From the Guidelines
Merkel cells are specialized epithelial cells that play a crucial role in touch sensation and can give rise to Merkel cell carcinoma, a rare and aggressive form of skin cancer. These cells are found in the epidermis, the outermost layer of the skin, and are concentrated in areas with high tactile sensitivity such as fingertips, lips, and the soles of feet 1. They form connections with sensory nerve endings, creating structures called Merkel cell-neurite complexes that transmit information about touch to the brain. Merkel cells contain dense-core granules that release neurotransmitters when stimulated by mechanical pressure.
The significance of Merkel cells in medicine is highlighted by their association with Merkel cell carcinoma, a rare but aggressive form of skin cancer that typically appears as a painless, firm, flesh-colored or bluish-red nodule on sun-exposed areas of the skin, particularly in older adults or those with compromised immune systems 1. According to the NCCN Guidelines, Merkel cell carcinoma has a high mortality rate exceeding that of melanoma, with 5-year relative or MCC-specific survival rates ranging from 41% to 77% 1.
Key characteristics of Merkel cell carcinoma include:
- High rate of local, regional, and distant recurrence
- Aggressive nature, with rapid growth and early metastasis
- Association with immunosuppression, such as in individuals with organ transplants, lymphoproliferative malignancies, or HIV infections 1
- Detection of Merkel cell polyomavirus (MCV) in 43% to 100% of patient samples, although the role of MCV in the pathogenesis of MCC is still under investigation 1.
In terms of management and treatment, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MCC provide up-to-date, best evidence–based, and consensus-driven management pathways 1. Multidisciplinary management with consensus treatment recommendations is optimal, taking into account the individual patient's needs and circumstances.
From the Research
Definition of Merkel Cell
- Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate 2.
- It is a type of metastatic, nonmelanoma skin cancer derived from Merkel cells in the epidermis 3.
- MCC is a rare, aggressive form of skin cancer that metastasizes to other parts of the body, mainly affecting older people, with most cases generally occurring over the age of 50 years 4.
Causes and Risk Factors
- Merkel cell polyomavirus (MCV) is found in most patients with MCC and is associated with a lower recurrence rate of MCC 3.
- MCV has been shown to induce gene mutations resulting in this skin cancer, with immunosuppression and ultraviolet radiation being other key risk factors in its pathogenesis 4.
- Chronic exposure to ultraviolet light (UV) can cause a characteristic pattern of multiple DNA mutations, contributing to MCC pathogenesis 5.
Clinical Presentation and Diagnosis
- MCC presents with a solitary cutaneous or subcutaneous nodule, most frequently in sun-exposed areas 5.
- Histologic examination is performed using unique markers to differentiate it from other diagnoses 3.
- Immunohistochemistry plays a crucial role in diagnosis, with the characteristic perinuclear staining with cytokeratin-20 helping to differentiate it from other morphologically similar tumours 4.
Treatment and Prognosis
- Surgical excision is the mainstay of treatment for localized disease, although adjuvant radiotherapy is often required 4.
- Metastatic disease involves a very poor prognosis, and immune checkpoint inhibitors have recently shown promise in the treatment of metastatic disease 4.
- Treatment with checkpoint inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC, with a high objective response rate (ORR), prolonged durable responses, and good tolerability 2.