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Metastatic Merkel Cell

Gloria Fabris, Alessandro Lucantonio, Nico Hampe, Erik Noetzel, Bernd Hoffmann, Antonio DeSimone, Rudolf Merkel
Basement membranes (BMs) are thin layers of condensed extracellular matrix proteins serving as permeability filters, cellular anchoring sites, and barriers against cancer cell invasion. It is believed that their biomechanical properties play a crucial role in determining cellular behavior and response, especially in mechanically active tissues like breast glands. Despite this, so far, relatively little attention has been dedicated to their analysis because of the difficulty of isolating and handling such thin layers of material...
September 29, 2018: Biophysical Journal
Paul W Harms, Kelly L Harms, Patrick S Moore, James A DeCaprio, Paul Nghiem, Michael K K Wong, Isaac Brownell
Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer associated with advanced age and immunosuppression. Over the past decade, an association has been discovered between MCC and either integration of the Merkel cell polyomavirus, which likely drives tumorigenesis, or somatic mutations owing to ultraviolet-induced DNA damage. Both virus-positive and virus-negative MCCs are immunogenic, and inhibition of the programmed cell death protein 1 (PD-1)-programmed cell death 1 ligand 1 (PD-L1) immune checkpoint has proved to be highly effective in treating patients with metastatic MCC; however, not all patients have a durable response to immunotherapy...
October 4, 2018: Nature Reviews. Clinical Oncology
K G Paulson, V Voillet, M S McAfee, D S Hunter, F D Wagener, M Perdicchio, W J Valente, S J Koelle, C D Church, N Vandeven, H Thomas, A G Colunga, J G Iyer, C Yee, R Kulikauskas, D M Koelle, R H Pierce, J H Bielas, P D Greenberg, S Bhatia, R Gottardo, P Nghiem, A G Chapuis
Understanding mechanisms of late/acquired cancer immunotherapy resistance is critical to improve outcomes; cellular immunotherapy trials offer a means to probe complex tumor-immune interfaces through defined T cell/antigen interactions. We treated two patients with metastatic Merkel cell carcinoma with autologous Merkel cell polyomavirus specific CD8+ T cells and immune-checkpoint inhibitors. In both cases, dramatic remissions were associated with dense infiltration of activated CD8+s into the regressing tumors...
September 24, 2018: Nature Communications
Marco Rastrelli, Beatrice Ferrazzi, Francesco Cavallin, Vanna Chiarion Sileni, Jacopo Pigozzo, Alessio Fabozzi, Saveria Tropea, Antonella Vecchiato, Alessandra Costa, Alessandro Parisi, Carlo Riccardo Rossi, Paolo Del Fiore, Mauro Alaibac
Merkel Cell Carcinoma (MCC) is a rare but highly aggressive neuroendocrine neoplasm of the skin. This study aimed at describing characteristics, treatment, and prognosis of a series of consecutive cases of MCC patients, in order to contribute to the investigation of this rare malignancy and provide better patient care. This is a retrospective cohort study including all 90 patients diagnosed and/or treated for MCC between 1991 and 2018 at the Veneto Institute of Oncology in Padua (Italy). Patient and tumor characteristics, treatment, and immunohistochemical data were extracted from a prospectively collected local database...
September 24, 2018: Cancers
Mary E Laschinger, Lina Naga, Anthony A Gaspari
Neuroendocrine carcinomas with distant metastases are rarely reported in the literature, with cutaneous metastases being among the most infrequently reported sites. The importance of distinguishing metastatic neuroendocrine carcinoma (NEC) from primary neuroendocrine carcinoma in the skin, or Merkel cell carcinoma (MCC), has been stressed in the literature, with CK20 positivity traditionally being reported as the key diagnostic feature of MCC. Our case not only serves as one of the few reported cases of cutaneous metastases of a visceral NEC, but also serves to caution providers as to the use of CK20 positivity as an absolute diagnostic feature...
October 2018: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
Kotaro Nagase, Yutaka Narisawa
Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin, with frequent recurrences, metastasis, and a high mortality rate. For primary or locoregional MCC, a wide local excision followed by radiation therapy is the basic treatment modality for preventing recurrence at the primary site and involved lymph nodes. Cytotoxic chemotherapy has been commonly used to treat patients with metastatic MCC, but not as an adjuvant therapy for high-risk resected MCC. Although MCC is often chemotherapy-sensitive in the first-line setting, responses are rarely durable and most patients subsequently relapse and develop metastasis...
September 20, 2018: Current Treatment Options in Oncology
Nnenna Nwogu, James R Boyne, Samuel J Dobson, Krzysztof Poterlowicz, G Eric Blair, Andrew Macdonald, Jamel Mankouri, Adrian Whitehouse
Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high propensity for recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is recognised as the causative factor in the majority of MCC cases. The MCPyV small tumour antigen (ST) is considered to be the main viral transforming factor, however potential mechanisms linking ST expression to the highly metastatic nature of MCC are yet to be fully elucidated. Metastasis is a complex process, with several discrete steps required for the formation of secondary tumour sites...
September 2018: PLoS Pathogens
Jacob Appelbaum, David Wells, Joseph B Hiatt, Gideon Steinbach, F Marc Stewart, Hannah Thomas, Paul Nghiem, Raj P Kapur, John A Thompson, Shailender Bhatia
BACKGROUND: Immune checkpoint inhibitors (ICIs) are the treatment of choice for several cancers and can be associated with remarkable clinical benefit, but can also cause serious immune-related adverse events (irAEs). Management of rare and severe irAEs is challenged by an incomplete knowledge of their natural history and pathogenetic mechanisms. We report a case of fatal acute-onset gastro-intestinal (GI) hypomotility from myenteric plexus neuropathy following a single dose of ipilimumab plus nivolumab given for treatment of Merkel cell carcinoma (MCC)...
August 31, 2018: Journal for Immunotherapy of Cancer
Murtuza Bharmal, Alexia Marrel, Meliessa Hennessy, Fatoumata Fofana, Jérémy Lambert, Benoit Arnould
AIM: To assess patient experience with chemotherapy and avelumab in metastatic Merkel cell carcinoma (mMCC). METHODS: In the JAVELIN Merkel 200 trial, chemotherapy-refractory mMCC patients could participate in optional qualitative interviews at baseline documenting recollection of previous chemotherapy experience, and at weeks 13/25 documenting current experience with avelumab. Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT-M) was administered in parallel...
September 2018: Journal of Comparative Effectiveness Research
Reinhard Dummer, Olivier Michielin, Mirjam Chantal Nägeli, Simone M Goldinger, Federico Campigotto, Ulrike Kriemler-Krahn, Herbert Schmid, Alberto Pedroncelli, Sara Micaletto, Dirk Schadendorf
Introduction: Somatostatin analogues exert antitumour activity via direct and indirect mechanisms. The present study was designed to assess the safety and efficacy of pasireotide in patients with BRAF -wild type (WT) and NRAS -WT metastatic melanoma. Patients and methods: Patients with unresectable and/or metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was administered at different doses for ≤8 weeks in dose-escalation phase, followed by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up phase up to six additional months...
2018: ESMO Open
Shailender Bhatia, Natalie J Miller, Hailing Lu, Natalie Vandeven Vandeven, Dafina Ibrani, Michi Shinohara, David Byrd, Upendra Parvathaneni, Rima M Kulikauskas, Jan Ter Meulen, Frank J Hsu, David M Koelle, Paul Nghiem
PURPOSE: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and adaptive anti-tumor immune responses in preclinical models. This pilot study assessed the safety, efficacy, and immunologic activity of intratumoral (IT) administration of G100 in patients with Merkel cell carcinoma (MCC). EXPERIMENTAL DESIGN: Patients with loco-regional MCC (n=3; Cohort A) received neoadjuvant IT G100 (2 weekly doses at 5 μg/dose) followed by surgery and radiotherapy; patients with metastatic MCC (n=7; Cohort B) received 3 doses in a 6-week cycle and could receive additional cycles with/without radiotherapy...
August 9, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Mohammed T Lilo, Youdinghuan Chen, Robert E LeBlanc
Merkel cell carcinoma (MCC) is an extremely aggressive skin cancer that must be distinguished from other basaloid cutaneous neoplasms that have different treatments and prognoses. This is sometimes challenging in small shave specimens, crushed samples, lymph nodes, and core needle biopsies. Insulinoma-associated protein 1 (INSM1) immunohistochemistry is a sensitive nuclear marker of neuroendocrine differentiation. INSM1 staining was performed on 56 MCC (47 primary tumors, 9 nodal metastases), 50 skin control cases that included basal cell carcinomas, basaloid squamous cell carcinomas, Bowen disease, sebaceous neoplasms, melanoma, and B-cell lymphomas, and 28 lymph node control cases that included metastatic neuroendocrine neoplasms, melanomas, squamous cell carcinomas, lymphomas, and adenocarcinomas...
November 2018: American Journal of Surgical Pathology
Daniela Femia, Natalie Prinzi, Andrea Anichini, Roberta Mortarini, Federico Nichetti, Francesca Corti, Martina Torchio, Giorgia Peverelli, Filippo Pagani, Andrea Maurichi, Ilaria Mattavelli, Massimo Milione, Nice Bedini, Ambra Corti, Maria Di Bartolomeo, Filippo de Braud, Sara Pusceddu
Advanced Merkel cell carcinoma (MCC) is a very aggressive, rare neuroendocrine tumor of the skin with a high frequency of locoregional recurrence and metastasis, and a high mortality rate. Surgical resection, sentinel lymph node biopsy, and radiotherapy represent the gold standard of treatment in patients with localized disease, while chemotherapy has a significant role in the treatment of advanced disease. However, no definitive evidence on the survival impact of radiotherapy in the advanced stages has been provided to date, and response to chemotherapy remains brief in the majority of cases, indicating an urgent need for alternative approaches...
October 2018: Targeted Oncology
Justin P Bandino, Caitlin G Purvis, Blake R Shaffer, AbdAllah Gad, Dirk M Elston
BACKGROUND: Merkel cell carcinoma (MCC) is a rare neuroendocrine cutaneous malignancy that shares cytologic, histopathologic, and immunohistochemical features with other small round blue cell (SRBC) tumors. Although the trabecular pattern is anecdotally associated with MCC, objective data are lacking. METHODS: This was a retrospective institutional review board-approved observational study conducted on microscopic images of 79 MCCs and 74 other SRBC tumors (desmoplastic small round cell tumor, primitive neuroectodermal tumor, neuroblastoma, embryonal rhabdomyosarcoma, alveolar rhabdomyosarcoma, synovial sarcoma, carcinoid, metastatic small cell lung cancer, non-Hodgkin small cell lymphoma, retinoblastoma, medulloblastoma, nephroblastoma, small cell osteosarcoma, and round cell liposarcoma)...
July 24, 2018: American Journal of Dermatopathology
Kashif Aziz, Amir Shahbaz, Muhammad Umair, Isaac Sachmechi
Avelumab is an anti-PD-L1 (programmed death-ligand 1) immune checkpoint inhibitor (ICIs) and the monoclonal antibody that constitutes a major development in the immunotherapy of cancer. In 2017, The European Medicine Agency (EMA) approved it as an orphan drug for treatment of gastric cancer. Avelumab has recently been approved in the United States, Europe and Japan for treatment of metastatic Merkel cell carcinoma (MCC). Avelumab inhibits the interaction of Programmed cell death protein 1 (PD-1) on immune cells with PD-L1 on tumor cells, thus banishing immunosuppressive signals and leading to enhanced immune cell activation...
2018: EXCLI Journal
Amanda Teets, Linda Pham, Emma Lan Tran, Lana Hochmuth, Rahul Deshmukh
Long-term treatment in the setting of metastatic Merkel cell carcinoma (MCC) and urothelial carcinoma (UC) has shown that current first-line chemotherapeutic agents are losing effectiveness and that there are limited treatment options available outside of radiation therapy and surgical interventions. The use of immunotherapeutic agents such as monoclonal antibodies has been considered a promising alternative for cancers that progress despite treatment with radiation therapy, surgery, and/or chemotherapeutic agents...
2018: Critical Reviews in Immunology
Kristina Buder-Bakhaya, Jessica C Hassel
Background: Immune checkpoint inhibition (ICI) with anti-CTLA-4 and/or anti-PD-1 antibodies is standard treatment for metastatic melanoma. Anti-PD-1 (pembrolizumab, nivolumab) and anti-PD-L1 antibodies (atezolizumab, durvalumab, and avelumab) have been approved for treatment of several other advanced malignancies, including non-small-cell lung cancer (NSCLC); renal cell, and urothelial carcinoma; head and neck cancer; gastric, hepatocellular, and Merkel-cell carcinoma; and classical Hodgkin lymphoma...
2018: Frontiers in Immunology
Timothy O'Brien, Derek G Power
Merkel-cell carcinoma (MCC) is a rare but aggressive cutaneous malignancy arising most often in sun-exposed Caucasians who are immunosuppressed or the elderly. Patients with metastatic disease treated with chemotherapy have a median progression-free survival of just 3 months. This report describes a 58-year-old man with a background history of psoriasis treated with immunosuppressive therapy and subsequently diagnosed with metastatic MCC. Chemotherapy produced a partial response. Then, a novel immunotherapy agent, pembrolizumab, induced a complete response maintained for at least 19 months...
July 11, 2018: BMJ Case Reports
Steven K Jones, Kirk Douglas, Anthony F Shields, Olivia M Merkel
Using an orthotopic model of ovarian cancer, we studied the delivery of siRNA in nanoparticles of tri-block copolymers consisting of hyperbranched polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol) (hyPEI-g-PCL-b-PEG) with and without a folic acid targeting ligand. A SKOV-3/LUC FRα overexpressing cell line was employed to mimic the clinical manifestations of ovarian cancer. Both targeted and non-targeted micelleplexes were able to effectively deliver siRNA to the primary tumor and its metastases, as measured by gamma scintillation counting and confocal microscopy...
September 2018: Biomaterials
U Wollina, G Hansel, J Schönlebe
Cutaneous polypoid melanoma is an uncommon subtype of malignant melanoma. The clinical behavior of this subtype has been described as aggressive. Tumors can be sessile or pedunculated. The typical patient is a younger adult. Authors have analyzed the case histories of patients with polypoid melanomas of the head and neck region treated at our clinic from 2001 to 2018. We identified 3 female patients with tumors of the neck and cheek. In contrast to other reports, all patients were older than 80-years of age...
May 2018: Georgian Medical News
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