Merkel cell carcinoma demographics, morphology, and survival based on 3870 cases: a population based study.
J Cutan Pathol. 2009 Jul 21
Albores-Saavedra J, Batich K, Chable-Montero F, Sagy N, Schwartz AM, Henson DE.
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City.
Correspondence to Jorge Albores-Saavedra, MD, Department of Pathology, Instituto Nacional de Ciencias Medicas y Nutricion, Vasco de Quiroga 15, Col. Seccion XVI, Salvador Zubiran, Mexico City Tlalpan, CP 14000, MexicoTel: + 52 55 548 70900Fax: + 52 55 548 53489e-mail:alboresjorge@yahoo.com
Background: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor arising predominantly on sun-exposed skin of older and usually immunosuppressed individuals.
Methods: Using data from NCI's SEER (Surveillance, Epidemiology, and End Results) Program from 1973 to 2006, we analyzed the demographics and survival of MCC.
Results: SEER had recorded 3870 cases of MCC. The incidence was higher in men (2380 cases, 61.5%) than in women (1490 cases, 38.5%). Most patients were White (94.9%) between 60 and 85 years of age. MCC was rare in Blacks. The most common location was the head and neck. The salivary glands, nasal cavity, lip, lymph nodes, vulva, vagina and esophagus were the most common extracutaneous sites. The 10-year relative survival rate was higher in women than men (64.8% vs. 50.5%, p <>
Conclusions: MCC arises predominantly in the skin of head and neck in White men above 70 years of age. Cases also occurred in extracutaneous sites. Age did not predict survival, yet gender, site and tumor size revealed clear differences. The most significant predictor of survival was tumor stage.
Wiley InterScience
Monday, September 21, 2009
Thursday, September 17, 2009
Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
Quantitation of human seroresponsiveness to Merkel cell polyomavirus.
PLoS Pathog. 2009 Sep
PLoS Pathog. 2009 Sep
Pastrana DV, Tolstov YL, Becker JC, Moore PS, Chang Y, Buck CB.
Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, USA.
Merkel cell carcinoma (MCC) is a relatively uncommon but highly lethal form of skin cancer. A majority of MCC tumors carry DNA sequences derived from a newly identified virus called Merkel cell polyomavirus (MCV or MCPyV), a candidate etiologic agent underlying the development of MCC. To further investigate the role of MCV infection in the development of MCC, we developed a reporter vector-based neutralization assay to quantitate MCV-specific serum antibody responses in human subjects. Our results showed that 21 MCC patients whose tumors harbored MCV DNA all displayed vigorous MCV-specific antibody responses. Although 88% (42/48) of adult subjects without MCC were MCV seropositive, the geometric mean titer of the control group was 59-fold lower than the MCC patient group (p less then 0.0001). protein, Only 4% (2/48) of control subjects displayed neutralizing titers greater than the mean titer of the MCV-positive MCC patient population. MCC tumors were found not to express detectable amounts of MCV VP1 capsid protein, suggesting that the strong humoral responses observed in MCC patients were primed by an unusually immunogenic MCV infection, and not by viral antigen expressed by the MCC tumor itself. The occurrence of highly immunogenic MCV infection in MCC patients is unlikely to reflect a failure to control polyomavirus infections in general, as seroreactivity to BK polyomavirus was similar among MCC patients and control subjects. The results support the concept that MCV infection is a causative factor in the development of most cases of MCC. Although MCC tumorigenesis can evidently proceed in the face of effective MCV-specific antibody responses, a small pilot animal immunization study revealed that a candidate vaccine based on MCV virus-like particles (VLPs) elicits antibody responses that robustly neutralize MCV reporter vectors in vitro. This suggests that a VLP-based vaccine could be effective for preventing the initial establishment of MCV infection.
The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.
The Interdisciplinary Treatment of Merkel Cell Carcinoma: A Retrospective Case Analysis and Review of the Current Literature.
Zentralbl Chir. 2009 Sept
Strub B, Weindel S, Witt P, Grünert J.
Klinik für Hand-, Plastische und Wiederherstellungschirurgie Kantonsspital St. Gallen, Schweiz.
BACKGROUND: Merkel cell carcinoma is a rare, -aggressive, neuroendocrine malignancy of the skin. Over the period from June 2005 to January 2007 (18 months) 7 Merkel cell carcinomas in different tumour stages and localisations were -treated in our department for hand, plastic and reconstructive surgery. Given an incidence rate of approximately 0.1-0.4 per 100 000 habitants, this accumulation of cases is considerably higher than would be statistically expected. This led us to analyse our cases retrospectively and provided the opportunity to discuss the treatment modalities on the basis of the current literature.
PATIENTS AND METHODS: All patients were referred to our clinic after incomplete tumour excision and histopathological diagnosis elsewhere, for fur-ther surgical treatment. Two female and 5 male patients, aged 63 to 83 years, were treated. The patients' data were collected and analysed retrospectively.
RESULTS: In all cases an R0 resection could be achieved, with safety resection margins between 1.5 cm and 4.5 cm. The reconstruction of the resulting defects was achieved by skin transplants in six cases and a primary suture in one case. All patients received adjuvant radiotherapy. Furthermore, three patients received adjuvant chemotherapy due to metastases of the progressed Merkel cell carcinoma. Three patients remained free of recurrence and in two patients a progression of the tumour disease could be impeded, whilst two patients succumbed to their disease.
CONCLUSIONS: In the case of an early diagnosis, an R0 resection can usually be achieved. A safety -resection margin of a minimum of 1.5 cm in the face and 3 cm for localisation on the extremities should be obtained. To reduce the local recurrence rate, adjuvant radiotherapy should be conducted. The benefit from chemotherapy still -remains unclear. © Georg Thieme Verlag Stuttgart ˙ New York.
PubMed
Zentralbl Chir. 2009 Sept
Strub B, Weindel S, Witt P, Grünert J.
Klinik für Hand-, Plastische und Wiederherstellungschirurgie Kantonsspital St. Gallen, Schweiz.
BACKGROUND: Merkel cell carcinoma is a rare, -aggressive, neuroendocrine malignancy of the skin. Over the period from June 2005 to January 2007 (18 months) 7 Merkel cell carcinomas in different tumour stages and localisations were -treated in our department for hand, plastic and reconstructive surgery. Given an incidence rate of approximately 0.1-0.4 per 100 000 habitants, this accumulation of cases is considerably higher than would be statistically expected. This led us to analyse our cases retrospectively and provided the opportunity to discuss the treatment modalities on the basis of the current literature.
PATIENTS AND METHODS: All patients were referred to our clinic after incomplete tumour excision and histopathological diagnosis elsewhere, for fur-ther surgical treatment. Two female and 5 male patients, aged 63 to 83 years, were treated. The patients' data were collected and analysed retrospectively.
RESULTS: In all cases an R0 resection could be achieved, with safety resection margins between 1.5 cm and 4.5 cm. The reconstruction of the resulting defects was achieved by skin transplants in six cases and a primary suture in one case. All patients received adjuvant radiotherapy. Furthermore, three patients received adjuvant chemotherapy due to metastases of the progressed Merkel cell carcinoma. Three patients remained free of recurrence and in two patients a progression of the tumour disease could be impeded, whilst two patients succumbed to their disease.
CONCLUSIONS: In the case of an early diagnosis, an R0 resection can usually be achieved. A safety -resection margin of a minimum of 1.5 cm in the face and 3 cm for localisation on the extremities should be obtained. To reduce the local recurrence rate, adjuvant radiotherapy should be conducted. The benefit from chemotherapy still -remains unclear. © Georg Thieme Verlag Stuttgart ˙ New York.
PubMed
Monday, June 8, 2009
Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.
Detection of Merkel cell polyomavirus DNA in Merkel cell carcinomas.
Br J Dermatol. 2009 May
Varga E, Kiss M, Szabó K, Kemény L.
Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary.
Background Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology. Objectives To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms. Methods Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis. Results The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA. Conclusions Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.
WileyInterScience
Br J Dermatol. 2009 May
Varga E, Kiss M, Szabó K, Kemény L.
Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, H-6720 Szeged, Hungary.
Background Merkel cell carcinoma (MCC) is a rare, aggressive tumour for which an increasing incidence has been reported. A new human polyomavirus, Merkel cell polyomavirus (MCV), was recently isolated from these tumours by applying digital transcriptome subtraction methodology. Objectives To detect the presence or absence of MCV in MCCs and other, randomly selected neoplasms. Methods Nine primary or recurrent MCCs from seven patients were examined; 29 other tumours (squamous cell, basal cell and basosquamous carcinomas and malignant melanomas) were examined for comparative purposes. Viral large T protein (LT1 and LT3), and viral capsid protein (VP1) were detected by primer-directed amplification, using a polymerase chain reaction (PCR)-based method, and the amplified PCR products were analysed by agarose gel electrophoresis and subsequent sequence analysis. Results The presence of viral T antigen and/or viral capsid DNA sequences was demonstrated in seven of the eight MCC lesions. None of the comparative samples contained MCV DNA. Conclusions Our findings strongly support the hypothesis that MCV infection may well be specific for MCC, and MCV may play a role in the pathogenesis of MCC.
WileyInterScience
Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
Human Merkel cell polyomavirus infection I. MCV T antigen expression in Merkel cell carcinoma, lymphoid tissues and lymphoid tumors.
Int J Cancer. 2009 Apr
Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, Tolstov Y, Gjoerup O, Mansukhani MM, Swerdlow SH, Chaudhary PM, Kirkwood JM, Nalesnik MA, Kant JA, Weiss LM, Moore PS, Chang Y.
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in approximately 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.
PubMed
Int J Cancer. 2009 Apr
Shuda M, Arora R, Kwun HJ, Feng H, Sarid R, Fernández-Figueras MT, Tolstov Y, Gjoerup O, Mansukhani MM, Swerdlow SH, Chaudhary PM, Kirkwood JM, Nalesnik MA, Kant JA, Weiss LM, Moore PS, Chang Y.
Molecular Virology Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA.
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in approximately 80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8-14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV.
PubMed
Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.
Human Merkel cell polyomavirus infection II. MCV is a common human infection that can be detected by conformational capsid epitope immunoassays.
Int J Cancer. 2009 Apr
Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS.
Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA.
Merkel cell polyomavirus (MCV) is a newly-discovered human tumor virus found in approximately 80% of Merkel cell carcinoma (MCC). The rate of MCV infection among persons without MCC is unknown. We developed a MCV virus-like particle (VLP) enzyme-linked immunoassay (EIA) that does not cross-react with human BK or murine polyomaviruses. Peptide mapping of the MCV VP1 gene and immunoblotting with denatured MCV VLP are less sensitive than the MCV EIA in detecting MCV antibodies suggesting antibody reactivity in this assay primarily targets conformational but not linear epitopes. Among MCC patients, all 21 (100%) patients tested with MCV-positive tumors had high serum MCV IgG but not high MCV IgM levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were positive for MCV antibodies. Sera from most adults, including 107 of 166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50 (74%) systemic lupus erythematosus patients, show evidence for prior MCV exposure. Age-specific MCV prevalence was determined by examining a cross-sectional distribution of 150 Langerhans cell histiocytosis (an unrelated neoplasm) patient sera. MCV prevalence increases from 50% among children age 15 years or younger to 80% among persons older than 50 years. We did not find evidence for vertical transmission among infants. Although past exposure to MCV is common among all adult groups, MCC patients have a markedly elevated MCV IgG response compared with control patients. Our study demonstrates that MCV is a widespread but previously unrecognized human infection.
Wiley InterScience
Int J Cancer. 2009 Apr
Tolstov YL, Pastrana DV, Feng H, Becker JC, Jenkins FJ, Moschos S, Chang Y, Buck CB, Moore PS.
Molecular Virology Program, University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA.
Merkel cell polyomavirus (MCV) is a newly-discovered human tumor virus found in approximately 80% of Merkel cell carcinoma (MCC). The rate of MCV infection among persons without MCC is unknown. We developed a MCV virus-like particle (VLP) enzyme-linked immunoassay (EIA) that does not cross-react with human BK or murine polyomaviruses. Peptide mapping of the MCV VP1 gene and immunoblotting with denatured MCV VLP are less sensitive than the MCV EIA in detecting MCV antibodies suggesting antibody reactivity in this assay primarily targets conformational but not linear epitopes. Among MCC patients, all 21 (100%) patients tested with MCV-positive tumors had high serum MCV IgG but not high MCV IgM levels. Only 3 of 6 (50%) MCC patients with MCV-negative tumors were positive for MCV antibodies. Sera from most adults, including 107 of 166 (64%) blood donors, 63 of 100 (63%) commercial donors and 37 of 50 (74%) systemic lupus erythematosus patients, show evidence for prior MCV exposure. Age-specific MCV prevalence was determined by examining a cross-sectional distribution of 150 Langerhans cell histiocytosis (an unrelated neoplasm) patient sera. MCV prevalence increases from 50% among children age 15 years or younger to 80% among persons older than 50 years. We did not find evidence for vertical transmission among infants. Although past exposure to MCV is common among all adult groups, MCC patients have a markedly elevated MCV IgG response compared with control patients. Our study demonstrates that MCV is a widespread but previously unrecognized human infection.
Wiley InterScience
Tuesday, May 19, 2009
Molecular pathogenesis of Merkel cell carcinoma
Molecular pathogenesis of Merkel cell carcinoma
Exp Dermatol. 2009 Mar
Houben R, Schrama D, Becker JC.
Department of Dermatology, Julius Maximilians University, Würzburg, Germany.
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer which is twice as lethal as melanoma as more than one-third of MCC patients will die from this cancer. Although MCC, which primarily affects elderly and immune suppressed individuals, is very rare to date, its incidence is rapidly increasing. In contrast to the immense progress that has been made in the elucidation of the molecular pathogenesis of other cancer entities, until recently there were no clear-cut indications which events drive the carcinogenesis of MCC. Important findings published last year have changed this radically. Hypermethylation of the p14(ARF) promoter and a striking correlation between expression of p63 and the clinical course of MCC have been reported. Most important, however, is the discovery that MCC development in the majority of cases is preceded by the integration of genomic sequences of the hitherto unknown Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the understanding of MCC pathogenesis as well as the development of new therapeutic approaches based on this knowledge appear to be possible within the near future.
Wiley/InterScience
Exp Dermatol. 2009 Mar
Houben R, Schrama D, Becker JC.
Department of Dermatology, Julius Maximilians University, Würzburg, Germany.
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine skin cancer which is twice as lethal as melanoma as more than one-third of MCC patients will die from this cancer. Although MCC, which primarily affects elderly and immune suppressed individuals, is very rare to date, its incidence is rapidly increasing. In contrast to the immense progress that has been made in the elucidation of the molecular pathogenesis of other cancer entities, until recently there were no clear-cut indications which events drive the carcinogenesis of MCC. Important findings published last year have changed this radically. Hypermethylation of the p14(ARF) promoter and a striking correlation between expression of p63 and the clinical course of MCC have been reported. Most important, however, is the discovery that MCC development in the majority of cases is preceded by the integration of genomic sequences of the hitherto unknown Merkel cell polyomavirus (MCPyV). Now a fundamental improvement in the understanding of MCC pathogenesis as well as the development of new therapeutic approaches based on this knowledge appear to be possible within the near future.
Wiley/InterScience
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