Increased risk of recurrence and disease-specific death following delayed postoperative radiation for Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is often treated with surgery and postoperative radiation therapy (PORT). The optimal time to initiate PORT (Time-to-PORT [ttPORT]) is unknown. PURPOSE: We assessed if delays in ttPORT were associated with inferior outcomes. METHODS: Competing risk regression was used to evaluate associations between ttPORT and locoregional recurrence (LRR) for patients with stage I/II MCC in a prospective registry and adjust for covariates. Distant metastasis and death were competing risks. RESULTS: The cohort included 124 patients with median ttPORT of 41 days (range: 8-125 days). Median follow-up was 55 months. 17 (14%) patients experienced a LRR, 14 (82%) of which arose outside the radiation field. LRR at 5 years was increased for ttPORT >8 weeks vs ≤ 8 weeks, 28.0% vs 9.2%, P = .006. There was an increase in the cumulative incidence of MCC-specific death with increasing ttPORT (HR = 1.14 per 1-week increase, P = .016). LIMITATIONS: The relatively low number of LRRs limited the extent of our multivariable analyses. CONCLUSIONS: Delay of PORT was associated with increased LRR, usually beyond the radiation field. This is consistent with the tendency of MCC to spread quickly via lymphatics. Initiation of PORT within 8 weeks was associated with improved locoregional control and MCC-specific survival.

Metastatic Merkel Cell Carcinoma After Simultaneous Pancreas-Kidney Transplantation: Fatal Outcomes.

Merkel cell carcinoma (MCC) is a rare, highly aggressive cutaneous malignancy. Immunosuppression increases the risk of MCC and is associated with poor prognosis. Organ transplant recipients (OTR) have worse overall survival (OS) than patients with immunosuppression due to other causes. Treating MCC after organ transplantation is challenging, as checkpoint inhibitor immunotherapy, the standard of care for treating MCC, increases the risk of transplant rejection. This paper reviews the cases of two simultaneous pancreas-kidney transplant (SPKT) recipients with MCC and explores the role of immunosuppression in the development of MCC. Immunosuppression was discontinued and checkpoint inhibitor therapy was initiated in the first patient and considered by the second patient. In both cases, treatment failed, and the patients died shortly after developing metastatic MCC. These cases illustrate the need for improved multidisciplinary treatment regimens for MCC in OTRs. J Drugs Dermatol. 2024;23(5):376-377.     doi:10.36849/JDD.8234  .

Interdisciplinary management of skin cancer. / Die interdisziplinäre Behandlung von Hautkrebs.

The interdisciplinary treatment of skin cancer in the head and neck area requires close collaboration between different specialist disciplines. The most common non-melanoma skin cancer tumor entities are cutaneous squamous cell carcinoma and basal cell carcinoma as well as their precursor lesions. One of the less common tumors is Merkel cell carcinoma, which also occurs primarily in light-exposed areas and, in contrast to squamous and basal cell carcinoma, is more likely to metastasize. Due to the low tendency of basal cell carcinoma as well as cutaneous squamous cell carcinoma to metastasize, a cure can often be achieved by surgery. If the tumor growth exceeds certain levels it may require collaboration between dermatology and otorhinolaryngology. The primary goal of this interdisciplinary collaboration is to achieve a functional, cosmetically and aesthetically acceptable result in addition to adequate tumor treatment. Depending on the stage of the tumor and the clinical course, a case may be discussed in an interdisciplinary tumor board in order to determine a personalised, appropriate and adequate treatment concept for each patient, including prevention, therapy and follow-up.

Early postoperative infection in patient with IgM deficiency.

Selective IgM deficiency is a rare immunological disorder, with patients presenting with recurrent infections and allergic manifestations. However, the association with early postoperative infection has not been widely reported in the literature. We describe a rare case of a patient who had an early wound infection 1 day after excision of a Merkel cell carcinoma from his right buttock and was later found to have decreased IgM levels. Selective IgM deficiency should therefore be considered in patients presenting with recurrent infections or in patients who have previously undergone surgery and subsequently developed early infection postoperatively. In this subset of patients, extra precautions may need to be taken pre- and postoperatively to reduce the risk of developing a postoperative infection.

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.

Radiation, Lymph Node Dissection, or Both: Management of Lymph Node Micrometastases from Merkel Cell Carcinoma.

BACKGROUND: Regional lymph node micrometastases from Merkel cell carcinoma (MCC) can be treated with completion lymph node dissection (CLND) and/or radiation therapy (RT). It is unclear how these options compare in terms of survival benefits for patients. PATIENTS AND METHODS: This retrospective cohort study used data from years 2012-2019 of the National Cancer Database. Patients with MCC and clinically negative, but pathologically positive, lymph node metastases who received RT to and/or CLND of the regional lymph node basin were included. Inverse probability weight balancing was performed using covariates followed by Cox proportional hazards modeling for survival analysis. RESULTS: A total of 962 patients were included [median (interquartile range) age, 74 (67-80) years, 662 (68.8%) male patients, 926 (96.3%) white patients]. The majority (63%, n = 606) had a CLND only, while 18% (n = 173) had RT only, and 19% (n = 183) had both CLND and RT. From 2016 to 2019, usage of RT only increased from 10% to 31.8%. Multivariate analysis demonstrated that treatment modality was not associated with survival [RT versus CLND, hazard ratio (HR) 0.842, 95% confidence interval (CI) 0.621-1.142, p = 0.269, RT+CLND versus CLND, HR 1.029, 95% CI 0.775-1.367, p = 0.844]. This persisted after balancing weights (RT versus CLND, HR 0.837, 95% CI 0.614-1.142, p = 0.262, RT+CLND versus CLND, HR 1.085, 95% CI 0.801-1.470, p = 0.599). CONCLUSIONS: The usage of RT for nodal micrometastasis in MCC is increasing as compared with CLND. This strategy appears to be safe, with no significant difference in survival outcomes.

Delayed time to radiation and overall survival in Merkel cell carcinoma.

BACKGROUND: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied. METHODS: This retrospective study used data from the National Cancer Database (2006-2019). Patients with clinically localized MCC who received surgical excision and adjuvant radiotherapy were included. Multivariate regressions were used to account for various patient and tumor factors. The primary outcome was 5-year OS, and the secondary outcome was time from diagnosis to adjuvant radiation (TTR). RESULTS: Of the 1965 patients included, most were male (n = 1242, 63.2%) and white (n = 1915, 97.5%), and the median age was 74 years (interquartile range [IQR]: 66-81). The median TTR was 83 days (IQR: 65-106). A total of 83.6% of patients received radiotherapy to the primary site, 21.3% to the draining nodal basin, 17.1% to both, and 12.2% whose target location of radiotherapy was not recorded in the data. TTR of ≥79 days (the 45th percentile) was associated with worse OS on both univariate and multivariate analyses (log-rank p = 0.0014; hazard ratio [HR]: 1.258, 95% confidence interval [CI]: 1.055-1.500, p = 0.010). This persisted on sub-analyses of patients <80 years old (n = 1407; HR: 1.380, 95% CI: 1.080-1.764, p = 0.010) and of patients with Charlson comorbidity index (CCI) of 0 (n = 1411; HR: 1.284, 95% CI: 1.034-1.595, p = 0.024). Factors associated with delayed TTR included greater age (p = 0.039), male sex (p = 0.04), CCI > 1 (p = 0.036), academic facility (p < 0.001), rural county (p = 0.034), AJCC T2 stage (p = 0.010), negative margins (p = 0.017), 2+ pathologically positive regional nodes (p = 0.011), and margin size >2 cm (p = 0.015). CONCLUSIONS: Delayed radiotherapy (≥79 days) was associated with worse OS of MCC patients. Further study in controlled cohorts is needed to ascertain this relationship.

Surgery in the Era of Immunotherapy for Advanced Head and Neck Non-melanoma Skin Cancer.

PURPOSE OF REVIEW: Surgery remains the mainstay of treatment for non-melanoma skin cancer (NMSC). Immunotherapy (IO) has emerged as an alternative option. This review provides a contemporary summary of how to incorporate IO into the management of advanced NMSC. Evidence-based outcomes and recent clinical trials are provided with emphasis on the three most common NMSC diagnoses: cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), and merkel cell carcinoma (MCC). RECENT FINDINGS: Surgical resection while preserving form and function remains the standard of care for the majority of NMSCs. In recalcitrant cases failing traditional surgery and/or primary radiation, patient ineligible for such treatments, or unresectable disease, IO has emerged as a promising alternative. In the majority of cases, it is a supplanting primary chemotherapy. Surgery remains the standard of care for NMSC. Immunotherapy has emerged as an alternative option for non-surgical candidates and as a neoadjuvant means to minimize morbidity.

Reactive Eccrine Syringofibroadenoma (ESFA) in Association With a Merkel Cell Carcinoma Excision Scar.

ABSTRACT: Eccrine syringofibroadenoma (ESFA) is a rare benign skin adnexal lesion of the acrosyringium of eccrine sweat ducts. Reactive ESFA, a subtype of ESFA, is usually associated with non-neoplastic cutaneous dermatoses or neoplastic skin tumors. Clinically, the lesions can be solitary or multiple, pink, or skin-colored coalescing papules or nodules of variable sizes. Histopathologically, this tumor is composed of numerous anastomosing cords of monomorphic cuboidal epithelial cells with eccrine duct formation. The association of reactive ESFA with benign conditions, such as psoriasis, diabetic polyneuropathy, scars, and leprosy, has been reported. However, the association of reactive ESFA with malignant tumors is extremely rare, with very few cases reported in the literature. We present a case of a 72-year-old woman who developed reactive ESFA associated with Merkel cell carcinoma excision scar. The ESFA tumors developed in the area of the surgical graft 10 months after the Merkel cell carcinoma had been excised. New ESFA tumors have continued to appear in the scar on a yearly basis while, so far, has been no recurrence of the original tumor. However, the presence of new tumor growths in the area suggested the possibility of recurrence of the Merkel cell carcinoma. That possibility was enhanced by the fact that PET scans revealed hypermetabolic activity in the ESFA papules.

Mohs Micrographic Surgery for Facial Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor with frequent metastases. They often appear in the face where cosmetic and functional outcome is critical. Mohs micrographic surgery (MMS) is a controlled intervention that optimizes negative margins without sacrificing tissue. OBJECTIVE: A comprehensive assessment of outcomes of MMS-treated facial MCC will help guide clinicians in surgical and medical management. METHODS & MATERIALS: Retrospective review identified facial MCC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded and descriptive and predictive analyses were performed. RESULTS: 34 cases were reviewed with a mean followup of 34.4 months. The most common sites were the forehead, cheek-jaw region, and nasal ala. 2 (5.9%) patients had local recurrence by a mean of 4.3 months. No documented variables were significantly associated with local recurrence. 8 (23.5%) patients had progression to metastasis by a mean of 9.4 months. Younger age at biopsy and surgery, male sex, and intraoperative detection of in-transit disease were significantly associated with progression to metastasis. CONCLUSIONS: In summary, the tissue-sparing approach of MMS may be beneficial for MCC in cosmetically and functionally sensitive facial locations as it preserves tissue without compromising outcomes.

Reconstruction of Rapidly Growing Merkel Cell Carcinoma of the Cheek With Multidisciplinary Cooperation.

Merkel cell carcinoma (MCC) is a rare and very aggressive skin cancer. An 83-year-old female presented with a 1.5 cm-sized non-tender mass on her left cheek and was diagnosed with MCC. The margin of MCC was well-defined and there was no cervical node metastasis on pre-operative computed tomography. Three weeks after the first visit, the mass rapidly increased in size. We checked the magnetic resonance imaging, a rapid-growing 2.5 cm sized nodular region and metastatic cervical lymph node were found. We performed wide excision of the MCC and neck lymph need dissection with multidisciplinary cooperation. The soft tissue defect was about 6.0×5.0 cm 2 in size and reconstructed with radial forearm free flap. On permanent biopsy, the size of MCC was 3.0×2.3 cm 2 . There was no recurrence of MCC with radiation therapy during an 18-month follow-up. We experienced an older patient with a rapid - growing MCC and cervical lymph node metastasis in a brief time. With our experience, we discuss the evaluation and treatment plan of the rapid-growing MCC for good results.

Merkel cell carcinoma of unknown primary: Clinical presentation and outcomes.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy that usually occurs in the head/neck or extremities. However, there are reports of MCC developing in the lymph nodes or parotid gland without evidence of a primary cutaneous lesion. METHODS: We reviewed 415 patients with biopsy-proven MCC. Patients with MCC of unknown primary (n = 37, 9%, MCCUP) made up the study cohort. The primary endpoints of the study were rate of recurrence, disease-free survival, and overall survival. RESULTS: Patients with MCCUP presented with tumors in lymph nodes (n = 34) or parotid gland (n = 3). Nodal disease was most commonly detected in the inguinal/external iliac (n = 15) or axillary (n = 14) regions. The mean age at diagnosis was 70 years and 24% were female. Patients presented with distant metastases in 24.3% of cases. Patients with stage IIIA disease treated with regional lymph node dissection (RLND) had a lower risk of disease recurrence (hazard ratio 0.26, p = 0.046). Recurrence-free survival was 59.3% at 5 years. Disease-specific survival was 63.3% at 5 years. CONCLUSION: Patients with MCCUP have a high risk of recurrence and mortality. The optimal treatment for MCCUP has yet to be elucidated, although therapeutic RLND appears beneficial for these patients.

Predictors of time to definitive surgery and survival in Merkel cell carcinoma: analysis of the US National Cancer Database.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive cancer, and it has been suggested that earlier treatment would allow for better patient outcomes. However, the causes of delays in the initiation of treatment and the effects of delayed treatment on survival of patients have not fully been explored, and the effects of treatment delays for MCC are not yet fully understood. AIM: To determine the effect of time to treatment initiation (TTI) on mortality in MCC and to determine the predictors of TTI itself. METHODS: This was a retrospective cohort analysis of the US National Cancer Database (NCDB) for cases of MCC from 2004 to 2016, excluding individuals with Stage IV MCC, as surgery is not the preferred treatment for this group. The time difference between initial biopsy of MCC and definitive surgery (TTI) was stratified into five groups by 30-day intervals. RESULTS: In total, 12 157 patients [7491 (61.6%) men, 4666 (38.4%) women; mean ± SD age 74.4 ± 10.9 years] were included in the study. A risk for longer TTI was seen in black individuals (OR = 1.7, 95% CI 1.2-2.6) and in elderly individuals aged > 70 years (OR = 1.7, 95% CI 1.2-2.5). Kaplan-Meier survival analysis showed that individuals with TTI < 30 days had a significantly longer overall survival than those with TTI > 120 days (6.1 vs. 4.8 years, P < 0.001). However, after controlling for clinical and tumour factors in Cox multivariable analysis, no difference in survival was noted for TTI < 30 days and TTI > 120 days [hazard ratio (HR) = 0.9, 95% CI 0.8-1.1). Worse outcomes were also associated with increasing age (HR = 2.0, 95% CI 1.7-2.5), male sex (HR = 1.2, 95% CI 1.2-1.3), higher Charlson-Deyo comorbidity score (HR = 1.4, 95% CI 1.3-1.5), lack of radiation therapy (HR = 0.8, 95% CI 0.8-0.9), lack of private insurance (HR = 0.7, 95% CI 0.6-1.0), and use of surgical technique other than Mohs micrographic surgery or wide local excision (HR = 1.2, 95% CI 1.2-1.3). CONCLUSION: Although TTI is a useful prognostic metric in isolated survival analysis, its utility declines when other factors are controlled for in the analysis. Age, radiotherapy, type of surgery performed, comorbidities, tumour size and lymph node involvement may be important predictors of survival.

Merkel Cell Carcinoma, the Impact of Clinical Excision Margins and Mohs Micrographic Surgery on Recurrence and Survival: A Systematic Review.

BACKGROUND: When treating Merkel cell carcinoma (MCC), the relation between wide local excision (WLE) margin and recurrence or survival is unclear. Mohs micrographic surgery (MMS) is an alternative surgical option for MCC, but it is unknown whether the local recurrence rate differs between MMS and WLE. OBJECTIVE: To systematically assess the available literature to determine the recurrence and survival rates when treating MCC with MMS and different clinical excision margins. MATERIALS AND METHODS: The MEDLINE, EMBASE, and CENTRAL databases were searched. Two independent reviewers selected studies that defined clear excision margins and either recurrence or survival. When possible, individual cases were extracted from case series and included in the analyses. Other studies were reviewed narratively. RESULTS: Overall, 1108 studies were identified; of which, 19 case series (168 cases) and 12 cohort studies were eligible. None of the cohort studies showed significant differences in recurrence or survival for either excision margins or MMS. Equally, logistic and Cox regression analyses of the case series revealed no significant differences in recurrence or survival between different excision margins and MMS. CONCLUSION: Synthesis of the available data does not indicate differences in recurrence and/or survival rates for MCC between different clinical excision margins and MMS.

Mohs Micrographic Surgery Versus Wide Local Excision in the Treatment of Merkel Cell Carcinoma: A Systematic Review.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neoplasm with high rates of recurrences. Current guidelines recommend wide local excision (WLE) with 1 to 2 cm margins. However, Mohs micrographic surgery (MMS) offers a potential advantage over WLE because of its ability of sparing healthy tissue and assessing 100% of margins. OBJECTIVE: To systematically evaluate the surgical modalities for the treatment of MCC. MATERIALS AND METHODS: Eligible articles were identified using MEDLINE, Scopus, EMBASE, and Cochrane Library. All available studies investigating surgical treatment of MCC with WLE or MMS were considered. RESULTS: Forty studies met the inclusion criteria. Thirty-one studies described patients treated with WLE, 3 with MMS, and 6 with either WLE or MMS. Subgroup analysis of Stage I MCC showed recurrence rates similar in both surgical modalities with local recurrence rate of 6.8% for WLE versus 8.5% for MMS (p = .64) and a regional recurrence rate of 15.2% for WLE versus 15.3% for MMS (p = .99). CONCLUSION: Overall WLE cases were at a higher stage at presentation. Subgroup analysis showed that MMS is not inferior to WLE excision for the treatment of Stage I MCC and is a reasonable option for anatomic locations where tissue sparing is important.

Merkel Cell Carcinoma In Situ: No More Serendipity?

ABSTRACT: A 50-year-old man, with a history of extensive sun exposure and multiple previous non-melanoma skin cancers, presented with an asymptomatic 8-× 10-millimeter scaly, skin-colored papule on his right shoulder. Subsequent biopsy and excision revealed epidermal hyperplasia containing large atypical basaloid cells with pagetoid spread. Immunoperoxidase staining for cytokeratin-20 demonstrated a focal perinuclear dot-like pattern, and after excluding other in situ entities, a diagnosis of Merkel cell carcinoma In Situ (MCCIS) was rendered. MCCIS is a very rare entity. Although approximately 18% of Merkel cell carcinomas have epidermal involvement, currently only 17 cases of MCCIS have been reported, of which only 7 had no associated neoplasm. Previously, MCCIS was considered a serendipitous or incidental finding, as most cases co-existed with squamous cell carcinoma in situ. This case is unique in that it was not associated with a squamous lesion, and in addition, the pagetoid spread was unusual and has only occasionally been described. As such, MCCIS should be added to list of in situ epidermal lesions with pagetoid spread.

Merkel Cell Carcinosarcoma With a Bland Sarcomatous Component.

ABSTRACT: Merkel cell carcinoma with a sarcomatous component is very rare, with only 12 cases reported in the literature, often with overtly malignant myoid differentiation. We report a case of metastatic Merkel cell carcinosarcoma presenting in a lymph node 6 months after a diagnosis of cutaneous Merkel cell carcinoma with conventional histologic features. The metastatic lesion showed a unique biphasic appearance with admixed populations of neuroendocrine epithelial cells and fascicles of mitotically active spindle cells with mild cytological atypia. In addition to the immunomorphological features, a common molecular profile between the epithelial and mesenchymal components further supported the notion of carcinosarcoma in this case. To the best of our knowledge, a bland sarcomatous component has not been previously described in Merkel cell carcinosarcoma, which can be easily overlooked as a reactive stromal reaction microscopically.

Merkel Cell Carcinoma of the Upper Eye Lid with Atypical Clinical Appearance. / Merkel-Zell-Karzinome des Oberlides mit ungewöhnlichem klinischem Erscheinungsbild.

Merkel cell carcinoma (MCC) is a rare aggressive neuroendocrine skin tumor that occurs mainly in the sun-exposed head and neck region, but rarely in the eyelid region. Early lymphogenic spread often leads to locoregional metastases, which is why early diagnosis is crucial. Classically, periocular MCC presents as a reddish-livid nodule in elderly patients, a visual diagnosis. However, given its low incidence and variable appearance, diagnosis can also be challenging. In both cases presented here, the MCC presented as a skin-colored swelling. In patient 1, the tumor showed a partially deep subaponeurotic localization and mimicked a B-cell lymphoma histopathologically, whereas in patient 2 it imitated a diffuse chalazion clinically. After immunohistochemical characterization and exclusion of metastases, the initial clinically benign appearing lesions in both patients were classified as CK20 negative MCC. The extensive upper eyelid defects were reconstructed by Cutler-Beard plastic surgery, a particular challenge in patient 1 given the oculus unicus situation. Our two cases demonstrate that Merkel cell carcinomas not only manifest as deep red cherry-shaped tumors, but can be skin-colored and mimic benign changes when atypical in location or infiltration pattern.

A Challenging Nodular Lesion of the Ear.

Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion Merkel cell carcinoma arise. It is a rare neuroendocrine skin tumor highly aggressive, not easy to diagnose at first stage, since at first diagnosis it is already widespreading all over the body. In order to renew interest in this letal skin tumori is mandatory to remind high risk population which include elderly people, white skin, chronically exposed to UV immunocompromised. Our unhappy case was described to increase awareness on this kind of skin tumor, since new drug appeared in the market can give an hope to these patients.

Merkel cell carcinoma. / Merkelcellekarsinom.

Merkel cell carcinoma is an uncommon but aggressive tumour with a high metastatic potential. A rapidly growing, non-tender cutaneous tumour on sun-exposed areas of the body in older patients should raise suspicion of the condition. It may be necessary to combine the patient history with clinical, radiological and pathological findings in order to make the correct diagnosis. Excision with a 1-2 cm margin, direct closure and simultaneous sentinel-node biopsy should be performed without delay. Adjuvant radiation therapy of the tumour site may be relevant. After the diagnosis is made, assessment and treatment should take place in hospitals with special experience of the condition.