Merkel Cell Carcinoma Research Articles

Large cell neuroendocrine carcinoma of oral cavity: A rare case report with review of literature

Abstract Neuroendocrine tumours (NETs) primarily affect the lungs and larynx. Primary neuroendocrine carcinomas (NECs) rarely occur in the oral cavity. The classification of these tumours is ambiguous; however, the literature acknowledges their aggressiveness. Merkel cell carcinoma (MCC) is rare and more common in the skin but could occur intraorally. MCC and NECs are aggressive neoplasms and recommend intensive treatment. In this case report, a 22-year-old female presented with an ulceroinfiltrative lesion in the left buccal mucosa of the cheek, which was diagnosed as primary NEC in the oral cavity. This patient underwent wide local lesion excision of oral cavity mass, ipsilateral selective neck node dissection of levels 1–4 and postoperative chemotherapy. This aggressive tumour type requires large local excisions with margins like Merkel cell skin carcinomas. To our knowledge, this is the youngest oral cavity primary neuroendocrine cancer patient to date in the literature.

Merkel cell: Friend or felon

Abstract Merkel cells are perceived as tactile receptors within skin and oral mucosa containing abundant intermediate filaments but lacking characteristic condensation of tonofilaments, hence are also referred to as non-keratinocytes. Merkel cell carcinomas (MCCs) are primary aggressive neuroendocrine neoplasms occurring in elderly individuals. Toker in 1972 reported MCC of skin pointing towards sweat glands as the source of origin which was later rectified by Tang with the aid of ultrastructural studies as Merkel cells to be a lineage of such tumours. Normally, Merkel cells are abundant in the gingiva and vermillion border of the lip and thus these are the common sites for this neoplasm. Histopathologically, MCC mimics varied other carcinomas, hence requiring a thorough diagnostic protocol. We present a case of challenging histopathology which on immunohistochemical analysis with a unique cytokeratin profile and neurofilament staining pattern helped in reaching a definitive diagnosis.

Dermoscopic characteristics of Merkel cell carcinoma

BackgroundMerkel cell carcinoma (MCC) is a rare, aggressive, cutaneous tumour with high mortality and frequently delayed diagnosis. Clinically, it often manifests as a rapidly growing erythematous to purple nodule usually located on the lower extremities or face and scalp of elderly patients. There is limited available data on the dermoscopic findings of MCC, and there are no specific features that can be used to definitively diagnose MCC.Aim of the studyHere, we aimed to summarize existing published literature on dermatoscopic and reflectance confocal microscopy (RCM) features of MCC.Materials and methodsTo find relevant studies, we searched the PubMed and Scopus databases from inception to April 12, 2023. Our goal was to identify all pertinent research that had been written in English. The following search strategy was employed: (“ dermoscopy” OR “ dermatoscopy” OR “ videodermoscopy” OR “ videodermatoscopy” OR “ reflectance confocal microscopy”) AND “ Merkel cell carcinoma”. Two dermatologists, DK and GE, evaluated the titles and abstracts separately for eligibility. For inclusion, only works written in English were taken into account.ResultsIn total 16 articles were retrieved (68 cases). The main dermoscopic findings of MCC are a polymorphous vascular pattern including linear irregular, arborizing, glomerular, and dotted vessels on a milky red background, with shiny or non-shiny white areas. Pigmentation was lacking in all cases. The RCM images showed a thin and disarranged epidermis, and small hypo-reflective cells that resembled lymphocytes arranged in solid aggregates outlined by fibrous tissue in the dermis. Additionally, there were larger polymorphic hyper-reflective cells that likely represented highly proliferative cells.ConclusionDermoscopic findings of MCC may play a valuable role in evaluating MCC, aiding in the early detection and differentiation from other skin lesions. Further prospective case-control studies are needed to validate these results.

Quality of life and patient-reported toxicities in patients with advanced Merkel cell carcinoma treated with combined nivolumab and ipilimumab with or without stereotactic body radiation therapy.

Merkel cell carcinoma is a rare skin cancer associated with poor survival. Based on a previous Phase II trial of adults with advanced Merkel cell carcinoma by Kim and colleagues (2022), there is now a strong rationale for combination therapy (i.e., nivolumab and ipilimumab) to become a treatment option for patients with advanced Merkel cell carcinoma. The goal of this paper was to report on the secondary outcome of quality of life (QOL) among patients on this trial. Patients receiving combined nivolumab and ipilimumab, with or without stereotactic body radiation therapy (SBRT), completed the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 prior to starting treatment and every 2 weeks thereafter. Changes in QOL during treatment and post-treatment were evaluated using piecewise random-effects mixed models. Exploratory analyses compared changes in QOL between study arms. The original trial was registered with ClinicalTrials.gov (NCT03071406). Study participants (n = 50) reported no changes in overall QOL (ps > 0.05), but emotional functioning improved during treatment (p = 0.01). Cognitive and social functioning worsened post-treatment (ps < 0.01). In general, patients treated with combination therapy only (n = 25) reported no change in QOL over time, whereas patients also treated with SBRT (n = 25) consistently demonstrated worsening QOL post-treatment. QOL is generally preserved in patients treated with combination therapy, but the addition of SBRT may worsen QOL. Combined with clinical efficacy data published previously, results support the use of combination therapy with nivolumab and ipilimumab as a treatment option for patients with advanced Merkel cell carcinoma.

Magnetic seed localization is feasible for non-palpable melanoma, Merkel cell carcinoma, and soft tissue sarcoma lesions

BackgroundLocalization of non-palpable melanoma, Merkel cell carcinoma (MCC) and soft tissue sarcoma (STS) lesions can be difficult due to size, location, and obesity of patients or fibrosis due to previous treatments. Magnetic seed localization (MSL) is a common method to localize non-palpable breast lesions, but the feasibility of MSL for non-palpable melanoma, MCC and STS lesions has not yet been described. MethodsIn this retrospective single center cohort study, all consecutive patients between January 2021 and October 2023 who had a resection of a non-palpable melanoma, MCC or STS lesion guided by Sirius Pintuition, a MSL technique, were included. The primary endpoint was successful lesion localization during surgery and the secondary endpoints were seed migration, negative resection margins, and complications. ResultsSeventy-nine seeds were placed for 76 lesions, which were resected during 68 surgeries in 61 patients. All lesions (100 %) were localized and resected. Median time of surgery was 44 min. No seed migration was observed. A negative resection margin was achieved for 60 (78.9 %) lesions. Clavien Dindo grade ≥2 complications occurred in 7.4 %. ConclusionMagnetic seed localization with Sirius Pintuition is feasible for both non-palpable melanoma, MCC, and STS lesions.

Therapeutic Approaches for Non-Melanoma Skin Cancer: Standard of Care and Emerging Modalities.

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.

Upper and Lower Eyelid Malignancies: Differences in Clinical Presentation, Metastasis, and Treatment.

Approximately 5-15% of all dermatologic malignancies manifest in the upper and lower eyelids. The primary types include basal cell carcinoma, squamous cell carcinoma, and sebaceous cell carcinoma, with Merkel cell carcinoma and melanoma following closely behind. Basal cell carcinoma predominantly affects the lower eyelid, yet various other carcinomas, melanomas, metastases, and neoplasms of diverse origins can arise on both upper and lower eyelids. Risk factors such as advanced age, smoking, and notably, exposure to UV light significantly contribute to the development of these eyelid lesions. Despite the increasing incidence, research on dermatologic eyelid malignancies remains limited. However, such study is imperative given that many systemic oncologic malignancies initially present as metastatic eyelid lesions. This paper provides an in-depth exploration of eyelid anatomy, clinical presentation, diagnosis, and treatment management.Key Points: Eyelid metastases represent less than one percent of all eyelid cancers, yet they often serve as the initial indication of an underlying systemic malignancy. Early detection and treatment is crucial in improving prognosis and quality of life for patients. Treatment options encompass a range of modalities, with Mohs surgery as the gold standard for the removal of ocular tumors. Additional treatment options include local excision as well as non-surgical interventions such as radiotherapy, cryotherapy, immunotherapy, and topical medications.

Hispanic patients with Merkel cell carcinoma have lower mortality compared to non-Hispanic patients in the National Cancer Database

Hispanic patients with Merkel cell carcinoma have lower mortality compared to non-Hispanic patients in the National Cancer Database

Merkel Cell Polyomavirus targets SET/PP2A complex to promote cellular proliferation and migration

Merkel Cell Carcinoma (MCC) is a rare neuroendocrine skin cancer. In our previous work, we decoded genes specifically deregulated by MCPyV early genes as opposed to other polyomaviruses and established functional importance of NDRG1 in inhibiting cellular proliferation and migration in MCC. In the present work, we found the SET protein, (I2PP2A, intrinsic inhibitor of PP2A) upstream of NDRG1 which was modulated by MCPyV early genes, both in hTERT-HK-MCPyV and MCPyV-positive (+) MCC cell lines. Additionally, MCC dermal tumour nodule tissues showed strong SET expression. Inhibition of the SET-PP2A interaction in hTERT-HK-MCPyV using the small molecule inhibitor, FTY720, increased NDRG1 expression and inhibited cell cycle regulators, cyclinD1 and CDK2. SET inhibition by shRNA and FTY720 also decreased cell proliferation and colony formation in MCPyV(+) MCC cells. Overall, these results pave a path for use of drugs targeting SET protein for the treatment of MCC.

EE413 Predictive and Interpretable Machine Learning of Economic Burden: The Role of Chronic Conditions Among Patients with Incident Primary Merkel Cell Carcinoma

EE413 Predictive and Interpretable Machine Learning of Economic Burden: The Role of Chronic Conditions Among Patients with Incident Primary Merkel Cell Carcinoma

Different prognosis in cutaneous early-onset and late-onset Merkel cell carcinoma: a population-based retrospective study.

Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC. Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome. The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog-rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone. We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone.

ASO Visual Abstract: The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis.

ASO Visual Abstract: The Role of Neoadjuvant Immunotherapy in the Management of Merkel Cell Carcinoma with Clinically Detected Regional Lymph Node Metastasis.

Incidence and Relative Survival of Patients with Merkel Cell Carcinoma in North Rhine-Westphalia, Germany, 2008-2021.

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. 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. 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. 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.

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment

Brazilian Society of Surgical Oncology recommendations on Merkel cell carcinoma surgical treatment

Phase 1b trial of IFx-Hu2.0, a novel in situ cancer vaccine, in checkpoint inhibitor-resistant Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC).

9592 Background: MCC and cSCC have limited treatment options when refractory to immune checkpoint inhibitor (ICI) therapy. IFx-Hu2.0 (IFx) is a plasmid DNA encoding for an immunogenic bacterial protein, Emm55, formulated with a transfection agent for direct intra-tumoral (IT) injection. In this Phase 1b study, we evaluated the safety and efficacy of different schedules of IT IFx in patients (pts) with advanced MCC or cSCC. Methods: In the first trial stage (n=9), IT IFx was administered in up to 3 lesions on 3 schedules following a 3+3 exposure escalation schema; weekly x 1, 2, or 3. In the second trial expansion stage (n=11), IT IFx was administered weekly x 3. The primary objective of the study was to establish safety and feasibility of repeated IT administrations of the investigational agent. ≥80% completion of planned study therapy was predefined as a successful feasibility outcome. Given the proposed potential for immune priming effects of IFx, we performed an unplanned exploratory analysis of post-protocol treatment efficacy to evaluate response to ICI rechallenge. Results: We treated 22 pts (MCC, 13; cSCC, 9). All pts had received prior anti-PD(L)1 based treatment with disease progression being the reason for ICI discontinuation in all patients but one. Two pts did not complete planned study therapy due to rapid clinical progression and were replaced but included in the safety analysis. IT IFx was well tolerated at all dose schedules evaluated with 1 high-grade toxicity deemed possibly treatment related (G3 hepatitis in a patient recently treated with ICI). The study therefore met predefined study endpoints for safety and efficacy. After protocol specified IT therapy, 11 MCC pts and 6 cSCC pts were treated with anti-PD(L)1 based therapy as the immediate post-protocol treatment. Five of 9 (56%) evaluable MCC patients and 1 of 7 (14%) cSCC patients experienced an objective response to this ICI rechallenge, with duration of response ongoing in 4 patients (6+, 19+, 21+, 23+ months) and the two other responses lasting 23 and 33 months. The two remaining MCC patients were not evaluable for response from IO rechallenge due to radiation administered to the only measurable disease site(s), but both remain progression free at 11+ and 13+ months with previously progressive disease. Conclusions: IT IFx-Hu2.0 is safe and feasible to administer at weekly dosing repeated up to 3 weeks. An unplanned exploratory analysis revealed frequent (56%) and durable responses in advanced MCC to ICI re-challenge despite prior resistance to this class of drug, suggesting that IFx induced an immune priming effect. Preliminary biomarker analyses to investigate this phenomenon are ongoing and will be presented. Clinical trial information: NCT04160065 .

Durability of immune checkpoint inhibitor (ICI) response following treatment discontinuation in advanced merkel cell carcinoma (MCC).

9596 Background: Advanced MCC has a high response rate to ICI therapy, but the durability of responses once treatment is discontinued remains unclear. We therefore reviewed the long-term outcomes of advanced MCC patients at our institution who discontinued ICI treatment after achieving favorable initial response. Methods: In an IRB-approved single institution retrospective review of advanced MCC patients, we analyzed all patients who received at least one dose of anti-PD(L)1 monotherapy for unresectable or metastatic disease, achieved stable disease (SD) or better, and discontinued treatment for a reason other than disease progression. Duration of response and outcomes of subsequent therapy were assessed. Results: Of 195 advanced MCC patients treated with ICI, we identified 45 who met study criteria. Of these, 21 (47%) had a complete response (CR) to initial ICI treatment, 23 (51%) a partial response (PR) and 1 (2%) SD. Twenty-five (56%) patients discontinued ICI electively and 20 (44%) discontinued due to toxicity. In total, 21 of the 45 patients (47%) experienced disease progression at a median of 11.2 months (range 2.1-22.7 months) from ICI cessation. The median follow-up after ICI discontinuation for patients who have not experienced progression is 22.8 months (5.8-82.0 months). There was a lower rate of progression in patients who achieved CR vs. non-CR (24% vs 67%, p=0.006) and a trend towards a lower rate in those who discontinued electively vs. due to toxicity (36% vs 60%, p=0.14). For patients in whom the molecular subtype was known, there was a higher risk for progression in patients with viral MCC (12 of 16, 75%) compared to UV-associated MCC (4 of 13, 31%, p=0.02). Fifteen of the 21 patients (71%) who experienced progression were rechallenged with ICI therapy, including both single agent (12 patients, 57%) and combination (3, 14%) therapy. The remaining patients received locally-directed therapy only (3, 14%), chemotherapy (1, 5%), declined further treatment (1, 5%), or transferred care and were lost to follow up (1, 5%). Eleven of 15 ICI-retreated patients (73%) achieved an objective response to rechallenge, including all 3 patients who received combination therapy with ipilimumab+nivolumab. Twelve of the 45 patients have expired; 6 due to progressive MCC and remaining 6 known or suspected from unrelated causes. Conclusions: Patients with advanced MCC have a substantial risk of disease progression following treatment discontinuation despite initial favorable ICI response, 47% in our series with a median time to event of 11.2 months, particularly in those that achieve less than a complete response. In the setting of disease progression post-ICI discontinuation, most patients maintain sensitivity to retreatment with the same drug class. Virus-positive MCC may be a risk factor for post-discontinuation relapse, which should be validated in future studies.

TRICK-MCC: A proof-of-concept, investigator-initiated study of combination therapy with anti–PD-1, anti–LAG-3, and anti–TIM-3 in participants with advanced or metastatic PD-(L)1 refractory Merkel cell carcinoma.

TPS9618 Background: Merkel cell carcinoma (MCC) is an aggressive and highly immunogenic skin cancer often associated with the Merkel cell polyomavirus (MCPyV). Immune checkpoint inhibition (ICI) via PD-(L)1 blockade can promote durable responses among patients with metastatic MCC, yet &gt;50% of MCC patients experience disease progression. There is an unmet need for effective treatment options for these patients. One possible strategy to overcome primary and secondary resistance in PD-(L)1 refractory MCC is concurrent targeting of multiple immune checkpoints to facilitate reversal of chronic T cell exhaustion. Based on our preliminary data revealing high expression of PD-1, LAG-3 and TIM-3 on MCC-specific CD8 T cells, which appear to increase upon clinical disease progression in the context of treatment with PD-(L)1 blockade, we hypothesize that concurrent blockade of PD-1, LAG-3 and TIM-3 will overcome immune evasion in patients with PD-(L) refractory MCC. Methods: TRICK-MCC (Triple Immune Checkpoint Inhibition in MCC) is an investigator initiated, Phase 2 clinical trial investigating concurrent treatment with anti-PD-1 (retifanlimab), anti-LAG3 (INCAGN02385) and anti-TIM-3 (INCAGN02390) in patients with advanced/metastatic MCC that has progressed after treatment with anti-PD-(L)1. Target enrollment is 20 patients total, with 5 patients enrolled as of Jan 2024. Patients will receive anti-PD-1 q4w and anti-TIM-3 and LAG-3 q2w for up to 24 weeks (Induction Phase) followed by all drugs q6w (Maintenance Phase). Treatment will end 2 years after starting the study drugs, or upon disease progression, unacceptable toxicity, or study withdrawal. Primary objective is objective response rate (ORR). Secondary objectives are duration of response, progression free survival, overall survival, and incidence and severity of adverse events. Interim analysis will be done after 10 patients have been enrolled and followed sufficiently long to assess ORR. An observed ORR of 25%will be considered as clinically meaningful in this population with no reliable standard treatments. Serial tumor biopsies and blood samples will be obtained in all patients, unless deemed unsafe or not feasible. Planned correlative studies aim to better characterize the prevalence and significance of cancer-specific T cell exhaustion (through rigorous study of MCPyV-specific T cells), the immunologic effects of triple ICI, and alternative mechanisms of PD-(L)1 resistance beyond T cell exhaustion in PD-(L)1 resistant tumors. We hope to gain insights that are broadly applicable to solid tumor immunotherapy. Clinical trial information: NCT06056895 .

Survival in de novo metastatic merkel cell carcinoma according to sites of metastases.

e21511 Background: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a propensity to form regional and distant metastases. Due to the low incidence of MCC, there is a dearth of studies evaluating the impact of the sites of metastases on clinical outcomes. Recently, we found that liver and bone metastases were associated with shorter overall survival (OS) in patients with recurrent metastatic MCC. Herein, we report on the prognostic impact associated with specific metastatic sites in patients who presented with de novo Stage IV MCC at Dana-Farber Cancer Institute. Methods: Patients were included if they consented to participate in a biobanking study (DF/HCC #09-156) and presented with one or more distant sites of metastases on imaging at the time of diagnosis due to MCC. The following data were collected: age at diagnosis, gender, race, metastatic site(s) at the time of diagnosis, date of diagnosis, first-line treatment, treatment type, best response on imaging, progression, and vital status. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Fisher’s exact test was used for response rate analysis. Results were considered statically significant if p &lt; 0.05. Results: 34 participants presented with one or more distant metastatic sites of MCC between the years 2010 and 2022. There was no association between the number of metastatic sites at presentation and OS (p= 0.58), PFS (p= 0.79), or response rates (p= 0.53). Among the organ sites we examined, bone metastases were associated with shorter OS (8.2 versus 25.2 months, HR = 2.4; 95% CI 1.01 – 5.7, p= 0.04). There were non-significant associations between OS and metastases in lymph nodes (p= 0.07) and in liver (p= 0.16). The location of metastases was not associated with the response rate to first-line treatment. There was no statistically significant association between any site of metastases and PFS. Conclusions: In this cohort of patients with de novo metastatic MCC, the presence of bone metastases, but not the number of overall organs involved, was associated with significantly worse overall survival. If bone involvement is confirmed to be a negative prognostic factor in an independent dataset, it would warrant mechanistic studies to further our understanding of this interplay and a re-examination of the AJCC staging for metastatic disease.

The effect of selinexor on prostaglandin synthesis in virus-positive Merkel cell carcinoma cell lines.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with high rates of metastasis and mortality. In vitro studies suggest that selinexor (KPT-330), an inhibitor of exportin 1, may be a targeted therapeutic option for MCC. This selective inhibitor prevents the transport of oncogenic mRNA out of the nucleus. Of note, 80% of MCC tumors are integrated with Merkel cell polyomavirus (MCPyV), and virally encoded tumor-antigens, small T (sT) and large T (LT) mRNAs may require an exportin transporter to relocate to the cytoplasm and modulate host tumor-suppressing pathways. To explore selinexor as a targeted therapy for MCC, we examine its ability to inhibit LT and sT antigen expression in vitro and its impact on the prostaglandin synthesis pathway. Protein expression was determined through immunoblotting and quantified by densitometric analysis. Statistical significance was determined with t-test. Treatment of MCPyV-infected cell lines with selinexor resulted in a significant dose-dependent downregulation of key mediators of the prostaglandin synthesis pathway. Given the role of prostaglandin synthesis pathway in MCC, our findings suggest that selinexor, alone or in combination with immunotherapy, could be a promising treatment for MCPyV-infected MCC patients who are resistant to chemotherapy and immunotherapy.

Merkel cell carcinoma - particularities and morphological aspect of a unique and rare entity

Abstract Introduction: Merkel cell carcinoma is a very rare malignant neoplasm which presents high aggressivity, high recurrence rate and has meta-static potential. Our purpose is to present the histological and immunohistochemical particularities of Merkel Cell Carcinoma while reviewing potential differential diagnoses and challenges that we can encounter in daily practice. Case presentation: We present the case of an 86-year-old female patient who presented with a nodular tumour located in the left forearm, raising suspicion of a soft tissue tumour. The histological appearance of this unique type of cancer is highlighted on the Haematoxylin-eosin stain as a solid tumour composed of nests and chords of monomorphic cells. The nuclei of these tumoral cells appear characteristically as enlarged with dispersed chromatin. The immunohistochemical reactions have been performed and it was observed that the tumoral cells exhibited positivity for synaptophysin, CD56, NSE, EMA, as well as a “dot-like” expression for CK20. These histopathological and immunohistochemical features were consistent with a diagnosis of MCC, stage pT3, based on the assessment of tumour size. Conclusions: Sometimes, differentiating this tumour from other primary malignant neoplasms of the skin or even cutaneous metastases can be difficult. Immunohistochemistry remains the most important tool of diagnosis, especially for differentiating this neoplasm from metastatic neuroendocrine tumours that can affect the skin.