Diagnosis Of Merkel Cell Carcinoma Research Articles

Clinical and dermoscopic characteristics of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy with a high mortality rate. Diagnosis is often delayed. To characterize the dermoscopic features of MCC. Clinical and dermoscopic images of 12 biopsy-proven MCCs were analysed in a retrospective manner, with existing dermoscopic criteria being scored independently by three dermatologists. The four most frequent clinical features were cherry red colour, shiny surface, sharp circumscription and nodular morphology. Significant dermoscopic features included linear irregular and polymorphous vessels, poorly focused vessels, milky pink areas, white areas, structureless areas and architectural disorder. Pigmented structures were absent from all lesions. The dermoscopic features described herein help the clinician to distinguish MCC from other benign and malignant red nodules. Increasing recognition of the presenting features will facilitate earlier diagnosis of MCC and reduced mortality.

Neuroendocrine carcinoma of the skin—An updated review

Primary neuroendocrine carcinoma of the skin, or Merkel Cell carcinoma (MCC), is a rare but aggressive tumor. Many recent advances on the morphology, immunophenotype, and pathogenesis have come to light in recent years. This review highlights the clinical features, varying histologies, histogenesis, advances in molecular pathology, prognosis, and current management of MCC. It also aims to aid in the differential diagnosis, with an emphasis on neuroendocrine tumors, and approach to the diagnosis of MCC with the use of immunohistochemistry and molecular studies.

CARCINOMA DE CÉLULAS DE MERKEL – NORMAS DE ORIENTAÇÃO CLÍNICA

Introdução: O carcinoma de células de Merkel (CCM) é considerado um tumor cutâneo raro, cuja incidência triplicou nos últimos 20 anos, em parte devido a uma maior acuidade diagnóstica. A taxa de mortali- dade ultrapassa a do melanoma, com importante morbilidade associada e metastização loco-regional. Material e métodos: Os autores reviram a literatura disponível com o intuito de fornecer normas de orientação clínica para o diagnóstico e tratamento do CCM. Resultados: Recentemente o American Joint Commitee on Cancer elaborou um sistema de estadiamento (TNM), que divide o CCM em 4 estadios (I-IV) consoante o grau de agressividade da neo- plasia. A cirurgia é a terapêutica de 1a linha na abordagem do CCM, com margens cirúrgicas que variam entre 1-2cm, consoante as características do tumor primário. Actualmente é consensual o benefício da biopsia do gânglio sentinela, sendo o status do gânglio sentinela o factor prognóstico mais importante. A radioterapia adjuvante no leito tumoral e nas cadeias ganglionares regionais assume particular importância associada à linfadenectomia radical. Apesar de se tratar de um tumor quimiossensível, o estadio IV do CCM tem prognóstico reservado, sendo discutível o benefício da quimioterapia. Conclusões: É importante manter um baixo limiar de suspeita para o CCM no sentido de optimizar o tratamento deste tumor agressivo. PALAVRAS-CHAVE – Carcinoma de células de Merkel; Biopsia de gânglio sentinela; Estadiamento; Normas de orientação clínica.

Investigation of the diagnostic precision and utility of sentinel lymph node biopsy in the treatment of patients with Merkel cell carcinoma (MCC).

9042 Background: Merkel cell carcinoma (MCC) is a relatively uncommon and aggressive cutaneous neuroendocrine neoplasm with a high incidence of local recurrence and regional and distant metastasis. The management and identification of prognostic factors remains of value in the treatment of these patients. Although the optimal multidisciplinary treatment of MCC has yet to be determined, the purpose of this study was to investigate whether sentinel lymph node biopsy confers a lower risk of recurrent disease in patients with Merkel cell carcinoma at our institution. Methods: After obtaining institutional review board approvals, all patients with a diagnosis of MCC from 2002-2012 were obtained from our tumor registries. Clinical features, pathologic characteristics, management modalities, and patient outcomes were retrospectively reviewed. Results: Of 20 patients with MCC, nine patients underwent sentinel lymph node biopsy, another four received therapeutic lymph node dissections, and seven patients did not have lymph node evaluation at the initial operation. The most common nodal basins involved were cervical and axillary. Recurrent disease was observed in seven patients (35%). Three patients underwent complete regional lymph node dissection after developing clinically positive nodal disease subsequent to only wide local excision at the index operation (15%). Three patients developed locoregional recurrence and the seventh patient developed metastatic disease to the liver. Of these seven patients with recurrent disease, only two (28.57%) had initial lymph node evaluation. Twelve patients (60%) received adjuvant therapy with chemotherapy (carboplatin/etoposide) and/ or radiation therapy. Conclusions: Merkel cell carcinoma continues to demonstrate its propensity for high rates of recurrence and metastatic disease. Of the seven patients with recurrent locoregional and/or nodal disease in our study, only two patients had initial lymph node evaluation, which was statistically significant with a p value of 0.01175. Further analysis focusing on additional prognostic factors is necessary to optimize our management algorithms and patient outcomes.

Vitamin D deficiency is associated with greater tumor size and poorer outcome in Merkel cell carcinoma patients

Merkel cell polyomavirus has been recognized to be associated with Merkel cell carcinoma (MCC), but the evolution of this cancer probably depends on various factors. Vitamin D deficiency, defined by serum 25-hydroxyvitamin D levels <50nmol/L, seems to influence cancer behavior and progression, but has never been assessed in MCC patients. First, to evaluate whether vitamin D deficiency was associated with tumor characteristics and prognosis in a cohort of MCC patients. Second, to assess expression of the vitamin D receptor (VDR) in MCC tumors. Clinical findings, Merkel cell polyomavirus markers and vitamin D status were assessed in a cohort of French MCC patients. The study was limited to the 89 patients for whom the serum sample had been collected within 3years after the diagnosis of MCC. Correlation between vitamin D deficiency and MCC characteristics and outcome were determined in regression analyses. VDR expression in MCC tumours was assessed by immunohistochemistry. Vitamin D deficiency was noted in 65.1% of the patients and was independently associated with greater tumor size at diagnosis (P=0.006) and with metastasis recurrence (HR, 2.89; 95% CI, 1.03 to 8.13; P=0.043), but not with death from MCC, although there was a trend (HR, 5.28; 95% CI, 0.75 to 36.96; P=0.093). VDR was found to be strongly expressed in all 28 MCC tumor specimens investigated. The association between vitamin D deficiency and MCC characteristics and outcome, together with detection of the VDR in MCC cells, suggest that vitamin D could influence the biology of MCC.

Carcinome de Merkel : un nouveau cancer radio-induit ?

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. 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. 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.

CD99 expression in Merkel cell carcinoma: a case series with an unusual paranuclear dot‐like staining pattern

Merkel cell carcinoma (MCC) is a rare neuroendocrine cancer of the skin. The utility of CD99 (MIC-2) in the diagnosis of MCC has been previously studied, with reported rates of expression ranging from 13 to 55%. When specified, a membranous or cytoplasmic staining pattern was considered significant. Recent studies of CD99 have identified a paranuclear dot-like expression pattern in certain non-neuroendocrine pancreatic and colonic lesions. We recently noted paranuclear dot-like staining in several cases of MCC, including cases lacking cytokeratin 20 (CK20) expression. Fourteen cases of MCC were stained with CK20 and CD99 antibody, and the pattern and intensity of staining were recorded. Seven cases of pulmonary small cell carcinoma (PSCC) and one case of primitive neuroectodermal tumor (PNET) were used for comparison. All 14 cases of MCC showed at least focal CD99 staining, with both membranous and paranuclear dot-like staining patterns identified. CK20 staining was present in 12/14 cases, with the characteristic dot-like pattern identified. Four of seven cases of PSCC showed CD99 staining, with two showing a finely granular dot-like staining pattern. We report an unusual pattern of paranuclear dot-like expression of CD99 in 14 cases of MCC, two of which did not express CK20. This previously unrecognized expression pattern may be of use in differentiating MCC from other cutaneous malignancies, especially when CK20 expression is limited or absent.

68Ga-DOTATATE-PET/CT Positive Metastatic Lymph Node in a 69-Year-Old Woman With Merkel Cell Carcinoma

We report the case of a 69-year-old woman with a Merkel cell carcinoma (MCC) in whom subsequent lymph node metastasis was first diagnosed by 68Ga-Dotatate-PET/CT followed by histopathological confirmation. MCC is an extraordinarily rare and aggressive neuroendocrine tumor of dermal origin with a high rate of postoperative recurrence. Owing to its rarity, the diagnosis of MCC remains a significant challenge. In our case, 68Ga-Dotatate-PET/CT proved clinically useful for diagnosing the lymph node metastasis of a MCC.

The clinical profile of Merkel cell carcinoma in mainland China.

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy, but little is known about the presence or characteristics of MCC in mainland China. A retrospective chart review was conducted to describe the clinical profile of MCC in China. At 18 cancer or dermatology hospitals in metropolitan centers from the six geographical regions of mainland China, approximately 3,100,000 pathology database and medical records were searched for cases that had a pathological diagnosis of MCC between 1970 and 2009. A case series was compiled from retrospective chart reviews of identified patients with MCC. Eight out of 18 participating hospitals reported at least one record of a patient with a pathological diagnosis of MCC, and a total of 22 cases were identified. The median age of patients was 65.5 years, and 59% were female. The median time from the appearance of a lesion to the time of biopsy was six months, and the most common location of lesions was the head and neck. The most common treatment used was surgery alone. Merkel cell carcinoma appears to be uncommon in mainland China. Patients in this series are elderly, often had lesions on the head/neck region, and most commonly received surgery alone as treatment. In contrast with MCC in Western countries, the current series' patients were all of Asian ethnicity, had larger lesions at presentation, and none was documented as having HIV or other forms of immunosuppression.

Increasing Tumor Thickness is Associated with Recurrence and Poorer Survival in Patients with Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous neuroendocrine tumor usually occurring on sun-exposed skin in elderly patients. Clinical and pathologic factors associated with disease progression and mortality in patients with MCC are poorly defined. Recently, it has been reported that p63 expression in primary MCC is strongly associated with clinical outcome. MCC patients diagnosed between July 1, 1993 and July 31, 2009 were identified from the surgical pathology records of the Sydney South West Area Health Service. Clinical, pathologic, treatment, and survival data were obtained and immunohistochemical analyses for p53, p63, and Ki-67 were performed. The associations of clinical and pathologic features with disease-free and disease-specific survival were analyzed. Ninety-five patients were identified (67 males, 28 females; median age at diagnosis of primary MCC 76 [range, 42-93] years). Increasing primary tumor thickness was significantly associated with poorer disease-free survival (5-year survival 18 % in tumors >10 mm thick compared with 69 % for patients with tumors ≤10 mm thick, p = 0.002) and disease-specific survival (5-year survival 74 % in tumors >10 mm thick compared with 97 % for patients with tumors ≤10 mm thick, p = 0.006). There was a strong positive correlation between the Ki-67 index (proportion of Ki-67-positive tumor nuclei) and tumor thickness (r = 0.39, n = 45, p = 0.008). Positive staining for p63 in MCC was infrequent (9 % of primary MCC) and showed no significant association with disease outcome. Tumor thickness is significantly associated with disease-free survival in MCC. We recommend that primary tumor thickness be routinely recorded in the pathology reports of patients with primary MCC.

Case for diagnosis

An 80-year-old Caucasian male patient was referred for evaluation of a rapidly growing, asymptomatic, erythematous nodule measuring 2 cm in diameter on his left cheek. The lesion had been present for four months. Dermoscopy revealed a homogeneous pink background with polymorphous telangiectatic vessels. Histopathology showed tumors in the deep dermis and subcutis composed of round cells with scant cytoplasm. Immunohistochemical staining was positive for CK20 confirming the diagnosis of Merkel cell carcinoma.

Guidelines for the diagnosis and treatment of Merkel cell carcinoma – Cutaneous Oncology Group of the French Society of Dermatology

Merkel cell carcinoma (MCC) is a rare neuroendocrine tumor of the skin. The epidemiological factors strongly associated with this tumor are: age over 65 years, fair skin, chronic sun exposure and immune suppression. Data are sparse in the literature and many questions remain unanswered regarding the diagnosis and treatment of this tumor. To provide clinical practice guidelines for the diagnosis and treatment of MCC. The literature data were analyzed and the current American and German practice guidelines were compared. Consensus items between these two guidelines were adopted as recommendations. Regarding discordant points, a formalized expert consensus process was devised. The guidelines were then written up by an editorial panel and validated by the Cutaneous Oncology Group of the French Society of Dermatology. The guidelines were drawn up according to three levels of scientific evidence: (a) complete agreement between the American and German guidelines; (b) the results of the formalized expert consensus process; and (c) the expert opinion of the steering group, based on analysis of the available evidence. The guidelines presented here are up-to-date recommendations on the clinical and pathological procedures for MCC diagnosis, staging, surgical treatment, sentinel node biopsy, radiotherapy and follow-up. These guidelines for diagnosis and treatment of MCC should standardize MCC management, which may not be optimal in France today.

Merkel cell carcinoma in a patient with noninvasive vulvar Paget's disease

We present the first case of inguinal Merkel cell carcinoma of unknown primary origin in a patient with vulvar Paget's disease. Correlation with immune suppression of both entities warrants further investigation. Additionally, this case highlights the value of ultrasound scanning in the detection of inguinal metastasis.

Increased incidence of chronic lymphocytic leukaemia and lymphomas in patients with Merkel cell carcinoma – a population based study of 335 cases with neuroendocrine skin tumour

Merkel cell carcinoma (MCC) is a rare aggressive skin tumour that appears to be associated with a large number of other tumours. We collected all reported cases in Israel and estimated its association with other tumours, including haematological malignancies. The population based Israel Cancer Registry identified 335 patients with MCC diagnosed between1989 and 2010. Ninety-seven percent were in the Jewish population; median age at diagnosis for Jewish patients was 73·4 and 55·6years for the Arab population. Other associated malignancies were encountered in 92 patients (27·4%) with MCC (90 Jews, two Arabs). Of the Jewish cases, 66 presented with an associated malignancy before, and 24 after, the diagnosis of MCC. Solid tumours were not significantly increased among patients with MCC. Thirty-one of these associated cancers (34·4%) were haemato-oncological malignancies, 24 were detected before and seven after the diagnosis of MCC. The standardized incidence ratio (SIR) for haematological malignancy was 3·67 for males and 3·62 for females, and the most frequent haemato-oncological neoplasias recorded were chronic lymphocytic leukaemia (45%) and lymphomas (29%). Although MCC is rare, clinicians should be aware of the possible association with B-cell lymphoproliferative disorders when evaluating patients with neuroendocrine skin tumours.

Chronic Lymphocytic Leukemia Is Associated With Decreased Survival of Patients With Malignant Melanoma and Merkel Cell Carcinoma in a SEER Population-Based Study

To delineate outcomes of malignant melanoma (MM) and Merkel cell carcinoma (MCC) in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL). We identified patients with MM or MCC reported to the Surveillance, Epidemiology, and End Results program and analyzed the effects of history of CLL/NHL on overall (OS) and cause-specific survival after MM or MCC. Expected survival was derived from patients with MM or MCC without CLL/NHL. From 1990 to 2006, 212,245 patients with MM and 3,613 patients with MCC were identified, of whom 1,246 with MM and 90 with MCC had a prior diagnosis of CLL/NHL. Patients with MM and a history of CLL/NHL had worse-than-expected OS as measured by standardized mortality ratio (SMR; SMR for CLL, 2.6; 95% CI, 2.3 to 3.0; SMR for NHL, 2.3; 95% CI, 2.1 to 2.6). MM cause-specific survival was worse than expected for patients with a history of CLL (SMR, 2.8; 95% CI, 2.2 to 3.4) or NHL (SMR, 2.1; 95% CI, 1.7 to 2.6). Among patients with MCC, OS was worse than expected for those with a history of CLL (SMR, 3.1; 95% CI, 2.2 to 4.3) or NHL (SMR, 1.9; 95% CI, 1.3 to 2.8). MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR, 3.8; 95% CI, 2.5 to 5.9), but no difference was observed for NHL (SMR, 0.9; 95% CI, 0.4 to 2.1). Patients with CLL before diagnosis of MM or MCC have significantly worse OS and MM or MCC cause-specific survival than those without a history of CLL/NHL.

Dermatoscopic vascular patterns in cutaneous Merkel cell carcinoma

Merkel cell carcinoma (MCC) is one of the most aggressive primary cutaneous malignancies. The clinical diagnosis of MCC is often delayed. Although the rarity of this skin cancer partially explains the low clinical suspicion by physicians, the absence of characteristic clinical features contributes to the delay in diagnosis. Dermatoscopy has proven a useful diagnostic tool in other cutaneous malignancies; however, the dermatoscopic features of cutaneous MCC are unknown. We performed dermatoscopy on 10 primary cutaneous MCC to describe the dermatoscopic features and correlate these findings with the histopathologic parameters. Consecutive patients with cutaneous MCC were identified and their tumors were evaluated under dermatoscopy. An 8-point MCC histopathology profile was recorded for each primary tumor in an attempt to correlate individual parameters with dermatoscopic features. All 10 tumors showed an irregular vascular pattern under dermatoscopy and demonstrated milky-red areas/globules and numerous linear irregular vessels. No correlation was noted between dermatoscopic and histopathologic features. The patients were from a single institution and tumors evaluated by a single dermatoscopic reviewer. Because of the rarity of this tumor, a small number of tumors were evaluated (10). MCC exhibits a variety of dermatoscopic vascular patterns, most commonly milky-red areas/globules, polymorphous vessels, and linear-irregular vessels. Although we found no specific dermatoscopic pattern for MCC in our series, the polymorphous vascular pattern was atypical and suggestive of a malignant process. Further studies should be done to investigate the potential correlation between dermatoscopic features and histopathologic parameters.

The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites

Most Merkel cell carcinomas display pure neuroendocrine differentiation (pure Merkel cell carcinoma), whereas a minority show combined neuroendocrine and nonneuroendocrine elements (combined Merkel cell carcinoma). Recent identification of Merkel cell polyomavirus DNA and Merkel cell polyomavirus large T antigen expression in a proportion of Merkel cell carcinomas has suggested viral-induced oncogenesis. To date, Merkel cell polyomavirus immunohistochemistry has shown an absence of viral large T antigen expression in combined Merkel cell carcinoma as well as select non-Merkel cell carcinoma cutaneous lesions and visceral neuroendocrine tumors. In our series, we aimed to further characterize the frequency and pattern of Merkel cell polyomavirus large T antigen expression by CM2B4 immunohistochemistry in primary and metastatic Merkel cell carcinoma (pure Merkel cell carcinoma and combined Merkel cell carcinoma) and various non-Merkel cell carcinoma lesions from patients with Merkel cell carcinoma, patients without Merkel cell carcinoma, and individuals with altered immune function. Merkel cell polyomavirus large T antigen was detected in 17 (63%) of 27 pure Merkel cell carcinomas and absent in all 15 (0%) combined Merkel cell carcinomas. Furthermore, complete concordance (100%) of Merkel cell polyomavirus large T antigen expression was observed in 10 cases of primary Merkel cell carcinoma and subsequent tumor metastases. We also evaluated 70 non-Merkel cell carcinoma lesions including 15 cases each of pulmonary and gastrointestinal neuroendocrine tumors. All 70 non-Merkel cell carcinoma lesions were negative for Merkel cell polyomavirus by CM2B4 immunohistochemistry, irrespective of any known Merkel cell carcinoma diagnosis and immune status. In summary, our identification of Merkel cell polyomavirus large T antigen expression in a subset of Merkel cell carcinoma and lack of findings in combined Merkel cell carcinomas and non-Merkel cell carcinoma lesions concur with earlier findings and implicate Merkel cell polyomavirus-independent pathogenesis in these cases. Overall, CM2B4 immunohistochemistry appears to be a specific method for Merkel cell polyomavirus detection and has the potential to play an important role in the diagnosis and classification of Merkel cell carcinoma in the future.

Consensus formalisé d’experts pour la prise en charge du carcinome à cellules de Merkel

Merkel cell carcinoma (MCC) is a rare form of tumour that develops from neuroendocrine skin cells. There is no consensus concerning diagnosis and therapy for this disease. To establish recommendations, the Skin Oncology Group of the French Dermatology Society drew on existing recommendations in the US and Germany. Concordance between the two sets of recommendations was validated by the group, who, in view of the large number of discrepancies, decided to use the formalised expert consensus method. Twelve practitioners known for their experience in the management of Merkel cell carcinoma completed a standardised questionnaire. This group consisted of seven dermatologists, three radiotherapists and two plastic surgeons. They answered a total of 82 questions concerning the diagnosis, treatment and follow-up of MCC. A strong consensus was declared where all answers were in the same third of the table; a weak or relative consensus was declared where answers overlapped for adjacent scores, and an absence of consensus was declared in the event of dispersal of values. On completion of this process, the method revealed strong concordance on the following points: value of CK7 and CK20 immunolabelling; lack of value of chest radiography in the initial work-up, but value of lymph node ultrasound; inadequacy of an excision margin of 1cm but lack of any need for a margin greater than 3cm; absence of any value of chemotherapy for inoperable tumours; value of seeking sentinel nodes in tumours measuring less than 2cm outside the head and neck and more than 2cm for head and neck tumours; value of additional radiotherapy at the initial tumour site. Relative agreement was reached concerning the value of thoracic-abdominal-pelvic computed tomography (CT) scans in all cases, together with a head CT scan for cervical-facial tumour sites. The creation of a formalised expert consensus helps complete the existing recommendations, particularly on those points where no consensus exists between the American and German recommendations and where no strong evidence is to be found in the literature.

Value of Merkel cell Polyomavirus DNA Detection in Routine Pathology

To the Editor: With great interest, we studied the recently published article from Duncavage et al1 “Merkel Cell Polyomavirus-A Specific Marker for Merkel Cell Carcinoma in Histologically Similar Tumors”. We agree that molecular pathologic investigation for Merkel cell polyomavirus (MCPyV) of tumors, which are histologically similar to Merkel cell carcinoma (MCC) is a very interesting and important issue. It is beyond debate that analysis of MCPyV prevalence in other skin conditions than MCC is necessary to get insight in the relevance of MCPyV infection. Our group is intensively working in this field, and we discuss the value of MCPyV detection as a diagnostic tool in routine histopathology in the light of the latest literature. Duncavage et al1 screened 74 cases of visceral high-grade neuroendocrine tumors (which are histologically similar to MCC) for MCPyV DNA by means of polymerase chain reaction (PCR). They detected MCPyV DNA just in 1 case (1.4%). Interestingly this case is, “upon detailed review, actually a misclassified case of metastatic MCC”, displaying the problem of distinguishing these entities. Therefore they suggest PCR-based testing for MCPyV DNA as helpful and specific marker in differentiating those histologically similar tumors. Furthermore, they report and discuss frequent absence of MCPyV DNA in several cutaneous and extracutaneous neoplasms.1 We agree with Duncavage et al1 that detection of MCPyV DNA is highly dependent upon a number of different methodical parameters such as tissue fixation, methods of DNA extraction and specific sequence detection, such as PCR method, selection of PCR primer sets, and last but not least dependent upon the amount of available tissue. Among others, Duncavage et al1 investigated 16 small cell carcinomas of the lung reporting absence of MCPyV DNA. We analyzed in a prior study, 30 small cell carcinomas of the lung and detected MCPyV DNA in 2 of 30 patients (7.5%), in 3 of 35 samples (2 of these 3 samples were from the same patient), respectively.2 Furthermore, there is enough evidence that MCPyV DNA is a common and frequent finding in tissues of immunosuppressed and immunocompetent individuals as well. MCPyV DNA was found in several benign, semimalignant and malignant skin tumors as well as in inflammatory skin diseases and clinical healthy skin from non-MCC patients.3-12Table 1 summarizes an incomplete selection of results from various research groups analyzing MCPyV DNA prevalence in different entities. For example, prevalence of MCPyV DNA in basal cell carcinomas was investigated from 4 independent research groups and taken together MCPyV DNA was detected in 66 of 221 samples (29.9%), ranging from 0% to 72%.3,5,6,8 We think, this situation nicely shows that MCPyV DNA analysis is most likely dependent on various before mentioned technical parameters, resulting in variable MCPyV DNA detection rates. Nevertheless, almost any of these studies point to the fact that MCPyV is ubiquitously present, even detectable in healthy and non-MCC tissue. Of special interest is that various groups reported significant differences in MCPyV viral load with usually higher copy numbers in MCC tissues and lower ones in non-MCC tissues, representing a possible parameter for differentiation.5,6,9 However, one must consider that most routine pathology laboratories use standard PCR-based methods for MCPyV detection as a qualitative test without analyzing quantitative viral load.TABLE 1: Prevalence of MCPyV DNA in Different Entities Analyzed by PCR-Based MethodsIn summary, latest reports proved that MCPyV DNA is abundantly detectable in tissues of various entities including clinical healthy skin (Table 1). Therefore, a qualitative proof of MCPyV DNA in a tissue sample is by far not specific for MCC. To us, the value of an ancillary MCPyV DNA-analysis in the differential diagnosis of MCC and similar tumors is questionable, and results have to be interpreted in the context of the recent literature suggesting a high prevalence of MCPyV. ACKNOWLEDGMENTS This study was in part supported by the Dr. H. Legerlotz, the R. Bartling and the M. Lackas Foundation. Christian Andres, MD* Benedetta Belloni, MD* *Department of Dermatology and Allergy, Ludwig-Maximilians-Universität München, Munich, Germany Michael J. Flaig, MD† †Department of Dermatology and Allergy Biederstein, Technische Universität München, Munich, Germany

Immunohistochemistry for Merkel cell polyomavirus is highly specific but not sensitive for the diagnosis of Merkel cell carcinoma in the Australian population

Recent studies have demonstrated a high frequency of detection of Merkel cell polyomavirus in Merkel cell carcinoma. However, most of these studies are from European or North American centers that have relatively low sun exposure and may have a higher incidence of virus-driven oncogenesis compared with the highly sun-exposed but predominantly fair-skinned Australian population. We performed immunohistochemistry for Merkel cell polyomavirus on 104 cases of Merkel cell carcinoma and 74 cases of noncutaneous small cell-undifferentiated carcinoma from 3 major Australian centers. Nineteen (18.3%) cases of Merkel cell carcinoma showed positive staining for Merkel cell polyomavirus versus 1 (1.3%) of small cell-undifferentiated carcinoma. All 15 cases (14.3%) of Merkel cell carcinoma with areas of mixed squamous differentiation showed negative staining. We found positive staining in only 3 (7.7%) of 39 Merkel cell carcinoma from the head and neck (the most sun-exposed area) versus 16 (24.6%) of 65 of tumors from other sites (P < .05). Our findings support the concept of a Merkel cell polyomavirus-driven and a non-Merkel cell polyomavirus-driven (primarily sun-dependent) pathway in Merkel cell carcinoma carcinogenesis, with the latter being significantly more frequent in Australia and in mixed squamous-Merkel cell carcinoma (which is also more frequent in Australia). Although immunohistochemistry for Merkel cell polyomavirus seems to be highly specific in all populations, the low incidence of Merkel cell polyomavirus-positive Merkel cell carcinoma in a highly sun-exposed population limits its diagnostic utility in this setting.