Metastatic merkel cell carcinoma in the bone marrow of a patient with plasma cell myeloma and therapy-related myelodysplastic syndrome.

2012

Kressin MK, Kim AS.

Source

Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center Nashville, TN, USA ; Department of Pathology & Laboratory Medicine, Tennessee Valley Healthcare System Veterans Affairs Nashville, TN, USA ; Current address: Austin Pathology Associates 901 W. Ben White Blvd., Austin, TX, USA.

Abstract

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.

PubMed

Merkel cell carcinoma.

Dec 2012

Han SY, North JP, Canavan T, Kim N, Yu SS.

Source

Department of Dermatology, University of California, San Francisco, 1701 Divisadero Street, 3rd Floor, San Francisco, CA 94115, USA.

Abstract

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.

SciVerse

Expression of CXCR4, E-cadherin, Bcl-2, and survivin in merkel cell carcinoma: an immunohistochemical study using a tissue microarray.

Aug 2012

Knapp CF, Sayegh Z, Schell MJ, Rawal B, Ochoa T, Sondak VK, Messina JL.

Source

Department of Dermatology, University of South Florida College of Medicine, Tampa, FL 33612-4272, USA. cknapp@health.usf.edu

Abstract

Merkel cell carcinoma (MCC) is a rare but highly aggressive cutaneous malignancy with a mortality rate exceeding that of melanoma. Although smaller studies of markers of progression have been performed, large-scale investigation has been difficult due to the rarity of this tumor. Investigation of 4 potential immunohistochemical progression markers using an MCC tissue microarray was performed. An immunohistochemical analysis of CXCR4, E-cadherin, Bcl-2, and Survivin was performed on a tissue microarray of two hundred twenty-seven 0.6-mm tumor cores-110 primary, 73 local/regional metastatic, and 44 distant metastatic-from 87 patients, 23 of which were sampled 2 or more times. There was a statistically significant increase in immunoreactivity to CXCR4 and Survivin in local/regional nodal MCC metastases compared with primary and distant metastatic lesions. No significant differences by disease location were found for either Bcl-2 or E-cadherin. These results suggest a potential role for CXCR4 and Survivin in MCC tumor progression. However, previous data from other studies suggesting a role for Bcl-2 and E-cadherin in MCC progression are not confirmed in this larger sample. Further discovery of additional markers are needed to better characterize this rare but deadly malignancy.

Lippincott, Williams & Wilkins

Bcl-2 expression indicates better prognosis of Merkel cell carcinoma regardless of the presence of Merkel cellpolyomavirus.

Nov 2012

Sahi H, Koljonen V, Kavola H, Haglund C, Tukiainen E, Sihto H, Böhling T.

Source

Department of Plastic and Reconstructive Surgery, Helsinki University Hospital, Helsinki, Finland, helka.sahi@helsinki.fi.

Abstract

Merkel cell carcinoma (MCC) is an aggressive dermal tumour of neuroendocrine origin. The recently found Merkel cellpolyomavirus (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.

Springerlink

Detection of Merkel Cell Polyomavirus in the Human Tissues from 41 Japanese Autopsy Cases Using Polymerase Chain Reaction.

Sept 2012

Matsushita M, Kuwamoto S, Iwasaki T, Higaki-Mori H, Yashima S, Kato M, Murakami I, Horie Y, Kitamura Y, Hayashi K.

Source

Division of Molecular Pathology, Department of Pathology, Tottori University Faculty of Medicine, Yonago, Japan.

Abstract

It has recently been shown that approximately 80% of Merkel cell carcinomas harbor a novel polyomavirus named Merkel cellpolyomavirus (MCPyV). MCPyV has been detected in human tissue samples. However, detailed distribution of MCPyV in non-neoplastic Japanese human tissues remains unclear. To address this, we used single or real-time quantitative polymerase chain reaction (PCR) for 41 autopsy cases. PCR revealed MCPyV-DNA in non-neoplastic samples: total, 29/41 (71%); adult, 29/39 (74%); fetus or infant, 0/2; men, 24/28 (86%); women, 5/13 (38%); total human tissues, 66/572 (12%); skin, 8/15 (53%); adrenal gland, 9/33 (27%), and other 16 organs (4-25%). This study first reported the presence of MCPyV-DNA in non-neoplastic tissues of thyroid gland, adrenal gland, spleen, bone marrow, stomach, gallbladder, pancreas, heart, and aorta. PCR revealed that viral load ranged from 0.00026 to 0.22 in all MCPyV-positive tissues compared with Merkel cell carcinoma samples. These detailed PCR data showed higher prevalence of MCPyV infection in Japanese men than women (p = 0.004) and broad distribution of MCPyV with low viral load in more non-neoplastic human tissues than in the previous reports. These data provide valuable insights for further studies of MCPyV infection and MCPyV-related diseases.

Karger

Merkel cell carcinoma: a retrospective study on 48 cases and review of literature.

Sept 2012

Cirillo F, Vismarra M, Cafaro I, Martinotti M.

Source

Department of General Surgery, General Surgery Unit, Rare Hormonal Tumors Group, Surgery of Rare Hormonal Tumors, Azienda Ospedaliera Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona, Italy.

Abstract

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine tumor of the skin. Fourty-eight patients with MCC were observed at the Rare Hormonal Tumors Group of Cremona Hospital, 15 of these with unknown primary site. Due to rarity of Merkel cell carcinoma, clinical experience is generally limited. Data from our series confirm the current recommendations. Wide surgical excision must be associated with radiotherapy also in early stages in order to avoid local relapse and the rapid progression of disease. In advanced stages chemotherapy is the standard despite the short duration of responses and poor quality of life. The data of our series, characterized by a high demand for second opinion, offer some insight about the real rarity of the tumor, the difficulty of managing of disease in our country secondary to a wrong cultural approach to the problem, the indiscriminate use of molecules unnecessary and often expensive, the lack of protocols, and the presence of guidelines often ignored. This results in very poor survival associated with a very low quality of life, requiring to find the right direction towards a correct management of disease.

NIH

Improved detection suggests all Merkel cell carcinomas harbor Merkel polyomavirus.

Nov 2012

Rodig SJ, Cheng J, Wardzala J, Dorosario A, Scanlon JJ, Laga AC, Martinez-Fernandez A, Barletta JA, Bellizzi AM,Sadasivam S, Holloway DT, Cooper DJ, Kupper TS, Wang LC, Decaprio JA.

Abstract

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.

PubMed