First description of Merkel Cell polyomavirus DNA detection in a patient with Stevens-Johnson syndrome.

May 2013

Maximova N, Granzotto M, Kiren V, Zanon D, Comar M.

Source

Institute for Maternal and Child Health, IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy.

Abstract

Merkel Cell polyomavirus (MCPyV), a ubiquitous DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukaemia while other associations are still being explored. MCPyV sequences have also been detected in normal tissues of tumor patients and in the blood of healthy donors. This report documents a new MCPyV association with the Stevens-Johnson syndrome, a rare immune-modulated mucocutaneous process particularly associated with specific drugs and infective agents. A high MCPyV viral load was detected simultaneously in fluid from skin lesions (2.0 × 10(4) copies/ml) and in matched blood (7.4 × 10(5) copies/ml) from a young adult patient after bone marrow transplant for a relapsed T-cell acute lymphatic leukaemia. MCPyV clearance concurred with the complete resolution of skin lesions after 5 days of cidofovir treatment. DNA sequencing classified the amplicons as the European/Italian MKL-1 strain. Given its ubiquitous nature, MCPyV could account for part of Stevens-Johnson syndrome idiopathic cases. J. Med. Virol. 85:918-923, 2013.

Wiley Online

Merkel cell carcinoma with divergent differentiation: histopathological and immunohistochemical study of 15 cases with PCR analysis for Merkel cell polyomavirus.

Apr 2013

Martin B, Poblet E, Rios JJ, Kazakov D, Kutzner H, Brenn T, Calonje E.

Source

Dermatopathology Department, St John's Institute of Dermatology, St Thomas' Hospital, London, UK.

Abstract

AIMS:

To report on 15 cases of Merkel cell carcinoma (MCC) with divergent differentiation, to characterize its clinicopathological spectrum and its relationship with Merkel cell polyomavirus (MCV).

METHODS AND RESULTS: Fifteen patients with a mean age of 81 years were included. Follow-up was available for 13 cases (range 12 days to 6 years; median 6 months). Recurrence, metastasis and mortality rates were 15.4%, 53.8% and 61.5%, respectively. All tumours showed the typical histological and immunohistochemical features of MCC, with at least one additional divergent component. Eight cases had a single aberrant component (squamous in six cases, follicular in one case, and porocarcinoma in one case), six cases had two aberrant components (squamous and sarcomatous in three cases, glandular and squamous in two cases, and sarcomatous and neuroblastic in one case), and one case had three aberrant components (glandular, squamous, and sarcomatous). All cases had dysplastic changes in the overlying epithelium, and four of 15 showed epidermotropism. PCR analysis for Merkel cell polyomavirus (MCV) gave negative results in all 12 cases tested.

CONCLUSIONS:

Merkel cell carcinoma with divergent differentiation is a highly aggressive tumour that might be difficult to recognize, owing to its wide histological variability. Negativity for MCV suggests that the virus is not implicated in the development of this subtype of MCC.

Wiley Online Library

Sentinel lymph node in Merkel cell carcinoma: To biopsy or not to biopsy?

Feb 2013

Sattler E, Geimer T, Sick I, Flaig MJ, Ruzicka T, Berking C, Kunte C.

Source

Department of Dermatology and Allergology, Ludwig-Maximilian University of Munich, Munich, Germany.

Abstract

Sentinel lymph node biopsy (SLNB) is commonly recommended for patients with primary Merkel cell carcinoma (MCC). However, it is critically discussed whether survival rates improve by SLNB in MCC patients in general or in subgroups of higher risk (e.g. with primary tumor size >1 cm). The present study correlates clinical data, histology and lymph node status with follow-up and survival data to see if subgroups can be identified for modification of the current recommendations. The medical records of 47 patients with histologically confirmed MCC treated between 1995 and 2010 at a German dermatosurgery department were reviewed. Nineteen patients with excision of the primary tumor and SLNB were compared to 28 patients with excision of the primary tumor but without SLNB. End-points of this study were disease-free survival (DFS) and overall survival (OS). In addition, clinical course was correlated with tumor size and size of safety margin. The group of patients who received SLNB showed a significant advantage in terms of OS (P < 0.05), but not in terms of DFS. Tumors of smaller size were associated with a significantly better DFS and a trend towards better OS. Comparing the groups with different safety margins (1-3 cm), no differences in DFS and OS could be found. Our data support the current recommendation for SLNB in all MCC patients and question the use of extensive safety margins in MCC surgery. Larger prospective multicenter studies with multivariate analysis are needed to confirm whether a prolonged OS is really due to the SLNB procedure or biased by other factors.

PubMed

Merkel cell carcinoma: interdisciplinary management of a rare disease.

2013

Schneider S, Thurnher D, Erovic BM.

Source

Department of Otolaryngology-Head and Neck Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.

Abstract

Background. The goal of this paper is to review contemporary multidisciplinary treatment with reference to Merkel cell carcinoma. Management of this rare but highly aggressive skin cancer is a complex undertaking that necessitates an understanding of its etiology, epidemiology, clinical presentation, and the coordinated work of several clinical specializations. 

Recent Findings. The contemporary literature employs a multidisciplinary approach to achieve the best patient's treatment. 

Conclusion. This paper presents an algorithm for contemporary management for the rare and aggressive Merkel cell carcinoma. Multidisciplinary approach in a tumor center provides high-quality care for patients with Merkel cell carcinoma.

Full Text Article

Journal of Skin Cancer

Neuroembolization of metastatic Merkel cell cancer to the face for treatment of Kasabach-Merritt syndrome.

Feb 2013

Lee JH, Roychowdhury S, Nissenblatt MJ.

Source

Department of Radiology, UMDNJ Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA.

Abstract

Kasabach-Merritt syndrome is defined as a consumptive thrombocytopenia in the presence of a highly vascular tumor. Multiple treatment options, including transarterial embolization, have been described. We demonstrate that transarterial embolization is a viable option in the treatment of a rapidly progressive and debilitating Merkel cell tumor metastasizing to the head and neck presenting with Kasabach-Merritt syndrome.

BMJ - NeuroInterventional Surgery

A rare case of merkel cell carcinoma metastasis to the adrenal resected robotically.

Feb 2013

Alguraan Z, Agcaoglu O, Aliyev S, Berber E.

Source

Endocrinology and Metabolism Institute, Division of Endocrine Surgery, Cleveland Clinic, Cleveland, OH.

Abstract

INTRODUCTION:

 Merkel cell carcinoma (MCC) is an uncommon skin malignancy that has a high propensity for metastatic spread and there is no consensus regarding the optimal therapeutic approach. The relative roles of surgery, radiotherapy, and chemotherapy are still controversial. As the robotic approaches are gaining more popularity over the recent years, herein we report our result for MCC using robotics.

METHODS:

We herein describe a patient with MCC metastases to the left adrenal gland, which was resected robotically. The procedure was performed under general anesthesia using the robotic camera and 2 robotic working ports.

RESULTS:

A 59-year-old woman, who was diagnosed to have MCC of the left forearm 1 year ago with stage T2 N1 and removed by wide excision, underwent left robotic lateral transabdominal adrenalectomy because of MCC metastasis to the left adrenal gland. She was discharged home on postoperative day 2 uneventfully and is currently alive at 18 months with no evidence of recurrent disease on imaging studies.

CONCLUSIONS:

 This case report demonstrates that minimally invasive adrenalectomy may be performed for isolated MCC metastasis.

PubMed

Vascular E-selectin expression correlates with CD8 lymphocyte infiltration and improved outcome in Merkel cell carcinoma.

Jan 2013

Afanasiev OK, Nagase K, Simonson W, Vandeven N, Blom A, Koelle DM, Clark R, Nghiem P.

Source

1] Department of Medicine/Dermatology, University of Washington, Seattle Washington, USA [2] Department of Pathology, University of Washington, Seattle Washington, USA.

Abstract

Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-linked skin cancer. While CD8 lymphocyte infiltration into the tumor is strongly correlated with improved survival, these cells are absent or sparse in most MCCs. We investigated whether specific mechanisms of T-cell migration may be commonly disrupted in MCC tumors with poor CD8 lymphocyte infiltration. Intratumoral vascular E-selectin, critical for T-cell entry into skin, was downregulated in the majority - 52% - of MCCs , and its loss was associated with poor intratumoral CD8 lymphocyte infiltration). Importantly, survival was improved in MCC patients whose tumors had higher vascular E-selectin expression. 

Local nitric oxide production is one mechanism of E-selectin downregulation and it can be tracked by quantifying nitrotyrosine, a stable biomarker of NO-induced reactive nitrogen species (RNS). Indeed, increasing levels of nitrotyrosine within MCC tumors were associated with low E-selectin expression and decreased CD8 lymphocyte infiltration. These data suggest that one mechanism of immune evasion in MCC may be restriction of T cell entry into the tumor. 

Existing therapeutic agents that modulate E-selectin expression and/or RNS generation may restore T cell entry and could potentially synergize with other immune-stimulating therapies.Journal of Investigative Dermatology accepted article preview online, 25 January 2013

Nature

Immunohistochemical expression of PAX5 and TdT by Merkel cell carcinoma and pulmonary small cellcarcinoma: a potential diagnostic pitfall but useful discriminatory marker.

2013

Kolhe R, Reid MD, Lee JR, Cohen C, Ramalingam P.

Source

Department of Pathology, Georgia Health Sciences University Augusta, GA.

Abstract

BACKGROUND:

Merkel cell carcinoma is a high-grade neuroendocrine carcinoma of skin that is characterized by immature cells which, because of its striking morphologic similarity, may be confused with other small round blue cell tumors such as pulmonary small cell carcinoma or lymphoblastic leukemia/lymphoma. Immunohistochemistry is therefore paramount to ensuring accurate diagnostic distinction between these tumors. The aim of our study was to evaluate and compare the expression of PAX5 and Terminal deoxynucleotidyl transferase (TdT), in Merkel cell carcinoma and pulmonary small cellcarcinoma.

DESIGN:

PAX5 and TdT immunohistochemical stains were performed on 27 Merkel cell carcinomas and 10 pulmonary smallcell carcinomas.

RESULTS:

PAX5 was expressed in 24/27 (89%) Merkel cell carcinomas and 0/10 (0%) pulmonary small cell carcinomas. TdT was expressed in 21/27 (78%) Merkel cell carcinomas and 9/10 (90%) pulmonary small cell carcinomas.

CONCLUSIONS:

Our study confirms that PAX5 and TdT expression can be expressed in a high percentage of Merkel cellcarcinomas and so when positive are not diagnostic of lymphoblastic leukemia/lymphoma. When dealing with metastatic lesions, PAX5 negativity would favor a diagnosis of pulmonary small cell carcinoma over Merkel cell carcinoma. In addition, TTF-1 negative pulmonary small cell carcinoma is to be differentiated from Merkel cell carcinoma.

Full Length Article

PMC-IJCEP

Merkel cell carcinoma: A new radiation-induced cancer?

Jan 2013

[Article in French]

Bertrand M, Mirabel X, Desmedt E, Vercambre-Darras S, Martin de Lassalle E, Bouchindhomme B, Guerreschi P, Martinot V, Mortier L.

Source

Service de dermatologie, hôpital Claude-Huriez, CHRU de Lille, rue Michel-Polonovski, 59037 Lille cedex, France. Electronic address: marie_bertrand13@yahoo.fr.

Abstract

BACKGROUND:

Merkel cell carcinoma (MCC), a rare and aggressive neuroendocrine tumour, appears primarily on sun-exposed areas in light-skinned elderly subjects. UV exposure and profound immunosuppression (particularly in a setting of solid organ transplantation, haematological malignancies, HIV) constitute the principal risk factors. The aetiopathogenesis of this cancer is not known, although a polyomavirus involved in the oncogenic process was recently discovered. The carcinogenic effect of ionizing radiation, while not clearly established, has been suspected in rare cases involving the onset of MCC in irradiated zones. We report a new case of case of MCC in a patient previously undergoing radiotherapy.

CASE REPORT:

A 59-year-old-man underwent radiotherapy for a Darier-Ferrand dermatofibrosarcoma on the left shoulder and developed MCC at the same site 38 years later.

DISCUSSION:

The time between radiotherapy and diagnosis of MCC, its site within the radiation field (radio-dermatitis), the description of similar cases in the literature concerning the onset of MCC in irradiated areas, and the known carcinogenic effects of ionizing radiation all militate strongly in favour of the radiation-induced nature of MCC.

PubMed

Which are the cells of origin in merkel cell carcinoma?

2012

Tilling T, Moll I.

Source

Department of Dermatology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.

Abstract

Merkel cell carcinoma (MCC), a highly aggressive skin tumour with increasing incidence, is associated with the newly discovered Merkel cell polyomavirus (MCPyV). Studies on MCC and MCPyV as well as other risk factors have significantly increased our knowledge of MCC pathogenesis, but the cells of origin, which could be important targets in future therapies, are still unknown. Merkel cells (MCs), the neuroendocrine cells of the skin, were believed to be at the origin of MCC due to their phenotypic similarities. However, for several reasons, for example, heterogeneous differentiation of MCCs and postmitotic character of MCs, it is not very likely that MCC develops from differentiated MCs. Skin stem cells, probably from the epidermal lineage, are more likely to be cells of origin in MCC. Future studies will have to address these questions more directly in order to identify the physiological cells which are transformed to MCC cells.

PubMed

Correction: Diagnostic Biopsy Does Not Commonly Induce Intratumoral CD8 T Cell Infiltration in Merkel Cell Carcinoma.

2012

Koba S, Paulson KG, Nagase K, Tegeder A, Thibodeau R, Iyer JG, Narisawa Y, Nghiem P.

There were multiple errors throughout the article.

There was a formatting error that inserted the text "_ENREF_#" in numerous occasions throughout the article. These insertions should not exist.

In the Figure 1 legend, the symbol á should be α.

In the fourth paragraph of the Discussion section, the symbol "â" in the term "â-interferon" should be "beta," making the term "beta-interferon."

This corrects the article "Diagnostic Biopsy Does Not Commonly Induce Intratumoral CD8 T Cell Infiltration in Merkel Cell Carcinoma" , e41465.

PLOS/NIH

Merkel cell carcinoma with sarcomatous differentiation: is it a poor prognostic factor?

Jan 2013

Gomez-Moyano E, Vera-Casaño A, Sanz-Trelles A, Martinez L.

Source

Departments of Dermatology Pathology, Hospital Carlos Haya, Málaga, Spain.

Abstract

Background:  Poor prognostic factors in Merkel cell carcinoma include male sex, advanced stage at diagnosis, large tumor size (>5 mm), diffuse growth pattern, heavy lymphocytic infiltrate, and high mitotic rate. To date only six cases of Merkel cell carcinoma with sarcomatous or pseudosarcomatous differentiation and poor prognosis have been documented. Methods  We present a new case of Merkel cell carcinoma with sarcomatous differentiation. Results  The immunohistochemical staining patterns reflected the morphologic differentiation of the epithelial and sarcomatous pattern. After two months of follow-up, there were no signs of local recurrence or metastases. Conclusion  In all cases of merkelomas with sarcomatous differentiation described to date, lymph node metastases have been found, except in the presented case. However, larger series of cases will be required to determine if sarcomatous differentiation represents another negative prognostic factor.

Wiley OnLine

Incipient Merkel Cell Carcinoma: A Report of 2 Cases.

Dec 2012

Requena C, Traves V, Llombart B, Guillén C.

Source

Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain. Electronic address: celiareq@hotmail.com.

Abstract

Merkel cell carcinoma is a malignant skin tumor with a poor prognosis that primarily affects photoexposed areas of elderly patients. Tumor size is a very strong prognostic factor, with much better outcomes associated with small lesions, measuring less than 1cm. However, such lesions are rarely seen in the clinic in view of the rapid growth of this tumor. We report 2 cases of incipient Merkel cell carcinoma. Both cases of incipient Merkel cell carcinoma measured approximately 5mm in diameter. One tumor was confined to the epidermis and papillary dermis on the nose of a 79-year-old man and the other was located in the deep dermis, almost in the hypodermis, on the buttock of an 82-year-old woman. In both cases, the lesions had appeared weeks earlier. The first tumor seemed to originate in the dermoepidermal junction whereas the second originated almost in the hypodermis. Although the lesions were at a similar disease stage and had a similar size, their different locations within the dermis highlight once again the controversy about which cells give rise to Merkel cell carcinoma. The precursor cells could feasibly be Merkel cells in the first case but not in the second.

ACTAS/ Dermo-Sifiliograficas