The Etiology and Epidemiology of Merkel Cell Carcinoma

Agelli, Maria; Clegg, Limin X.; Becker, Jürgen C.; Rollison, Dana E.

doi:10.1016/j.currproblcancer.2010.01.001

Cited by 156 publications

(109 citation statements)

References 115 publications

(137 reference statements)

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“…1 The incidence of Merkel cell carcinoma has increased in the last several decades, and the United States has an estimated incidence rate of 0.32 per 100 000 persons per year. 2 Merkel cell carcinoma has a predilection for sun exposed areas, most often occurring in the head and neck region. 3 There is an overall 5-year survival rate of 40%, with stage being a significant prognosticator.…”

mentioning

confidence: 99%

Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma

et al. 2014

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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 polyomaviruspositive 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 polyomavirusdependent (viral large T antigen expression) or polyomavirus-independent (host somatic mutation) mechanism. Modern Pathology (2014) 27, 1073-1087; doi:10.1038/modpathol.2013.235; published online 10 January 2014Keywords: Merkel cell carcinoma; retinoblastoma; whole exome sequencing; polyomavirus Merkel cell carcinoma is a rare neuroendocrine tumor of the skin with an aggressive clinical course and an increased prevalence in the elderly and immunosuppressed. 1 The incidence of Merkel cell carcinoma has increased in the last several decades, and the United States has an estimated incidence rate of 0.32 per 100 000 persons per year. 2 Merkel cell carcinoma has a predilection for sun exposed areas, most often occurring in the head and neck region. 3 There is an overall 5-year survival rate of 40%, with stage being a significant prognosticator. 3,4 Merkel cell polyomavirus was discovered in Merkel cell carcinoma and found to be clonally integ...

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Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma

et al. 2014

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“…Ekstremite yerleşimliler daha sınırlı hastalık ile ilişkili iken diğer bölgeler, örneğin gövde yerleşimlilerde uzak metastaz bulunmaktadır. [7] Tanı anında hastaların %50'sinde hastalık lokalizedir ve lokalize hastalıklarda 5 yıllık sağkalım %75 iken uzak metastaz bulunan hastalarda bu oran %25 'tir. [8] Olguların yaklaşık %40'ında eşlik eden Bowen hastalığı veya SHK bulunmaktadır.…”

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Mixed Merkel cell carcinoma and squamous cell carcinoma: case report

Süren¹,

Elal²,

Yıldırım³

et al. 2013

J Kartal TR

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GirişMerkel hücreli karsinom (MHK) derinin küçük hücre-li karsinomu olarak da bilinen malign kutanöz nöro-endokrin bir tümördür. Nadiren görülmekle birlikte genellikle ileri yaşlarda ve güneşe daha fazla maruz kalan baş-boyun bölgesinde ortaya çıkar.[1] Diğer malign deri hastalıkları ile ilişkili olabileceği bilinmektedir.Literatürde bazal hücreli karsinom, in-situ veya invaziv skuamöz hücreli karsinom (SHK) ve malign melanom ile senkron veya metakron olarak görülebilen olgular bildirilmiştir.[1] Klinik seyri oldukça agresif olan bu tü-mörün tanısını koymak her zaman kolay değildir.Bu yazıda, nadir görülmesi nedeniyle mikst MHK ve SHK tanılı olgu güncel literatür eşliğinde tartışıldı. ÖzetMerkel hücreli karsinom derinin küçük hücreli karsinomu olarak da bilinen malign kutanöz nöroendokrin bir tümör-dür. Seyrek tanı alan bu kanserin yüksek lokal nüks, böl-gesel lenf nodu metastazı ve uzak metastaz eğilimi yanı sıra mortalite oranı da yüksektir. Bu sebeplerden dolayı immünohistokimyasal çalışmalar ile kesin olarak tanın-ması veya tanının dışlanması gereklidir. Bu yazıda nadir görülmesi nedeniyle mikst Merkel hücreli karsinom ve skuamöz hücreli karsinom tanılı olgu güncel literatür eş-liğinde tartışıldı.

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“…There are several other risk factors associated with MCC: immunosuppression, history of organ transplantation, and Merkel cell polyomavirus infection. 1,9,15 Furthermore, there appears to be an advanced age predilection as the mean age for initial diagnosis for men is 73 years and 76 years for women. 2 Clinically, MCC presents as a persistent asymptomatic red/pink shaped nodule, and less frequently as blue/violaceous.…”

Section: Introductionmentioning

confidence: 99%

“…28 An inherently aggressive disease, MCC is biologically characterized by high incidence of local recurrence, distant metastases, regional nodal metastases, and high mortality. 1,17 These factors in combination with often delayed presentation make MCC a challenge to control. It is believed to arise from the Merkel's cell, first described by Friedrich Sigmund Merkel, a histopathologist, in 1875 as Tastzellen (touch cells).…”

Section: Introductionmentioning

confidence: 99%

Merkel Cell Carcinoma of the Hand

Westerveld

Hall

Richards

2016

Hand (New York, N,Y.)

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Background: Merkel cell carcinoma (MCC) is a relatively rare and aggressive cutaneous neuroendocrine malignancy characterized by high incidence of local recurrence, distant metastases, regional nodal metastases, and high mortality. Clinically, MCC presents as a persistent asymptomatic red/pink shaped nodule, usually smaller than 2 cm with nontender intracutaneous swelling, with rapidly growing localized disease with lymph node metastases preceding distant metastases. Because of its rare nature and the lack of comprehensive understanding of the disease, management of MCC has been controversial. Methods: An 87-year-old retired Caucasian male with a history of tobacco use, chronic sun exposure, and multiple squamous and basal cell carcinomas presented with a 1.8 × 1.3 cm red, nontender nodule on the dorsum of the proximal phalanx of the left long finger first noticed 6 months prior to presentation. Biopsy was consistent with MCC after which he was treated with wide local excision, full-thickness skin grafting, and sentinel lymphadenectomy (1/4 nodes positive) followed by adjuvant radiation therapy. Results: He recovered appropriately and was clinically and radiographically disease free at 2.5-year follow-up. Conclusion: Although it remains rare, MCC has increased in incidence over the last several decades and has a predilection to occur over sun exposed areas. Highly aggressive, it has a high incidence of regional and distant metastasis as well as local recurrence. As a result, it is important that practitioners involved in the care of skin and hand lesions be aware of this condition and the need for a multidisciplinary treatment approach.

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The Etiology and Epidemiology of Merkel Cell Carcinoma

Cited by 156 publications

References 115 publications

Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma

Retinoblastoma gene mutations detected by whole exome sequencing of Merkel cell carcinoma

Mixed Merkel cell carcinoma and squamous cell carcinoma: case report

Merkel Cell Carcinoma of the Hand

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