Elsevier

Cancer Epidemiology

Volume 34, Issue 1, February 2010, Pages 62-65
Cancer Epidemiology

Second cancers following the diagnosis of Merkel cell carcinoma: A nationwide cohort study

https://doi.org/10.1016/j.canep.2009.12.007Get rights and content

Abstract

Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin. MCCs and some other skin cancers, such as basal cell carcinomas, frequently harbour Merkel cell polyomavirus DNA. The purpose of the study was to investigate the frequency of second cancers following the diagnosis of MCC. We studied the incidence of second primary cancers after the diagnosis of MCC from the files of the Finnish Cancer Registry in 1979–2006. Among the 172 MCC patients identified a total of 34 second primary cancers were detected in 30 individuals after the diagnosis of MCC. Female MCC patients were diagnosed with 25 subsequent cancers (SIR, 2.35; 95% CI, 1.52–3.47; p < 0.001) and male patients with 9 cancers (SIR, 2.32, 95% CI, 1.06–4.40; p < 0.05). The MCC patients had an increased risk for a subsequent cancer (any site) compared to age-, gender- and calendar period-matched general population (standardized incidence ratio [SIR] 2.34; 95% confidence interval [CI], 1.62–3.27). The risks for basal cell carcinoma of the skin (O = 11), SIR, 3.48; 95% CI, 1.74–6.22 and chronic lymphocytic leukemia (O = 2), SIR, 17.9; 95% CI, 2.16–64.6 were significantly elevated. The SIRs for an overall second primary cancer risk did not change markedly with time since the diagnosis of MCC. We conclude that patients diagnosed with MCC have an increased risk for a second cancer. This risk may in part result from shared etiological factors between MCC and other tumour types, such as immunosuppression or possibly Merkel cell polyomavirus infection.

Introduction

Merkel cell carcinoma (MCC) is a rare and often highly malignant neuroendocrine tumour of the skin, first described by Toker in 1972 [1]. According to the surveillance, epidemiology, and end results (SEER) program registry of the United States statistics, the annual incidence of MCC increased from 1.5 cases per million to 4.4 cases per million in 15 years [2].

A marked proportion of primary MCCs has been reported to occur in an intimate association with a malignant epithelial neoplasm, mainly squamous cell carcinoma of the skin or of the head and neck [3], [4]. Besides other skin tumours, MCCs have been reported to be associated with haematological B-cell malignancies [5], [6] adenocarcinomas of the breast and the ovaries [4] and cancers of the rectum and the prostate [7].

MCCs were recently found to frequently harbour a novel, clonally integrated virus named Merkel cell polyomavirus (MCPyV) [8]. MCPyV DNA is present in approximately 70–80% of the MCCs [8], [9], [10], [11], [12]. The importance of viral infection in the pathogenesis of MCC is not yet fully understood, but it may be associated with genesis and progression of many MCCs. Patients whose MCC contains MCPyV DNA have often a tumour arising in the limbs, and they have more favourable prognosis compared to patients whose MCC does not contain viral DNA, which findings lend support to a role of MCPyV infection in the molecular pathogenesis of MCC [13].

The purpose of the present study was to investigate whether individuals diagnosed with MCC have an increased risk for developing a second primary cancer after the diagnosis of MCC, some of which might be associated with viral infection. The study is based on the files of the Finnish Cancer Registry, where virtually all cancers diagnosed in Finland are registered. A great majority of cancers registered are diagnosed histologically, which creates a reliable basis for assessment of the risk of second cancers following the diagnosis of MCC.

Section snippets

Patients and methods

Subjects diagnosed with MCC were identified from the files of the Finnish Cancer Registry, founded in 1952. The registry is a population-based registry that covers the entire Finnish population (5.3 million in 2009). Hospitals, practicing physicians, and pathology and haematology laboratories are requested to report to the Finnish Cancer Registry all cases of cancer that come to their attention. Data of all death certificates that mention cancer are transferred to the registry annually. Deaths

Results

A total of 172 individuals were diagnosed with MCC as a first cancer in Finland in 1979–2006. All MCC diagnoses were based on histological examination. Only fourteen (8.1%) cases were diagnosed before the year 1990. All patients were Caucasian. Only 4 (2.3%) patients were younger then 45 years at the time of the diagnosis, while 104 (60.5%) were 75 years of age or older. Most (n = 119, 69.2%) patients were female, resulting in a female-to-male ratio of 2.2:1. The mean follow-up time after the

Discussion

Patients diagnosed with MCC had a significantly increased risk for being diagnosed with a second primary cancer. Yet, approximately one third of the second tumours were basal cell carcinomas of the skin, which are usually cured by surgery. Patients diagnosed with MCC were also more likely than the general population to be diagnosed with CLL.

MCC disease is a relatively new entity. Although first described in 1972 with the designation of “trabecular carcinoma of the skin” [1] the term “Merkel

Conflict of interest statement

On behalf of myself and my co-authors, no financial or other conflict of interest exists regarding financial or other relationship. Funding of this article was from departmental sources only.

References (23)

  • C. Bedane et al.

    Neuroendocrine primary cutaneous carcinoma, Therapeutic aspects in 13 patients

    Ann Dermatol Venereol

    (1996)
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      Although the incidence is reportedly rising, it is unclear whether this represents a true increased incidence or an increased recognition of MCC. Risk factors for MCC are sun exposure and immune suppression, including chronic lymphocytic leukemia, solid organ transplant, and HIV [4-6]. Human polyoma virus appears to be etiologic in a significant proportion of patients with MCC; the presence of human polyoma virus DNA in the MCC cells may be associated with an improved prognosis [5].

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