children [2] and young adults with congenital ectodermal dysplasia [3]. Caucasians are most frequently affected, with an equal male, female incidence. 50% occur on the head and neck, with 40% affecting the extremities and 10% the trunk and mucous membranes [4, 5].

Tumours present as individual nodules or indurated plaques with the colour varying from red to deep purple, often with a shiny surface and overlying telangiectasia [3, 4, 6, 7]. The epidermis may be ulcerated or intact. Merkel cell tumours may simulate squamous cell carcinomas, basal cell carcinomas, pyogenic granulomas, oat cell metastases and malignant melanomas [1, 4, 6].

Histologically they can be difficult to distinguish from other, poorly differentiated, small-cell tumours. They express both epithelial and neuroendocrine markers which aids the diagnosis. The majority have cytoplasm which stains positive with neuron-specific enolase, a marker for neuroendocrine tumours [8]. As epithelial-derived tumours, they show globular, juxtanuclear staining with monoclonal antibodies to cytokeratins 8, 18 and 19 [9].

Merkel cells are found in or near the basal layer, closely associated with terminal axons. They are thought to function as mechanoreceptors. The origin of the Merkel cell remains in dispute. Suggestions include derivation from the neural crest, like melanocytes, the cells being part of the amine precursor uptake and decarboxylation (APUD) system or that they represent modified keratinocytes [10].

Merkel cell carcinoma is aggressive with a high incidence of local recurrence, regional and systemic spread. Metastasis to the lungs is well recognised, however liver, bone and brain are the most common sites. Long term prognosis is unfavourable with the 3 year survival rate estimated as 55% [11].

Wide surgical excision is accepted as the treatment of choice for primary tumours [5, 10]. The role of adjunctive radiotherapy and elective lymph node dissection in these cases is controversial, but is recommended where primary disease has recurred or regional nodes are involved. Systemic chemotherapy has been used in patients with regional metastatic disease and distant metastases [5, 11]. A very poor prognosis is associated with this latter group.

This is a classical case of cutaneous Merkel cell carcinoma, which presented late with distant metastases. We must encourage our medical colleagues not to forget to remove leg ulcer dressings as part of a physical examination. The findings may be suprising!

REFERENCES

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2. Schmid C, Beham A, Feichtinger T, et al. Recurrent and subsequent metastasising Merkel cell carcinoma in a 7 year old girl. Histopathology 1992; 20: 437-9.

3. Wick M, Thomas J, Scheithauer B et al. Multifocal Merkel cell tumours with a cutaneous dysplasia syndrome. Arch Dermatol 1983; 119: 409-14.

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11. Wick MR, Goellner JR, Scheithauer BW, et al. Primary neuroendocrine carcinomas of the skin: a clinical, and ultrastructural study of thirteen cases. Am J Clin Pathol 1983; 79: 6-13.