scholarly journals CYTOLOGICAL DIAGNOSTICS OF MERKEL CELL CARCINOMA (PRIMARY NEURO-ENDOCRINE SKIN CANCER) IN THE MATERIAL OF A SUPERFICIAL SHAVE BIOPSY

Author(s):  
V. N. Vysotskaya ◽  
Y. V. Karpova ◽  
E. S. Sukhovskaya ◽  
A. V. Babushkin ◽  
Ni. V. Boriskin

Merkel cell carcinoma is a rare malignant primary skin tumor with epithelial and neuroendocrine differentiation. In the presented diagnostic case, the possibility of a cytological method in this material is a scarification biopsy.

2020 ◽  
Vol 66 (2) ◽  
pp. 109-119
Author(s):  
Nikolay Avksentev ◽  
Lev Demidov ◽  
Maksim Frolov ◽  
Aleksandr Makarov

Merkel cell carcinoma (MCC) is a rare primary malignant skin tumor with epithelial and neuroendocrine differentiation. According to the Russian clinical recommendations, MCC accounts for around 650 new cases per year in Russia. Avelumab is a human IgG1 monoclonal antibody that targets cancer cells through the inhibition of the immune checkpoint protein PD-L1 and can be used as a 2nd line treatment of metastatic MCC (mMCC). The aim of the study is to conduct a clinical and economic evaluation of avelumab as a second-line treatment in patients with mMCC from the perspective of Russian health care. Methods. Standard chemotherapy regimens were considered as a comparator for avelumab. We proposed a mathematical model of MCC progression and calculated direct medical costs during 6 years of treatment. Incremental cost-effectiveness ratios for avelumab (vs chemotherapy) were compared with the corresponding ratios for another PD-1 inhibitor included in Vital and Essential Drug List (VEDL). Results. Life-years gained (LYG) for avelumab were 2.21 years, compared to 0.39 LYG for chemotherapy. The average costs of using avelumab were 9 156 731 RUB per patient, compared to 60 743 RUB when using chemotherapy. Incremental cost-effectiveness ratio (ICER) for avelumab (vs chemotherapy) was 5 012 867.70 RUB per one LYG, which was 54.8% lower than ICER for pembrolizumab (vs docetaxel) as a second-line treatment in patients with non-small cell lung cancer. ICER for avelumab vs chemotherapy was 11,940,043.38 RUB per one progression-free LYG, which was 40.9% lower than ICER for pembrolizumab (vs chemotherapy) as a treatment in patients with ipilimumab-refractory advanced melanoma.


Author(s):  
Costantino Ricci ◽  
Luca Morandi ◽  
Francesca Ambrosi ◽  
Alberto Righi ◽  
Dino Gibertoni ◽  
...  

AbstractMerkel cell carcinoma (MCC) is an aggressive skin tumor with neuroendocrine differentiation, mainly affecting elderly population or immunocompromised individuals. As methylation of the human telomerase reverse transcriptase (mhTERT) has been shown to be a prognostic factor in different tumors, we investigated its role in MCC, in particular in intron 4–5 where rs10069690 has been mapped and recognized as a cancer susceptibility locus. DNA methylation analysis of hTERT gene was assessed retrospectively in a cohort of 69 MCC patients from the University of Bologna, University of Turin and University of Insubria. Overall mortality was evaluated with Kaplan-Meier curves and multivariable Royston-Parmar models. High levels of mhTERT (mhTERThigh) (HR = 2.500, p = 0.015) and p63 (HR = 2.659, p = 0.016) were the only two clinico-pathological features significantly associated with a higher overall mortality at the multivariate analysis. We did not find different levels of mhTERT between MCPyV (+) and (−) cases (21 vs 14, p = 0.554); furthermore, mhTERThigh was strongly associated with older age (80.5 vs 72 years, p = 0.026), no angioinvasion (40.7% vs 71.0%, p = 0.015), lower Ki67 (50 vs 70%, p = 0.005), and PD-L1 expressions in both tumor (0 vs 3%, p = 0.021) and immune cells (0 vs 10%, p = 0.002). mhTERT is a frequently involved epigenetic mechanism and a relevant prognostic factor in MCC. In addition, it belongs to the shared oncogenic pathways of MCC (MCPyV and UV-radiations) and it could be crucial, together with other epigenetic and genetic mechanisms as gene amplification, in determining the final levels of hTERT mRNA and telomerase activity in these patients.


2003 ◽  
Vol 127 (3) ◽  
pp. 367-369 ◽  
Author(s):  
Michael O. Idowu ◽  
Melissa Contos ◽  
Satinder Gill ◽  
Celeste Powers

Abstract Merkel cell carcinoma (MCC) is an uncommon, highly aggressive cutaneous neoplasm of neuroendocrine differentiation with a poor prognosis. MCC most often presents as a painless, firm, raised lesion in sun-exposed sites of the head and neck region of the elderly. We report a case of a metastatic MCC to the stomach presenting as upper gastrointestinal bleeding. To our knowledge, this is the second reported case of MCC presenting as upper gastrointestinal bleeding and the first case confirmed by the newer immunohistochemical techniques. The literature is reviewed.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21567-e21567
Author(s):  
Richard Cheng Han Wu ◽  
Kari Lynn Kendra ◽  
Dukagjin Blakaj ◽  
Hiral A. Shah ◽  
Joanne M. Jeter ◽  
...  

e21567 Background: Merkel Cell Carcinoma (MCC) is a cutaneous malignancy with neuroendocrine differentiation, linked to infection with polyomavirus (MCPyV) in 80% of cases. PD1 inhibitors have recently been approved for this indication with ORR, 33-56%; CR, 11-24%; PFS, about 17 months; OS, about 12 months. Nivolumab was tested in the neoadjuvant setting with similar responses with pathological CR, 47%. Methods: Adjuvant pilot study (NCT03798639) with two immunotherapy regimens administered for one year to patients with completely resected MCC at high risk of recurrence (primary lesion of 2 cm or greater, positive or close margins ( < 2 cm), perineural or lymphovascular invasion, mitotic index ≥ 20 mitotic figures per mm2, lymph node involvement (stage pIIIA or pIIIB) with or without extracapsular extension, or completely resected stage IV disease). Arm 1, nivolumab 480 mg q 4 wks and radiation therapy (RT) 50-60 Gy in 25-30 fractions, per standard of care. Arm 2, nivolumab 240 mg q 2 wks and ipilimumab 1 mg/kg q 6 wks. Primary objective was feasibility and completion of treatment in this population. Safety profile (CTCAE v5.0) and recurrence-free survival (RFS) after 18 months were secondary endpoints. Patients were randomly allocated 1:1. Results: Ten patients were screened from January 2019 until April 2020, when COVID put the study on hold and the sponsor discontinued the free drug supply. Seven were enrolled. Four were allocated to Arm 1 and three to Arm 2. Patient characteristics in Table. All patients have completed treatment and are in follow-up. Arm 1: all four patients completed radiation therapy and immunotherapy with no dose modifications or delays. Arm 2: one patient had nivolumab delayed 2 weeks for cellulitis, and another missed the last four last doses of nivolumab for cholecystitis and pancreatitis requiring surgery, unrelated to the immunotherapy. Adverse events (AE) were as expected. Arm1 caused more grade 2 and 3 AEs then Arm2 (no grade 3). One patient each discontinued treatment, in Arm 1 for progression and Arm 2 for immunotoxicity (temporal arteritis grade 2). One recurrence was observed in Arm 1 and none in Arm 2. Conclusions: The number of patients expected to recur at 1 year is 20%. Our observed data is insufficient to establish efficacy. However with no patient recurring in the ipilimumab arm after 18 months of follow-up and lower observed side effects, we would favor this regimen for the next trial. Clinical trial information: NCT03798639. [Table: see text]


2018 ◽  
Vol 78 (5) ◽  
pp. 964-972.e3 ◽  
Author(s):  
Thibault Kervarrec ◽  
Julia Zaragoza ◽  
Pauline Gaboriaud ◽  
Amélie Le Gouge ◽  
Agnès Beby-Defaux ◽  
...  

2019 ◽  
Vol 69 (3-4) ◽  
pp. 111-116
Author(s):  
Monika Dudzisz-Śledź ◽  
Marcin Zdzienicki ◽  
Piotr Rutkowski

2019 ◽  
Vol 10 ◽  
pp. 172
Author(s):  
Ricardo Lourenço Caramanti ◽  
Feres Eduardo Chaddad Neto ◽  
Lucas Crociati Meguins ◽  
Carlos Eduardo Rocha ◽  
Dionei Freitas de Moraes ◽  
...  

Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine skin tumor. In our knowledge, only 30 cases of brain metastasis were reported in literature. The authors report a case of 57-year-old male with elevated intracranial pressure signs, which a frontal mass with pathological diagnosis of MCC. Case Description: A 57-year-old male was admitted with a 3-month history of progressive headache, associated with nausea and dizziness. The magnetic resonance imaging showed a left frontal lobe, parasagittal, and nodular lesion with perilesional edema. The patient underwent complete surgical resection with success. The adjuvant treatment was radiotherapy and chemotherapy. Conclusion: In our knowledge, there is a little number of cases of MCC reported in literature. Surgical management is considered in cases with intracranial hypertension or focal signs. The adjuvant treatment options are immunotherapy and radiotherapy.


2014 ◽  
Vol 89 (1) ◽  
pp. 35-47 ◽  
Author(s):  
Laura M. Knight ◽  
Gabriele Stakaityte ◽  
Jennifer, J. Wood ◽  
Hussein Abdul-Sada ◽  
David A. Griffiths ◽  
...  

ABSTRACTMerkel cell carcinoma (MCC) is an aggressive skin cancer of neuroendocrine origin with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) causes the majority of MCC cases due to the expression of the MCPyV small and large tumor antigens (ST and LT, respectively). Although a number of molecular mechanisms have been attributed to MCPyV tumor antigen-mediated cellular transformation or replication, to date, no studies have investigated any potential link between MCPyV T antigen expression and the highly metastatic nature of MCC. Here we use a quantitative proteomic approach to show that MCPyV ST promotes differential expression of cellular proteins implicated in microtubule-associated cytoskeletal organization and dynamics. Intriguingly, we demonstrate that MCPyV ST expression promotes microtubule destabilization, leading to a motile and migratory phenotype. We further highlight the essential role of the microtubule-associated protein stathmin in MCPyV ST-mediated microtubule destabilization and cell motility and implicate the cellular phosphatase catalytic subunit protein phosphatase 4C (PP4C) in the regulation of this process. These findings suggest a possible molecular mechanism for the highly metastatic phenotype associated with MCC.IMPORTANCEMerkel cell polyomavirus (MCPyV) causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer with a high metastatic potential. However, the molecular mechanisms leading to virally induced cancer development have yet to be fully elucidated. In particular, no studies have investigated any potential link between the virus and the highly metastatic nature of MCC. We demonstrate that the MCPyV small tumor antigen (ST) promotes the destabilization of the host cell microtubule network, which leads to a more motile and migratory cell phenotype. We further show that MCPyV ST induces this process by regulating the phosphorylation status of the cellular microtubule-associated protein stathmin by its known association with the cellular phosphatase catalytic subunit PP4C. These findings highlight stathmin as a possible biomarker of MCC and as a target for novel antitumoral therapies.


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