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1.
《Expert review of anticancer therapy》2013,13(3):441-445
Merkel cell carcinoma is an uncommon cutaneous malignancy. Although it is rare, Merkel cell carcinoma has been described as the most malignant primary skin tumor. It is therefore important that once diagnosed, Merkel cell carcinoma is treated appropriately. The aim of this short review is to provide a summary of the available literature to guide clinicians in the future management of such patients. Inevitably in such a rare disease, there are no randomized trials of therapy. The treatment of individual patients will rely on opinion as much as the ‘evidence’. 相似文献
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Charles J. Bechert MD Vicki Schnadig MD Ranjana Nawgiri MD 《Cancer cytopathology》2013,121(4):179-188
Merkel cell carcinoma (MCC) is a highly aggressive neuroendocrine carcinoma of the skin that occurs primarily in elderly or immunocompromised patients. For this report, the authors reviewed the diagnostic challenges associated with MCC encountered on their fine‐needle aspiration (FNA) service and also conducted an in‐depth review of the literature on MCC. A computer search for patients who were diagnosed with MCC by FNA at the authors' institution from 2006 to 2010 was conducted, and 5 patients were selected for cytologic and immunochemical analyses based on their varied and diagnostically challenging clinical presentations. The 5 selected patients had clinical findings commonly associated with MCC, including advanced age (4 of the 5 patients were ages 75‐85 years) and a history of previous malignancies (3 of the 5 patients had a history of previous malignancy), and 1 patient was diagnosed with a concomitant low‐grade lymphoma. The patients and their disease illustrated the protean clinical presentation of MCC and the clinical and cytologic challenges associated with this neoplasm. The current findings indicate the need for cytopathologists to be aware of the deceptive presentation of this neoplasm and its cytologic and immunochemical features to correctly diagnose this insidious neoplasm. Cancer (Cancer Cytopathol) 2013;121:179–188. © 2012 American Cancer Society. 相似文献
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S Lauttia H Sihto H Kavola V Koljonen T B?hling H Joensuu 《British journal of cancer》2014,110(6):1446-1455
Background:
Prokineticin-1 (PROK1) and prokineticin-2 (PROK2) are chemokine-like proteins that may influence cancer growth by regulating host defence and angiogenesis. Their significance in viral infection-associated cancer is incompletely understood. We studied prokineticins in Merkel cell carcinoma (MCC), a skin cancer linked with Merkel cell polyomavirus (MCPyV) infection.Methods:
Carcinoma cell expression of PROK1 and PROK2 and their receptors (PROKR1 and PROKR2) was investigated with immunohistochemistry, and tumour PROK1 and PROK2 mRNA content with quantitative PCR from 98 MCCs. Subsets of tumour infiltrating leukocytes were identified using immunohistochemistry.Results:
Merkel cell polyomavirus-positive MCCs had higher than the median PROK2 mRNA content, whereas MCPyV-negative MCCs contained frequently PROK1 mRNA. Cancers with high tumour PROK2 mRNA content had high counts of tumour infiltrating macrophages (CD68+ and CD163+ cells). Patients with higher than the median PROK2 mRNA content had 44.9% 5-year survival compared with 23.5% among those with a smaller content (hazard ratio (HR): 0.53; 95% confidence interval (CI): 0.34–0.84; P=0.005), whereas the presence of PROK1 mRNA in tumour was associated with unfavourable survival (P=0.052).Conclusions:
The results suggest that prokineticins are associated with MCPyV infection and participate in regulation of the immune response in MCC, and may influence outcome of MCC patients. 相似文献5.
BACKGROUND.
Currently, little is known regarding the potential prognostic value of histologic features in primary cutaneous neuroendocrine (Merkel cell) carcinomas (MCC).METHODS.
In a retrospective review of the tumor histology and clinical outcome data (median follow‐up, 51 months; range, 3‐224 months) of 156 patients with a diagnosis of MCC, the following histologic features were evaluated: tumor thickness, tumor size (greatest dimension of the tumor), microanatomic compartment involved by tumor (dermis and/or subcutis and/or deeper), tumor growth pattern (nodular circumscribed vs infiltrative), lymphovascular invasion (LVI), tumor‐infiltrating lymphocytes, tumor necrosis, ulceration, and solar elastosis.RESULTS.
The overall 5‐year survival rate was 67.5%. On univariate analysis, parameters that were associated significantly with survival were tumor thickness (P = .001), tumor size (P = .0002), deepest anatomic compartment involved by tumor (P = .0003), tumor growth pattern (P = .003), LVI (P < .00001), tumor‐infiltrating lymphocytes (P = .05), and solar elastosis (P = .04). On multivariate analysis, the presence of a nodular growth pattern, low tumor depth, and absence of LVI were associated with longer survival.CONCLUSIONS.
In addition to the known prognostic value of tumor stage, 3 histologic features were identified to have prognostic significance: tumor thickness (depth of tumor invasion), the presence of LVI, and tumor growth pattern. Cancer 2008. © 2008 American Cancer Society. 相似文献6.
Linde M. van Veenendaal MD Alexander C. J. van Akkooi MD PhD Cees Verhoef MD PhD Dirk Jan Grünhagen MD PhD W. Martin C. Klop MD PhD Gerlof D. Valk MD PhD Margot E. T. Tesselaar MD PhD 《Journal of surgical oncology》2018,117(8):1768-1775
Background
Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine carcinoma of the skin.Aim
To describe clinical outcome and prognostic factors of MCC patients in two expert‐centers.Method
Patients with histologically confirmed MCC in 1990‐2014 were included. Data on patient, tumor characteristics and treatment were retrospectively collected.Results
A total of 351 Patients were evaluated, 153 (44%) males, median age 74 years (range 28‐94). Median follow‐up time was 28 months (IQR 13‐58). Median primary tumor size was 17 mm (range 2‐135). At time of diagnosis 112 (32%) patients had lymph node metastases. The cohorts′ 5‐year overall survival (OS) was 58%. Using a competing risk analysis the 5‐year relapse and MCC related death was 42% and 22%. Adjuvant radiation therapy (XRT) was associated with reduced recurrence (SDH 0.54; CI 0.3‐0.9). Nodal involvement (SDH 2.7; CI 1.1‐6.6) and the male gender were associated with higher MCC related death (SDH 3.1; CI 1.2‐7.9)Conclusion
In a large cohort a low MCC related death, in the presence of a low OS was seen. This indicates that a significant number of MCC patients die due to other causes than MCC. Adjuvant XRT was associated with relapse. Male gender and nodal metastasis were associated with MCC related death. 相似文献7.
Loyo M Schussel J Colantuoni E Califano J Brait M Kang S Koch WM Sidransky D Westra WH Taube JM 《British journal of cancer》2012,106(7):1314-1319
Background:
Adjuvant treatment can dramatically improve the survival of patients with metastatic Merkel cell carcinoma (MCC), making early, accurate detection of nodal disease critical. The purpose of this study was to correlate Merkel cell virus (MCV) detection with histopathologic disease in sentinel lymph nodes (SLNs) of MCC.Methods:
Merkel cell carcinoma cases with SLN (n=25) were compared with negative controls (n=27). Viral load was obtained by quantitative polymerase chain reaction (PCR) for regions VP1 and LT3 of MCV. Histopathologic disease and viral load were correlated.Results:
Merkel cell virus was detected in 16 out of 17 (94%) of primary MCC (mean viral load (MVL)=1.44 copies per genome). Viral load in the negative controls was <0.01 copies per genome. Merkel cell carcinoma was present in 5 out of 25 (20%) SLN by histopathology, and MCV was detected in 11 out of 25 (44%) MCC SLN (MVL=1.68 copies per genome). In all, 15 out of 25 (60%) SLN showed correlation between histologic and MCV results. In all, 2 out of 25 (8%) samples were histopathologically positive and PCR negative. Of note, 8 out of 25 (32%) samples had detectable MCV without microscopic disease.Conclusion:
Patients with positive SLN for MCV even if negative by histopathology were identified. The application of molecular techniques to detect subhistologic disease in SLN of MCC patients may identify a subset of patients who would benefit from adjuvant nodal treatment. 相似文献8.
Waltari M Sihto H Kukko H Koljonen V Sankila R Böhling T Joensuu H 《International journal of cancer. Journal international du cancer》2011,129(3):619-628
Most Merkel cell carcinomas (MCCs) contain Merkel cell polyomavirus (MCPyV) DNA, and the virus likely has a pivotal role in tumor pathogenesis. p53 and the KIT receptor tyrosine kinase have also been implicated in MCC pathogenesis, but little is known about their association with MCPyV infection. We identified 207 patients diagnosed with MCC in Finland in 1979-2004 and reviewed the histological diagnoses. Adequate clinical information, tumor tissue and DNA were available from 87 confirmed MCC cases. Presence of MCPyV DNA was assessed using quantitative PCR; p53, KIT, phospho-KIT, stem cell factor (SCF) and PDGFRα expression using immunohistochemistry and presence of mutations in KIT exons 9, 11, 13 and 17 and PDGFRA exons 10, 12, 14 and 18 using DNA sequencing. Most (77.0%) of the 87 tumors contained MCPyV DNA and 37 (42.5%) expressed KIT, whereas PDGFRα, p53, SCF and pKIT expression was less common (31.9, 22.8, 8.6 and 4.8%, respectively). No KIT or PFGFRA mutations were detected, but 10 (12.5%) of the 80 tumors studied harbored common PDGFRA exon 10 S478P substitution. Tumor p53 and KIT expression were associated with absence of MCPyV DNA (p = 0.01 and 0.009, respectively). Tumor p53 expression was associated with unfavorable MCC-specific survival (p = 0.021) and overall survival (p = 0.046), but tumor KIT expression only when stratified by presence of MCPyV DNA. The results suggest that p53 and KIT expression are associated with absence of MCPyV DNA in MCC, and that the molecular pathogenesis of MCC is multifactorial. 相似文献
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Merkel cell carcinoma: changing incidence trends 总被引:3,自引:0,他引:3
Hodgson NC 《Journal of surgical oncology》2005,89(1):1-4
BACKGROUND: The objective of this study was to define the incidence trends of Merkel cell carcinoma (MCC), a rare and aggressive cutaneous malignancy. MATERIALS AND METHODS: All cases of MCC of the skin between 1986 and 2001 were identified using the surveillance, epidemiology, and end results (SEER) program. Overall age-adjusted, gender-specific, age-specific, stage-specific, and regional incidence rates were calculated. All rates are per 100,000 and age-adjusted to the 2000 US standard population. Estimated annual percent change (EAPC) was calculated using a linear least squares model. RESULTS: A total of 1,124 cases of MCC were identified in the SEER registries. The rate of MCC increased from 0.15 cases per 100,000 in 1986 to 0.44 cases per 100,000 in 2001. The EAPC for the time period was 8.08%. This was statistically significant (95% CI: 6.29, 9.90, P-value < 0.05). Age-specific incidence (5-year age groups) were highest in the elderly, 4.28 per 100,000 in the 85+ age group. CONCLUSIONS: MCC incidence rates have increased threefold over the 1986-2001 period. Rates are highest in the elderly population. Further etiologic studies and identification of high-risk populations are warranted. 相似文献
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Helena Faust Kristin Andersson Johanna Ekström Maria Hortlund Trude Eid Robsahm Joakim Dillner 《International journal of cancer. Journal international du cancer》2014,134(4):844-848
Merkel cell carcinoma (MCC) is a rare type of skin cancer that has a characteristically increased incidence among immunosuppressed subjects. The DNA of Merkel cell polyomavirus (MCV) is regularly found in most MCC tumors. We investigated whether Merkel cell polyomavirus (MCV) infection increases the risk for future MCC. Two large biobank cohorts (Southern Sweden Microbiology Biobank and the Janus Biobank), containing samples from 856,000 healthy donors, were linked to the Cancer Registries in Sweden and Norway to identify cases of MCC occurring up to 30 years after donation of a serum sample. For each of the 22 cases (nine males and 13 females), four matched controls were included. The serum samples were analyzed with an MCV neutralization assay and for IgG antibodies to MCV pseudovirions, using JC polyomavirus and cutaneous human papillomaviruses as control antigens. An increased risk for future MCC was associated both with high levels of MCV antibodies [OR 4.4, 95% CI 1.3–17.4] and with MCV neutralizing activity (OR 5.3, 95% CI 1.3–32.3). In males, MCV seropositivity was not associated to MCC risk, whereas the risk was strongly increased in females, both for high levels of MCV antibodies (OR 7.0, 95% CI 1.6–42.8) and for MCV neutralizing activity (OR 14.3, 95% CI 1.7–677). In conclusion, we found prospective evidence that MCV infection is associated with an increased risk for future MCC, in particular among females. 相似文献
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Yamana N Sueyama H Hamada M 《International journal of clinical oncology / Japan Society of Clinical Oncology》2004,9(3):210-212
A 54-year-old woman presented with cardiac metastasis of a Merkel cell carcinoma. Chemotherapy was not effective for the metastasis sites; therefore, radiotherapy was performed for the metastatic cardiac tumors, and it reduced the volume of the cardiac tumors. Cardiac metastasis from Merkel cell carcinoma is rare. Radiotherapy for metastatic cardiac tumors from Merkel cell carcinoma is useful as palliative treatment when the response to chemotherapy is poor. 相似文献
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Susan M. Snodgrass Howard Landy Arnold M. Markoe Lynn Feun 《Journal of neuro-oncology》1994,22(3):231-234
We describe a 61-year-old man with a multiple neurologic complication of Merkel cell carcinoma, a rare skin cancer. An enhancing brain mass, and cytologically proven leptomeningeal disease produced a succession of symptoms including seizures, bilateral radiculopathies, myoclonus, a cauda equina syndrome and altered mental status. Aggressive treatment prolonged his survival marginally. 相似文献
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David Schrama Eva-Maria Sarosi Christian Adam Cathrin Ritter Ulrike Kaemmerer Eva Klopocki Eva-Maria König Jochen Utikal Jürgen C. Becker Roland Houben 《International journal of cancer. Journal international du cancer》2019,145(4):1020-1032
Merkel cell carcinoma (MCC), an aggressive neuroendocrine skin tumor, is a polyomavirus-induced human cancer. To study the causal relationship of MCC carcinogenesis with the integrated Merkel cell polyomavirus (MCPyV) in detail, well-characterized MCC cell lines are needed. Consequently, in the current study, we established and characterized six MCPyV-positive MCC cell lines. Microarray-based comparative genomic hybridization revealed a stable genome carrying only a limited number of chromosomal gains and deletions. All cell lines expressed MCC markers Keratin-20 and neuron-specific enolase as well as truncated MCPyV-encoded large T antigen (LT). For five cell lines, we were able to identify the MCPyV-integration sites in introns of different genes. The LT-truncating stop codon mutations and integration sites were affirmed in the respective clinical patient samples. Inverse PCR suggested that three of the cell lines contained MCPyV genomes as concatemers. This notion was confirmed for the two cell lines with known integration sites. Importantly, our observation of distinct stop codon mutations in cell lines with concatemeric MCPyV integration indicates that these LT-truncating mutations occur before integration. In summary, we provide the detailed characterization of six MCPyV-positive MCC cell lines, which are likely to serve as valuable tools in future MCC research. 相似文献
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This case report of recurrent Merkel cell carcinoma between radiotherapy fields for primary site and regional nodes supports the value of postoperative radiotherapy to the primary site, the intervening lymphatics and draining nodes. 相似文献
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Lok B Khan S Mutter R Liu J Fields R Pulitzer M Shi W Zhang Z Kraus D Pfister D Busam KJ Brownell I Lee N 《Cancer》2012,118(16):3937-3944
BACKGROUND.
The role of radiotherapy (RT) in the management of Merkel cell carcinoma (MCC) is controversial. The authors of this report evaluated the rates and patterns of failure in a selected group of patients who underwent RT for MCC of the head and neck (HN).METHODS.
The records of 145 consecutive patients with MCC of the HN who presented to the authors' institution between 1988 and 2009 were reviewed. Only patients who received RT at the institution were included. The cumulative incidence of locoregional failure (LRF), distant metastatic failure (DMF), disease progression (DP) and disease‐specific death (DSD) were estimated with death as a competing risk.RESULTS.
Forty‐eight patients were identified. The median follow‐up was 51 months (range, 6‐220 months) for living patients. LRF developed in 5 patients (10%), and those patients had a median time to recurrence of 3 months. Two of the 5 LRFs were local and developed at the edge of the treatment field; the remaining 3 LRFs were in lymph nodes and occurred outside the treatment field. DMF developed in 12 patients (25%). The estimated 5‐year cumulative incidences of LRF, DP, and DSD were 10%, 30%, and 21%, respectively. Acute toxicities included 5 episodes (10%) of grade 3 dermatitis and 1 episode (2%) of grade 3 mucositis.CONCLUSIONS.
The authors report a site‐specific series of patients with HN MCC who received RT. In this group of patients with adverse features, RT was well tolerated, and LRF was low. The propensity for MCC to recur at the edge of the treatment field suggests that generous margins are appropriate when RT is administered. Cancer 2012. © 2011 American Cancer Society. 相似文献18.
RICHARD FOSTER GRAHAM STEVENS MATTHEW EGAN 《Journal of Medical Imaging and Radiation Oncology》1994,38(3):231-232
An unusual case of Merkel cell carcinoma is presented in which the time course to development of nodal and haematogenous metastases was protracted and the predominant site of metastatic disease was small bowel. 相似文献
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Masahiro Shuda Reety Arora Hyun Jin Kwun Huichen Feng Ronit Sarid María‐Teresa Fernández‐Figueras Yanis Tolstov Ole Gjoerup Mahesh M. Mansukhani Steven H. Swerdlow Preet M. Chaudhary John M. Kirkwood Michael A. Nalesnik Jeffrey A. Kant Lawrence M. Weiss Patrick S. Moore Yuan Chang 《International journal of cancer. Journal international du cancer》2009,125(6):1243-1249
Merkel cell polyomavirus (MCV) is a recently discovered human virus closely related to African green monkey lymphotropic polyomavirus. MCV DNA is integrated in ~80% of Merkel cell carcinomas (MCC), a neuroendocrine skin cancer linked to lymphoid malignancies such as chronic lymphocytic leukemia (CLL). To assess MCV infection and its association with human diseases, we developed a monoclonal antibody that specifically recognizes endogenous and transfected MCV large T (LT) antigen. We show expression of MCV LT protein localized to nuclei of tumor cells from MCC having PCR quantified MCV genome at an average of 5.2 (range 0.8–14.3) T antigen DNA copies per cell. Expression of this putative viral oncoprotein in tumor cells provides the mechanistic underpinning supporting the notion that MCV causes a subset of MCC. In contrast, although 2.2% of 325 hematolymphoid malignancies surveyed also showed evidence for MCV infection by DNA PCR, none were positive at high viral copy numbers, and none of 173 lymphoid malignancies examined on tissue microarrays expressed MCV LT protein in tumor cells. As with some of the other human polyomaviruses, lymphocytes may serve as a tissue reservoir for MCV infection, but hematolymphoid malignancies associated with MCC are unlikely to be caused by MCV. © 2009 UICC 相似文献