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