BACKGROUND: To date, only a few population-representative studies have been carried out on the rare Merkel cell carcinoma (MCC). We provide incidence and survival estimates of MCC, including the conditional relative survival.
METHODS: We analyzed data from the cancer registry of North Rhine-Westphalia, Germany, 2008-2021, covering a population of 18 million. We included all newly diagnosed MCCs and calculated age-standardized (old European Standard population) incidence rates and unconditional and conditional relative survival.
RESULTS: Our analysis included 2164 MCC patients. The age-standardized incidence of MCC was 5.2 (men) and 3.8 (women) per million person-years. The 5-year relative survival was 58.8% (men) and 70.7% (women). Survival was lower among men than women in all age-sex groups and was highest for MCC of the upper extremity in both men (68.2%) and women (79.3%). The sex difference in survival is particularly due to the better survival of women with MCC of the head and neck. In terms of survival, the first two years are particularly critical.
CONCLUSIONS: Our data validate the worse survival among men and highlights a more favorable prognosis for MCCs located on the limbs. The first two years after diagnosis of MCC are the years with the highest excess mortality.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin cancer with poor 5-year survival rates. Surgery and radiation are the current first-line treatments for local and nodal disease.
OBJECTIVE: The Brazilian Society of Surgical Oncology developed this document aiming to guide the surgical oncology role in multimodal MCC management.
METHODS: The consensus was established in three rounds of online discussion, achieving consensus on specific topics including diagnosis, staging, treatment, and follow-up.
RESULTS: Patients suspected of having MCC should undergo immunohistochemical examination and preferably undergo pathology review by a dermatopathologist. Initial staging should be performed with dermatologic and nodal physical examination, combined with complementary imaging. Whole-body imaging, preferably with positron emission tomography (PET) or computed tomography (CT) scans, are recommended. Due to the need for multidisciplinary approaches, we recommend that all cases should be discussed in tumor boards and referred to other specialties as soon as possible, reducing potential treatment delays. We recommend that all patients with clinical stage I or II may undergo local excision associated with sentinel lymph node biopsy. The decision on margin size should consider time to recovery, patient\'s comorbidities, and risk factors. Patients with positive sentinel lymph nodes or the presence of risk factors should undergo postoperative radiation therapy at the primary site. Exclusive radiation is a viable option for patients with low performance. Patients with positive sentinel lymph node biopsy should undergo nodal radiation therapy or lymphadenectomy. In patients with nodal clinical disease, in addition to primary tumor treatment, nodal radiation therapy and/or lymphadenectomy are recommended. Patients with advanced disease should preferably be enrolled in clinical trials and discussed in multidisciplinary meetings. The role of surgery and radiation therapy in the metastatic/advanced setting should be discussed individually and always in tumor boards.
CONCLUSIONS: This document aims to standardize a protocol for initial assessment and treatment for Merkel cell carcinoma, optimizing oncologic outcomes in middle-income countries such as Brazil.

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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.
OBJECTIVE: 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).
CONCLUSIONS: 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.

Merkel cell carcinoma (MCC) is a rare skin tumor that shares a similar immunophenotype with Merkel cells, although its origin is debatable. More than 80% of human MCC cases are associated with Merkel cell polyomavirus infections and viral gene integration. Recent studies have shown that the clinical and pathological characteristics of feline MCC are comparable to those of human MCC, including its occurrence in aged individuals, aggressive behavior, histopathological findings, and the expression of Merkel cell markers. More than 90% of feline MCC are positive for the Felis catus papillomavirus type 2 (FcaPV2) gene. Molecular changes involved in papillomavirus-associated tumorigenesis, such as increased p16 and decreased retinoblastoma (Rb) and p53 protein levels, were observed in FcaPV2-positive MCC, but not in FcaPV2-negative MCC cases. These features were also confirmed in FcaPV2-positive and -negative MCC cell lines. The expression of papillomavirus E6 and E7 genes, responsible for p53 degradation and Rb inhibition, respectively, was detected in tumor cells by in situ hybridization. Whole genome sequencing revealed the integration of FcaPV2 DNA into the host feline genome. MCC cases often develop concurrent skin lesions, such as viral plaque and squamous cell carcinoma, which are also associated with papillomavirus infection. These findings suggest that FcaPV2 infection and integration of viral genes are involved in the development of MCC in cats. This review provides an overview of the comparative pathology of feline and human MCC caused by different viruses and discusses their cell of origin.

The mechanotransduction of light-touch sensory stimuli is considered to be the main physiological function of epidermal Merkel cells (MCs). Recently, however, MCs have been demonstrated to be also thermo-sensitive, suggesting that their role in skin physiologically extends well beyond mechanosensation. Here, we demonstrate that in healthy human skin epidermal MCs express functional olfactory receptors, namely OR2AT4, just like neighbouring keratinocytes. Selective stimulation of OR2AT4 by topical application of the synthetic odorant, Sandalore®, significantly increased Piccolo protein expression in MCs, as assessed by quantitative immunohistomorphometry, indicating increased vesicle trafficking and recycling, and significantly reduced nerve growth factor (NGF) immunoreactivity within MCs, possibly indicating increased neurotrophin release upon OR2AT4 activation. Live-cell imaging showed that Sandalore® rapidly induces a loss of FFN206-dependent fluorescence in MCs, suggesting OR2AT4-dependent MC depolarization and subsequent vesicle secretion. Yet, in contrast to keratinocytes, OR2AT4 stimulation by Sandalore® altered neither the number nor the proliferation status of MCs. These preliminary ex vivo findings demonstrate that epidermal MCs also exert OR-dependent chemosensory functions in human skin, and invite one to explore whether these newly identified properties are dysregulated in selected skin disorders, for example, in pruritic dermatoses, and if these novel MC functions can be therapeutically targeted to maintain/promote skin health.

Merkel cell carcinoma (MCC) is a rare tumor with a high risk of recurrence after definitive therapy; however, the optimal duration of surveillance is unclear. First recurrences typically occur within 3 years. National guidelines recommend that patients undergo physical examination and imaging for surveillance during this time period. However, the duration of surveillance beyond this is not defined. Here, we describe a case of a patient developing a recurrence of MCC 7 years after the primary diagnosis with interval in-transit and regional lymph node metastases 15 months following the treatment of the primary MCC. Such late recurrences are rare, largely not reported, and the risk factors contributing to late recurrences are not well described. This case highlights the possibility of late recurrences of MCC after an initial in-transit and nodal recurrence and underscores the importance of identifying predictors of recurrence that may better guide the duration of surveillance.

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BACKGROUND: Immune mechanisms are considered to be responsible for the pathogenesis of cicatricial alopecia in lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) diseases. CD200 has an immunomodulatory function in hair follicles. The functions of Merkel cells (MCs) in hair follicles remain to be fully understood.
OBJECTIVE: This study aimed to determine the number and distribution of MCs as well as CD200 expression in patients with DLE and LPP.
METHODS: Using immunohistochemistry, the number and distribution of MCs (staining with CK20) and CD200 expression in biopsy specimens of LPP and DLE patients were compared with control group patients.
RESULTS: The number of follicular MCs, total MCs, mean follicular MCs, and CD200 expression were significantly lower in the case groups compared to the control group. In CD200- cases, the number of follicular MCs and mean follicular MCs were significantly lower than in CD200+ cases. Retrospective design, lack of data regarding the history of alopecia in the control group, and unknown stage of disease in patients were the limitations.
CONCLUSIONS: MC loss might play a role in immune privilege collapse in hair follicles. This study is novel in terms of investigating MCs in DLE and LPP patients.

Merkel cells (MCs) and associated primary sensory afferents of the whisker follicle-sinus complex, accurately code whisker self-movement, angle, and whisk phase during whisking. However, little is known about their roles played in cortical encoding of whisker movement. To this end, the spiking activity of primary somatosensory barrel cortex (wS1) neurons was measured in response to varying the whisker deflection amplitude and velocity in transgenic mice with previously established reduced mechanoelectrical coupling at MC-associated afferents. Under reduced MC activity, wS1 neurons exhibited increased sensitivity to whisker deflection. This appeared to arise from a lack of variation in response magnitude to varying the whisker deflection amplitude and velocity. This latter effect was further indicated by weaker variation in the temporal profile of the evoked spiking activity when either whisker deflection amplitude or velocity was varied. Nevertheless, under reduced MC activity, wS1 neurons retained the ability to differentiate stimulus features based on the timing of their first post-stimulus spike. Collectively, results from this study suggest that MCs contribute to cortical encoding of both whisker amplitude and velocity, predominantly by tuning wS1 response magnitude, and by patterning the evoked spiking activity, rather than by tuning wS1 response latency.