Merkel Cell Carcinoma
Merkel cell cancer (also known as trabecular cancer, or neuroendocrine cancer of the skin) is a rare type of malignancy developing on or just beneath the skin. These tumours can develop at any age, but the peak incidence is between ages 60 - 80. They are more frequent in white people, the most common sites of diseases are the face or scalp and other areas of high sun exposure. The Merkel cell polyomavirus (MCPyV), identified in humans in 2008, is suspected to have a role in the cause of most, but not all, cases of MCC.
Information for Health Professionals / Researchers
Latest Research Publications
Information Patients and the Public (5 links)
Merkel Cell Carcinoma - Information for patients and their physicians
An information website set up by a collaborative group of physicians and researchers who work on MCC. The site includes an FAQ and information on symptoms, causes, treatment and multidisciplinary management, staging and prognosis, a glossary of terms, and clinical photos of MCC tumors.
Merkel Cell Carcinoma Treatment
National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info.
Cancer Research UK
CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info.
Questions and Answers
A brief summary of MCC, diagnosis and treatment.
Information for Health Professionals / Researchers (7 links)
- PubMed search for publications about Merkel Cell Carcinoma - Limit search to: [Reviews]
PubMed Central search for free-access publications about Merkel Cell Carcinoma
MeSH term: Carcinoma, Merkel Cell
US National Library of Medicine
PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Merkel Cell Carcinoma Treatment
National Cancer Institute
PDQ summaries are written and frequently updated by editorial boards of experts Further info.
Clinical Images of Merkel Cell Carcinoma
Overview and 4 images of MCC. DermIS.net is a dermatology information service (multilingual support; English, German, Spanish, French and other languages). It is a collaboration between two German Universities (Heidelberg and Erlangen).
Skin Cancer Foundation
An article by Paul Nghiem, MD and Jayasri Iyer, MD from the Seattle Cancer Care Alliance. It includes images and compares MCC with other skin cancers, risk factors, link with Merkel cell polyomavirus, challenges in diagnosis and treatment and sentinal lymph node biopsy.
National Cancer Intelligence Network
A brief report on population-based data for rare skin cancers, including Merkel Cell Carcinoma and Dermatofibrosarcoma. It includes number of cases by histology incidence rates and trends in incidence over the 10 year period 1999 to 2008. Published 2011.
Latest Research Publications
This list of publications is regularly updated (Source: PubMed).
Left-sided laterality of Merkel cell carcinoma in a German population: more than just sun exposure.
J Cancer Res Clin Oncol. 2017; 143(2):347-350 [PubMed] Related Publications
OBJECTIVES: The aim of this study was to explore whether patients from Germany also show asymmetrical lateral distribution of Merkel cell carcinoma (MCC).
METHODS: In total, 115 patients with MCC were studied for laterality of the primary tumour. Correlation of clinical variables with lateral distribution of MCC was investigated as well.
RESULTS: In 64/115 (55.7%) patients, primary tumours were present on the left side, in 37/115 (32.2%) on the right side, and in 14/115 (12.2%) in the midline (P < 0.0001). Excluding the latter localization occurrence of left-sided MCCs (64 of 101/63.4%) was significantly (P = 0.0072) more often observed (1.73-fold) when compared to right-sided tumours (37 of 101/36.6%). The excess of left-sided tumours was found on the head with a left-right ratio of 1.8, trunk of 8, arm of 1.2, and leg of 1.8. There was no significant association between laterality and gender, age, MCPyV status, and anatomic localization of primary tumours including the occurrence in sun-exposed sites.
CONCLUSIONS: Occurrence of left-sided MCCs was significantly more often observed when compared to right-sided tumours. Laterality was not associated with tumour presentation at chronically ultraviolet-exposed sites. Hence, the reason for laterality in MCC remains obscure, but likely goes beyond UV exposure.
Complete Spontaneous Regression of Merkel Cell Carcinoma After Biopsy: A Case Report and Review of the Literature.
Am J Dermatopathol. 2016; 38(11):e154-e158 [PubMed] Related Publications
A Case of Nasal Merkel Cell Carcinoma Draining to a Buccinator Sentinel Lymph Node.
Clin Nucl Med. 2016; 41(11):e480-e481 [PubMed] Related Publications
Prognostic relevance of high atonal homolog-1 expression in Merkel cell carcinoma.
J Cancer Res Clin Oncol. 2017; 143(1):43-49 [PubMed] Related Publications
OBJECTIVES: We aimed to test for ATOH1 gene mutations and expression levels in MCC tissues and cell lines.
METHODS: Genomic DNA isolation and amplification via PCR was successfully performed in 33 MCCs on formalin-fixed paraffin-embedded tissue and three MCC cell lines, followed by Sanger sequencing of the whole ATOH1 gene to detect genomic aberrations. ATOH1 mRNA levels were determined by RT-PCR. Immunohistochemistry of ATOH1 was performed to quantify protein expression in tumor samples and cell lines.
RESULTS: Neither in any of the 33 MCC tissue samples nor in the three cell lines ATOH1 mutations were present. ATOH1 was expressed in all lesions, albeit at different expression levels. Univariate analysis revealed that the total immunohistology score significantly correlated with the occurrence of tumor relapse (r = 0.57; P = 0.0008). This notion was confirmed in multivariate analysis suggesting that ATOH1 expression is a potential independent predictor for tumor relapse in MCC patients (P = 0.028). MCC-related death also correlated with ATOH1 expression (r = 0.4; P = 0.025); however, ATOH1 expression did not retain its predictive value in the regression model.
CONCLUSIONS: In contrast to anecdotal reports ATOH1 expression is not lost by genetic alterations in MCC. However, protein expression of ATOH1 is increased in advanced MCC indicating that ATOH1 is involved in MCC progression.
Rapidly Fatal Dissemination of Merkel Cell Carcinoma in a Patient Treated with Alemtuzumab for Chronic Lymphocytic Leukemia.
Conn Med. 2016 Jun-Jul; 80(6):353-8 [PubMed] Related Publications
Histological Features, p53, c-Kit, and Poliomavirus Status and Impact on Survival in Merkel Cell Carcinoma Patients.
Am J Dermatopathol. 2016; 38(8):571-9 [PubMed] Related Publications
METHOD: The design was a retrospective study. The specimens were taken between 1993 and 2013 in 2 referral hospitals of Southern Spain. Data were collected retrospectively and analyzed using SPSS software.
RESULTS: Thirteen lesions from 13 subjects were included in the study. Positivity for c-kit was associated with the absence of MCPyV viral DNA (P = 0.048) and positivity for p53 (P = 0.002). More rate of mitoses per high-power field was presented significantly in those specimens with: positivity for c-kit (P = 0.046), positivity for p53 (P = 0.05), lesions with infiltrative growth pattern (P = 0.008), and lymphovascular invasion (P = 0.034). We observed an inverse relationship between p53 expression and MCPyV infection (Pearson's coefficient: -0.524; P = 0.046) and between c-kit expression and MCPyV infection (Pearson's coefficient: -0.548; P = 0.05), whereas the relationship was positive between p53 expression and c-kit expression (Pearson's coefficient: 0.884; P < 0.001).
CONCLUSION: We conclude that presence of MCPyV DNA has no effect on overall survival. MCCs with p53 and c-kit expressions are associated with the absence of or low MCPyV DNA showing an inverse relationship. A multifactorial molecular pathogenesis where positivity for p53 and c-kit are associated with other mechanisms different than MCPyV (such as pro-mitotic factors) may lead to aggressive clinical behavior.
Frequent detection of human polyomavirus 6 in keratoacanthomas.
Diagn Pathol. 2016; 11(1):58 [PubMed] Free Access to Full Article Related Publications
METHODS: In the present study we tested a large number (n = 299) of NMSC specimens for the presence of human polyomavirus 6 (HPyV6) by DNA PCR and HPyV6 fluorescence in situ hybridization (FISH). In detail, 59 keratoacanthomas (KA), 109 basal cell carcinomas (BCC), 86 squamous cell carcinomas (SCC) and 45 trichoblastomas (TB) were tested for the presence of HPyV6.
RESULTS: HPyV6 DNA PCR and subsequent sequence analysis revealed that 25 KAs (42.3 %), 23 BCCs (21.1 %), 8 SCCs (9.3 %) and 10 TBs (22.2 %) were HPyV6 positive. The presence of HPyV6 DNA was visualized and validated on the single cell level within the histomorphological context by HPyV6 fluorescence in situ hybridization.
CONCLUSIONS: The high frequency of HPyV6 DNA in 42.3 % of KA possibly points to a role for HPyV6 in the etiopathogenesis of KAs. Although the detection rate of HPyV6 DNA in BCCs and TBs is within the previously reported detection range in normal skin, it does not exclude a possible role for HPyV6 in the carcinogenesis in a significant subset of these skin tumors.
TTF-1 and PAX5 Are Frequently Expressed in Combined Merkel Cell Carcinoma.
Am J Dermatopathol. 2016; 38(7):513-6 [PubMed] Related Publications
SATB2 is expressed in Merkel cell carcinoma.
Arch Dermatol Res. 2016; 308(6):449-54 [PubMed] Related Publications
Isolated limb perfusion in Merkel cell carcinoma offers high rate of complete response and durable local-regional control: Systematic review and institutional experience.
J Surg Oncol. 2016; 114(2):187-92 [PubMed] Related Publications
METHODS: Retrospective review of our institutional experience with HILP for MCC was conducted (2009-2015). Literature search was performed through 04/2015 and 10 studies met inclusion criteria.
RESULTS: Four patients underwent HILP for MCC at our institution. There were no major complications and complete response was achieved in all patients. Early metastatic recurrence developed in two patients. The remaining two had no evidence of disease at last follow-up (36 months) or death (39 months). Systematic review identified an additional 12 pts that underwent HILP for MCC, for a total of 16 cases. Median age was 73 [IQR 69-78] years and 56% were men. Of the patients with reported follow-up, 12 (86%) had complete response, 1 had stable disease, and 1 partial response. Four patients developed local-regional recurrence and six distant metastases, all within 6 months. Overall median follow-up time was 15 [7-36] months.
CONCLUSION: Among a highly selective group of patients, regional perfusion for MCC is safe and has a high complete response rate. HILP is an acceptable therapeutic modality for obtaining durable loco-regional control but early distant metastatic disease remains a significant cause of mortality. J. Surg. Oncol. 2016;114:187-192. © 2016 Wiley Periodicals, Inc.
PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma.
N Engl J Med. 2016; 374(26):2542-52 [PubMed] Free Access to Full Article Related Publications
METHODS: In this multicenter, phase 2, noncontrolled study, we assigned adults with advanced Merkel-cell carcinoma who had received no previous systemic therapy to receive pembrolizumab (anti-PD-1) at a dose of 2 mg per kilogram of body weight every 3 weeks. The primary end point was the objective response rate according to Response Evaluation Criteria in Solid Tumors, version 1.1. Efficacy was correlated with tumor viral status, as assessed by serologic and immunohistochemical testing.
RESULTS: A total of 26 patients received at least one dose of pembrolizumab. The objective response rate among the 25 patients with at least one evaluation during treatment was 56% (95% confidence interval [CI], 35 to 76); 4 patients had a complete response, and 10 had a partial response. With a median follow-up of 33 weeks (range, 7 to 53), relapses occurred in 2 of the 14 patients who had had a response (14%). The response duration ranged from at least 2.2 months to at least 9.7 months. The rate of progression-free survival at 6 months was 67% (95% CI, 49 to 86). A total of 17 of the 26 patients (65%) had virus-positive tumors. The response rate was 62% among patients with MCPyV-positive tumors (10 of 16 patients) and 44% among those with virus-negative tumors (4 of 9 patients). Drug-related grade 3 or 4 adverse events occurred in 15% of the patients.
CONCLUSIONS: In this study, first-line therapy with pembrolizumab in patients with advanced Merkel-cell carcinoma was associated with an objective response rate of 56%. Responses were observed in patients with virus-positive tumors and those with virus-negative tumors. (Funded by the National Cancer Institute and Merck; ClinicalTrials.gov number, NCT02267603.).
Metabolic assessment of Merkel cell carcinoma: the role of 18F-FDG PET/CT.
Nucl Med Commun. 2016; 37(8):865-73 [PubMed] Related Publications
METHODS: A total of 101 consecutive F-FDG PET/CT studies of 46 patients with MCC (28 men, 68±15.4 years) were retrospectively evaluated and the role in clinical care was documented.
RESULTS: There were 40 positive studies (40%) in 28 patients (61%); of these, 33 studies (33%) in 27 patients (59%) showed metastatic disease. Fifty-two PET/CT studies (51%) in 23/46 (50%) patients were negative. Fifty-three studies (52%) were performed for staging or restaging in 41 patients, 29 scans (29%) were performed for routine follow-up in 10 patients, nine studies were carried out for suspected recurrent disease in eight patients, and 10 studies were carried out for assessment of response to therapy in seven patients. On the basis of PET/CT results, there was a change in disease stage in 12 studies in 12 patients (26%) and further change in the management of seven patients (15%). Overall, 2/29 routine follow-up studies were positive with further impact on management in one patient.
CONCLUSION: F-FDG PET-CT altered the stage of one of four patients and changed the management of one of seven MCC patients. In the majority of patients, a negative F-FDG PET-CT study excluded active MCC with a high degree of confidence. PET-CT contributed toward patient management when performed for staging and restaging, monitoring response to treatment, and suspected recurrent disease, but not in the routine follow-up of asymptomatic patients with MCC.
A pilot study of SPECT/CT-based mixed-reality navigation towards the sentinel node in patients with melanoma or Merkel cell carcinoma of a lower extremity.
Nucl Med Commun. 2016; 37(8):812-7 [PubMed] Related Publications
MATERIALS AND METHODS: Patients with a melanoma (n=4) or Merkel cell carcinoma (n=1) of a lower extremity scheduled for wide re-excision of the primary lesion site and SN biopsy were studied. Following a Tc-nanocolloid injection and lymphoscintigraphy, SPECT/CT images were acquired with a reference target (ReTp) fixed on the leg or the iliac spine. Intraoperatively, a sterile ReTp was placed at the same site to enable SPECT/CT-based mixed-reality navigation of a gamma ray detection probe also containing a reference target (ReTgp).The accuracy of the navigation procedure was determined in the coronal plane (x, y-axis) by measuring the discrepancy between standard gamma probe-based SN localization and mixed-reality-based navigation to the SN. To determine the depth accuracy (z-axis), the depth estimation provided by the navigation system was compared to the skin surface-to-node distance measured in the computed tomography component of the SPECT/CT images.
RESULTS: In four of five patients, it was possible to navigate towards the preoperatively defined SN. The average navigational error was 8.0 mm in the sagittal direction and 8.5 mm in the coronal direction. Intraoperative sterile ReTp positioning and tissue movement during surgery exerted a distinct influence on the accuracy of navigation.
CONCLUSION: Intraoperative navigation during melanoma or Merkel cell carcinoma surgery is feasible and can provide the surgeon with an interactive 3D roadmap towards the SN or SNs in the groin. However, further technical optimization of the modality is required before this technology can become routine practice.
Patterns of lymphatic spread and the management of eyelid carcinomas.
Auris Nasus Larynx. 2016; 43(6):666-71 [PubMed] Related Publications
METHODS: This study was a retrospective review of patient data from a single institution. From a series of 268 eyelid carcinomas, we selected the 21 patients with lymph node metastasis, and we analyzed the patterns of lymphatic spread, approach to treatment and outcomes.
RESULTS: The most common histological type of eyelid carcinoma with regional metastasis was sebaceous carcinoma (17/21, 81.0%). Submandibular area metastases were seen only in the patients with the primary tumor originating in the medial half of the eyelid, but parotid area metastases were seen in both the patients whose tumors had a medial-half origin and those with a lateral-half origin. Although 11 of the 16 patients with parotid-area metastases underwent a tumorectomy or superficial parotidectomy (which resulted in four cases of recurrence in the parotid area), none of the five patients who underwent a total parotidectomy developed parotid-area recurrence. The incidence of regional recurrence of the patients who received adjuvant radiotherapy (14.3%) was lower than that of the patients without adjuvant radiotherapy (57.1%).
CONCLUSION: Continued surveillance and optimal management of regional lymph node metastases are important for the control and survival of eyelid carcinomas.
Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma.
Sci Rep. 2016; 6:21678 [PubMed] Free Access to Full Article Related Publications
Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.
Am J Pathol. 2016; 186(4):1025-35 [PubMed] Related Publications
Merkel cell carcinoma of the head and neck: poorer prognosis than non-head and neck sites.
J Laryngol Otol. 2016; 130(4):393-7 [PubMed] Related Publications
METHODS: A retrospective study was performed of patients with Merkel cell carcinoma treated at the Jewish General Hospital in Montréal, Canada, from 1993 to 2013. Associations between clinicopathological characteristics and disease-free and disease-specific survival rates were examined according to the Kaplan-Meier method.
RESULTS: Twenty-seven patients were identified. Although basic clinicopathological characteristics and treatments were similar between head and neck and non-head and neck Merkel cell carcinoma groups, disease-free and disease-specific survival rates were significantly lower in the head and neck Merkel cell carcinoma group (log-rank test; p = 0.043 and p = 0.001, respectively). Mortality was mainly due to distant metastasis.
CONCLUSION: Patients with head and neck Merkel cell carcinoma had poorer survival rates than patients with non-head and neck Merkel cell carcinoma in our study. The tendency to obtain close margins, a less predictable metastatic pattern, and/or intrinsic tumour factors related to the head and neck may explain this discrepancy.
Lymphatic mapping and sentinel node biopsy in a patient with upper limb Merkel Cell Carcinoma: a case report and brief review of literature.
Nucl Med Rev Cent East Eur. 2016; 19(1):42-5 [PubMed] Related Publications
The dual specificity phosphatase 2 gene is hypermethylated in human cancer and regulated by epigenetic mechanisms.
BMC Cancer. 2016; 16:49 [PubMed] Free Access to Full Article Related Publications
METHODS: We analyzed the promoter hypermethylation of DUSP2 in human cancer, including primary Merkel cell carcinoma by bisulfite restriction analysis and pyrosequencing. Moreover we analyzed the impact of a DNA methyltransferase inhibitor (5-Aza-dC) and CTCF on the epigenetic regulation of DUSP2 by qRT-PCR, promoter assay, chromatin immuno-precipitation and methylation analysis.
RESULTS: Here we report a significant tumor-specific hypermethylation of DUSP2 in primary Merkel cell carcinoma (p = 0.05). An increase in methylation of DUSP2 was also found in 17 out of 24 (71%) cancer cell lines, including skin and lung cancer. Treatment of cancer cells with 5-Aza-dC induced DUSP2 expression by its promoter demethylation, Additionally we observed that CTCF induces DUSP2 expression in cell lines that exhibit silencing of DUSP2. This reactivation was accompanied by increased CTCF binding and demethylation of the DUSP2 promoter.
CONCLUSIONS: Our data show that aberrant epigenetic inactivation of DUSP2 occurs in carcinogenesis and that CTCF is involved in the epigenetic regulation of DUSP2 expression.
ABCB5-Targeted Chemoresistance Reversal Inhibits Merkel Cell Carcinoma Growth.
J Invest Dermatol. 2016; 136(4):838-46 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Recommendations for Solid Organ Transplantation for Transplant Candidates With a Pretransplant Diagnosis of Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma and Melanoma: A Consensus Opinion From the International Transplant Skin Cancer Collaborative (ITSCC).
Am J Transplant. 2016; 16(2):407-13 [PubMed] Related Publications
Molecular characteristics and potential therapeutic targets in Merkel cell carcinoma.
J Clin Pathol. 2016; 69(5):382-90 [PubMed] Related Publications
Emerging differential roles of the pRb tumor suppressor in trichodysplasia spinulosa-associated polyomavirus and Merkel cell polyomavirus pathogeneses.
J Clin Virol. 2016; 76:40-3 [PubMed] Related Publications
OBJECTIVES: The present study aims to explore the proliferative potential of MCPyV and TSPyV sT antigens by investigating their regulatory effects on the retinoblastoma protein (pRb) tumor suppressor.
STUDY DESIGN: Inducible cell lines expressing MCPyV sT or TSPyV sT were created using a lentiviral packaging system. Cellular proteins were extracted and subjected to SDS-PAGE followed by Western blot detection and densitometric analysis.
RESULTS: Expression of TSPyV sT markedly enhanced the phosphorylation of pRb in Western blot experiments. In contrast, expression of MCPyV sT did not alter pRb phosphorylation under the same experimental conditions. Densitometric analysis revealed that TSPyV sT antigen expression nearly doubled the ratio of phosphorylated to total pRb (P<0.001, Student's T-test), while MCPyV sT antigen expression did not cause significant change in pRb phosphorylation status.
CONCLUSION: Given that hyperphosphorylation of pRb is associated with dysregulation of the cell cycle, S-phase induction, and increased cell proliferation, our findings support an important role of TSPyV-mediated pRb deactivation in the development of TS. The observation that the pRb tumor suppressor is inactivated by TSPyV sT but not MCPyV sT provides further insights into the distinct pathobiological mechanisms of MCC and TS.
Lower expression of CADM1 and higher expression of MAL in Merkel cell carcinomas are associated with Merkel cell polyomavirus infection and better prognosis.
Hum Pathol. 2016; 48:1-8 [PubMed] Related Publications
Next generation sequencing of Cytokeratin 20-negative Merkel cell carcinoma reveals ultraviolet-signature mutations and recurrent TP53 and RB1 inactivation.
Mod Pathol. 2016; 29(3):240-8 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
Hotspot mutations in polyomavirus positive and negative Merkel cell carcinomas.
Cancer Genet. 2016 Jan-Feb; 209(1-2):30-5 [PubMed] Related Publications
Merkel cell carcinoma: Do you know your guidelines?
Head Neck. 2016; 38(5):647-52 [PubMed] Related Publications
METHODS: This article will review the current literature and National Comprehensive Cancer Network practice guidelines in the treatment of MCC.
RESULTS: Resection of MCC with negative margins remains the mainstay of therapy. Positive nodal disease should be treated with neck dissection and adjuvant radiotherapy. High-risk patients should undergo adjuvant radiotherapy, which improves oncologic outcomes. The role of chemotherapy is less clear and is currently reserved for advanced-stage MCC and palliative therapy.
CONCLUSION: The pathogenesis of MCC has recently been impacted with the discovery of the Merkel cell polyomavirus (MCPyV). Research to establish targeted and immunologic therapeutic options are ongoing.
Unexpected histopathologic result of a wide surgical excision of a bleeding lesion of the skin: a case of Merkel cell carcinoma of the leg.
G Chir. 2015 Sep-Oct; 36(5):231-5 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
METHODS: The authors report a case of a bleeding Merkel Cell Carcinoma of the right leg in a 83 years old man with HCV infection, chronic kidney disease and diabetes mellitus type 2 that required local excision.
RESULTS: Lesion was entirely removed and then patient was sent to oncologists. After two months from surgical excision, healing process is regular and without complications.
CONCLUSIONS: This type of tumor can be misdiagnosed and, if bleeding, it can represent a serious surgical emergency.
Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy.
Oncotarget. 2016; 7(3):3403-15 [PubMed] Article available free on PMC after 01/04/2017 Related Publications
UV-Associated Mutations Underlie the Etiology of MCV-Negative Merkel Cell Carcinomas.
Cancer Res. 2015; 75(24):5228-34 [PubMed] Related Publications