MERKEL CELL CARCINOMA
Merkel cell carcinoma is an uncommonly encountered
neuroendocrine malignant skin tumor that has an aggressive behavior. This tumor
is derived from specialized nerve endings within the skin. The tumor promoting Merkel cell polyomavirus has been implicated in its pathogenesis. The
prognosis of Merkel cell carcinoma is worse than that of melanoma. This tumor
has a high rate of recurrence and often has spread to the regional lymph nodes
by the time of diagnosis.
Clinical Findings: Merkel cell carcinoma is a rare cutaneous
malignancy with an estimated incidence of 1 in 200,000. Merkel cell carcinoma
is much more common in Caucasian individuals. The tumor has a slight male
predilection. The average age at onset is in the fifth to seventh decades of
life. The lesions occur most often on the head and neck. This distribution is
consistent with the notion that chronic sun exposure is a predisposing factor
in the development of this tumor. These tumors also occur more commonly in
patients taking chronic immunosuppressive medications. The tumors often appear
as red papules or plaques that quickly increase in size. They can also appear
as rapidly enlarging nodules. On occasion, the tumor ulcerates. The clinical
differential diagnosis is often between Merkel cell carcinoma and basal cell
carcinoma, inflamed cyst, squamous cell carcinoma, or an adnexal tumor. These
tumors are so rare that they are infrequently in the original differential
diagnosis.
It has been estimated that up to 50%
of all patients diagnosed with a Merkel cell carcinoma will develop lymph node
metastasis. Other notable areas of metastasis include the skin, lungs, and
liver. The staging of this tumor is based on its size (<2 cm or >2 cm),
the involvement of regional lymph nodes, and the presence of metastasis.
Patients with higher-stage disease have a progressively worse prognosis.
Patients with metastatic disease (stage IV) have a 5-year survival rate of 0%.
In contrast, the 5-year survival rate for local stage I or II disease is 65% to
75% and approximately 50% to 60% for stage III (lymph node involvement).
Grouping all stages together, one third of the patients diagnosed with Merkel
cell carcinoma will die from their disease.
Pathogenesis: Merkel cell carcinoma is derived from a
specialized cutaneous nerve ending. The normal Merkel cells function in
mechanoreception of the skin. Merkel cells, like melanocytes, are
embryologically derived from the neural crest tissue. Chronic immuno-
suppression is believed to be one of the largest risk factors. Patients taking
immunosuppressive medica- tions after organ transplantation are at much higher
risk than age-matched controls. Chronic sun exposure and its effect on
downregulating local immunity in the skin have also been theorized to play an
etiological role. The Merkel cell polyomavirus has been studied to assess its
role in the development of Merkel cell carcinoma.
Polyomaviruses are similar in nature
and structure to the better-known papillomaviruses. There are at least five
polyomaviruses that cause human disease. Most of them affect patients who are
chronically immunosuppressed at a higher rate than healthy matched controls.
Researchers have implicated the Merkel cell polyomavirus as a potential cause
of Merkel cell carcinoma. This virus has been isolated from a high percentage
of Merkel cell tumors, but not from all of them. It is likely to be a player in
the pathogenesis of a subset of patients with Merkel cell carcinoma, but it is
unlikely to be the only explanation. The discovery of this virus may lead to
therapeutic options in the future.
Histology: Merkel cell carcinoma is a neuroendocrine tumor.
The tumor is composed of small, uni- formly shaped, basophilic-staining cells.
The tumor is poorly circumscribed and grows in an infiltrative pattern between
dermal collagen bundles and subcutaneous fat lobules. The cells have a
characteristic nuclear chromatin pattern. These tumors can be stained with
various immunohistochemical stains. The most helpful one is the cytokeratin 20
stain. It has a characteristic, if not pathognomonic perinuclear dot, staining
pattern.
Treatment: Surgical excision with wide (2-3 cm) margins is
still the standard therapeutic treatment. Sentinel node sampling has been
helpful in staging. Those patients with localized disease often undergo
postoperative irradiation of the surgical removal site. Those with widespread
metastatic disease are often treated with cisplatin-based chemotherapeutic
regimens.
