Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus DNAs and antibodies in blood among the elderly

Merkel cell polyomavirus and trichodysplasia spinulosa-associated polyomavirus DNAs and antibodies in blood among the elderly

Merkel cell polyomavirus (MCPyV) and trichodysplasia spinulosa-associated polyomavirus (TSPyV) are recently found pathogens causing two rare skin disorders, Merkel cell carcinoma (MCC) and trichodysplasia spinulosa (TS). MCC is proportionally common in the elderly and most often is associated with immunosuppression.

TS is a folliculocentric infection seen in patients in an immunocompromised state. Little or no baseline information exists, however, on the prevalences of these two viruses among the elderly.

Epidemiologic data on this population could help in understanding their natural biology. We wished to determine the occurrences and blood levels of MCPyV and TSPyV DNAs among the elderly and any association between the prevalences of their corresponding antiviral IgG antibodies. 

Methods: From 394 hospitalized elderly individuals (age >=65 years) with respiratory symptoms, cardiovascular, and other diseases, we studied 621 serum samples by four different real-time quantitative (q) PCRs, two for the DNAs of MCPyV and two for TSPyV.

The IgG antibodies for both viruses among 481 serum samples of 326 subjects were measured with enzyme immunoassays (EIAs), using as antigen recombinant virus-like particles (VLPs). 

Results: Of the 394 patients, 39 (9.9%) were positive at least once for MCPyV DNA by the LT PCR, and 33 (8.4%) by the VP1 PCR, while 6 (1.5%) were positive by both PCR assays. In general, the viral DNA copy numbers were low.

In sharp contrast, no TSPyV DNA was detectable with qPCRs for the corresponding genomic regions. The IgG seroprevalence of MCPyV was 59.6% and of TSPyV, 67.3%. 

Conclusions: MCPyV DNA, unlike TSPyV DNA, occurs in low copy number in serum samples from a notable proportion of aging individuals.

Whether this reflects enhanced viral replication possibly due to waning immune surveillance, and is associated with increased MCC risk, deserves exploration.

Author: Mohammadreza SadeghiMatti AronenTingting ChenLaura JarttiTuomas JarttiOlli RuuskanenMaria Söderlund-VenermoKlaus Hedman
Credits/Source: BMC Infectious Diseases 2012, 12:383

7th Space

Merkel cell carcinoma arising in a patient with a history of multiple malignancies.

Oct 2012

Stevenson ML, Saggar S, Amin B, Mann RE.

Source

Department of Dermatology, Columbia University School of Physicians and Surgeons, New York, New York, USA. marylstevenson@gmail.com

Abstract

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.

PubMed

Metastatic Merkel cell carcinoma of the oral cavity in a human immunodeficiency virus-positive patient and the detection of Merkel cell polyomavirus

Dec 2011

Li M, Saghafi N, Freymiller E, Basile JR, Lin YL.

Source

Division of Diagnostic and Surgical Sciences, School of Dentistry, University of California, Los Angeles, California.

Abstract

The etiology of Merkel cell carcinoma (MCC) was recently linked to a newly identified human virus, the Merkel cellpolyomavirus (MCPyV). The discovery that MCPyV plays an important role in the tumorigenesis of >80% of MCCs provides an explanation for the increased incidence of this rare malignancy in human immunodeficiency virus (HIV)-positive and immunocompromised patients. We report an unusual metastasis of MCC to the mandibular gingiva of an HIV-positive patient. In addition to routine hematoxylin-eosin and immunohistochemical studies, we also performed a molecular biologic analysis to look for the presence of MCPyV in this case. We detected evidence of the MCPyV genome in this lesion similar to what has been observed for MCCs reported in other immunocompromised patients. These results stress the importance of combining morphologic and molecular biologic analyses in the evaluation of MCC, because confirmation of viral etiology would likely affect the choice of treatment and prognosis when specific antiviral therapy becomes available for this aggressive tumor

Science Direct.

Sarcoid reaction associated with Merkel cell carcinoma revealed by fluorodeoxyglucose positron emission tomography: a case report

2011

Yuko Higashi,¹ Kentaro Mera,¹ Mitsuyoshi Shimokawa,¹ Mitsuhiro Hisadome,¹ Atsunori Baba,¹Shigeto Matsushita,¹ Masakazu Yanagi,² and Takuro Kanekura¹

^Abstract

Introduction

Although the association between cancer and sarcoidosis  or sarcoid reaction is known, sarcoid reaction associated with Merkel cell carcinoma is rare.

Case presentation

We report the case of a 57-year-old Japanese woman with Merkel cell carcinoma in the inguinal area associated with sarcoid reaction. Fluorodeoxyglucose positron emission tomography demonstrated elevated fluorodeoxyglucose uptake by mediastinal lymph nodes and at the carcinoma site. Histopathologically, the mediastinal lymph nodes contained no Merkel cell carcinoma components. Sarcoid lesions were identified. Systemic examinations returned no sarcoidosis-specific findings.

Conclusion

Fluorodeoxyglucose positron emission tomographic scans can be used to assess neoplastic lesions and depict sarcoidosis. Sarcoid reactions must be considered in the interpretation of fluorodeoxyglucose positron emission tomographic scans.

NCBI-NIH

A review of radiotherapy for merkel cell carcinoma of the head and neck.

2012

Lee J, Poon I, Balogh J, Tsao M, Barnes E.

Source

Odette Cancer Centre, Sunnybrook Health Sciences Centre, Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.

Abstract

Merkel cell carcinoma of the head and neck (MCCHN) presents a clinical challenge due to its aggressive natural history, unpredictable lymphatic drainage, and high degree of treatment related morbidity. Histological examination of the regional lymph nodes is very important in determining the optimal treatment and is usually achieved by sentinel lymph node biopsy. Radiotherapy plays a critical role in the treatment of most patients with MCCHN. Surgery with adjuvant radiotherapy to the primary tumour site is associated with high local control rates. If lymph nodes are clinically or microscopically positive, adjuvant radiotherapy is indicated to decrease the risk of regional recurrence. The majority of locoregional recurrences occur at the edge or just outside of the radiation field, reflecting both the inherent radiosensitivity of MCC and the importance of relatively large volumes to include "in-transit" dermal lymphatic pathways. When surgical excision of the primary or nodal disease is not feasible, primary radiotherapy alone should be considered as a potentially curative modality and confers good loco-regional control. Concurrent chemoradiotherapy is well tolerated and may further improve outcomes. 

Full text article

PubMed - Journal of Skin Cancer

Merkel cell polyomavirus: A newly discovered human virus with oncogenic potential.

Jan 2013

Spurgeon ME, Lambert PF.

Source

Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin School of Medicine and Public Health, 1400 University Ave. Madison, WI 53706, USA.

Abstract

Keywords:

• DNA tumor virus; 
• Merkel; 
• Tumor antigen; 
• Merkel cell polyomavirus; 
• MCV; 
• MCPyV; 
• Polyomavirus; 
• Merkel cell carcinoma

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.

Elsevier - Scielo

Tumor-infiltrating lymphocytes and outcome in Merkel cell carcinoma, a virus-associated cancer.

Nov 2012 

Sihto H, Joensuu H.

Source

Laboratory of Molecular Oncology and Molecular Cancer Biology Program; University of Helsinki; Helsinki, Finland.

Abstract

Keywords: Merkel cell carcinoma, Merkel cell polyomavirus, cytotoxic T cells, survival, tumor-infiltrating lymphocytes

An intense immune infiltrate, enriched in T cells, is associated with the presence of Merkel cell polyomavirus (MCPyV) DNA in Merkel cell carcinoma (MCC), a rare skin cancer. High tumor-infiltrating T-cell counts are associated with favorable survival regardless of the tumor MCPyV status. Hence, boosting host immune functions might constitute a new approach for the treatment of MCC.

Full text article with images:

NCBI-NLM

The Merkel cell carcinoma challenge: A review from the fine needle aspiration service.

Dec 2012

Bechert CJ, Schnadig V, Nawgiri R.

Source

Division of Cytopathology, University of Texas Medical Branch, Galveston, Texas.

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin that occurs primarily in elderly or immunocompromised patients. For this report, the authors reviewed the diagnostic challenges associated with MCC encountered on their fine-needle aspiration (FNA) service and also conducted an in-depth review of the literature on MCC. A computer search for patients who were diagnosed with MCC by FNA at the authors' institution from 2006 to 2010 was conducted, and 5 patients were selected for cytologic and immunochemical analyses based on their varied and diagnostically challenging clinical presentations. The 5 selected patients had clinical findings commonly associated with MCC, including advanced age (4 of the 5 patients were ages 75-85 years) and a history of previous malignancies (3 of the 5 patients had a history of previous malignancy), and 1 patient was diagnosed with a concomitant low-grade lymphoma. The patients and their disease illustrated the protean clinical presentation of MCC and the clinical and cytologic challenges associated with this neoplasm. The current findings indicate the need for cytopathologists to be aware of the deceptive presentation of this neoplasm and its cytologic and immunochemical features to correctly diagnose this insidious neoplasm.

Wiley Online

Additional Information:

Small Needle Biopsy (fine needle aspiration)

Merkel cell carcinoma with lymph node metastasis in the absence of a primary site: Case report and literature review.

Dec 2012

Zhao M, Meng MB.

Source

Tianjin University of Traditional Chinese Medicine; ; Tianjin Tasly Co. Ltd.;

Abstract 

Merkel cell carcinoma (MCC) is a rare malignant skin neoplasm with the potential for local recurrence, spreading to regional lymph nodes (LNs) and distant metastases. Although it has been identified in various anatomical sites, LN metastatic MCC in the absence of a primary site is extremely rare. The present case reports a 54-year-old male who initially underwent histological examination of a biopsy specimen from the right inguinal LNs. A diagnosis of metastatic small cell carcinoma was made. Nine months later, this diagnosis was changed to MCC with multiple metastases following observation of a tumour mass in the right dorsal thigh. Additionally, in the present study a summary is provided of 23 published cases of MCC with initial LN metastasis in the absence of a primary site, with details of clinical characteristics, natural history and pertinent therapy of this uncommon tumour. The present patient with LN metastatic MCC in the absence of a primary site and the other reported cases demonstrate that although multimodal treatment with surgery, radiotherapy (RT) and chemotherapy provides excellent local control, local recurrence and distant metastases commonly develop in this uncommon tumour. LN metastatic MCC in the absence of a primary site is a highly malignant disease and the role of adjuvant postoperative RT and/or chemotherapy remains to be fully determined.

PubMed