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Metastatic Merkel Cell

S A Zafar, O M Ahmed, M R Boland, N Aucharaz, A Lal
Introduction Merkel cell carcinoma (MCC) is a rare cutaneous tumour that is clinically aggressive with a high local, regional, and distant metastatic potential. Cases Three male patients presented to University Hospital Limerick (UHL) in 2015 with cutaneous lesions of the thorax, buttock and forearm. Once MCC was confirmed, management included surgical wide local excision (WLE) with regional lymph node dissection followed by adjuvant radiotherapy. One patient is in remission. The second has residual locoregional lymph node disease and is undergoing annual CT surveillance...
October 11, 2018: Irish Medical Journal
Ajay Prakash, Alhossain A Khalafallah
Hairy cell leukemia (HCL) and Merkel cell carcinoma (MCC) are two rare malignancies with distinct cells of origin. HCL is a lymphoid malignancy of mature B cells, and MCC derives from neuroendocrine cell origin. HCL has a favorable prognosis with most patients achieving long-term remission and potential cure. In contrast, MCC is an aggressive malignancy affecting the skin and can metastasize quickly with a dismal prognosis. Immunocompromised patients, such as those with AIDS, posttransplant, and the elderly, have higher incidences than the general population, suggesting a possible immune mechanism...
2018: Case Reports in Oncological Medicine
Robert H Goldstein, James A DeCaprio
Merkel cell carcinoma (MCC) is a highly aggressive, primary neuroendocrine cancer of the skin. The majority of MCC cases are associated with the recently discovered Merkel cell polyomavirus (MCPyV), while the remaining are caused by ultraviolet (UV) light-induced mutations from excessive sunlight exposure. The risk of developing MCC is much higher in the white population relative to all other races. Approximately 10% of all patients with MCC have some form of immunosuppression including HIV-1/AIDS, chronic inflammatory conditions, solid organ transplantation, or hematological malignancies...
2019: Cancer Treatment and Research
Julie M Collins, James L Gulley
Although immunotherapies have been employed for many decades, immune checkpoint inhibitors have only recently entered the oncologic landscape. Avelumab is a fully human monoclonal antibody that blocks the interaction between PD-L1 on tumor cells and PD-1 on T cells, thereby inhibiting immunosuppression in the tumor microenvironment and reducing tumor growth. Most early clinical trials of avelumab as monotherapy and in combination regimens were part of the international JAVELIN clinical trial program, which included more than 7000 patients in more than 30 trials with at least 15 tumor types...
November 27, 2018: Human Vaccines & Immunotherapeutics
Rebecca W Knackstedt, Thomas Knackstedt, Brian Gastman
BACKGROUND: Merkel cell carcinoma (MCC) is a relatively rare skin cancer with high rates of regional lymph node involvement and metastatic spread. National Comprehensive Cancer Network guidelines recommend sentinel lymph node biopsy (SLNB) for staging purposes. The goal of this study is to report our experience utilizing indocyanine green (ICG) fluorescence-based technology to aid in SLNB detection in MCC. METHODS: Consecutive MCC patients who underwent SLNB with radioisotope lymphoscintigraphy, with intraoperative handheld gamma probe, and ICG-based fluorescence imaging from 2012 to 2017 were prospectively studied (Cohort A)...
December 2018: Journal of Surgical Research
Lubna Suaiti, Oluwakemi Onajin, Omar Sangueza
The coexistence of Merkel cell carcinoma (MCC) and squamous cell carcinoma (SCC) in the same cutaneous lesion is well known. The pathogenesis is believed to be distinct from conventional polyomavirus-related MCC, and it has a more aggressive course. Metastasis of MCC and SCC to the same lymph node is exceedingly rare with only one previously reported case in the English literature. To the best of our knowledge, this is the second case of MCC and SCC with metastasis to the same lymph node. Our case demonstrates the aggressive nature of the combined MCC and SCC in the setting of immunosuppression...
November 15, 2018: American Journal of Dermatopathology
Adriana Iuliano, Fausto Tranfa, Lidia Clemente, Federica Fossataro, Diego Strianese
Merkel cell carcinoma (MCC) is one of the rarest eyelid tumors, with high mortality rate due to lymphatic and metastatic spread. We hereby report six cases of patients with histological diagnosis of MCC referred to our Orbit Unit between 2012 and 2018, focusing on diagnosis, treatment, and subsequent follow up. All patients underwent surgical excision and systemic work-up. Both MCC TNM and eyelid MCC TNM were used to stage lesions. MCC of the eyelid is usually misdiagnosed as benign or other malignant lesions...
October 29, 2018: Orbit
Deepika Narayanan, Hung Doan, Rebecca Simonette, Peter L Rady, Stephen K Tyring
We read with interest the recent article titled 'Expression of 15-lipoxygenase-1 in Merkel cell carcinoma is linked to advanced disease'. Frochman-Frana and colleagues concluded that ALOX15 expression is seen in primary MCC tumor samples as well as lymph node metastasis samples. Primary tumors of metastatic MCC had a higher expression rate of ALOX15 compared to samples without metastatic disease, providing evidence in support of ALOX15's association with cancer development. This article is protected by copyright...
October 26, 2018: Clinical Otolaryngology
Priyamvada Singh, Jon Visger, Jason Prosek, Thomas Olencki, Deepali Pandey, Brad Rovin, Todd E Pesavento
No abstract text is available yet for this article.
October 26, 2018: Transplantation
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...
November 6, 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
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