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

Merkel Cell Carcinoma of Unknown Primary Origin.

Jan 2012

Deneve JL, Messina JL, Marzban SS, Gonzalez RJ, Walls BM, Fisher KJ, Ann Chen Y, Wayne Cruse C, Sondak VK, Zager JS.

Source

Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Abstract

BACKGROUND:

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. MCC from an unknown primary origin (MCCUP) can present a diagnostic and therapeutic challenge. We describe our single-institution experience with the diagnosis and management of MCCUP presenting as metastases to lymph nodes.

METHODS:

After institutional review board approval, our institutional database spanning the years 1998-2010 was queried for patients with MCCUP. Clinicopathologic variables and outcomes were assessed.

RESULTS:

From a database of 321 patients with MCC, 38 (12%) were identified as having nodal MCCUP. Median age was 67 years, and 79% were men. Nodal basins involved at presentation were cervical (58%), axillary/epitrochlear (21%), or inguinal/iliac (21%). CK20 staining was positive in 93% of tumors tested, and all were negative for thyroid transcription factor-1. Twenty-nine patients (76%) underwent complete regional lymph node dissection (LND): 3 had LND alone, ten had LND and adjuvant radiotherapy, and 16 underwent LND followed by chemoradiotherapy. Definitive chemoradiotherapy without surgery was provided to six patients (16%), while radiotherapy alone was provided to three (8%). Recurrence was observed in 34% of patients. Median recurrence-free survival was 35 months. Ten patients (26%) died, five of disease and five of other causes. The median overall survival was 104 months.

CONCLUSIONS:

Nodal MCCUP is a rare disease affecting primarily elderly white men. Recurrence is observed in approximately one-third of patients, with a 104 month median overall survival after a multimodal treatment approach consisting of surgery along with adjuvant chemotherapy and radiotherapy in the majority of patients.

Springerlink

Sentinel lymph node biopsy in patients with Merkel cell carcinoma

Sentinel lymph node biopsy in patients with Merkel cell carcinoma: An emerging role and the Westmead hospital experience.

Feb 2012

Howle J, Veness M.

Source

Departments of Surgical Oncology Radiation Oncology, University of Sydney, Westmead Hospital, Sydney, New South Wales, Australia.

Abstract

Background: 

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy which has a high rate of nodal metastasis. Sentinel lymph node biopsy (SLNB) enables the identification of occult nodal metastases. We sought to calculate the rates of positive and false negative SLNB and to evaluate the impact of SLNB on the staging and management of patients with MCC at our institution.

Methods: 

A total of 16 patients with stage I or II MCC who had undergone SLNB were identified from a prospectively maintained database of 114 patients with MCC who presented to Westmead Hospital, Sydney, Australia between 2000 and 2010. Data on patient characteristics, tumour and treatment details and patient follow up were extracted from a computer database and patient medical records.

Results: 

Eight patients (50%) had a positive SLNB and eight had a negative SLNB. The median follow up from diagnosis was 19.5 months (range 4-40) with most patients (69%) alive without evidence of disease at the time of last follow up. All eight patients with a positive SLNB subsequently underwent nodal treatment. This consisted of radiotherapy in five and completion lymphadenectomy and adjuvant radiotherapy in three. None of the eight patients who had a negative SLNB underwent any nodal treatment following SLNB. Two of these patients developed nodal relapse, giving a false negative rate of 20%.

Conclusion: 

Half of our patients were upstaged and underwent nodal treatment as a result of their SLNB. Given the high rate of SLNB positivity, we believe that SLNB has a role in the management of MCC. As there is a risk of a false negative SLNB, close observation of the regional nodal basins is warranted in patients who have had a negative SLNB. Further studies are required to investigate the impact of SLNB on survival.

PubMed

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