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https://www.readbyqxmd.com/read/28190531/cutaneous-adverse-effects-of-the-immune-checkpoint-inhibitors
#1
REVIEW
Lindsey K Collins, M Shane Chapman, Joi B Carter, Faramarz H Samie
The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms...
December 14, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28174141/checkpoint-inhibition-for-advanced-mucosal-melanoma
#2
Julia Thierauf, Johannes A Veit, Jochen Hess, Nicolai Treiber, Catharina Lisson, Stephanie E Weissinger, Martin Bommer, Thomas K Hoffmann
BACKGROUND: Whereas anti-PD-1 therapy has demonstrated a significant and durable response against advanced cutaneous melanoma, conventional chemotherapies have shown only minor benefit against advanced mucosal melanoma. OBJECTIVES: To investigate the efficacy of anti-PD-1 therapy in a small cohort of patients with mucosal melanoma of the head and neck. MATERIAL & METHODS: We analysed five patients with mucosal melanoma of the head and neck who received nivolumab or pembrolizumab, at an advanced stage...
February 3, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28170118/image-guided-interstitial-high-dose-rate-brachytherapy-in-the-treatment-of-inoperable-recurrent-head-and-neck-malignancies-an-effective-option-of-reirradiation
#3
Nikolaos Tselis, Efstratios Karagiannis, Christos Kolotas, Mehran Baghi, Natasa Milickovic, Nikolaos Zamboglou
BACKGROUND: In recurrent head and neck cancer, therapeutic options are limited and high-quality evidence is rare. The purpose of this report was to present our experience of CT-guided interstitial high-dose rate (HDR) brachytherapy in 4 challenging cases of inoperable recurrent head and neck cancer. METHODS: A 53-year-old man with mucosal melanoma of the paranasal sinuses, a 61-year-old man with myofibroblastic sarcoma of the nasal cavity, a 51-year-old woman with nasopharyngeal cancer, and a 44-year-old woman with orbital leiomyosarcoma were treated with reirradiation by HDR brachytherapy after previous comprehensive therapy, including full course external radiotherapy (RT)...
February 7, 2017: Head & Neck
https://www.readbyqxmd.com/read/28160456/primary-anorectal-mucosal-melanoma-detected-by-anorectal-cytology
#4
Ryan Paul Lau, Jeanine Chiaffarano, Melissa Alexander, Jolene Octavius, Omar Azar, Yan Shi, Melissa Yee-Chang
The detection of primary anorectal melanoma on anal cytology is a rare and challenging diagnosis. We report a case where anorectal cytology showed isolated malignant cells with oval nuclei, prominent nucleoli, and elongated wispy cytoplasmic projections. There was no evidence of squamous dysplasia or melanin pigment identified. To the best of our knowledge, this is the first reported case of a primary anorectal melanoma detected in anorectal cytology. Detection of malignancies other than squamous cell carcinoma can be seen on anorectal cytology and should be considered when there is no evidence of anal intraepithelial neoplasia...
February 3, 2017: Diagnostic Cytopathology
https://www.readbyqxmd.com/read/28154916/-diagnostics-of-malignant-melanoma-of-the-skin-recommendations-of-the-current-s3-guidelines-on-histology-and-molecular-pathology
#5
C Rose
The updated S3 guidelines on malignant melanoma were established in August 2016. The principles of diagnostics and classification are based on the histopathological results from the primary tumor and if necessary the sentinel lymph nodes. The most important factor for prognosis is the tumor thickness according to Breslow and the detection of sentinel node micrometastases. The surgical safety margin after excision is dependent on the tumor thickness. Furthermore, ulceration of the primary tumor and presence of mitosis in melanomas less than 1 mm in thickness are also considered in the T‑classification...
February 2, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28150890/further-assessment-of-exome-wide-uvr-footprints-in-melanoma-and-their-possible-relevance
#6
Pamela Mukhopadhyay, James Roberts, Graeme J Walker
C > T substitutions at dipyrimidine sites dominate the melanoma genome. We recently analyzed the exomes of spontaneous and neonatal UVR-induced murine melanomas, noting a dramatic change in the genomic footprint at C > T substitutions in the latter. Here we re-analyzed published exome-wide footprints in human melanomas stratified in terms of likely previous sun exposure. Acral and mucosal melanomas were heterogeneous in terms of base substitution types, but most C > Ts occurred in the context of 3'G, probably resulting from spontaneous deamination of the cytosine...
February 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28134726/mutational-status-of-nras-and-braf-genes-and-protein-expression-analysis-in-a-series-of-primary-oral-mucosal-melanoma
#7
Ricardo Hsieh, Marcello M S Nico, Cláudia M C Camillo, Kátia K Oliveira, Martin Sangueza, Silvia V Lourenço
Primary oral mucosal melanoma is an extremely rare and aggressive tumor arising from melanocytes located in the mucosal epithelium of the oral cavity. Although malignant melanoma of oral mucosa shares some clinical features with its cutaneous counterpart, it has been associated with a worst prognosis; its etiopathogenesis are still only partially unraveled as there is no influence of UV radiation. It is known that the mitogen-activated protein kinase pathway mediates cellular responses to growth signals and its activation is an important phenomenon in melanoma...
February 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28132411/a-case-report-of-disappearing-pigmented-skin-lesions-associated-with-pembrolizumab-treatment-for-metastatic-melanoma
#8
Z J Wolner, A A Marghoob, M P Pulitzer, M A Postow, M A Marchetti
Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death (PD)-1 receptor. Common cutaneous adverse side effects of PD-1 inhibitors include maculopapular rash, pruritus, vitiligo, and lichenoid skin and mucosal reactions. Here, we describe a man in his sixties with metastatic melanoma treated with pembrolizumab who subsequently developed fading or disappearance of pigmented skin lesions, lightening of the skin, and poliosis of the eyebrows, eyelashes, and scalp and body hair. Compared to baseline high-resolution three-dimensional total body photography, we observed fading or disappearing of solar lentigines, seborrheic keratoses, and melanocytic naevi, suggesting that PD-1 inhibitors may affect the evolution of these benign skin lesions...
January 28, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28128848/head-and-neck-cancers-major-changes-in-the-american-joint-committee-on-cancer-eighth-edition-cancer-staging-manual
#9
William M Lydiatt, Snehal G Patel, Brian O'Sullivan, Margaret S Brandwein, John A Ridge, Jocelyn C Migliacci, Ashley M Loomis, Jatin P Shah
Answer questions and earn CME/CNE The recently released eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual, Head and Neck Section, introduces significant modifications from the prior seventh edition. This article details several of the most significant modifications, and the rationale for the revisions, to alert the reader to evolution of the field. The most significant update creates a separate staging algorithm for high-risk human papillomavirus-associated cancer of the oropharynx, distinguishing it from oropharyngeal cancer with other causes...
January 27, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28121085/management-and-treatment-of-mucosal-melanoma-of-the-genital-tract
#10
Sabina Vaccari, Alessia Barisani, Emi Dika, Pier A Fanti, Pierandrea DE Iaco, Carlotta Gurioli, Giulio Tosti
Melanoma of the genital mucosa is a rare melanocytic neoplasm that affects both sexes. The diagnosis is often delayed; a useful diagnostic tool may be represented by videodermatoscopy, The treatment is complex and multidisciplinary. We report the main diagnostic features and therapeutic approaches for mucosal melanoma of the genital tract.
January 24, 2017: Giornale Italiano di Dermatologia e Venereologia: Organo Ufficiale, Società Italiana di Dermatologia e Sifilografia
https://www.readbyqxmd.com/read/28103611/phase-ii-randomised-discontinuation-trial-of-the-met-vegf-receptor-inhibitor-cabozantinib-in-metastatic-melanoma
#11
Adil Daud, Harriet M Kluger, Razelle Kurzrock, Frauke Schimmoller, Aaron L Weitzman, Thomas A Samuel, Ali H Moussa, Michael S Gordon, Geoffrey I Shapiro
BACKGROUND: A phase II randomised discontinuation trial assessed cabozantinib (XL184), an orally bioavailable inhibitor of tyrosine kinases including VEGF receptors, MET, and AXL, in a cohort of patients with metastatic melanoma. METHODS: Patients received cabozantinib 100 mg daily during a 12-week lead-in. Patients with stable disease (SD) per Response Evaluation Criteria in Solid Tumours (RECIST) at week 12 were randomised to cabozantinib or placebo. Primary endpoints were objective response rate (ORR) at week 12 and postrandomisation progression-free survival (PFS)...
February 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28096700/sequential-combination-chemotherapy-of-dacarbazine-dtic-with-carboplatin-and-paclitaxel-for-patients-with-metastatic-mucosal-melanoma-of-nasal-cavity-and-paranasal-sinuses
#12
W Omata, A Tsutsumida, K Namikawa, A Takahashi, K Oashi, N Yamazaki
By the recent introduction of molecular targeting drugs against BRAF mutation and immune checkpoint inhibitors, the prognosis of patients with melanoma in advanced stage is now improving, but still in the minority. Mucosal melanoma lacks the BRAF mutations, and hence conventional chemotherapeutic regimens must be improved. We have conventionally used dacarbazine (DTIC) for patients with metastatic mucosal melanoma. However, the efficacy of DTIC in patients with metastatic mucosal melanoma has been limited. Therefore, we explored other possibilities to improve the prognosis of patients suffering from metastatic mucosal melanoma...
2017: Clinical Medicine Insights. Case Reports
https://www.readbyqxmd.com/read/28092667/oncogenic-braf-fusions-in-mucosal-melanomas-activate-the-mapk-pathway-and-are-sensitive-to-mek-pi3k-inhibition-or-mek-cdk4-6-inhibition
#13
H S Kim, M Jung, H N Kang, H Kim, C-W Park, S-M Kim, S J Shin, S H Kim, S G Kim, E K Kim, M R Yun, Z Zheng, K Y Chung, J Greenbowe, S M Ali, T-M Kim, B C Cho
Despite remarkable progress in cutaneous melanoma genomic profiling, the mutational landscape of primary mucosal melanomas (PMM) remains unclear. Forty-six PMMs underwent targeted exome sequencing of 111 cancer-associated genes. Seventy-six somatic nonsynonymous mutations in 42 genes were observed, and recurrent mutations were noted on eight genes, including TP53 (13%), NRAS (13%), SNX31 (9%), NF1 (9%), KIT (7%) and APC (7%). Mitogen-activated protein kinase (MAPK; 37%), cell cycle (20%) and phosphatidylinositol 3-kinase (PI3K)-mTOR (15%) pathways were frequently mutated...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28092366/malignant-melanoma-of-sun-protected-sites-a-review-of-clinical-histological-and-molecular-features
#14
Emily A Merkel, Pedram Gerami
In most cases of cutaneous melanoma, ultraviolet (UV) radiation is recognized as a prominent risk factor. Less is known regarding the mechanisms of mutagenesis for melanoma arising in sun-protected sites, such as acral and mucosal melanoma. Acral and mucosal melanoma share many common features, including a late age of onset, a broad radial growth phase with prominent lentiginous growth, the presence of field cancerization cells, and, in most cases, lack of a precursor nevus. In addition to early chromosomal instability, many of the same genes are also involved in these two distinct melanoma subtypes...
January 16, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28072717/clinics-prognosis-and-new-therapeutic-options-in-patients-with-mucosal-melanoma-a-retrospective-analysis-of-75-patients
#15
Tim Schaefer, Imke Satzger, Ralf Gutzmer
Mucosal melanomas represent a rare entity with different risk factors and molecular features compared to cutaneous melanomas. They arise most commonly from mucosal surfaces in the head/neck region, the female genital tract (FGT) and the anorectal region. The aim of this study was to evaluate clinics, prognosis, and treatment options of patients with mucosal melanoma, in particular with regard to different primary sites.We retrospectively analyzed 75 patients with mucosal melanomas diagnosed in the years 1993 to 2015 in our department...
January 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28056206/efficacy-and-safety-of-nivolumab-alone-or-in-combination-with-ipilimumab-in-patients-with-mucosal-melanoma-a-pooled-analysis
#16
Sandra P D'Angelo, James Larkin, Jeffrey A Sosman, Celeste Lebbé, Benjamin Brady, Bart Neyns, Henrik Schmidt, Jessica C Hassel, F Stephen Hodi, Paul Lorigan, Kerry J Savage, Wilson H Miller, Peter Mohr, Ivan Marquez-Rodas, Julie Charles, Martin Kaatz, Mario Sznol, Jeffrey S Weber, Alexander N Shoushtari, Mary Ruisi, Joel Jiang, Jedd D Wolchok
Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28056100/chimeric-l2-based-virus-like-particle-vlp-vaccines-targeting-cutaneous-human-papillomaviruses-hpv
#17
Bettina Huber, Christina Schellenbacher, Saeed Shafti-Keramat, Christoph Jindra, Neil Christensen, Reinhard Kirnbauer
Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV...
2017: PloS One
https://www.readbyqxmd.com/read/28044299/mucosal-malignant-melanoma-of-nasal-cavity-recurring-a-year-after-radiotherapy
#18
Cem Çomunoğlu, Gamze Mocan Kuzey, Mete Inançli, Füsun Baba, Hanife Özkayalar
OBJECTIVE: Sinonasal mucosal malignant melanoma is a rare entity. In this report we present a nasal mucosal malignant melanoma case with its histopathological and clinical features. CASE REPORT: An 88-year-old female patient presented with epistaxis a month ago. Examination revealed a polypoid mass lesion of right nasal cavity originating from the middle concha. Her medical history revealed that she had been found to have a mass lesion in the right nasal cavity 15 months ago...
2017: Türk Patoloji Dergisi
https://www.readbyqxmd.com/read/28039178/the-natural-history-and-patterns-of-metastases-from-mucosal-melanoma-an-analysis-of-706-prospectively-followed-patients
#19
B Lian, C L Cui, L Zhou, X Song, X S Zhang, D Wu, L Si, Z H Chi, X N Sheng, L L Mao, X Wang, B X Tang, X Q Yan, Y Kong, J Dai, S M Li, X Bai, N Zheng, Charles M Balch, J Guo
BACKGROUND: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. PATIENTS AND METHODS: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28028129/long-term-outcomes-after-carbon-ion-radiotherapy-for-oral-mucosal-malignant-melanoma
#20
Kensuke Naganawa, Masashi Koto, Ryo Takagi, Azusa Hasegawa, Hiroaki Ikawa, Kazuo Shimozato, Tadashi Kamada, Yoshitaka Okamoto
Oral mucosal malignant melanoma (OMM) is extremely rare and has a poor prognosis. Owing to its rarity, it has not yet been possible to establish an optimal treatment modality. The objective of this study was to evaluate the long-term efficacy of carbon-ion radiotherapy (C-ion RT) for OMM. Between 1997 and 2013, 19 patients with OMM were treated with C-ion RT alone. Patient ages ranged from 44 to 84 years (median, 69 years). Nine men and 10 women were included. OMMs were restaged in accordance with the seventh edition of the tumour/node/metastasis (TNM) Staging System of the International Union Against Cancer...
December 26, 2016: Journal of Radiation Research
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