Significant overexpression of the Merkel cell polyomavirus (MCPyV) large T antigen in Merkel cell carcinoma.

Feb 2012

Erovic BM, Al Habeeb A, Harris L, Goldstein DP, Ghazarian D, Irish JC.

Source

Department of Otolaryngology-Head and Neck Surgery/Surgical Oncology, University Health Network, Princess Margaret Hospital, Toronto, Ontario, Canada.

Abstract

BACKGROUND:

The purpose of this study was to determine the expression pattern of the Merkel cell polyomavirus (MCPyV) large T-protein antigen in patients with Merkel cell carcinoma.

METHODS:

A tissue microarray (TMA) containing 30 specimens was constructed and stained for the MCPyV large T protein. Immunohistochemical expression was determined semiquantitively and was compared to patients' outcome.

RESULTS:

Nuclear expression of MCPyV large T protein was detected in 29 of 30 specimens (97%). In particular, 60% to 100%, 30% to 60%, and 10% to 30% of tumor cells were positive in 27 specimens (90%), 1 (3%), and 1 (3%), respectively. There was no difference in positivity between primary and metastatic lesions. Clinical data could not be correlated to MCPyV large T-protein expression.

CONCLUSION:

MCPyV large T protein was significantly overexpressed in 97% of all specimens. Although we could not demonstrate a predictive effect, MCPyV large T protein may represent a molecular marker with utility in pathological diagnosis as well as a potential new therapeutic target in patients with Merkel cell carcinoma. .

Wiley Online

Merkel Cell Carcinoma Concurrent with Bowen's Disease.

Feb 2012

Park HC, Kang HS, Park KT, Oh YH, Yu HJ, Kim JS.

Source

Department of Dermatology, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea.

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy of the elderly and immunocompromised patients. It is occasionally found coexisting with other diseases, such as squamous cell carcinoma, basal cell carcinoma, actinic keratosis, miscellaneous adnexal tumors, and rarely Bowen disease. A 75-year-old woman presented with a 6-month history of an irregularly shaped erythematous patch on the left mandibular angle. Three months later, a 1.5×1.0 cm sized painless and rapidly growing erythematous nodule developed on the patch. Microscopically, the patch lesion was consistent with that of Bowen disease. The nodular lesion showed a number of small uniform hyperchromatic cells with scanty cytoplasm. It showed dense small-cell like nodular infiltration in the dermis. Immunohistochemical staining for cytokeratin 20 showed a positive result with a dot-like perinuclear pattern. Additionally, the result for thyroid transcription factor-1 was negative, which is positive in small cell neuroendocrine carcinoma. From these findings, we diagnosed this lesion as MCC concurrent with Bowen disease.

Annals of Dermatology

Merkel cell carcinoma: case report.

Dec 2011

Richardson B, Avshalumova L, Miller R.

Source

University Hospitals Case Medical Center, Cleveland, Ohio, USA. blakely.richardson@uhhospitals.org

Abstract

Merkel cell carcinoma (MCC), also termed cutaneous small cell carcinoma or trabecular carcinoma, is a rare tumor that most often presents as a solitary nodule on the head, neck, or extremities of older adults. It is an aggressive tumor that usually is fatal due to rapid metastasis. Involvement of lymph nodes at presentation can be used to predict survival. Because MCC is sensitive to radiation, it can be used as an adjunct to surgery. We report a case of MCC to alert clinicians of this potentially fatal tumor because early diagnosis and proper treatment may improve patient survival rates.

PubMed

Merkel cell carcinoma.

Swann MH, Yoon J.

Source

Department of Dermatology, University of Missouri-Columbia, Columbia, MO 65212, USA. swann.mike@gmail.com

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous cancer that predominately affects elderly Caucasians with fair skin and has a propensity for local recurrence and regional lymph node metastases. A variety of terms have been used to describe this tumor, including trabecular cell carcinoma, neuroendocrine or primary small cell carcinoma of the skin, and anaplastic cancer of the skin. Although the skin lesion is most commonly found on sun-exposed areas of the head and neck or extremities, it can occur on the trunk, genitalia, and perianal region. The median age is 69 years, but it may occur earlier and more frequently in immunosuppressed patients. Patients with MCC frequently present with a nonspecific erythematous or violaceous firm nodule or small plaque that may be surrounded by small satellite tumors. MCC usually arises in the dermis and extends into the subcutis. It may be difficult to accurately diagnose MCC by light microscopy alone and ancillary techniques, including electron microscopy and immunohistochemistry, may be necessary to make a definitive diagnosis. Management of MCC is dependent on stage of the disease and is hampered by its rarity and lack of randomized trials. Nonetheless, for localized disease most guidelines include wide local excision of the primary tumor either alone or with radiation therapy. Sentinel lymph node biopsy can be helpful in staging and prognosis, but its benefit in survival remains to be seen. Systemic chemotherapy, akin to regimens for small cell carcinoma of the lung, may be considered as an adjuvant following surgery or to treat locoregional or distant disease. The prognosis of MCC is variable. Some patients with localized disease have an indolent course and are well controlled with local excision alone. On the other hand, many tumors are aggressive and have a tendency for locoregional recurrence and distant metastases. Such patients have a grim prognosis with a median survival of 9 months. Successful outcomes are most often seen in patients with early diagnosis and complete excision.

Elsevier

Genetic variability and integration of Merkel cell polyomavirus in Merkel cell carcinoma.

Feb 2012

Martel-Jantin C, Filippone C, Cassar O, Peter M, Tomasic G, Vielh P, Brière J, Petrella T, Aubriot-Lorton MH, Mortier L,Jouvion G, Sastre-Garau X, Robert C, Gessain A.

Source

Unité d'Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France.

Abstract

Merkel cell polyomavirus (MCPyV) is associated to Merkel cell carcinoma (MCC). We studied 113 MCC tumoral skin lesions originating from 97 patients. MCPyV detection was higher in fresh-frozen (FF) biopsies (94%) than in formalin-fixed paraffin-embedded biopsies (39-47%). Mean viral load in FF tumor was of 7.5 copies per cell with a very wide range (0.01-95.4). Nineteen complete sequences of LTAg were obtained, mainly from FF biopsies when the viral load was high. Seventeen showed stop codons, all localized downstream of the pRb protein binding domain. Sequence comparison and phylogenetic analysis showed that all sequences clustered in the large C clade of MCPyV strains. MCPyV integration was demonstrated in 19 out of 27 FF MCC DNA biopsies without evidence of specific host cellular genome integration site. In 13/19 cases, the viral junction was located within the second exon of the LTAg, after the pRB binding domain.

Elsevier Inc.

Primary marginal zone B-cell lymphoma of the larynx.

Jan 2012

Yilmaz M, Ibrahimov M, Mamanov M, Rasidov R, Oktem F.

Source

From the Otolaryngology Head and Neck Surgery Department of Cerrahpaşa Medical School, Istanbul University, Istanbul, Turkey.

ABSTRACT: Extranodal non-Hodgkin lymphomas limited to the larynx are rare, accounting for less than 1% of all laryngeal neoplasms. The most common site of development of primary laryngeal lymphomas is the supraglottic region. In most cases, the presenting symptoms are hoarseness, dysphagia, dyspnea, and cervical lymphadenopathy. In these cases,

larynx lymphoma was the mucosa-associated lymphoid tissue type and located in the supraglottic area.

Lippincott, Williams & Wilkins

OncoSec Initiates Phase II Merkel Cell Carcinoma Study and Doses Several Patients

Feb 13, 2012

AN DIEGO, Feb. 13, 2012 /PRNewswire via COMTEX/ -- OncoSec Medical Incorporated,ONCS +2.86% which is developing its advanced-stage OncoSec Medical System (OMS) ElectroOncology therapies to treat solid tumor cancers, today announced that physicians at the University of Washington and Seattle Cancer Care Alliance in conjunction with the Fred Hutchinson Cancer Center, have treated several patients in an open-label Phase II clinical trial evaluating OncoSec's OMS ElectroImmunotherapy for the treatment of Merkel cell carcinoma (MCC). The clinical trial is designed to test DNA IL-12 administered using OncoSec's novel treatment approach for immunotherapy (referred to as OMS ElectroImmunotherapy), in patients with local and distant Merkel cell carcinoma.

A total of up to 15 patients with local and distant Merkel cell carcinoma will be enrolled in this Phase II, single-arm, open-label, multi-center study. The trial is designed to assess the clinical and biologic effects of increased local expression of IL-12 protein in the tumor microenvironment following treatment with OMS ElectroImmunotherapy. It is anticipated that marked local expression of IL-12 in the tumor will induce an immunologic response in the tumor microenvironment, which may result in clinical benefit for the patient. Investigators at the University of Washington, a world leader in the treatment of Merkel cell carcinoma, have received Investigational Review Board (IRB) approval and will continue recruitment for this clinical trial as the lead enrollment center. Several patients have been enrolled with the first patient successfully completing treatment on January 6, 2012.

"We were impressed by the results of the Phase I study in malignant melanoma patients and strongly believe that OMS ElectroImmunotherapy will be especially effective in an immunogenic cancer such as Merkel cell carcinoma," commented Dr. Shailender Bhatia, principal investigator at the University of Washington. Dr. Paul Nghiem, co-investigator at the Fred Hutchinson cancer center, added, "Our clinical and research teams have been working with Merkel cell carcinoma for many years, and we are delighted that OncoSec is now taking the industry lead in developing a cancer immunotherapy for this deadly disease."

Punit Dhillon, President and CEO of OncoSec, said, "The University of Washington is a leading institution in the treatment and research of Merkel cell carcinoma, and patients with this rare and deadly skin cancer have few treatment options. This new clinical study is the only active immunotherapy trial that is focused specifically on this disease."

OMS ElectroImmunotherapy utilizes OncoSec's proprietary technology to deliver a DNA-based cytokine coded for the immune stimulating agent interleukin-12, or DNA IL-12. The OMS applies short electric impulses to the tumor, causing pores to open in the membrane of cancer cells that significantly increases DNA IL-12 uptake into these cells. Phase I data using OMS ElectroImmunotherapy to treat malignant melanoma demonstrated that this therapy was safe and well tolerated. In addition, 53% of patients with distant metastatic lesions demonstrated an objective response, with 15% of these patients having a complete response to the treatment.

About Merkel Cell Carcinoma

Merkel cell carcinoma is a rare and highly aggressive cancer, with approximately 1,500 new cases each year, in which malignant cancer cells develop on or just beneath the skin and in hair follicles. The majority of Merkel cell carcinomas appear to be caused in part by a virus, Merkel cell polyomavirus. If this cancer metastasizes to the lymph nodes, the five-year survival rate is about 50 percent. A patient with a small tumor (less than 2 cm) that has not metastasized to the lymph nodes may have a five-year survival rate of more than 80 percent. The current treatment options for these patients are surgery, radiation and chemotherapy; however, up to half of patients suffer a recurrence. Rapid advances in the biology of this disease provide a strong rationale for immunotherapy of this virus-associated cancer.

Market Watch

Rising incidence of Merkel cell carcinoma.

Dec 2011

Lyhne D, Lock-Andersen J, Dahlstrøm K, Drzewiecki KT, Balslev E, Muhic A, Krarup-Hansen A.

Source

Department of Plastic Surgery and Burns Unit , Rigshospitalet , Copenhagen.

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive, skin cancer of obscure histogenesis, the incidence of which is rising. There is no consensus on the optimal treatment. Our aim was to evaluate the staging, investigation, treatment, and follow-up of MCC in eastern Denmark, and to investigate the incidence. We suggest guidelines for treatment. First we reviewed the medical records of 51 patients diagnosed with MCC from 1995 until 2006 in eastern Denmark. The nation-wide incidence of MCC was extracted from the Danish Cancer Registry for the calculations for the period 1986-2003. We reviwed published papers about MCC based on a MEDLINE search. Fourteen of the 51 patients developed recurrence, and 37 (73%) died during the study period. Mean follow-up was 13 months (range 1-122). A total of 153 patients were identified in the Danish Cancer Registry, and showed that incidence rates had increased 5.4 fold over the 18 year period from 1986 until 2003. Rates were highest in people over the age of 65. Recommended treatment with curative intent includes excision of the primary tumour with wide margins, excision of the sentinel node, computed tomogram (CT) or positron emission tomography (PET) of the thorax and abdomen, and adjuvant radiotherapy to the surgical bed. In the case of advanced disease, systemic palliative chemotherapy remains a possibility. There is a need for prospective multicentre evaluation of staging investigations and treatment of MCC.

PubMed