Overall Survival After Mohs Surgery for Early-Stage Merkel Cell Carcinoma.

Importance: Merkel cell carcinoma (MCC) is a rare cutaneous malignant neoplasm with increasing incidence and high mortality. Although it is accepted that the optimal treatment for localized tumors is surgical, the data surrounding the optimal surgical approach are mixed, and current National Comprehensive Cancer Network guidelines state that Mohs micrographic surgery (MMS) and wide local excision (WLE) can both be used. The current National Comprehensive Cancer Network guidelines do not advocate a preference for MMS or WLE and suggest that they can be used interchangeably. Objective: To evaluate the association of surgical approach with overall survival after excision of localized T1/T2 MCC. Design, Setting, and Participants: This retrospective cohort study used the National Cancer Database to assess adults with T1/T2 MCC who were diagnosed between January 1, 2004, and December 31, 2018, with pathologically confirmed, negative regional lymph nodes and treated with surgery. The National Cancer Database includes all reportable cases from Commission on Cancer-accredited facilities. Data analysis was performed from October 2022 to May 2023. Exposure: Surgical approach. Main Outcomes and Measures: Overall survival. Results: A total of 2313 patients (mean [SD] age, 71 [10.6] years; 1340 [57.9%] male) were included in the study. Excision with MMS had the best unadjusted survival, with mean (SE) survival rates of 87.4% (3.4%) at 3 years, 84.5% (3.9%) at 5 years, and 81.8% (4.6%) at 10 years vs 86.1% (0.9%) at 3 years, 76.9% (1.2%) at 5 years, and 60.9% (2.0%) at 10 years for patients treated with WLE. Patients treated with narrow-margin excision had similar survival as those treated with WLE, with mean (SE) survival rates of 84.8% (1.4%) at 3 years, 78.3% (1.7%) at 5 years, and 60.8% (3.6%) at 10 years. On multivariable survival analysis, excision with MMS was associated with significantly improved survival compared with WLE (hazard ratio, 0.59; 95% CI, 0.36-0.97; P = .04). High-volume MCC centers were significantly more likely to use MMS over WLE compared with other centers (odds ratio, 1.99; 95% CI, 1.63-2.44; P < .001). Conclusions and Relevance: In this cohort study, the use of MMS (compared with WLE) was associated with significantly improved survival for patients with localized MCC with pathologically confirmed negative lymph nodes treated with surgery. These data suggest that Mohs surgery may provide a more effective treatment for MCC primary tumors than conventional WLE, although the lack of randomization and potential for selection bias in this study highlight the need for future prospective work evaluating this issue.

Best practices in surgical and nonsurgical management of head and neck Merkel cell carcinoma: An update.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous neuroendocrine carcinoma. Controversy exists regarding optimal management of MCC as high-quality randomized studies and clinical trials are limited, and physicians are bound to interpret highly heterogeneous, retrospective literature in their clinical practice. Furthermore, the rising incidence and notably poor prognosis of MCC urges the establishment of best practices for optimal management of the primary tumor and its metastases. Herein, we summarized the relevant evidence and provided an algorithm for decision-making in MCC management based on the latest 2021 National Comprehensive Cancer Network guidelines. Additionally, we report current active MCC clinical trials in the United States. The initial management of MCC is dependent upon the pathology of the primary tumor and presence of metastatic disease. Patients with no clinical evidence of regional lymph node involvement generally require sentinel node biopsy (SLNB) while clinically node-positive patients should undergo fine needle aspiration (FNA) or core biopsy and full imaging workup. If SLNB or FNA/core biopsy are positive, a multidisciplinary team should be assembled to discuss if additional node dissection or adjuvant therapy is necessary. Wide local excision is optimal for primary tumor management and SLNB remains the preferred staging and predictive tool in MCC. The management of MCC has progressively improved in the last decade, particularly due to the establishment of immunotherapy as a new treatment option in advanced MCC. Ongoing trials and prospective studies are needed to further establish the best practices for MCC management.

An update on local and systemic therapies for nonmelanoma skin cancer.

INTRODUCTION: Nonmelanoma skin cancers (NMSC) as a group exceed the incidence of all other malignancies combined. NMSC includes basal cell carcinoma, squamous cell carcinoma, and Merkel cell carcinoma. As the incidence continues to rise, it is important to appreciate the available treatment options. AREAS COVERED: This article discusses the treatment of NMSC through surgical, topical, regional, and systemic modalities. EXPERT OPINION: As there are many treatment options available for these diseases, selection of the appropriate method can be difficult. With time, we expect treatment decisions to become even more complex and personalized. The role of systemic immunotherapies and neoadjuvant therapies in the treatment of NMSC is still not well defined. Local treatment with intralesional injections and isolated limb infusion may prove to be promising alternative therapies.

Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options.

Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation. Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.

Survival Benefit of Guideline-Concordant Postoperative Radiation for Local Merkel Cell Carcinoma.

BACKGROUND: Postoperative radiation therapy (RT) for early-stage Merkel Cell Carcinoma (MCC) decreases the risk of locoregional recurrence and improve overall survival. However, concordance with RT guidelines is unknown. MATERIALS AND METHODS: The National Cancer Database was queried for stage I/II MCC patients receiving surgical intervention from 2006-2017. The cohort was stratified by patients who had and did not have indication(s) for adjuvant RT of the primary tumor site based on National Comprehensive Cancer Network guidelines. We captured the use of RT, patient demographics, socioeconomic characteristics, and clinical characteristics. Logistic regression, Kaplan-Meier method, and propensity score weighted Cox proportional hazards model examined associations and survival benefits of RT. RESULTS: 2,330 stage I/II MCC patients underwent surgical intervention. 1,858 (79.7%) met National Comprehensive Cancer Network criteria for RT of the primary tumor site, of which 1,062 (57.2%) received RT. 472 (20.3%) did not meet criteria for RT, of which 203 (43.0%) received RT. Five-year overall survival advantage was identified for patients who received RT when it was indicated (P < 0.003). There was no evidence of overall survival advantage when patients received guideline-discordant RT (P = 0.478). CONCLUSIONS: Surgical resection with adjuvant RT of the primary tumor site has an overall survival benefit for local MCC when patients meet criteria for RT. This study found a group who received guideline-discordant RT with no survival advantage. Further investigation is warranted to identify the socio-demographic and oncologic reasons for guideline discordance in the treatment of MCC for both under- and over-treatment.

Merkel Cell Carcinoma of the Head and Neck Compared to Other Anatomical Sites in a Real-World Setting: Importance of Surgical Therapy for Facial Tumors.

Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with a high propensity for nodal involvement, local recurrence, and distant metastases. Up to 50% of MCC arises on head and neck (HN), which may impede oncological treatment due to insufficiently wide excisions and a lower rate of sentinel lymph node detection due to more complicated lymph drainage. Several studies have compared the clinical outcome of HN-MCC with those of non-head and neck (NHN) MCC yielding inconsistent results. This single-center, retrospective analysis compared the clinical outcome of 26 HN-MCC patients with 30 NHN-MCC patients. Overall survival (OS) and disease-free survival (DFS) were calculated with the Kaplan-Meier method assuming proportional hazards. The mean resection margins were 1.6 and 2.0 cm for the HN and NHN cohort, respectively. Local relapses were more frequently observed in patients with HN-MCC (19 vs. 10%). Patients with HN-MCC had a median OS of 4.3 years compared with 7.5 years in patients with NHN-MCC (p = 0.277). The median OS by tumor stage was 11, 3, 2, and 3 years in stage I, II, III, and IV disease, respectively (p = 0.009). The median DFS in HN-MCC was 10 years and not reached in the cohort with NHN-MCC patients (p = 0.939). Our data suggest a trend toward poorer outcomes of HN-MCC compared with NHN-MCC. Patients with MCC on the head and neck carry a higher risk for local relapse, requiring resolute surgical treatment also in facial localizations at early stages.

A pilot study of alternative TrkAIII splicing in Merkel cell carcinoma: a potential oncogenic mechanism and novel therapeutic target.

BACKGROUND: Merkel cell carcinomas (MCCs) are rare, aggressive, therapeutically-challenging skin tumours that are increasing in incidence and have poor survival rates. The majority are caused by genomic Merkel cell polyomavirus (MCPyV) integration and MCPyV T-antigen expression. Recently, a potential oncogenic role for the tropomyosin-related tyrosine kinase A receptor (TrkA) has been proposed in MCC. Alternative TrkAIII splicing is a TrkA oncogenic activation mechanism that can be promoted by SV40 large T-antigen, an analogue of MCPyV large T-antigen. In this pilot study, therefore, we have evaluated TrkAIII splicing as a novel potential oncogenic mechanism and therapeutic target in MCPyV positive MCC. METHODS: Formalin-fixed paraffin-embedded MCC tissues, consisting of 10 stage IV, 1 stage IIIB, 1 stage IIB, 4 stage IIA and 2 stage I tumours, from patients diagnosed and treated from September 2006 to March, 2019, at the University of L'Aquila, L'Aquila, Italy, were compared to 3 primary basal cell carcinomas (BCCs), 3 primary squamous cell carcinomas (SCCs) and 2 normal skin samples by RT-PCR for MCPyV large T-antigen, small T-antigen, VP-1 expression and alternative TrkAIII splicing and by indirect IF for evidence of intracellular TrkA isoform expression and activation. RESULTS: 9 of 10 Recurrent stage IV MCCs were from patients (P.1-3) treated with surgery plus loco-regional Melphalan chemotherapy and remaining MMCs, including 1 stage IV tumour, were from patients treated with surgery alone (P. 4-11). All MCPyV positive MCCs exhibiting MCPyV large T-antigen expression (17 of 18MCCs, 90%) exhibited alternative TrkAIII mRNA splicing (100%), which was exclusive in a significant number and predominant (> 50%) in all stage IV MCCs and the majority of stage 1-III MCCs. MCCs with higher TrkAIII to 18S rRNA expression ratios also exhibited strong or intermediate immunoreactivity to anti-TrkA antibodies, consistent with cytoplasmic TrkAIII expression and activation. In contrast, the MCPyV negative MCC, BCCs, SCCs and normal skin tissues all exhibited exclusive fully-spliced TrkA mRNA expression, associated with variable immunoreactivity for non-phosphorylated but not phosphorylated TrkA. CONCLUSIONS: MCPyV positive MCCs but not MCPyV negative MCC, BCCs and SCCs exhibit predominant alternative TrkAIII splicing, with evidence of intracellular TrkAIII activation. This establishes a new potential MCC subset, unveils a novel potential MCPyV oncogenic mechanism and identifies TrkAIII as a novel potential therapeutic target in MCPyV positive MCC.

Merkel Cell Carcinoma: Updates on Staging and Management.

Merkel cell carcinoma is an aggressive neuroendocrine carcinoma with increasing incidence over the past few decades. The TNM Staging System used for Merkel cell carcinoma was updated by the American Joint Committee on Cancer in 2017. Clinical practice guidelines were updated by the National Comprehensive Cancer Network on August 31, 2018. This article reviews the most recent evidence-based updates on staging and management.

Diagnosis and Treatment of Merkel Cell Carcinoma in Specialized Dermatology Units: A Clinical Practice Guideline of the Spanish Academy of Dermatology and Venereology. / Carcinoma de células de Merkel: diagnóstico y tratamiento en atención especializada dermatológica. Guía de práctica clínica de la Academia Española de Dermatología y Venerología.

BACKGROUND AND OBJECTIVE: Merkel cell carcinoma is a rare, aggressive skin cancer that is managed in a great variety of ways. However, international clinical practice guidelines give only partial coverage to issues considered major problems.The recommendations presented here aim to provide Spanish dermatologists with a guide to improving disputed aspects of diagnosis, staging, and treatment of localized Merkel cell carcinomas. MATERIAL AND METHODS: The ADAPTE process was used. Members of the Spanish Group of Oncologic Dermatology and Surgery (GEDOC) with experience in treating Merkel cell carcinoma and interest in drafting these guidelines were selected. The group described the care process and listed the most important clinical questions. They then searched for guidelines and assessed them with the AGREE II (Appraisal of Guidelines for Research and Evaluation) tool. After consulting the guidelines for answers to their clinical questions, the group drafted the present statementand sent it for external review. RESULTS: The guidelines that scored highest in the AGREE II assessment step were the consensus-based interdisciplinary guideline of the European Association of Dermato-Oncology and the European Organization of Research and Treatment of Cancer, and those of the Comprehensive Cancer Network, the Alberta Health Services in Canada, the American Cancer Society, and the Cutaneous Oncology Group of the French Society of Dermatology. A total of 9 clinical questions were answered based on these guidelines. CONCLUSIONS: The guidelines presented here answer clinical questions that arise in routine practice. They can provide dermatologists with a starting point for decision-making, although available resources and patient preferences must always be borne in mind.

New perspectives in Merkel cell carcinoma.

PURPOSE OF REVIEW: Merkel cell carcinoma (MCC), a rapidly progressing skin cancer, has poor prognosis. We reviewed the epidemiology, pathogenesis, diagnosis and treatment of MCC, with a focus on recent therapeutic advancements. RECENT FINDINGS: Risk factors for MCC, such as old age, immunosuppression, polyomavirus infection and exposure to UV radiation have already been identified, but the underlying mechanisms leading to carcinogenesis still need clarification. On the basis of recent advances, immunotherapy - in particular, inhibition targeting the programmed cell death protein 1/programmed death-ligand 1 (PD1)/PDL1) immune checkpoint blockade - is currently being investigated in the treatment of metastatic MCC. Avelumab, an anti-PDL1 antibody, was the first drug to be approved internationally as second-line monotherapy for patients with advanced MCC, based on results from the JAVELIN Merkel 200 clinical trial. Avelumab has also recently been approved as first-line treatment for advanced MCC in Europe. Pembrolizumab (anti-PD1) in first-line and nivolumab (anti-PD1) in first-line and second-line treatments are two other checkpoint inhibitors that are under investigation, and showing promising results. New innovative therapies are also in development. SUMMARY: New insights concerning advances in MCC diagnosis and treatment have been highlighted. Immunotherapy for metastatic MCC constitutes a recent breakthrough in an unmet medical need, but alternative therapies should continue to be investigated.

Utilization of Indocyanine Green to Aid in Identifying Sentinel Lymph Nodes in Merkel Cell Cancer.

BACKGROUND: Merkel cell carcinoma (MCC) is a relatively rare skin cancer with high rates of regional lymph node involvement and metastatic spread. National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for staging purposes. The goal of this study is to report our experience utilizing indocyanine green (ICG) fluorescence-based technology to aid in SLNB detection in MCC. METHODS: Consecutive MCC patients who underwent SLNB with radioisotope lymphoscintigraphy, with intraoperative handheld gamma probe, and ICG-based fluorescence imaging from 2012 to 2017 were prospectively studied (Cohort A). A group of historical controls that underwent SLNB for MCC with radioisotope lymphoscintigraphy and vital blue dye (VBD) (lymphazurin or methylene blue dye) was also analyzed (Cohort B). RESULTS: Twenty-four consecutive patients underwent SLNB with lymphoscintigraphy and ICG-based fluorescence and 11 controls underwent SLNB with lymphoscintigraphy and VBD. The localization rate by node with VBD was 63.6% and ICG-based fluorescence was 94.8%. For two patients, a positive sentinel lymph node (SLN) was detected only by ICG-based fluorescence and the nodes were not detected by gamma probe and one patient's only positive node was identified via ICG fluorescence only. VBD or gamma probe did not identify any unique positive SLNs in either cohort B or either cohort, respectively. CONCLUSIONS: In this study, we indicate that ICG-based fluorescence is not only feasible to augment SLN identification, but it has a higher node localization rate as compared to blue dye and it was able to identify positive SLNs otherwise missed by gamma probe. This study suggests the importance of utilizing two modalities to augment SLN identification and that ICG-based fluorescence may be able to identify nodes that would have been otherwise missed by gamma probe. We will continue to follow these patients and enroll more patients in this prospective study to further determine the role that ICG-based fluorescence has in identifying sentinel lymph nodes in MCC.

Immunotherapy for Merkel Cell Carcinoma.

OPINION STATEMENT: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy-sensitive in the first-line setting, responses are rarely durable and most patients subsequently relapse and develop metastasis. Treatment with checkpoint inhibitors (CPIs) has shown a major advancement in the treatment of advanced MCC. Systemic therapy against programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) is associated with a high objective response rate (ORR), prolonged durable responses, and good tolerability in advanced-stage MCC. CPIs are now included in the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of patients with metastatic MCC. Multiple clinical trials of CPIs administered as monotherapy or in combination with other agents or modalities, including the adjuvant setting, are ongoing. Immunotherapy offers a promising future for patients with MCC. In this review, we present an overview of emerging data on immunotherapy, especially CPIs of the PD-1/PD-L1 pathway, for patients with advanced MCC.

Resection Margins in Merkel Cell Carcinoma: Is a 1-cm Margin Wide Enough?

BACKGROUND: Guidelines regarding specific resection margins for primary Merkel cell carcinoma (MCC) are not well established. The current National Comprehensive Cancer Network (NCCN) guidelines recommend 1- to 2-cm resection margins. This study aimed to determine the impact of margin width on local recurrence (LR), disease-specific survival (DSS), overall survival (OS), and type of wound closure. METHODS: All patients who underwent resection of primary MCC at a single institution from 2000 to 2015 were reviewed. Patient demographics, clinicopathologic characteristics, treatments, and outcomes were reviewed. RESULTS: A total of 240 patients underwent resection of primary MCC with resection margin width identified in the operative report. The median age was 76 years, and 65.8% of the patients were men. Of the 240 patients, 85 (35.4%) had head and neck primaries, 140 (58.3%) had extremity primaries, and 15 (6.3%) had trunk primaries. In terms of margins, 69 patients (28.8%) had a margin of 1 cm, 36 patients (15%) had a margin of 1.1-1.9 cm, and 135 patients (56.2%) had a margin of 2 cm or more. The median follow-up period was 21 months. The LR rate was 2.9% for a margin of 1 cm, 2.8% for a margin of 1.1-1.9 cm, and 5.2% for a margin of 2 cm or more (p = 0.80). The 5-year OS was 63.6% for a margin of 1 cm, 59.7% for a margin of 1.1-1.9, and 70.7% for a margin of 2 cm or more (p = 0.66). The 5-year DSS was 80.3% for a margin of 1 cm, 66.2% for a margin of 1.1-1.9 cm, and 91.8% for a margin of 2 cm or more (p = 0.28). For wound closure, 43.5, 50, and 65.9% of the patients respectively required a flap or graft with a margin of 1, 1.1-1.9, and 2 cm or more (p = 0.006). CONCLUSIONS: A 1-cm resection margins did not increase the risk of LR. Margin width did not make a significant difference in DSS or OS. Larger resection margins increase the need for a graft or flap closure.

A 21-year course of Merkel cell carcinoma with adjuvant Viscum album extract treatment: A case report.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine skin tumor with frequent local recurrence, lymph node involvement, distant metastasis, and a high mortality rate. Viscum album extracts (VAE) are a widely used adjunct in cancer treatment and show cytotoxic and immune-modulating effects. CASE PRESENTATION: A 64-year-old woman was diagnosed with a MCC of the left forearm. In the following course of 21 years, she experienced 4 episodes of lymph node relapse (axillary, submandibular, axillary, clavicular). All lesions were surgically excised. The patient declined chemotherapy and radiation and opted for adjuvant treatment with local subcutaneous VAE injections. Currently-21 years after first diagnosis and 9.5 years after the last relapse-the patient is tumor-free, in good health, and without functional limitations. CONCLUSION: The presented case shows long-time survival in a patient with MCC treated with surgery and VAE injections. The immune system plays a key role in tumorigenesis of MCC. VAE enhances several immune pathways and might therefore contribute to immunologic tumor control in MCC. The role of VAE in MCC should further be investigated.

Factors associated with advanced-stage Merkel cell carcinoma at initial diagnosis and the use of radiation therapy: Results from the National Cancer Database.

BACKGROUND: The stage of disease at initial diagnosis and the use of radiation therapy (RT) are important determinants of survival in patients with Merkel cell carcinoma (MCC). OBJECTIVE: To define factors that are associated with advanced-stage MCC at the time of initial diagnosis and the use of RT. METHODS: Cross-sectional, retrospective analysis of patients with MCC registered in the National Cancer Database during the period from 2004 to 2013. RESULTS: A total of 11,917 patients were identified; 3152 and 4586 patients were excluded from the staging and RT analyses, respectively, because of lack of available data. African American ethnicity (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.06-2.10; P = .023), lack of medical insurance (OR, 2.15; 95% CI, 1.40-3.30; P < .001), Charlson-Deyo comorbidity score of at least 1 (OR, 1.21; 95% CI, 1.09-1.34; P < .001), residence more than 26 miles from a treatment facility (OR, 1.18; 95% CI, 1.03-1.35; P = .015), tumor located on the lower limb/hip (OR, 1.59; 95% CI, 1.42-1.78; P < .001) or trunk (OR, 2.05; 95% CI, 1.81-2.33; P < .001), and poorly (OR, 2.57; 95% CI, 1.13-5.82; P = .024) or undifferentiated (OR, 3.11; 95% CI, 1.36-7.15; P = .007) tumor histology predicted advanced-stage MCC at the time of initial diagnosis. The use of RT was associated with Native American ethnicity (OR, 5.04; 95% CI, 1.10-22.99; P = .037), tumor size between 1.5 and 2.7 cm (OR, 1.27; 95% CI, 1.10-1.47; P = .001), electing not to have surgery (OR, 2.77; 95% CI, 1.90-4.03; P < .001), positive postsurgical margins (OR, 1.39; 95% CI, 1.18-1.63; P < .001), and receiving treatment at a comprehensive cancer program (OR, 1.25; 95% CI, 1.03-1.50; P = .020). LIMITATIONS: Retrospective design limits generalizability of the results, and precise details of RT regimens utilized were not available. CONCLUSIONS: A number of factors are associated with advanced-stage MCC at initial diagnosis and the use of RT. Health care models should account for these factors, and efforts should be directed toward improving those that are modifiable.

Sentinel lymph node biopsy in periocular merkel cell carcinoma: a case report.

BACKGROUND: The National Comprehensive Cancer Network guidelines for Merkel cell carcinoma recommend performance of the sentinel lymph node biopsy in all patients with clinically negative nodal disease for staging and treatment. Nevertheless, sentinel lymph node biopsy in the periocular region is debated as tumors are typically smaller and lymphatic variability can make performance procedurally problematic. CASE PRESENTATION: We present a case of a Caucasian patient in their seventies who presented with a 1.0 cm periocular Merkel cell carcinoma, who underwent Mohs surgery with a Tenzel flap repair, that was found to have a positive sentinel lymph node biopsy, but who, despite parotidectomy, selective neck dissection, and radiation, succumbed to the disease. CONCLUSIONS: Evidence in both the site-specific and non-specific literature demonstrates: (1) Worsening prognosis with extent of lymph node burden, (2) improvements in our abilities to perform lymphoscintigraphy, (3) locoregional and distant metastatic disease in patients with tumor sizes ≤1 cm, and (4) significant rates of sentinel lymph node positivity in patients with tumor sizes ≤1 cm. Our case supports that sentinel lymph node biopsy should be considered in all clinically nodal negative periocular Merkel cell carcinoma, regardless of size, and despite limited site-specific studies on the subject.

Merkel Cell Carcinoma of the Head and Neck: Recommendations for Diagnostics and Treatment.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive tumor that often occurs in the head and neck region. Because of these features, the classifications and diagnostic and treatment regimens are frequently modified. Especially in the anatomically complex head and neck region, it is crucial to be aware of the current recommendations for diagnostics and treatment of MCC to ensure appropriate treatment. This overview aims to summarize the currently available literature. METHODS: The authors reviewed the relevant literature and international guidelines for MCC from 2012 to 2017 with respect to epidemiology and prognosis, diagnostic procedures and imaging, surgery, radiation, systemic treatment, and aftercare. These results were compared with existing guidelines, some of them current, and recommendations were derived. RESULTS: Marked developments in imaging have resulted in an increased use of functional imaging. The surgical concepts have changed regarding safety margins and the use of sentinel node biopsies. In systemic treatment, a move from conventional agents toward immuno-oncology can be observed. CONCLUSIONS: For staging, it is important to be as exact as possible using functional imaging (e.g., positron emission tomography/computed tomography scan), especially in the head and neck area with its complex lymph drainage. This often plays an especially important role in early stages of the tumor, when the resection margin can be reduced to preserve the organ. Aftercare also should include functional imaging. In an advanced, metastatic stage, immuno-oncology (PD-1, PD-L1, CTLA-4) is superior to the previous methods of systemic treatment.