When discussing malignant skin tumours, we often think of basal or squamous cell carcinoma and malignant melanoma. Melanoma is particularly of concern owing to its aggressive behaviour and an upward trend in incidence. However, it's not the only tumour that is raising concern on those two counts. If you mention the Merkel cell, most will recall a modified keratinocyte that acts as a mechanoreceptor on the base of the epidermis, but its malignant namesake is showing a rapid increase in incidence. Merkel cell carcinoma (MCC) is a rare, aggressive tumour of the skin which shows high rates of recurrence and distant metastasis. Most recent thinking suggests that although it shares its name with the Merkel Cell, the tumour probably arises from a stem cell and is of a different cell lineage to the epidermal cell.
The tumour (figure 1) is particularly seen in fair-skinned, older patients. The rise in incidence has been steep, despite being a rare tumour, in a fifteen-year period rates have nearly tripled [1] more than most other types of malignancy, and this trend is expected to continue for some time. The reason for the rise is possibly because diagnostic techniques have improved to detect this rare cancer.
Merkel Cell Carcinoma – Image from Ly & Walsh (2021)[2]
(Source : Click here)
The tumour is most commonly seen in patients over the age of 75, with men being affected twice as often as women. In the UK, it affects around 0.1 – 0.2 per 100 000 people annually. The tumour is in part caused by excessive exposure to UVB radiation, hence a preponderance in fair skin types but the main driving force is considered to be the presence of the Merkel Cell Polyomavirus, which has found to be present in around 80% of MCC [3, 4]. Patients who are immunosuppressed or had organ transplants are also more at risk of developing MCC.
Lesions are generally found on the head and neck, arms and legs. Research has shown around 14% occur on the lower limb [5]. The typical presentation of the lesion is as a solitary, red or violaceous firm nodule that grows rapidly (figure 1). Heath and colleagues in examining 195 cases describe the useful ‘AEIOU’ acronym [6]:
Asymptomatic/absence of tenderness
Expanding rapidly
Immunosuppression
Older than age 50
UV (exposed site fair-skinned individual).
Differential diagnosis includes basal cell and squamous cell carcinoma and any “EFG” (elevated firm growing) lesion should also raise suspicion of amelanotic melanoma. Ultimately, a biopsy can confirm the diagnosis. Careful evaluation of the patient is required to establish if there has been any spread of metastasis to the surrounding skin, lymph nodes or beyond. Additional investigations such as magnetic resonance imaging or positron emission tomography are often used to determine if the disease has spread elsewhere.
The prognosis is determined by the extent of the disease at diagnosis. Survival rates for local disease are greater than 90%, but reduce to 52% with lymph node involvement. If distant metastatic disease is present, expected survival is typically less than 10% at three years [6] which is lower than melanoma [7]. Treatment locally involves wide excision of the primary tumour. Radiotherapy is often employed at the tumour site and affected lymph nodes to prevent recurrence. Chemotherapy is also used. New biologic agents such as pembrolizumab are showing promise in managing advanced disease [8].
In summary, MCC is a rare tumour but it is showing an increase in incidence. It can be observed on the legs and other sun-exposed sites. Any elevated firm growing (EFG) lesion on the skin should arouse suspicion and be urgently referred.
References
1. Paulson KG, Park SY, Vandeven NA, Lachance K, Thomas H, Chapuis AG, Harms KL, Thompson JA, Bhatia S, Stang A et al: Merkel cell carcinoma: Current US incidence and projected increases based on changing demographics. J Am Acad Dermatol 2018, 78(3):457-463.e452.
2. Ly, TY, Walsh (2021) Merkel Cell Carcinoma. Available from:[https://www.pathologyoutlines.com/topic/skintumornonmelanocyticmerkelcell.html]
3. Feng H, Shuda M, Chang Y, Moore PS: Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008, 319(5866):1096-1100.
4. Paolini F, Donati P, Amantea A, Bucher S, Migliano E, Venuti A: Merkel cell polyomavirus in Merkel cell carcinoma of Italian patients. Virol J 2011, 8:103-103.
5. Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE: Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study. J Cutan Pathol 2010, 37(1):20-27.
6. Heath M, Jaimes N, Lemos B, Mostaghimi A, Wang LC, Peñas PF, Nghiem P: Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. J Am Acad Dermatol 2008, 58(3):375-381.
7. Lemos B, Nghiem P: Merkel Cell Carcinoma: More Deaths but Still No Pathway to Blame. J Invest Dermatol 2007, 127(9):2100-2103.
8. Maniar R, Anderson M, Taback B, Khan S, McDonnell D, Saqi A, Niedt GW, Carvajal R: Case of Merkel cell carcinoma in a patient with pre-existing ILD. J Immunother Cancer 2020, 8(2):e001672.