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Extensive central nervous system involvement in Merkel cell carcinoma: a case report and review of the literature
© Abul-Kasim et al; licensee BioMed Central Ltd. 2011
Received: 18 May 2010
Accepted: 26 January 2011
Published: 26 January 2011
Merkel cell carcinoma is a rare malignant cutaneous neoplasm that is locally invasive and frequently metastasizes to lymph nodes, liver, lungs, bone and brain. The incidence of Merkel cell carcinoma has increased in the past three decades.
A 65-year-old Caucasian man presented with a sudden onset of severe headache and a three-month history of balance disturbance. Magnetic resonance imaging revealed a large meningeal metastasis. The radiologic workup showed retroperitoneal and inguinal lymph node metastases. Biopsy of the inguinal lymph nodes showed metastases of Merkel cell carcinoma. Biopsy from three different suspected skin lesions revealed no Merkel cell carcinoma, and the primary site of Merkel cell carcinoma remained unknown. Leptomeningeal metastases, new axillary lymph node metastases, and intraspinal (epidural and intradural) metastases were detected within six, seven and eight months, respectively, from the start of symptoms despite treating the intracranial metastasis with gamma knife and the abdominal metastases with surgical dissection and external radiotherapy. This indicates the aggressive nature of the disease.
To the best of our knowledge, this is the first report in the literature of an intracranial meningeal metastasis of Merkel cell carcinoma treated with gamma knife and of intraspinal intradural metastases of Merkel cell carcinoma. Despite good initial response to radiotherapy, recurrence and occurrence of new metastases are common in Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare malignant neoplasm of the skin that is locally invasive and frequently metastasizes to lymph nodes, liver, lungs, bone and brain . The tumor was first described by Toker in 1972  as a trabecular cell carcinoma. The fact that MCC is now considered a neuroendocrine tumor is supported by the presence of calcitonin and neuron-specific enolase within the tumor . The diagnosis of MCC is based on the clinical findings of aggressive cutaneous tumors and the histopathologic examination of specimens using light and electron microscopy with a defined panel of immunoperoxidase stains . Hodgson  reported that the incidence of MCC has increased threefold between 1986 and 2001 (the rate of MCC increased from 0.15 cases per 100,000 in 1986 to 0.44 cases per 100,000 in 2001) . MCC often affects elderly patients with a mean age at presentation of about 75 years . The head and neck are the most common sites affected by MCC followed by the legs . A review of the literature showed a 27% to 60% incidence of local recurrence, a 45% to 91% incidence of lymph node metastases and an 18% to 52% incidence of distant metastases .
We report a case of MCC with extensive central nervous system (CNS) metastases with (1) intracranial meningeal, (2) intraspinal epidural and (3) intraspinal intradural metastases. A literature review of the reported cases of the intracranial and the intraspinal spread of MCC was also performed and presented.
The large supratentorial meningeal tumor was treated with gamma knife. MRI control 13 days after treatment with gamma knife showed marked reduction of the volume of the intracranial meningeal tumor (Figure 1D). Retroperitoneal and inguinal lymph node dissection was performed. Histopathology showed small cell carcinoma consistent with MCC (immunohistopathologic analysis was positive for the epithelial markers [AE1/AE3 and CK20] and neurofilament but negative for lymphoma and melanoma markers [CD45 and HMB45, respectively]). Cerebrospinal fluid cytology also showed MCC.
Compiled from the literature review recently presented by Feletti et al  and a few other reports
Total number of patients reported
18, including our case report
12/4 (two not defined)
Location of CNS metastases
Hypophysis and cavernous sinus
13 of 18
Time since the detection of the primary tumor
0-4 years (50% <1 year)
Treatment for brain metastasis
Radiotherapy + chemotherapy
Surgical removal + radiotherapy + chemotherapy
Surgical removal only
Survival after diagnosis
1 month to >3 years
This is the first report in the literature of intracranial metastasis of MCC that was treated with gamma knife, although the primary indication at the time of gamma knife surgery was removal of a large meningeal tumor of unknown origin. The patient and his relatives arranged the gamma knife treatment at another institution because the neurosurgeons in our regional institution regarded the tumor as meningioma with no need for rapid surgical intervention even though the radiologic report raised the suspicion of meningeal metastases. Based on the knowledge of the occurrence of lymph node metastases, the treating oncologists and surgeons aimed to treat the meningeal tumor with a less invasive method (treatment with gamma knife surgery instead of conventional surgery). In the past few years, the role of gamma knife surgery in the treatment of brain metastasis has proven to be associated with a longer survival time and better local tumor control in lung cancer metastases  and melanoma metastases  and in one series has been shown to provide excellent results in selected patients with one to 10 brain lesions without prophylactic whole-brain radiotherapy . Even in our case report, treatment with gamma knife proved to be successful in providing good local disease control.
Intraspinal metastases of Merkel cell carcinoma reported in the literature
Time since detection of the primary tumor
Survival after diagnosis
Moayed et al 
Turgut et al 
Turgut et al 
Vijay et al 
T8, L4, S1
Ng et al 
Our patient with extensive CNS, abdominal and inguinal metastases showed a good initial response to radiation therapy. However, evidence of progressive metastatic spread was demonstrated already six months after the onset of the patient's symptoms. This is the first report in the literature of spinal intradural metastases of MCC, which further contributed to worsening the patient's prognosis because it restrained a debulking and decompressive laminectomy.
Written informed consent was obtained from the patient's next of kin for publication of this case report and the accompanying images. A copy of the written consent is available for review by the Editor-in-Chief.
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