Merkel cell carcinoma

Opinion statement Merkel cell carcinoma is a rare cutaneous neoplasm most commonly affecting the head and neck of elderly white patients. Even with treatment, Merkel cell carcinoma has a strong propensity toward local recurrence, lymphatic spread, and distant metastasis. Because of its rarity and the subsequent lack of well-controlled clinical trials, no single standard of care exists for the treatment of this aggressive tumor. In our institution, primary lesions are excised with wide margins or by Mohs’ micrographic surgery. After local removal, the excision site is treated locally with external radiation therapy. Sentinel lymph node mapping and biopsy are performed. Patients with tumor within a sentinel lymph node undergo lymph node dissection and radiation to the lymphatic basin. Adjuvant chemotherapy is offered to high-risk patients with local disease and to patients with metastases. Patients with distant metastases are treated with a combination of salvage chemotherapy and radiation therapy.     

Prokineticins and Merkel cell polyomavirus infection in Merkel cell carcinoma

Background:

Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell polyomavirus (MCPyV) infection.

Methods:

Carcinoma cell expression of PROK1 and PROK2 and their receptors (PROKR1 and PROKR2) was investigated with immunohistochemistry, and tumour PROK1 and PROK2 mRNA content with quantitative PCR from 98 MCCs. Subsets of tumour infiltrating leukocytes were identified using immunohistochemistry.

Results:

Merkel cell polyomavirus-positive MCCs had higher than the median PROK2 mRNA content, whereas MCPyV-negative MCCs contained frequently PROK1 mRNA. Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). Patients with higher than the median PROK2 mRNA content had 44.9% 5-year survival compared with 23.5% among those with a smaller content (hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.34–0.84; P=0.005), whereas the presence of PROK1 mRNA in tumour was associated with unfavourable survival (P=0.052).

Conclusions:

The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients.     

The Merkel cell carcinoma challenge

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin that occurs primarily in elderly or immunocompromised patients. For this report, the authors reviewed the diagnostic challenges associated with MCC encountered on their fine‐needle aspiration (FNA) service and also conducted an in‐depth review of the literature on MCC. A computer search for patients who were diagnosed with MCC by FNA at the authors' institution from 2006 to 2010 was conducted, and 5 patients were selected for cytologic and immunochemical analyses based on their varied and diagnostically challenging clinical presentations. The 5 selected patients had clinical findings commonly associated with MCC, including advanced age (4 of the 5 patients were ages 75‐85 years) and a history of previous malignancies (3 of the 5 patients had a history of previous malignancy), and 1 patient was diagnosed with a concomitant low‐grade lymphoma. The patients and their disease illustrated the protean clinical presentation of MCC and the clinical and cytologic challenges associated with this neoplasm. The current findings indicate the need for cytopathologists to be aware of the deceptive presentation of this neoplasm and its cytologic and immunochemical features to correctly diagnose this insidious neoplasm. Cancer (Cancer Cytopathol) 2013;121:179–188. © 2012 American Cancer Society.     

Management of Merkel cell carcinoma

Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the ‘evidence’.     

Management of Merkel cell carcinoma

Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the 'evidence'.     

Prospective study of Merkel cell polyomavirus and risk of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future MCC. Two large biobank cohorts (Southern Sweden Microbiology Biobank and the Janus Biobank), containing samples from 856,000 healthy donors, were linked to the Cancer Registries in Sweden and Norway to identify cases of MCC occurring up to 30 years after donation of a serum sample. For each of the 22 cases (nine males and 13 females), four matched controls were included. The serum samples were analyzed with an MCV neutralization assay and for IgG antibodies to MCV pseudovirions, using JC polyomavirus and cutaneous human papillomaviruses as control antigens. An increased risk for future MCC was associated both with high levels of MCV antibodies [OR 4.4, 95% CI 1.3–17.4] and with MCV neutralizing activity (OR 5.3, 95% CI 1.3–32.3). In males, MCV seropositivity was not associated to MCC risk, whereas the risk was strongly increased in females, both for high levels of MCV antibodies (OR 7.0, 95% CI 1.6–42.8) and for MCV neutralizing activity (OR 14.3, 95% CI 1.7–677). In conclusion, we found prospective evidence that MCV infection is associated with an increased risk for future MCC, in particular among females.     

Neurologic complications of Merkel cell carcinoma

We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered mental status. Aggressive treatment prolonged his survival marginally.     

Merkel cell carcinoma: a challenge

A 70-year-old man presented with an enlarging, recurrent tumor of the left buttock which, on initial biopsies, was interpreted as a histiocytic malignant lymphoma. Further biopsies showed numerous monomorphic, hyperchromatic, noncohesive cells, arranged in compact sheets, throughout the dermis, the fat, and the underlying muscle. Neuron specific enolase stain for neuroendocrine granules was positive. Electron microscopy showed cytoplasmic perinuclear microfilaments and round membrane-bound dense core granules. The histologic, enzymatic, and ultrastructural findings confirmed the diagnosis of Merkel cell carcinoma. Early diagnosis and treatment are imperative for a favorable outcome.     

皮肤Ｍｅｒｋｅｌ细胞癌的研究进展

Ｍｅｒｋｅｌ细胞癌（ＭＣＣ）是一种好发于皮肤的少见恶性神经内分泌瘤,预后较差,易局部复发和转移。ＭＣＣ的临床诊断可参考“ＡＥＩＯＵ”五元音法,但必须由组织病理学确诊。ＭＣＣ在高度紫外线暴露的地区较常见,且与免疫抑制密切相关。ＭＣＣ可能与Ｍｅｒｋｅｌ细胞多瘤病毒（ＭＣＰｙＶ）相关。目前ＭＣＣ尚无成熟的治疗方案,但首选手术治疗并常常辅助放疗或化疗。     

Merkel cell carcinoma subgroups by Merkel cell polyomavirus DNA relative abundance and oncogene expression

Merkel cell polyomavirus (MCPyV) was recently discovered in Merkel cell carcinoma (MCC), a clinically and pathologically heterogeneous malignancy of dermal neuroendocrine cells. To investigate this heterogeneity, we developed a tissue microarray (TMA) to characterize immunohistochemical staining of candidate tumor cell proteins and a quantitative PCR assay to detect MCPyV and measure viral loads. MCPyV was detected in 19 of 23 (74%) primary MCC tumors, but 8 of these had less than 1 viral copy per 300 cells. Viral abundance of 0.06–1.2 viral copies/cell was directly related to presence of retinoblastoma gene product (pRb) and terminal deoxyribonucleotidyl transferase (TdT) by immunohistochemical staining (p ≤ 0.003). Higher viral abundance tumors tended to be associated with less p53 expression, younger age at diagnosis and longer survival (p ≤ 0.08). These data suggest that MCC may arise through different oncogenic pathways, including ones independent of pRb and MCPyV.