Merkel Cell Carcinoma
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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.

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Skin Cancer

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Information for Health Professionals / Researchers (7 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Gaba S, Chopra P, Pankaj P, et al.
Merkel cell carcinoma--a rare cause of non-healing skin ulcer: a case report.
J Indian Med Assoc. 2012; 110(7):496-8 [PubMed]
Merkel cell carcinoma (MCC) is a rare tumour of skin which needs to be differentiated from other small cell tumours like small-cell carcinoma of lung, melanoma, and lymphoma. Definitive diagnosis is made by immunohistochemistry and staining positively with cytokeratin. There is very little data regarding treatment of metastatic MCC and many questions remain unanswered. MCC is a chemosensitive tumour and many different chemotherapeutic regimens have been used alone or in combination with radiotherapy to treat metastatic MCC. Although complete and partial responses are achieved, they are mostly short lived and tumour usually recurs. Here a case is reported who had partial remission with chemotherapy (etoposide and cisplatin) and radiation therapy in a patient with metastatic MCC.


DeCaprio JA, Garcea RL
A cornucopia of human polyomaviruses.
Nat Rev Microbiol. 2013; 11(4):264-76 [PubMed]
During the past 6 years, focused virus hunting has led to the discovery of nine new human polyomaviruses, including Merkel cell polyomavirus, which has been linked to Merkel cell carcinoma, a lethal skin cell cancer. The discovery of so many new and highly divergent human polyomaviruses raises key questions regarding their evolution, tropism, latency, reactivation, immune evasion and contribution to disease. This Review describes the similarities and differences among the new human polyomaviruses and discusses how these viruses might interact with their human host.


Snovak N, Bilić M, Zarković K
Merkel cell carcinoma of the head and neck and associated second primary cancers: report of three cases.
Coll Antropol. 2012; 36 Suppl 2:213-7 [PubMed]
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin carcinoma. The purpose of this study is to describe clinical and pathological characteristics, diagnostic procedure and treatment outcomes of the patients with MCC of the head and neck treated in Otorhinolaryngology, Head and Neck Surgery Department of the University Hospital Center Zagreb between the years 2007 and 2011. Three patients with MCC of the head and neck were treated during this period. First patient was diagnosed with MCC of the left retroauricular region with metastases in the lymph nodes of the left side of the neck, pT2N2M0 Stage IIIB. Second patient was diagnosed with anaplastic carcinoma of the lower lip, pT1N1bM0 Stage IIIB and third patient was diagnosed with MCC of the face which was previously treated as benign lesion, cT1N1bM0 Stage IIIB. Two of the patients had second primary tumor of different histology. All of the patients were treated with wide surgical excision of the tumor and neck dissection combined with adjuvant radiotherapy. Treatment outcome was poor and reason for this was late detection of disease. Menagment of the MCC patients requires multidisciplinary approach with high clinical suspicion of the treating specialist and pathologist due to immunohistochemical techniques required for diagnosis. Detection of the MCC in earlier stages is necessary for the better survival rate.


Amber K, McLeod MP, Nouri K
The Merkel cell polyomavirus and its involvement in Merkel cell carcinoma.
Dermatol Surg. 2013; 39(2):232-8 [PubMed]
BACKGROUND: The discovery of the Merkel cell polyomavirus (MCV) in a large number of Merkel cell carcinomas (MCCs) has led to many investigations into its potential role as an oncovirus. Many studies have recently explored the differences between MCCs infected and not infected with MCV.
OBJECTIVE: To review the role of MCV in MCC and its potential to influence diagnosis, prognosis, and treatment.
METHODS AND MATERIALS: An extensive literature search was performed on MCV and its relationship with other polyomaviruses and MCC. The immune system's role in MCC was also investigated.
RESULTS: We included 60 articles regarding MCC and MCV and seven pertinent to general processes involved with MCC and MCV.
CONCLUSION: Merkel cell polyomavirus appears to affect many aspects of MCC. An understanding of this virus may aid in future therapy options and current pathology protocols in diagnosing MCC. The host's immune function appears to affect MCV's ability to cause cellular transformation leading to MCC.


Lee JH, Roychowdhury S, Nissenblatt MJ
Neuroembolization of metastatic Merkel cell cancer to the face for treatment of Kasabach-Merritt syndrome.
BMJ Case Rep. 2013; 2013 [PubMed]
Kasabach-Merritt syndrome is defined as a consumptive thrombocytopenia in the presence of a highly vascular tumor. Multiple treatment options, including transarterial embolization, have been described. We demonstrate that transarterial embolization is a viable option in the treatment of a rapidly progressive and debilitating Merkel cell tumor metastasizing to the head and neck presenting with Kasabach-Merritt syndrome.


Ross AD, Kumar P, Challacombe BJ, et al.
The addition of the surgical robot to skin cancer management.
Ann R Coll Surg Engl. 2013; 95(1):70-2 [PubMed]
We present the introduction of the surgical robot for pelvic lymphadenectomy for skin cancer through a cross-specialty collaboration. In this prospective series, we include the first report of cases undergoing robot-assisted pelvic lymph node dissection for Merkel cell carcinoma and melanoma in the recognised scientific literature.


Syal NG, Dang S, Rose J, et al.
Gastric metastasis of merkel cell cancer--uncommon complication of a rare neoplasm.
J Ark Med Soc. 2012; 109(7):134-6 [PubMed]
Merkel cell cancer is an aggressive cutaneous malignancy of neuroendocrine cell lineage which carries a poor prognosis. It usually affects elderly Caucasians and presents as a firm, painless, nodular lesion on the sun exposed areas of the body. Though it is highly metastatic, metastasis to the gastrointestinal tract is rarely reported. We describe a case of gastric metastasis from merkel cell cancer presenting with upper gastrointestinal bleeding. To our knowledge, only 8 such cases have been reported in English literature so far.


Iwasaki T, Kodama H, Matsushita M, et al.
Merkel cell polyomavirus infection in both components of a combined Merkel cell carcinoma and basal cell carcinoma with ductal differentiation; each component had a similar but different novel Merkel cell polyomavirus large T antigen truncating mutation.
Hum Pathol. 2013; 44(3):442-7 [PubMed]
Merkel cell polyomavirus infects up to 80% of patients with Merkel cell carcinoma. Combined Merkel cell carcinoma and cutaneous tumors occur occasionally. Previous reports have suggested that Merkel cell polyomavirus is absent from combined Merkel cell carcinoma and squamous cell carcinomas. This is the first report that Merkel cell polyomavirus infected in both lesions of a combined Merkel cell carcinoma and basal cell carcinoma. A 92-year-old Japanese man presented with a right thigh small subcutaneous mass. Histologic examination revealed a combined tumor with Merkel cell carcinoma and basal cell carcinoma with ductal differentiation. Both tumors and intermingled Merkel cells in basal cell carcinoma expressed Merkel cell polyomavirus large T antigen, and 17 and 240 copies of Merkel cell polyomavirus/cell were detected in the microdissected Merkel cell carcinoma and basal cell carcinoma specimens, respectively. Mutation analysis of Merkel cell polyomavirus large T antigen revealed a novel truncating mutation in Merkel cell carcinoma and a similar but different mutation in the basal cell carcinoma. These results suggest that each was infected by a different Merkel cell polyomavirus subclone derived from a single Merkel cell polyomavirus.


Stevenson ML, Saggar S, Amin B, Mann RE
Merkel cell carcinoma arising in a patient with a history of multiple malignancies.
Cutis. 2012; 90(4):183-5 [PubMed]
Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine carcinoma of the skin. Although the association between MCC and other primary malignancies has been documented, the mechanism of this association has not been elucidated. We report a case of MCC in a man with a history of multiple primary malignancies and treatment with immunomodulators. This case highlights the increased incidence of other malignancies in patients with MCC and is unique given the number and diversity of primary malignancies found in this patient.


Harms PW, Patel RM, Verhaegen ME, et al.
Distinct gene expression profiles of viral- and nonviral-associated merkel cell carcinoma revealed by transcriptome analysis.
J Invest Dermatol. 2013; 133(4):936-45 [PubMed] Article available free on PMC after 01/10/2013
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor with high mortality rates. Merkel cell polyomavirus (MCPyV), identified in the majority of MCCs, may drive tumorigenesis via viral T antigens. However, the mechanisms underlying pathogenesis in MCPyV-negative MCCs remain poorly understood. To nominate genes contributing to the pathogenesis of MCPyV-negative MCCs, we performed DNA microarray analysis on 30 MCCs. The MCPyV status of MCCs was determined by PCR for viral DNA and RNA. A total of 1,593 probe sets were differentially expressed between MCPyV-negative and MCPyV-positive MCCs, with significant differential expression defined as at least a 2-fold change in either direction and a P-value 0.05. MCPyV-negative tumors showed decreased RB1 expression, whereas MCPyV-positive tumors were enriched for immune response genes. Validation studies included immunohistochemistry demonstration of decreased RB protein expression in MCPyV-negative tumors and increased peritumoral CD8+ T lymphocytes surrounding MCPyV-positive tumors. In conclusion, our data suggest that loss of RB1 expression may have an important role in the tumorigenesis of MCPyV-negative MCCs. Functional and clinical validation studies are needed to determine whether this tumor-suppressor pathway represents an avenue for targeted therapy.


Spurgeon ME, Lambert PF
Merkel cell polyomavirus: a newly discovered human virus with oncogenic potential.
Virology. 2013; 435(1):118-30 [PubMed] Article available free on PMC after 05/01/2014
A marked escalation in the rate of discovery of new types of human polyomavirus has occurred over the last five years largely owing to recent technological advances in their detection. Among the newly discovered viruses, Merkel Cell Polyomavirus (MCPyV or MCV) has gained the most attention due to its link with a rare human cancer. Infection with MCPyV is common in the human population, and the virus is detected in several anatomical locations, but most frequently in skin. Study of MCPyV molecular virology has been complicated by the lack of straightforward cell culture models, but recent in vitro studies are making strides towards understanding the virus life cycle, its cellular tropism, and mode of transmission. While MCPyV shares several traditional traits with other human polyomaviruses, the burst of research since its discovery reveals insight into a virus with many unique genetic and mechanistic features. The evidence for a causal link between MCPyV and the rare neuroendocrine cancer, Merkel Cell Carcinoma (MCC), is compelling. A majority of MCCs contain clonally integrated viral DNA, express viral T antigen transcripts and protein, and exhibit an addiction to the viral large T and small t antigen oncoproteins. The MCPyV large T antigen contains MCC tumor-specific mutations that ablate its replication capacity but preserve its oncogenic functions, and the small t antigen promotes an environment favorable for cap-dependent translation. The mechanisms of MCPyV-induced transformation have not been fully elucidated, but the likely etiological role of this new polyomavirus in human cancer provides a strong opportunity to expand knowledge of virus-host interactions and viral oncology.


Tarantola TI, Vallow LA, Halyard MY, et al.
Prognostic factors in Merkel cell carcinoma: analysis of 240 cases.
J Am Acad Dermatol. 2013; 68(3):425-32 [PubMed]
BACKGROUND: Knowledge regarding behavior of and prognostic factors for Merkel cell carcinoma (MCC) is limited.
OBJECTIVE: We sought to further understand the characteristics, behavior, prognostic factors, and optimal treatment of MCC.
METHODS: A multicenter, retrospective, consecutive study of patients with known primary MCC was completed. Overall survival and survival free of locoregional recurrence were calculated and statistical analysis of characteristics and outcomes was performed.
RESULTS: Among the 240 patients, the mean age at diagnosis was 70.1 years, 168 (70.0%) were male, and the majority was Caucasian. The most common location was head and neck (111, 46.3%). Immunosuppressed patients had significantly worse survival, with an overall 3-year survival of 43.4% compared with 68.1% in immunocompetent patients. In our study, patients with stage II disease had improved overall survival versus those with stage I disease, in a statistically significant manner. Patients with stage III disease had significantly worse survival compared with stage I and with stage II. Primary tumor size did not predict nodal involvement.
CONCLUSION: The data presented represent one of the largest series of primary MCC in the literature and confirm that MCC of all sizes has metastatic potential, supporting sentinel lymph node biopsy for all primary MCC. Because of the unpredictable natural history of MCC, we recommend individualization of care based on the details of each patient's tumor and clinical presentation.


Tarantola TI, Vallow LA, Halyard MY, et al.
Unknown primary Merkel cell carcinoma: 23 new cases and a review.
J Am Acad Dermatol. 2013; 68(3):433-40 [PubMed]
BACKGROUND: Knowledge is limited regarding unknown primary Merkel cell carcinoma (UPMCC).
OBJECTIVE: We sought to document the characteristics and behavior of UPMCC, and determine the most appropriate treatment.
METHODS: A multicenter, retrospective, consecutive study reviewing patients given a diagnosis of UPMCC between 1981 and 2008 was completed. In addition, a literature review of cases of UPMCC was performed.
RESULTS: In all, 23 patients with UPMCC are described and 34 cases from previous reports are compiled. Among the 23 new cases of UPMCC, the average age at diagnosis was 66.0 years; the majority of patients were male (87%) and Caucasian (100% of those reported). One patient was immunosuppressed, and 39% had a history of other cancer. After the initial biopsy, 16 patients had further evaluation of the involved lymph node basin. Half of these had additional positive nodes (8 of 16). The majority of patients had lymph node basin involvement only (78%), whereas 22% had lymph node basin and distant metastasis. The most common lymph node basin involved was inguinal. The median size of the involved lymph node at diagnosis was 5.0 cm. At 2 years, the overall survival of stage IIIB UPMCC was significantly improved versus stage IIIB known primary Merkel cell carcinoma (MCC): 76.9% to 36.4%.
LIMITATIONS: Limited number of cases and retrospective review are limitations.
CONCLUSION: Our data demonstrate improved overall survival in patients with stage IIIB UPMCC versus those with stage IIIB known primary MCC. Because of the unpredictable natural history of UPMCC, we recommend individualization of care based on the details of each patient's clinical presentation.


Hawryluk EB, O'Regan KN, Sheehy N, et al.
Positron emission tomography/computed tomography imaging in Merkel cell carcinoma: a study of 270 scans in 97 patients at the Dana-Farber/Brigham and Women's Cancer Center.
J Am Acad Dermatol. 2013; 68(4):592-9 [PubMed]
BACKGROUND: Merkel cell carcinoma (MCC) is a rare and lethal cutaneous neuroendocrine carcinoma. Imaging is crucial for accurate staging, which remains a strong predictor of survival, as well as earlier detection of recurrence and progression, which are common despite aggressive management. There is no consensus on the role of initial and subsequent imaging for MCC.
OBJECTIVE: We sought to evaluate the use of 2-fluoro-[(18)F]-deoxy-2-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in the management of MCC.
METHODS: In all, 270 FDG-PET/CT studies were performed in 97 patients with pathology-proven MCC at the Dana-Farber/Brigham and Women's Cancer Center, Boston, Mass, from August 2003 to December 2010.
RESULTS: FDG-PET/CT scans were obtained as part of the initial (61 scans in 61 patients) and subsequent (209 scans in 79 patients) treatment strategies. MCCs were FDG-avid with a mean maximum standardized uptake value of primary lesions of 6.5 (range 1.3-12.9) and a mean maximum standardized uptake value of regional and distant metastases of 7.2 (range 1.5-9.9). FDG-PET/CT upstaged 16% of patients who underwent baseline scans. FDG-PET/CT studies showed that bone and bone-marrow metastases were more common than previously reported, and were often undetected by CT.
LIMITATIONS: Our study is limited by its retrospective design, and potential referral bias associated with a tertiary care center.
CONCLUSIONS: FDG-PET/CT performed as part of the initial management strategy tended to upstage patients with more advanced disease. FDG-PET/CT performed as part of the subsequent treatment strategy identified metastatic disease, particularly in bone/bone marrow, which was not seen on CT. FDG-PET/CT imaging is a valuable staging and restaging tool in MCC management.


Kressin MK, Kim AS
Metastatic Merkel cell carcinoma in the bone marrow of a patient with plasma cell myeloma and therapy-related myelodysplastic syndrome.
Int J Clin Exp Pathol. 2012; 5(9):1007-12 [PubMed] Article available free on PMC after 05/01/2014
Merkel cell carcinoma is an aggressive neoplasm of the skin that shows frequent lymph node metastases, but has only rarely been reported in the bone marrow. Herein we report a case of a 64-year-old male with a history of plasma cell myeloma and recent skin diagnosis of Merkel cell carcinoma who presented for a routine follow-up bone marrow to assess his myeloma. The biopsy showed persistent plasma cell myeloma, trilineage dysplasia, and clusters of neuroendocrine cells consistent with metastatic Merkel cell carcinoma. Discussion of this case, a review of metastatic Merkel cell carcinoma, and identification of clinical settings in which staging bone marrow biopsy may be warranted are presented.


Han SY, North JP, Canavan T, et al.
Merkel cell carcinoma.
Hematol Oncol Clin North Am. 2012; 26(6):1351-74 [PubMed]
Merkel cell carcinoma (MCC) is a rare but aggressive carcinoma of the skin, arising most commonly in sun-exposed sites of elderly patients. The diagnosis is based on characteristic histopathologic features. In 2008, the discovery of the Merkel cell polyomavirus led to intensified research into the viral pathogenesisis of MCC. MCC staging guidelines were established in 2010, and it demonstrated the importance of distinguishing clinical vs. pathologic evaluation of lymph nodes in MCC. Surgery and/or radiation is of the mainstay of therapy for early disease, while chemotherapy is reserved for more advanced disease. Treatments based on immunologic mechanisms are currently in development.


Rodig SJ, Cheng J, Wardzala J, et al.
Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus.
J Clin Invest. 2012; 122(12):4645-53 [PubMed] Article available free on PMC after 05/01/2014
A human polyomavirus was recently discovered in Merkel cell carcinoma (MCC) specimens. The Merkel cell polyomavirus (MCPyV) genome undergoes clonal integration into the host cell chromosomes of MCC tumors and expresses small T antigen and truncated large T antigen. Previous studies have consistently reported that MCPyV can be detected in approximately 80% of all MCC tumors. We sought to increase the sensitivity of detection of MCPyV in MCC by developing antibodies capable of detecting large T antigen by immunohistochemistry. In addition, we expanded the repertoire of quantitative PCR primers specific for MCPyV to improve the detection of viral DNA in MCC. Here we report that a novel monoclonal antibody detected MCPyV large T antigen expression in 56 of 58 (97%) unique MCC tumors. PCR analysis specifically detected viral DNA in all 60 unique MCC tumors tested. We also detected inactivating point substitution mutations of TP53 in the two MCC specimens that lacked large T antigen expression and in only 1 of 56 tumors positive for large T antigen. These results indicate that MCPyV is present in MCC tumors more frequently than previously reported and that mutations in TP53 tend to occur in MCC tumors that fail to express MCPyV large T antigen.


Reinstadler DR, Sinha UK
Uncommon cutaneous neoplasms of the head and neck.
Facial Plast Surg Clin North Am. 2012; 20(4):483-91 [PubMed]
This article concentrates on the less-common cutaneous malignancies such as merkel cell, atypical fibroxanthoma, malignant fibrous histiocytoma, dermatofibrosarcoma protuberans, microcystic adnexal carcinoma, and sebaceous carcinoma. The clinical and histopathologic descriptions of each, most current and emerging etiologies, diagnosis, staging, treatment, and prognosis are discussed.


Kang SH, Haydu LE, Goh RY, Fogarty GB
Radiotherapy is associated with significant improvement in local and regional control in Merkel cell carcinoma.
Radiat Oncol. 2012; 7:171 [PubMed] Article available free on PMC after 05/01/2014
INTRODUCTION: Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent's and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC.
METHOD: The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results.
RESULTS: Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049).
CONCLUSIONS: RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival.


Kouzmina M, Häyry V, Leikola J, et al.
BMI1 expression identifies subtypes of Merkel cell carcinoma.
Virchows Arch. 2012; 461(6):647-53 [PubMed]
Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine carcinoma. The aims of this study were to investigate the expression of the transcription factors B-lymphoma Moloney murine leukaemia virus insertion (BMI1), myelocytomatosis viral oncogene homologue (c-Myc) and Snail in MCC tumour specimens and to examine the relationship of these markers to Merkel cell polyoma virus (MCV). The study comprised of 133 patients with primary MCC. The expression of BMI1, Snail and c-Myc protein was assessed by immunohistochemistry and compared with clinical parameters, MCV status and patient survival. The presence of MCV was inversely correlated with the expression of BMI1 protein. Tumours expressing BMI1 protein more often presented with lymph node metastases. Snail protein expression was decreased in cases with metastatic dissemination. This study identified two subgroups of MCC: tumours expressing BMI1 but negative for MCV DNA and tumours negative for BMI1 expression but positive for MCV. Importantly, BMI1-positive cases often presented with lymph node metastases. Combined, these results suggest that subtypes of this malignancy exist.


Sidhu HK, Patel RV, Goldenberg G
Dermatology clinics: what's new in dermatopathology: news in nonmelanocytic neoplasia.
Dermatol Clin. 2012; 30(4):623-41, vi [PubMed]
This article reviews the recent dermatopathology literature involving nonmelanocytic neoplasia, with a focus on important work done over the last 5 years. The discussion includes advances in the understanding of Merkel cell carcinoma pathogenesis and prognosis; changes in the seventh edition of the American Joint Committee of Cancer staging manual in reference to staging of squamous cell carcinoma and Merkel cell carcinoma; newly described or rare histopathologic patterns and entities including squamoid eccrine ductal carcinoma, rippled-pattern adnexal neoplasms, onychomatricoma, spindle cell predominant trichodiscoma/neurofollicular hamartoma, and myoepithelioma; and microsatellite instability in sebaceous neoplasms of Muir-Torre syndrome and other tumors.


de Zeeuw S, Schouten van der Velden AP, de Wilt HJ, et al.
A Merkel cell carcinoma presenting as a solitary lymph node metastasis without a primary lesion. Report of a case and review of the literature.
Acta Chir Belg. 2012 Jul-Aug; 112(4):317-21 [PubMed]
Merkel cell carcinoma is an uncommon, aggressive neuroendocrine tumour of the skin. At presentation regional lymph nodes are involved in approximately one third of the patients. In this report a patient is presented in whom Merkel cell carcinoma presented as a solitary lymph node metastasis with an unknown primary skin lesion. The diagnosis of unknown primary merkel cell carcinoma including the use of immunohistochemical markers and treatment options based on data from the literature are discussed.


Schneider C, Schlaak M, Bludau M, et al.
68Ga-DOTATATE-PET/CT positive metastatic lymph node in a 69-year-old woman with Merkel cell carcinoma.
Clin Nucl Med. 2012; 37(11):1108-11 [PubMed]
We report the case of a 69-year-old woman with a Merkel cell carcinoma (MCC) in whom subsequent lymph node metastasis was first diagnosed by 68Ga-Dotatate-PET/CT followed by histopathological confirmation. MCC is an extraordinarily rare and aggressive neuroendocrine tumor of dermal origin with a high rate of postoperative recurrence. Owing to its rarity, the diagnosis of MCC remains a significant challenge. In our case, 68Ga-Dotatate-PET/CT proved clinically useful for diagnosing the lymph node metastasis of a MCC.


Sahi H, Koljonen V, Kavola H, et al.
Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cell polyomavirus.
Virchows Arch. 2012; 461(5):553-9 [PubMed]
Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. The recently found Merkel cell polyomavirus (MCV) integrates clonally in the tumour genome, which suggests an important role in the pathogenesis of the disease. Previous small-scale studies have detected anti-apoptotic protein bcl-2 in 80 % of MCC tumours, but its correlation to the prognosis of MCC remains controversial. Our aim was to clarify the correlation of immunohistochemical expression of bcl-2 to MCV presence and MCC prognosis. We analyzed 116 primary MCC specimens with corresponding clinical data by immunohistochemistry for bcl-2. The presence of MCV DNA had been analyzed by quantitative PCR for 108 tumours. The correlations were analyzed statistically. Of the primary MCC samples, 85 % were bcl-2 positive. No significant differences in MCV DNA occurred between the bcl-2-positive and bcl-2-negative tumours. Local and systemic metastasis was more common in patients with bcl-2 negative tumours (33 %) than in patients with bcl-2-positive tumours (12 %; p = 0.04) at the time of diagnosis. The mean overall survival was higher in patients with bcl-2-positive tumours than of those with negative tumours (mean survival 1,814 days (5.0 years) vs. 769 days (2.1 years), p = 0.01). Bcl-2 positivity indicates better clinical stage at the time of diagnosis and a longer survival in MCC.


Song PI, Liang H, Wei WQ, et al.
The clinical profile of Merkel cell carcinoma in mainland China.
Int J Dermatol. 2012; 51(9):1054-9 [PubMed]
BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy, but little is known about the presence or characteristics of MCC in mainland China. A retrospective chart review was conducted to describe the clinical profile of MCC in China.
MATERIALS AND METHODS: At 18 cancer or dermatology hospitals in metropolitan centers from the six geographical regions of mainland China, approximately 3,100,000 pathology database and medical records were searched for cases that had a pathological diagnosis of MCC between 1970 and 2009. A case series was compiled from retrospective chart reviews of identified patients with MCC.
RESULTS: Eight out of 18 participating hospitals reported at least one record of a patient with a pathological diagnosis of MCC, and a total of 22 cases were identified. The median age of patients was 65.5 years, and 59% were female. The median time from the appearance of a lesion to the time of biopsy was six months, and the most common location of lesions was the head and neck. The most common treatment used was surgery alone.
CONCLUSIONS: Merkel cell carcinoma appears to be uncommon in mainland China. Patients in this series are elderly, often had lesions on the head/neck region, and most commonly received surgery alone as treatment. In contrast with MCC in Western countries, the current series' patients were all of Asian ethnicity, had larger lesions at presentation, and none was documented as having HIV or other forms of immunosuppression.


Haws B, St Romain P, Mammen J, Fraga GR
Secondary review of external histopathology on cutaneous oncology patients referred for sentinel lymph node biopsy: how often does it happen and is it worth it?
J Cutan Pathol. 2012; 39(9):844-9 [PubMed]
BACKGROUND: We reviewed the data on external histopathology review for patients referred to our institution for sentinel lymph node biopsy (SLNB) associated with melanoma, Merkel cell carcinoma and adnexal carcinoma.
METHODS: We calculated the incidence of external histopathology review and the rate of discordance between internal and external histopathology diagnoses between January 1, 2010 and February 28, 2011. We conducted an anonymous poll of our community pathologists' experience with external histopathology review prior to SLNB. Financial charges and payments from 10 Medicare patients who underwent SLNB were obtained from our hospital's finance department.
RESULTS: Sixty-eight cases were identified (63 melanomas, 4 Merkel cell carcinomas and 1 spiradenocarcinoma). The external histopathology was reviewed as part of the patient's care in 14 of 68 cases. In 3 of 14 reviewed cases, SLNB was deemed unnecessary. Nine of eleven community pathologists reported reviewing external histopathology material in less than 11% SLNB patients in their hospitals. The average Medicare reimbursement for SLNB and secondary pathology review was $5738 and $80 respectively.
CONCLUSIONS: Our data show that review of external cutaneous histopathology diagnoses on patients referred for SLNB is uncommon in our practice area, but is cost-effective and should be required to reduce unnecessary treatment.


Hall BJ, Pincus LB, Yu SS, et al.
Immunohistochemical prognostication of Merkel cell carcinoma: p63 expression but not polyomavirus status correlates with outcome.
J Cutan Pathol. 2012; 39(10):911-7 [PubMed]
Merkel cell carcinoma (MCC) represents a cutaneous malignancy with high associated mortality. Numerous studies have attempted to define characteristics to more accurately predict outcome. Two recent studies have demonstrated that Merkel cell polyomavirus (MCPyV) seropositivity correlated with a better prognosis, while a third study revealed no difference. Expression of p63 by tumor cell nuclei has been shown to be associated with a worse prognosis in a European cohort. To better understand the relationship between prognosis and MCPyV or p63 status, we used immunohistochemistry to evaluate both attributes in 36 US patients with MCC. Our results show that when considered as a binary variable, p63 expression represents a strong risk factor (p < 0.0001, hazards ratio (HR) = ∞) for shortened survival. In addition, our results show that MCPyV status does not correlate with survival (p = 0.6067, HR = 1.27). Our study corroborates the European observation that p63 immunoexpression is useful as a prognostic tool. Larger studies will need to be performed in order to determine whether p63 status should be included in MCC staging, since our study is limited by its relative small size.


Koba S, Paulson KG, Nagase K, et al.
Diagnostic biopsy does not commonly induce intratumoral CD8 T cell infiltration in Merkel cell carcinoma.
PLoS One. 2012; 7(7):e41465 [PubMed] Article available free on PMC after 05/01/2014
BACKGROUND: Merkel cell carcinoma is a polyomavirus-associated cancer that is strongly linked with T lymphocyte immune suppression in epidemiologic studies. CD8+ T cell infiltration into MCC tumors (intratumoral) has recently been shown to be strongly predictive of improved survival. In contrast, the presence of CD8+ T cells at the border of the tumor (peritumoral) had no independent prognostic value. Spontaneous regression has been reported for MCC approximately one thousand times more often than would be expected given the frequency of this cancer. Many of these events began shortly after biopsy, and in some cases lymphocytic infiltration was described.
METHODOLOGY/PRINCIPAL FINDINGS: To determine whether CD8+ lymphocyte infiltration in MCC tumors is commonly altered by biopsy.33 MCC patients who had microscopic confirmation of MCC on both an initial biopsy and a re-excision specimen were included in this study. Intratumoral and peritumoral CD8 lymphocyte infiltration was quantitated using immunohistochemistry and compared using the paired t-test in biopsy versus re-excision samples. There was a trend toward increased CD8 infiltration after biopsy in a peritumoral ('stalled') pattern (p = 0.08), however, biopsy was not associated with a significant increase in CD8 T cells in the clinically more important intratumoral location (p = 0.58).
CONCLUSIONS/SIGNIFICANCE: The initial diagnostic biopsy for MCC does not commonly alter intratumoral CD8+ T cell infiltration, suggesting it does not directly induce immunologic recognition of this cancer. Because CD8 infiltration is typically stable after biopsy, this parameter may be useful to assess the efficacy of future immune therapies for this virus-associated, immunogenic, often-lethal cancer.


Mevio N, Bertino G, Occhini A, et al.
Electrochemotherapy for the treatment of recurrent head and neck cancers: preliminary results.
Tumori. 2012 May-Jun; 98(3):308-13 [PubMed]
AIMS AND BACKGROUND: Electrochemotherapy is a tumor ablation modality providing delivery into the cell interior of impermeant or poorly permeant chemotherapeutic drugs such as cisplatin and bleomycin. A locally applied electrical field enhances the membrane permeability allowing intracellular accumulation of the chemotherapeutic agent. The aim of the study was to evaluate the effectiveness of ECT for the treatment of a group of patients affected by recurrent of extended primary head and neck cancer and not suitable for standard therapeutic options.
METHODS AND STUDY DESIGN: From April 2009 to January 2011, we treated with electrochemotherapy a total of 15 patients with head and neck cancers, 13 with squamous cell carcinoma, 1 with basaloid carcinoma and 1 with Merkel cell carcinoma. Electrical pulses were delivered to 33 lesions (3 primaries, 30 recurrences) after an intravenous bolus injection of a dose of 15,000 IU/m2 of bleomycin. In 3 cases, the lesion treated was a pathologic lymph node.
RESULTS: Of the 31 lesions assessable for the study, 19 (61.5%) showed a complete response, 10 (32.5%) a partial response, 1 (3%) stable disease and 1 (3%) progression of the disease. The objective response 2 months after the procedure was 94%. All the lesions that underwent complete regression were less than 3 cm in their maximum diameter. The 2 assessable cases of pathologic lymph nodes showed a partial or no response. After a follow-up of 2 to 20 months, 29% of the patients were alive and free of disease, 50% were alive with disease, 14% died for disease and 7% died for other causes.
CONCLUSIONS: Our study confirms the effectiveness of electrochemotherapy in the treatment or local control of recurrent or extended primary head and neck cancer in patients not suitable for standard therapeutic options.


Lim CS, Whalley D, Haydu LE, et al.
Increasing tumor thickness is associated with recurrence and poorer survival in patients with Merkel cell carcinoma.
Ann Surg Oncol. 2012; 19(11):3325-34 [PubMed]
BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor usually occurring on sun-exposed skin in elderly patients. Clinical and pathologic factors associated with disease progression and mortality in patients with MCC are poorly defined. Recently, it has been reported that p63 expression in primary MCC is strongly associated with clinical outcome.
METHODS: MCC patients diagnosed between July 1, 1993 and July 31, 2009 were identified from the surgical pathology records of the Sydney South West Area Health Service. Clinical, pathologic, treatment, and survival data were obtained and immunohistochemical analyses for p53, p63, and Ki-67 were performed. The associations of clinical and pathologic features with disease-free and disease-specific survival were analyzed.
RESULTS: Ninety-five patients were identified (67 males, 28 females; median age at diagnosis of primary MCC 76 [range, 42-93] years). Increasing primary tumor thickness was significantly associated with poorer disease-free survival (5-year survival 18 % in tumors >10 mm thick compared with 69 % for patients with tumors ≤10 mm thick, p = 0.002) and disease-specific survival (5-year survival 74 % in tumors >10 mm thick compared with 97 % for patients with tumors ≤10 mm thick, p = 0.006). There was a strong positive correlation between the Ki-67 index (proportion of Ki-67-positive tumor nuclei) and tumor thickness (r = 0.39, n = 45, p = 0.008). Positive staining for p63 in MCC was infrequent (9 % of primary MCC) and showed no significant association with disease outcome.
CONCLUSIONS: Tumor thickness is significantly associated with disease-free survival in MCC. We recommend that primary tumor thickness be routinely recorded in the pathology reports of patients with primary MCC.


This page last updated: 22nd May 2013
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