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.

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.

Survival of Patients With Head and Neck Merkel Cell Cancer: Findings From the Pan-Canadian Merkel Cell Cancer Collaborative.

Importance: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine carcinoma. Due to its relatively low incidence and limited prospective trials, current recommendations are guided by historical single-institution retrospective studies. Objective: To evaluate the overall survival (OS) of patients in Canada with head and neck MCC (HNMCC) according to American Joint Committee on Cancer 8th edition staging and treatment modalities. Design, Setting, and Participants: A retrospective cohort study of 400 patients with a diagnosis of HNMCC between July 1, 2000, and June 31, 2018, was conducted using the Pan-Canadian Merkel Cell Cancer Collaborative, a multicenter national registry of patients with MCC. Statistical analyses were performed from January to December 2022. Main Outcomes and Measures: The primary outcome was 5-year OS. Multivariable analysis using a Cox proportional hazards regression model was performed to identify factors associated with survival. Results: Between 2000 and 2018, 400 patients (234 men [58.5%]; mean [SD] age at diagnosis, 78.4 [10.5] years) with malignant neoplasms found in the face, scalp, neck, ear, eyelid, or lip received a diagnosis of HNMCC. At diagnosis, 188 patients (47.0%) had stage I disease. The most common treatment overall was surgery followed by radiotherapy (161 [40.3%]), although radiotherapy alone was most common for stage IV disease (15 of 23 [52.2%]). Five-year OS was 49.8% (95% CI, 40.7%-58.2%), 39.8% (95% CI, 26.2%-53.1%), 36.2% (95% CI, 25.2%-47.4%), and 18.5% (95% CI, 3.9%-41.5%) for stage I, II, III, and IV disease, respectively, and was highest among patients treated with surgery and radiotherapy (49.9% [95% CI, 39.9%-59.1%]). On multivariable analysis, patients treated with surgery and radiotherapy had greater OS compared with those treated with surgery alone (hazard ratio [HR], 0.76 [95% CI, 0.46-1.25]); however, this was not statistically significant. In comparison, patients who received no treatment had significantly worse OS (HR, 1.93 [95% CI, 1.26-2.96)]. Conclusions and Relevance: In this cohort study of the largest Canada-wide evaluation of HNMCC survival outcomes, stage and treatment modality were associated with survival. Multimodal treatment was associated with greater OS across all disease stages.

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.

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.

Multidisciplinary Treatment of Merkel Cell Carcinoma of the Extremities: Outcomes and Factors Associated with Poor Survival in Nodal Disease.

Merkel cell carcinoma (MCC) has a tendency for lymphatic spread and locoregional recurrence, although there is little data examining the risk factors for patients with lymph node-positive extremity lesions. The purpose of the current study was to examine the outcomes and risk factors associated with nodal metastasis in extremity MCC. We retrospectively reviewed the medical record of 120 patients with extremity MCC evaluated at our institution between 1994 and 2021. The mean age of this cohort was 71 years; 33% of patients were female; and 98% were Caucasian. Seventy-eight (65%) patients presented with localized disease. Thirty-seven (31%) patients had stage III disease, and five (4%) patients had stage IV disease. Treatment of primary lesions consisted primarily of margin-negative excision and adjuvant radiotherapy. Nodal metastases were most treated with adjuvant radiation or completion lymph node dissection. Five-year disease-specific survival in our series was 88% for patients with localized disease, 89% for stage IIIa disease, 40% for stage IIIb disease and 42% for stage IV. Factors associated with worse survival included immunosuppression and macroscopic nodal disease. In conclusion, extremity MCC has a low rate of local recurrence when treated with margin-negative excision and adjuvant radiation. However, treatment of nodal metastases remains a challenge with high rates of recurrence and mortality, particularly for patients who are immunosuppressed or who have macroscopic nodal disease.

An Effective Primary Treatment Using Radiotherapy in Patients with Eyelid Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare type of neuroendocrine tumor. Palpebral localization represents 2.5% of MCCs. Surgery is not always possible due to the localization or comorbidities of elderly patients. We hypothesized that radiotherapy (RT) alone could be a curative treatment in patients contraindicated for oncological surgery. METHODS: We performed a retrospective monocentric study of patients with localized eyelid MCC treated with curative intent using curative radiotherapy. RESULTS: Overall, 11 patients with histologically confirmed eyelid MCC were treated with curative radiotherapy. The median age was 77 years old (range: 53-94). Curative RT was decided mainly due to difficult localization and significant co-morbidities. The median lesion dose was 57 Gy (range: 47-70). Most patients had adjuvant lymph nodes irradiation with a median dose of 50 Gy (n = 9; 82%). The median follow-up was 62 months (6-152 months). None of the seven deaths were MCC-related. None of our patients relapsed during follow-up. Side effects related to radiotherapy were mild (no grade ≥ 2) and rare (n = 3, 21%). CONCLUSION: Our data suggest that curative radiotherapy is an effective and safe treatment for Merkel cell carcinoma of the eyelid and periocular region. Radiotherapy alone allows limiting the aesthetic and functional sequelae in elderly and comorbid patients who are contraindicated for oncological surgery.

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.

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.

Adjuvant Radiotherapy for Dissected Parotid Lymph Nodes Containing Merkel Cell Carcinoma from an Unknown Primary Skin Site: 2 Case Reports.

BACKGROUND Merkel cell carcinoma (MCC) is an aggressive neuroendocrine malignancy that has increased in incidence in recent decades. The management of MCC should involve multidisciplinary experts to achieve optimal patient outcomes. Radiotherapy is commonly used as adjuvant therapy. Our literature review of MCC indicates that aggressive adjuvant radiotherapy might have a positive impact on overall local control and survival. CASE REPORT The first case is a 75-year-old male patient who discovered a right preauricular mass 2 weeks prior. He underwent right parotidectomy with tumor removal on 2012/07/09, and pathology revealed MCC in 3 lymph nodes. The patient received postoperative adjuvant radiotherapy (61.2 Gy) to the remaining right parotid tumor bed and right neck lymph nodes. The patient refused adjuvant chemotherapy. During long-term follow-up, the patient remained disease free for 10 years. The other case is a 73-year-old female patient with metastatic MCC in a left parotid lymph node. She also underwent left parotidectomy with tumor removal, and pathological staging performed according to the 8th edition of the AJCC staging system showed pTxN1aMx, stage IIIA. After the operation, she received postoperative adjuvant radiotherapy (56 Gy) to the remaining left parotid and left neck lymph nodes. The patient remained disease free for 14 months. CONCLUSIONS Metastatic MCC of the parotid lymph nodes without a detectable primary skin tumor is very rare. Adjuvant radiotherapy to the tumor bed and regional nodal basin might be beneficial for preventing disease recurrence despite the absence of systemic medical therapy.

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.