The Experts below are selected from a list of 10347 Experts worldwide ranked by ideXlab platform
Steven D Billings - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 20-negative Merkel Cell Carcinoma is infrequently associated with the Merkel Cell polyomavirus
Modern Pathology, 2015Co-Authors: Andrew G Miner, Rajiv M. Patel, Douglas R. Fullen, Deborah A Wilson, Gary W Procop, Eugen C Minca, Paul W Harms, Steven D BillingsAbstract:Merkel Cell Carcinoma is a rare, highly aggressive cutaneous neuroendocrine Carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round Cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in ∼95% of cases. In 2008, Merkel Cell Carcinoma was shown to be associated with a virus now known as Merkel Cell polyomavirus in ∼80% of cases. Prognostic and mechanistic differences between Merkel Cell polyomavirus-positive and Merkel Cell polyomavirus-negative Merkel Cell Carcinoma may exist. There has been the suggestion that CK20-negative Merkel Cell Carcinomas less frequently harbor Merkel Cell polyomavirus, but a systematic investigation for Merkel Cell polyomavirus incidence in CK20-negative Merkel Cell Carcinoma has not been done. To test the hypothesis that Merkel Cell polyomavirus is less frequently associated with CK20-negative Merkel Cell Carcinoma, we investigated 13 CK20-negative Merkel Cell Carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel Cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel Cell polyomavirus. Ten of these (77%) were negative for Merkel Cell polyomavirus and three (23%) were positive for Merkel Cell polyomavirus. Merkel Cell polyomavirus is less common in CK20-negative Merkel Cell Carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel Cell Carcinoma is mechanistically and prognostically unique.
Eric J. Duncavage - One of the best experts on this subject based on the ideXlab platform.
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Retinoblastoma gene mutations detected by whole exome sequencing of Merkel Cell Carcinoma
Modern Pathology, 2014Co-Authors: Patrick J Cimino, Diane H Robirds, Haley J Abel, John D Pfeifer, Sheryl R Tripp, Eric J. DuncavageAbstract:Merkel Cell Carcinoma is a highly aggressive cutaneous neuroendocrine tumor that has been associated with Merkel Cell polyomavirus in up to 80% of cases. Merkel Cell polyomavirus is believed to influence pathogenesis, at least in part, through expression of the large T antigen, which includes a retinoblastoma protein-binding domain. However, there appears to be significant clinical and morphological overlap between polyomavirus-positive and polyomavirus-negative Merkel Cell Carcinoma cases. Although much of the recent focus of Merkel Cell Carcinoma pathogenesis has been on polyomavirus, the pathogenesis of polyomavirus-negative cases is still poorly understood. We hypothesized that there are underlying human somatic mutations that unify Merkel Cell Carcinoma pathogenesis across polyomavirus status, and to investigate we performed whole exome sequencing on five polyomavirus-positive cases and three polyomavirus-negative cases. We found that there were no significant differences in the overall number of single-nucleotide variations, copy number variations, insertion/deletions, and chromosomal rearrangements when comparing polyomavirus-positive to polyomavirus-negative cases. However, we did find that the retinoblastoma pathway genes harbored a high number of mutations in Merkel Cell Carcinoma. Furthermore, the retinoblastoma gene ( RB1 ) was found to have nonsense truncating protein mutations in all three polyomavirus-negative cases; no such mutations were found in the polyomavirus-positive cases. In all eight cases, the retinoblastoma pathway dysregulation was confirmed by immunohistochemistry. Although polyomavirus-positive Merkel Cell Carcinoma is believed to undergo retinoblastoma dysregulation through viral large T antigen expression, our findings demonstrate that somatic mutations in polyomavirus-negative Merkel Cell Carcinoma lead to retinoblastoma dysregulation through an alternative pathway. This novel finding suggests that the retinoblastoma pathway dysregulation leads to an overlapping Merkel Cell Carcinoma phenotype and that oncogenesis occurs through either a polyomavirus-dependent (viral large T antigen expression) or polyomavirus-independent (host somatic mutation) mechanism.
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prevalence of Merkel Cell polyomavirus in Merkel Cell Carcinoma
Modern Pathology, 2009Co-Authors: Eric J. Duncavage, Barbara A Zehnbauer, John D PfeiferAbstract:It has recently been shown that Merkel Cell Carcinoma, a rare and often lethal cutaneous malignancy, frequently harbors a novel clonally integrated polyomavirus aptly named Merkel Cell polyomavirus. We aimed to study the prevalence of Merkel Cell polyomavirus in cases of Merkel Cell Carcinoma, using specimens from formalin-fixed, paraffin-embedded tissue blocks. In our archives we identified 41 cases of Merkel Cell Carcinoma (from 29 different patients). Of these, 20 cases were primary cutaneous tumors, 4 were local recurrences, and 17 were metastases. PCR using two previously published primer sets, LT1 (440 bp amplicon) and LT3 (308 bp amplicon), as well as a novel primer set MCVPS1 (109 bp amplicon), was performed on all cases. Selected PCR products were sequenced to confirm amplicon identity. In addition, the MCVPS1 products were digested with BamH1, yielding an 83 bp product. Amplifiable DNA was recovered in all 41 study cases. The detection rate of Merkel Cell polyomavirus for each of the three primer sets was 22 of 29 patients (76%) for MCVPS1, 12 of 29 (41%) for LT3, and 8 of 29 (28%) for LT1. The variation between primer set detection rates was largely due to poor DNA quality, as supported by poor amplification of the higher molecular weight markers in size control ladder products and the fact that all cases that were positive by LT1 and LT3 were positive by MCVPS1. Our findings provide further evidence to link Merkel Cell polyomavirus with a possible role in the oncogenesis of Merkel Cell Carcinoma. On a more practical level, our paraffin-optimized primer set may be used as an ancillary test to confirm the diagnosis of Merkel Cell Carcinoma in the clinical setting or for screening other rare tumor types for the causative virus, especially those tumor types that are underrepresented in frozen tissue repositories.
Andrew G Miner - One of the best experts on this subject based on the ideXlab platform.
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Cytokeratin 20-negative Merkel Cell Carcinoma is infrequently associated with the Merkel Cell polyomavirus
Modern Pathology, 2015Co-Authors: Andrew G Miner, Rajiv M. Patel, Douglas R. Fullen, Deborah A Wilson, Gary W Procop, Eugen C Minca, Paul W Harms, Steven D BillingsAbstract:Merkel Cell Carcinoma is a rare, highly aggressive cutaneous neuroendocrine Carcinoma most commonly seen in sun-damaged skin. Histologically, the tumor consists of primitive round Cells with fine chromatin and numerous mitoses. Immunohistochemical stains demonstrate expression of neuroendocrine markers. In addition, cytokeratin 20 (CK20) is expressed in ∼95% of cases. In 2008, Merkel Cell Carcinoma was shown to be associated with a virus now known as Merkel Cell polyomavirus in ∼80% of cases. Prognostic and mechanistic differences between Merkel Cell polyomavirus-positive and Merkel Cell polyomavirus-negative Merkel Cell Carcinoma may exist. There has been the suggestion that CK20-negative Merkel Cell Carcinomas less frequently harbor Merkel Cell polyomavirus, but a systematic investigation for Merkel Cell polyomavirus incidence in CK20-negative Merkel Cell Carcinoma has not been done. To test the hypothesis that Merkel Cell polyomavirus is less frequently associated with CK20-negative Merkel Cell Carcinoma, we investigated 13 CK20-negative Merkel Cell Carcinomas from the files of the Cleveland Clinic and the University of Michigan for the virus. The presence or absence of Merkel Cell polyomavirus was determined by quantitative PCR performed for Large T and small T antigens, with sequencing of PCR products to confirm the presence of Merkel Cell polyomavirus. Ten of these (77%) were negative for Merkel Cell polyomavirus and three (23%) were positive for Merkel Cell polyomavirus. Merkel Cell polyomavirus is less common in CK20-negative Merkel Cell Carcinoma. Larger series and clinical follow-up may help to determine whether CK20-negative Merkel Cell Carcinoma is mechanistically and prognostically unique.
Wen-guei Yang - One of the best experts on this subject based on the ideXlab platform.
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Metastatic Merkel Cell Carcinoma in the Rectum: Report of a Case
Diseases of the colon and rectum, 2007Co-Authors: Wen-shih Huang, Paul Y. Lin, I-lin Lee, Chih-chien Chin, Jeng-yi Wang, Wen-guei YangAbstract:Merkel Cell Carcinoma is a rare, aggressive skin malignancy of neuroendocrine origin with predominant occurrence in the elderly males. Approximately 50 percent of patients with Merkel Cell Carcinoma develop distant metastasis at some point during the disease course; hence, Merkel Cell Carcinoma always has a poor prognosis. Distant metastasis has never been disclosed in the rectum to the best of our knowledge. We present a 76-year-old male with clinical manifestation of massive hematochezia and final diagnosis of metastatic Merkel Cell Carcinoma in the rectum. We conclude that radical resection of rectal metastatic Merkel Cell Carcinoma is important in the management strategy of a patient with recurrence and lymph node metastases.
Myron Tanenbaum - One of the best experts on this subject based on the ideXlab platform.
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Management and prognosis of Merkel Cell Carcinoma of the eyelid
Ophthalmology, 2001Co-Authors: George B. Peters, Philip L. Custer, Dale R. Meyer, Jerry A. Shields, Peter A. D. Rubin, Ted H Wojno, Thomas A. Bersani, Myron TanenbaumAbstract:Abstract Objective To evaluate the clinical presentation, treatment, and long-term follow-up of eyelid Merkel Cell Carcinoma. Design Retrospective noncomparative interventional case series. Participants Fourteen patients with primary eyelid Merkel Cell Carcinoma. Methods Cases of Merkel Cell Carcinoma for which long-term follow-up was available were solicited from members of the American Society of Ophthalmic Plastic and Reconstructive Surgery through an on-line e-mail/news group. Main outcome measures Follow-up period, treatment history, presence and type of recurrence, and mortality. Results Average follow-up was 33.4 months. Of the 14 cases identified, only 2 patients (14%) received prophylactic therapy beyond wide surgical excision. Three patients (21%) had recurrences, none of whom initially received prophylactic therapy (i.e., radiation therapy, lymph node dissection, and/or chemotherapy) beyond wide surgical excision. One patient (7%) died of metastatic Merkel Cell Carcinoma. Conclusions Merkel Cell Carcinoma is a rare skin malignancy that occasionally affects the eyelid, with the potential for regional and distant metastasis. Consideration should be given to the use of prophylactic adjunctive therapies beyond wide surgical excision while simultaneously considering the morbidity of these therapies.
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Merkel Cell Carcinoma of the eyelid and periocular tissues
American journal of ophthalmology, 1992Co-Authors: Patrick E. Rubsamen, Myron Tanenbaum, Arthur S. Grove, Edwin GouldAbstract:Five patients had eyelid and periocular Merkel Cell Carcinoma. The tumor was located on the left lower eyelid in two patients, the left upper eyelid in one patient, the right upper eyelid in one patient, and was metastatic to the right outer canthus in one patient. The mean duration of symptoms was approximately four months. The diagnosis of Merkel Cell Carcinoma was not suspected clinically in any of the four primary eyelid cases, but was only established on histopathologic examination of biopsy specimens. Light microscopy disclosed Carcinoma with small primitive Cells in all five tumor biopsy specimens. Immunohistochemical studies showed neuron-specific enolase and keratin and transmission electron microscopy demonstrated neurosecretory granules typical for Merkel Cell Carcinoma. All five patients in this study were treated with wide surgical excision of the eyelid tumors with intraoperative frozen-section monitoring of the margins of resection. The left lower eyelid Merkel Cell Carcinoma spread to the preauricular lymph node in one patient. This patient subsequently died of metastatic Merkel Cell Carcinoma. One patient with metastatic right outer canthus Merkel Cell Carcinoma received radiotherapy (6,550 cGy). Eyelid Merkel Cell Carcinoma has the potential for recurrence and metastatic spread. We recommend lifetime follow-up for patients treated for eyelid Merkel Cell Carcinoma.