Recurrence Of Merkel Cell Carcinoma Research Articles

The Role of Sentinel Lymph Node Biopsy in the Management of Merkel Cell Carcinoma: A Systematic Review and Meta-analysis.

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy with high metastatic potential. Sentinel lymph node biopsy (SLNB) is used to assess locoregional spread, facilitate staging, and inform prognosis. Positive nodal status is associated with higher recurrence rates and reduced overall survival. A systematic search was conducted. Eligible articles included patients diagnosed with MCC, who would be candidates for or who had SLNB. The Covidence tool was used for screening and data extraction, including additional treatments, disease-free survival, overall survival, and recurrence. Methodological quality was assessed using the Newcastle-Ottowa Scale criteria. SLNB was associated with increased likelihood of completion lymphadenectomy (223 versus 41), regional radiotherapy (2167 versus 808), and systemic chemotherapy (138 versus 31). Overall survival for patients undergoing SLNB was 81% at 2 years, 75% at 3 years, and 72% at 5 years (odds ratio: 0.79). Hazard ratio for positive SLNB versus negative was 3.36 (P < 0.001). Five-year disease recurrence was 23.3% in patients undergoing SLNB. Lymph node metastases are associated with reduced overall survival and increased recurrence of MCC. Determining nodal status early can inform prognosis, facilitate staging, and determine need for adjuvant treatment. Adjuvant treatments are associated with reduced mortality and improved overall survival; SLNB is an important influencer of their use. Early prophylactic intervention should be considered in MCC in both positive and negative nodal status to improve overall outcomes. Widespread use of SLNB will allow more accurate assessment of the role of nodal status on adjuvant treatment and long-term outcomes.

Merkel cell carcinoma recurrence risk estimation is improved by integrating factors beyond cancer stage: A multivariable model and web-based calculator

Merkel cell carcinoma (MCC) recurs in 40% of patients. In addition to stage, factors known to affect recurrence risk include: sex, immunosuppression, unknown primary status, age, site of primary tumor, and time since diagnosis. Create a multivariable model and web-based calculator to predict MCC recurrence risk more accurately than stage alone. Data from 618 patients in a prospective cohort were used in a competing risk regression model to estimate recurrence risk using stage and other factors. In this multivariable model, the most impactful recurrence risk factors were: American Joint Committee on Cancer stage (P<.001), immunosuppression (hazard ratio 2.05; P<.001), male sex (1.59; P=.003) and unknown primary (0.65; P=.064). Compared to stage alone, the model improved prognostic accuracy (concordance index for 2-year risk, 0.66 vs 0.70; P<.001), and modified estimated recurrence risk by up to 4-fold (18% for low-risk stage IIIA vs 78% for high-risk IIIA over 5years). Lack of an external data set for model validation. As demonstrated by this multivariable model, accurate recurrence risk prediction requires integration of factors beyond stage. An online calculator based on this model (at merkelcell.org/recur) integrates time since diagnosis and provides new data for optimizing surveillance for MCC patients.

Insights into anti-tumor immunity via the polyomavirus shared across human Merkel cell carcinomas.

Understanding and augmenting cancer-specific immunity is impeded by the fact that most tumors are driven by patient-specific mutations that encode unique antigenic epitopes. The shared antigens in virus-driven tumors can help overcome this limitation. Merkel cell carcinoma (MCC) is a particularly interesting tumor immunity model because (1) 80% of cases are driven by Merkel cell polyomavirus (MCPyV) oncoproteins that must be continually expressed for tumor survival; (2) MCPyV oncoproteins are only ~400 amino acids in length and are essentially invariant between tumors; (3) MCPyV-specific T cell responses are robust and strongly linked to patient outcomes; (4) anti-MCPyV antibodies reliably increase with MCC recurrence, forming the basis of a standard clinical surveillance test; and (5) MCC has one of the highest response rates to PD-1 pathway blockade among all solid cancers. Leveraging these well-defined viral oncoproteins, a set of tools that includes over 20 peptide-MHC class I tetramers has been developed to facilitate the study of anti-tumor immunity across MCC patients. Additionally, the highly immunogenic nature of MCPyV oncoproteins forces MCC tumors to develop robust immune evasion mechanisms to survive. Indeed, several immune evasion mechanisms are active in MCC, including transcriptional downregulation of MHC expression by tumor cells and upregulation of inhibitory molecules including PD-L1 and immunosuppressive cytokines. About half of patients with advanced MCC do not persistently benefit from PD-1 pathway blockade. Herein, we (1) summarize the lessons learned from studying the anti-tumor T cell response to virus-positive MCC; (2) review immune evasion mechanisms in MCC; (3) review mechanisms of resistance to immune-based therapies in MCC and other cancers; and (4) discuss how recently developed tools can be used to address open questions in cancer immunotherapy. We believe detailed investigation of this model cancer will provide insight into tumor immunity that will likely also be applicable to more common cancers without shared tumor antigens.

From database to clinic: Using a multivariable recurrence risk calculator to guide Merkel cell carcinoma surveillance

Background and aims: Merkel cell carcinoma (MCC) has a high propensity (∼40%) to recur after initial treatment. Although AJCC stage at diagnosis provides important prognostic information, other patient and tumor characteristics are correlated with poorer outcomes, including male sex, advanced age, and immune suppression. Currently, there are no tools to assist clinicians in integrating stage and other significant factors to provide personalized recurrence risk estimates for MCC. We present an online tool that based on a multivariable model for predicting MCC recurrence risk which is more accurate than stage alone.

825 Assessment of a circulating tumor DNA test for detecting recurrence of Merkel cell carcinoma

Approximately 40% of patients with Merkel cell carcinoma (MCC) develop recurrence or metastasis. Early detection can result in better outcomes, and effective surveillance is critical in MCC management. We assessed whether circulating tumor DNA (ctDNA) can accurately detect clinically evident and/or occult MCC. We used the SignateraTM platform in which tumor-specific mutations are identified from archival tumors, and blood is interrogated for those mutations. Since April 2020, we have collected longitudinal ctDNA samples from 95 MCC patients.

The relationship between circulating tumor DNA with Merkel cell carcinoma tumor burden and detection of recurrence.

9566 Background: Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of 40%. Early detection of recurrence can improve outcomes, and effective surveillance is crucial for management of patients with MCC. While Merkel cell polyomavirus (MCPyV) oncoprotein serology is useful in surveillance for MCPyV-positive MCC tumors, patients with MCPyV-negative tumors have no available blood biomarkers and require frequent imaging. This prospective, multicenter study assessed whether circulating tumor DNA (ctDNA) can assess disease burden and detect recurrence regardless of virus status. Methods: A total of 328 blood samples were collected from 125 patients at various time points with a median follow-up of 6 months (range: 0-21 months) between April 2020 to January 2022. Whole-exome sequencing was performed on tumor tissue and matched normal blood to identify a set of somatic, clonal single nucleotide variants, which were tracked in subsequent blood (plasma) samples using a personalized and multiplex PCR-NGS based ctDNA assay (Signatera). Clinically evident disease was defined as MCC noted either by physical exam or by imaging, and molecular evidence of disease was defined as a positive ctDNA test. Surveillance phase began once there was no clinically evident or molecular evidence of disease. Results: Among 125 patients, 47 (38%) had clinically evident MCC and all were found to be ctDNA-positive at the first time point (sensitivity: 100%; 95% CI: 91-100%). Of the 47, 24 were newly diagnosed with MCC and had a median primary tumor size of 2.2 cm (range 0.5-8.5 cm) and a median ctDNA value of 26 mean tumor molecules (MTM)/mL (range: 0.08-1470 MTM/mL). Primary tumor diameter and ctDNA value were strongly correlated (Spearman’s r = 0.81, p &lt; 0.001). Of the 125 patients, 73 (58%) patients were assessed in the surveillance setting and had a total of 152 plasma samples available for longitudinal ctDNA testing. Over this period, 7 ctDNA tests were positive while 145 were negative. After a positive test, 5/7 developed a clinically evident recurrence (4 within 60 days). Of the remaining 2 without clinical recurrence, one had &lt; 60 days of follow-up at time of data analysis. The estimated risk of recurrence, accounting for incomplete follow-up, was 57% within 60 days of a positive ctDNA test (n = 7 tests). In contrast, after a negative ctDNA test (n = 145 tests), the risk of recurrence was 0% within 60 days and 3% between 60-90 days. Conclusions: To our knowledge, this is the largest study to explore ctDNA testing in MCC patients. This study demonstrates that ctDNA testing can detect MCC recurrence early and is a promising clinical surveillance tool regardless of tumor viral status.

Sentinel lymph node biopsy in Merkel cell carcinoma: A multi-institutional study from the Pan-Canadian Merkel Cell Collaborative.

9583 Background: There is controversy regarding sentinel lymph node biopsy (SLNB) in clinically node-negative Merkel Cell Carcinoma (MCC). We compared MCC recurrence and survival between patients who did versus did not undergo a SLNB. Methods: Patients with MCC across 13 Canadian centers were reviewed, from 2000-2018. Of a total cohort of 750 patients, 485 had clinically node-negative disease at presentation. A propensity score was created. The association between SLNB and local, regional and distant recurrence, and cancer-specific and overall survival were evaluated using competing risks and Cox proportional hazards regression. Results: 195 patients (40.2%) underwent a SLNB. SLNB was performed more commonly in younger, healthier patients with MCC located in the extremities or torso (Table). The results of 177 SLNBs were available; 60 (33.9%) were positive. SLNB-positive patients underwent completion dissection (n=15, 25%), completion dissection and nodal radiation (n=22, 36.7%), nodal radiation alone (n=18, 30%) or observation (n=5, 8.3%). Patients who did not undergo a SLNB underwent nodal radiation alone (n=40, 13.8%) or observation (n=250, 86.2%). The median follow-up was 2.7 years (range 0.2-14.4). The regional recurrence rate was 14.5% (n=17) among SLNB-negative versus 15% (n=9) among SLNB-positive patients. Among patients who did not undergo a SLNB, the regional recurrence rate was 25.2% (n=63) among those who underwent observation and 15% (n=6) among those who received nodal radiation alone. After propensity score matching, SLNB patients had a lower risk of regional recurrence (sHR 0.54 95% CI 0.34-0.86 p=0.01) and improved overall survival (HR 0.32 95% CI 0.23-0.45 p&lt;0.01), but there was no difference in local recurrence (sHR 0.92 95% CI 0.50-1.69 p=0.79), distant recurrence (sHR 0.88 95% CI 0.52-1.49 p=0.63), or cancer-specific survival (HR 0.67 95% CI 0.31-1.45 p=0.31). Conclusions: SLNB is associated with a reduced risk of regional recurrence and improved overall survival. The role of SLNB in selecting patients for emerging therapies, such as immunotherapy, needs to be evaluated. [Table: see text]

Recurrence and Mortality Risk of Merkel Cell Carcinoma by Cancer Stage and Time From Diagnosis

Merkel cell carcinoma (MCC) often behaves aggressively; however, disease-recurrence data are not captured in national databases, and it is unclear what proportion of patients with MCC experience a recurrence (estimates vary from 27%-77%). Stage-specific recurrence data that includes time from diagnosis would provide more precise prognostic information and contribute to risk-appropriate clinical surveillance. To estimate risk of stage-specific MCC recurrence and mortality over time since diagnosis. This prospective cohort study included 618 patients with MCC who were prospectively enrolled in a Seattle-based data repository between 2003 and 2019. Of these patients, 223 experienced a recurrence of MCC. Data analysis was performed July 2019 to November 2021. Stage-specific recurrence and survival, as well as cumulative incidence and Kaplan-Meier analyses. Among the 618 patients included in the analysis (median [range] age, 69 [11-98] years; 227 [37%] female), the 5-year recurrence rate for MCC was 40%. Risk of recurrence in the first year was high (11% for patients with pathologic stage I, 33% for pathologic stage IIA/IIB, 30% for pathologic stage IIIA, 45% for pathologic stage IIIB, and 58% for pathologic stage IV), with 95% of recurrences occurring within the first 3 years. Median follow-up among living patients was 4.3 years. Beyond stage, 4 factors were associated with increased recurrence risk in univariable analyses: immunosuppression (hazard ratio [HR], 2.4; 95% CI, 1.7-3.3; P < .001), male sex (HR, 1.9; 95% CI, 1.4-2.5; P < .001), known primary lesion among patients with clinically detectable nodal disease (HR, 2.3; 95% CI, 1.4-4.0; P = .001), and older age (HR, 1.1; 95% CI, 1.0-1.3; P = .06 for each 10-year increase). Among 187 deaths in the cohort, 121 (65%) were due to MCC. The MCC-specific survival rate was strongly stage dependent (95% at 5 years for patients with pathologic stage I vs 41% for pathologic stage IV). Among patients presenting with stage I to II MCC, a local recurrence (17 arising within/adjacent to the primary tumor scar) did not appreciably diminish survival compared with patients who had no recurrence (85% vs 88% MCC-specific survival at 5 years). In this cohort study, the MCC recurrence rate (approximately 40%) was notably different than that reported for invasive melanoma (approximately 19%), squamous cell carcinoma (approximately 5%-9%), or basal cell carcinoma (approximately 1%-2%) following definitive therapy. Because more than 90% of MCC recurrences arise within 3 years, it is appropriate to adjust surveillance intensity accordingly. Stage- and time-specific recurrence data can assist in appropriately focusing surveillance resources on patients and time intervals in which recurrence risk is highest.

Pan-immune-inflammation value independently predicts disease recurrence in patients with Merkel cell carcinoma

PurposeWe aimed to determine whether the pan-immune-inflammation value (PIV) of patients with Merkel cell carcinoma (MCC) at primary diagnosis differs from controls and whether it is associated with disease stage and outcome.MethodsIn this retrospective study, we recruited MCC patients with stage I–III. PIV was calculated from absolute complete blood cell counts obtained within one week at MCC diagnosis as follows: [neutrophils (103/mm3) × platelets (103/mm3) × monocytes (103/mm3)]/lymphocytes (103/mm3). As controls, we studied age–gender-matched cutaneous melanoma (CM, stage I–III) patients and healthy controls (HC). Univariate and multivariate statistics were used.ResultsThe median PIV in MCC patients was significantly increased compared to both CM patients as well as healthy controls. PIV of MCC patients in stage II and III was significantly higher compared to stage I patients. ROC analysis revealed that MCC recurrence was significantly associated with a PIV greater than 372 [p < 0.0001, Youden index 0.58; hazard ratio: 4 (95% confidence interval: 1.7 to 9.2)]. In multivariate analysis, only a PIV greater than 372 and higher MCC stage were determined as independent predictors for disease recurrence.ConclusionWe determined, for the first time, the prognostic ability of the promising blood-based biomarker PIV in MCC patients and observed that PIV is increased in MCC patients in dependence on disease stage and independently predicts MCC recurrence.

Changes in Merkel Cell Oncoprotein Antibodies (AMERK) After Radiation Therapy (RT) in Curatively Treated Merkel Cell Carcinoma (MCC) and Association With Recurrence

Serum antibodies to the Merkel oncoprotein (AMERK) are expressed in approximately 50% of patients (pts) with MCC and can be used to monitor for recurrence. This study aimed to describe changes in AMERK levels after RT for MCC and identify patterns that predict disease recurrence.Pts with MCC were identified retrospectively if they had curative-intent postoperative or definitive RT at a single institution from 2010-2020. Pts treated with RT at other institutions were excluded due to inability to assess RT quality, previously shown to impact MCC outcomes. All patients had a pre-RT AMERK and at least one post-RT AMERK (median no.5, range 1-10). Changes in AMERK were described and compared using Wilcoxon rank sum test for two-sample non-parametric comparisons and the Chi-square test for recurrence association.Of 202 MCC pts treated at our institution, 61 curatively treated pts had a pre-RT AMERK test performed. AMERK was detectable in 27 of the 61 patients (44%) with a median value of 2950 (range 127 to 115,000 [upper limit of assay]). Detectable pre-RT AMERK was associated with decreased MCC recurrence compared to pts with undetectable pre-RT AMERK (OR 0.35, 95% CI 0.12,1.04). The 27 pts with positive pre-RT AMERK had Stages I (n = 5), II (n = 1), and III (n = 21) from sites of the extremity (n = 14), head/neck (n = 7), unknown primary (n = 4), and trunk (n = 2). Pts with gross disease at RT (n = 11) had higher median pre-RT AMERK than those without gross disease at RT (n = 16) (median 8550 vs. 1840, P = 0.06). With a median follow-up of 20 months (range 2.3-61.3), there were 7 recurrences, all were distant. All AMERK-positive pts were alive at last follow-up except for the single immunosuppressed pt who recurred and died of MCC. A ≥50% AMERK reduction by 6-months after RT had a sensitivity of 95% (95% CI 74-100) for detecting disease-free status and a negative predictive value of 83% (95% CI 41-97%), reflecting the probability of recurrence if < 50% AMERK at 6-months. The sensitivity and negative predictive values of ≥50% 6-month AMERK reduction both increased to 100% respectively when excluding pre-RT borderline AMERK values (75-150). One pt who recurred after ≥50% AMERK reduction from an initial > 115,00 value, had initiated high-dose corticosteroids for a comorbid condition. Out of 8 recurrence-free patients with AMERK levels available more than 2-years post-RT, 50% (4 of 8) had detectable AMERK (range 239-1960, > 2 years post-RT).Reduction in AMERK post-RT can be used to predict MCC recurrence, which rarely occurs with a sustained ≥50% reduction by 6-months post-RT. AMERK may be persistently detectable in recurrence-free pts beyond 2 years. Further research is needed to determine the impact of corticosteroid initiation on AMERK levels.

A Unique Case of Metastatic Merkel Cell Carcinoma Without a Dermatologic Primary

INTRODUCTION: Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma. It is predominately seen on sun-exposed areas in elderly patients or in immunocompromised populations. About 80% of cases are associated with Merkel cell polyomavirus, suggesting a viral-induced oncogenesis. The most common presentation is a rapidly growing pink-red, dome-shaped nodule on the skin. We present a rare case of metastatic MCC diagnosed by endoscopic ultrasound of an incidentally discovered portacaval lymph node. CASE DESCRIPTION: An 81-year-old male with no dermatologic history presented to the emergency department with fever and chills. His fever was documented at 39.3 deg C, was tachycardic at a HR of 117, and a leukocyte count of 11.6. He also endorsed unintentional weight loss of nearly 20 lbs. The ED obtained abdomen/pelvis which noted radiographic evidence of diverticulitis as well as a large portacaval lymph node measuring 8.6 x 4.5 cm. He was discharged oral antibiotics for treatment of diverticulitis with plan for outpatient endoscopic evaluation of the enlarged lymph node. An upper endoscopy was performed and no intraluminal masses or lesions were noted. Next, linear endoscopic ultrasound was performed which identified the portacaval lymph node which measured 42.3 mm x 37.4 mm. We used a 25-gauge fine needle biopsy with on-site cytopathology confirming cellular adequacy. Cytology demonstrated positive CK20, CD56, and synaptophysin with high rate of KI-67 and negative TTF-1 consistent with neuroendocrine differentiation and a diagnosis of Merkel cell carcinoma. The patient was referred to oncology for further management. Staging workup with a PET/CT noted metastatic disease also involving the right shoulder and he was subsequently initiated on systemic immunotherapy with the checkpoint inhibitor pembrolizumab.1275_A.tif Figure 1: Coronal view of CT abdomen/pelvis which identified a bilobed porta-caval lymph node measuring 55.2 mm x 64.5 mm.1275_B.tif Figure 2: Endoscopic Ultrasound view of porta-caval lymph node measured at 48.5 mm sampled via FNA which diagnosed the finding of Merkel Cell Carcinoma.DISCUSSION: MCC is a rare, aggressive neuroendocrine carcinoma that usually presents with a skin lesion. Only 0.4% of cases have been reported in locations other than the skin. While there are multiple reports of recurrence of MCC in the gastrointestinal tract, very few cases present initially without an apparent skin lesion. Gastroenterologists should be aware of this uncommon neoplasm, given that MCC is an aggressive malignancy that requires prompt diagnosis and oncologic treatment in order to optimize patient outcomes.

Distant recurrence of Merkel cell carcinoma after spontaneous regression

Distant recurrence of Merkel cell carcinoma after spontaneous regression

Merkel cell carcinoma of the upper extremity

Merkel cell carcinoma is a rare, aggressive skin cancer which is usually characterized by lymph node involvement, distant metastases, and disease relapse. It is commonly seen in elder people and it affects the head, neck, and extremities. It can be difficult to differentiate macroscopically Merkel cell carcinoma from other small cells neoplasms. Herein is the case of a 66-year-old male patient, admitted in our department for a local recurrence of Merkel cell carcinoma on the posterolateral side of the proximal third right forearm. The surgical treatment included wide local excision with 2 cm safety margins, sentinel lymph node biopsy and grafting the residual defect using split-thickness skin. Postoperative no local or general complications were encountered. The final histological examination revealed Merkel cell carcinoma with all the excisional margins free of tumor and two positive sentinel lymph nodes. The patient has performed postoperative radiotherapy with monthly clinical examination. Six months after the last surgery and after undergoing radiotherapy, there were no local or distant signs of recurrence. Due to high rates of recurrence, close surveillance is demanded.

Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study.

Merkel cell carcinoma (MCC) is an aggressive skin cancer with a recurrence rate of >40%. Of the 2000 MCC cases per year in the United States, most are caused by the Merkel cell polyomavirus (MCPyV). Antibodies to MCPyV oncoprotein (T-antigens) have been correlated with MCC tumor burden. The present study assesses the clinical utility of MCPyV-oncoprotein antibody titers for MCC prognostication and surveillance. MCPyV-oncoprotein antibody detection was optimized in a clinical laboratory. A cohort of 219 patients with newly diagnosed MCC were followed prospectively (median follow-up, 1.9 years). Among the seropositive patients, antibody titer and disease status were serially tracked. Antibodies to MCPyV oncoproteins were rare among healthy individuals (1%) but were present in most patients with MCC (114 of 219 patients [52%]; P < .01). Seropositivity at diagnosis independently predicted decreased recurrence risk (hazard ratio, 0.58; P = .04) in multivariate analyses adjusted for age, sex, stage, and immunosuppression. After initial treatment, seropositive patients whose disease did not recur had rapidly falling titers that became negative by a median of 8.4 months. Among seropositive patients who underwent serial evaluation (71 patients; 282 time points), an increasing oncoprotein titer had a positive predictive value of 66% for clinically evident recurrence, whereas a decreasing titer had a negative predictive value of 97%. Determination of oncoprotein antibody titer assists in the clinical management of patients with newly diagnosed MCC by stratifying them into a higher risk seronegative cohort, in which radiologic imaging may play a more prominent role, and into a lower risk seropositive cohort, in which disease status can be tracked in part by oncoprotein antibody titer. Cancer 2017;123:1464-1474. © 2016 American Cancer Society.

Evaluating blood levels of neuron specific enolase, chromogranin A, and circulating tumor cells as Merkel cell carcinoma biomarkers.

Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine skin cancer. Although used to monitor MCC patients, the clinical utility of neuron-specific enolase (NSE) and chromogranin A (ChrA) blood levels is untested. EpCAM-positive circulating tumor cells (CTC) reflect disease status in several epithelial tumors. Here we investigate the use of NSE and ChrA blood levels and CTC counts as biomarkers for MCC disease behavior. NSE and ChrA blood levels from 60 patients with MCC were retrospectively analyzed; 30 patients were additionally screened for CTC. Biomarker values were correlated to clinical parameters. Despite routine use by some physicians, NSE and ChrA blood levels did not correlate with progression free survival, disease specific survival, or MCC recurrence. We found CTC in 97% of tested MCC patients. CTC counts were elevated in patients with active disease, suggesting their potential use in monitoring MCC. NSE and ChrA levels were not effective in predicting outcomes or detecting recurrences of MCC. In contrast, CTC counts have potential utility as a biomarker for MCC disease behavior.

Effect of host, tumor, diagnostic, and treatment variables on outcomes in a large cohort with Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes. To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival. Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes. Host, tumor, diagnostic, and treatment factors. Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific). We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes. Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.

Ileocaecal recurrence of Merkel cell carcinoma of the skin: a case report

IntroductionMerkel cell carcinoma is an uncommon skin malignancy that has a high propensity for metastatic spread. A systematic literature search identified 17 cases describing metastasis to the gastrointestinal tract, with 7 cases involving the small or large bowel. To the best of our knowledge, this is the only case described of Merkel cell carcinoma metastasising to the ileocaecal valve.Case presentationWe present a 74-year-old Filipino woman diagnosed with Merkel cell carcinoma of the skin with regional node involvement. Following excision and radiotherapy, the tumour recurred with metastasis to the ileocaecal valve. The patient died 28 months after the initial diagnosis.ConclusionThe prognosis of metastatic Merkel cell carcinoma is poor. Currently the optimal management for metastatic disease is unclear and lacks a firm evidence base due to the small number of cases reported.

Adjuvant Local Irradiation for Merkel Cell Carcinoma

To determine the effect of adjuvant local irradiation on (1) disease recurrence and (2) survival rates in Merkel cell carcinoma (MCC). An Ovid MEDLINE search (January 1966-May 26, 2004) was performed using the following criteria: group 1, "Merkel cell OR trabecular OR neuroendocrine skin OR APUDoma skin OR primary small cell skin OR primary undifferentiated skin OR endocrine skin OR neuroepithelial" AND group 2, "carcinoma OR tumor OR cancer" with mapping modifiers "-title, -abstract, -keyword, -subject heading." The search yielded 843 citations. The Ovid set was then searched using the following criteria: "surgery OR radiation OR radiotherapy," which yielded 242 discrete citations. Reports from all 242 citations were reviewed. For the remaining 601 citations, abstracts (when available) were reviewed to assess the level of relevance for potential inclusion; reports from 63 of these citations were reviewed. An additional 28 secondary references were reviewed, for a total of 333 reports. The following criteria for inclusion were applied to each potential patient: (1) a histopathologic diagnosis of MCC; (2) a single, primary tumor arising on the skin, for which (3) the primary treatment was surgical excision (local excision, wide excision, or Mohs surgery) with or without the use of adjuvant irradiation (to the tumor bed); (4) following surgery, negative (clear) surgical margins were obtained; (5) during the postoperative follow-up period, disease recurrence, progression, and survival and/or duration of event-free interval was documented with (6) a minimum follow-up of 1 month. A total of 1254 patients were included in the analysis. Statistically significant reductions in local (hazard ratio [HR], 0.27; P < .001) and regional (HR, 0.34; P < .001) recurrence were observed among patients treated with combination therapy compared with surgery alone. Similar rates of distant metastasis were observed between treatment groups (HR, 0.79; P = .31). Overall survival rates were 87% (1 year) and 49% (5 years). Cause-specific survival rates were 90% (1 year) and 62% (5 year). In general, differences in overall (HR, 0.78; P = .16) and cause-specific (due to MCC: HR, 0.72; P = .14) survival rates between treatment groups did not reach statistical significance. A subgroup analysis that excluded single-patient case reports and studies of only 1 treatment group revealed a significant overall (HR, 0.63; P = .02) and cause-specific (HR, 0.62; P = .04) survival advantage after treatment with combination therapy. Surgery plus local adjuvant irradiation was associated with significantly lower rates of local and regional recurrence of MCC than surgery alone. Prospective investigation is needed to clarify the presence of a survival benefit from combination therapy.

A case repot of Merkel cell carcinoma on chronic lymphocytic leukemia: differential diagnosis of coexisting lymphadenopathy and indications for early aggressive treatment

BackgroundChronic lymphocytic leukemia (CLL) is a monoclonal disorder, characterized by a progressive proliferation of functionally incompetent B lymphocytes. There is increased evidence of association between CLL and skin cancers, including the uncommon Merkel cell carcinoma (MCC).Case presentationA case report of an 84-year old male, who presented with an aggressively recurrent form of MCC on the lower lip, on the background of an 8-year history of untreated CLL. During the recurrences of MCC, coexisting regional lymphadenopathy, posed a problem in the differential diagnosis and treatment of lymph node involvement. Histopathology and immunoistochemistry showed that submandibular lymphadenopathy coexisting with the second recurrence of MCC, was due to B-cell small lymphocytic lymphoma. The subsequent and more aggressive recurrence of the skin tumor had involved the superficial and deep cervical lymph nodes. Surgical excision followed by involved field radiation therapy has been proven effective for both malignancies.ConclusionMCC has a high incidence of regional lymphadenopathy at presentation (12–45%) and even when it arises on the background of chronic leucemia, lymphadenopathy at presentation should be managed agressively with elective lymph node dissection. We overview the postulated correlation between Merkel tumor and CCL, the differential diagnosis of regional lymphadenopathy during the recurrences of the skin tumor and the strategies of treatment