Shifts in Cutaneous Melanocytic Tumor Diagnostic Terminology: Melanocytoma, MPATH-Dx V2.0 and the WHO Skin5.
Abstract In this Special Issue of the Journal of Cutaneous Pathology in memory of Dr. Martin C. Mihm, Jr, we highlight his many contributions over more than 50 years to the catalog of specific melanocytic tumor terminology. Dr. Mihm was an active participant in the International Melanoma Pathology Study Group (IMPSG). Discussions led to proposed recommendations for changes in the terminology of melanocytic tumors and their standardized diagnostic reporting. Histopathological reports of melanocytic tumors provide critical information that guides patient counseling and therapy. Importantly the pathology report must relay whether the melanocytic tumor is benign, intermediate, or malignant, and [...]
FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.
Abstract Background: Neoadjuvant immunotherapy has become the new standard of care for stage III melanoma. This study sought to describe the metabolic changes seen with fludeoxyglucose-18-positron emission tomography (FDG-PET) following neoadjuvant immunotherapy in patients with melanoma and explore associations with pathological response and recurrence-free survival (RFS). Methods: Data from patients with macroscopic stage III nodal melanoma treated with neoadjuvant checkpoint inhibitor therapy were pooled from five melanoma centers. All patients underwent baseline and preoperative FDG-PET and CT assessments, and all had surgery. Pathological response was determined using the International Neoadjuvant Melanoma Consortium criteria, radiological response using Response Evaluation Criteria in Solid [...]
In vivo reflectance confocal microscopy role for early to advanced lentigo maligna melanoma spectrum: A systematic review and pooled analysis.
Abstract Background: Lentigo maligna (LM) is a growing problem worldwide and the main type of melanoma in situ in some Caucasian populations. It presents as a spectrum from atypical intraepidermal melanocytic proliferation (AIMP) to invasive lentigo maligna melanoma (LMM). Accurate diagnosis and staging are crucial for determining appropriate management strategies. Objectives: To assess the role of in vivo reflectance confocal microscopy (RCM) in differentiating early and advanced stages of lentigo maligna. Methods: A systematic search was conducted on Medline, PubMed, Scopus, Web of Science, Proquest Central, Embase, Cochrane and Google Scholar. References of included and excluded studies were reviewed for additional sources. [...]
Neoadjuvant triplet immune checkpoint blockade in newly diagnosed glioblastoma.
Abstract Glioblastoma (GBM) is an aggressive primary adult brain tumor that rapidly recurs after standard-of-care treatments, including surgery, chemotherapy and radiotherapy. While immune checkpoint inhibitor therapies have transformed outcomes in many tumor types, particularly when used neoadjuvantly or as a first-line treatment, including in melanoma brain metastases, they have shown limited efficacy in patients with resected or recurrent GBM. The lack of efficacy has been attributed to the scarcity of tumor-infiltrating lymphocytes (TILs), an immunosuppressive tumor microenvironment and low tumor mutation burden typical of GBM tumors, plus exclusion of large molecules from the brain parenchyma. We hypothesized that upfront [...]
G9a Inhibition Enhances Checkpoint Inhibitor Blockade Response in Melanoma.
Abstract Purpose: G9a histone methyltransferase exerts oncogenic effects in several tumor types and its inhibition promotes anticancer effects. However, the impact on checkpoint inhibitor blockade response and the utility of G9a or its target genes as a biomarker is poorly studied. We aimed to examine whether G9a inhibition can augment the efficacy of checkpoint inhibitor blockade and whether LC3B, a G9a target gene, can predict treatment response. Experimental design: Clinical potential of LC3B as a biomarker of checkpoint inhibitor blockade was assessed using patient samples including tumor biopsies and circulating tumor cells from liquid biopsies. Efficacy of G9a inhibition to enhance checkpoint [...]
Response to han and liu.
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Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance.
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Mohs micrographic surgery for the treatment of invasive melanoma: A systematic review with meta-analyses.
Abstract Background: The use of Mohs micrographic surgery (MMS) in melanoma treatment has divided opinion and evidence-based guidelines are lacking. Objectives: This systematic review aimed to analyse clinical outcomes for patients with invasive melanomas treated with Mohs rather than wide local excision (WLE). Methods: Embase, MEDLINE and Cochrane databases (to 30 August 2023) were searched for studies using Mohs to treat invasive melanoma. Outcomes of interest were local recurrence and death from melanoma. Results: Thirty-five articles involving 41,499 patients with invasive melanoma treated with Mohs were identified. Sixteen studies compared Mohs with WLE and 19 were Mohs-only, non-comparative studies. Patients treated with Mohs [...]
Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB-D melanoma: a phase 1/2 trial.
Abstract Neoadjuvant immunotherapies have shown antitumor activity in melanoma. Substudy 02C of the global, rolling-arm, phase 1/2, adaptive-design KEYMAKER-U02 trial is evaluating neoadjuvant pembrolizumab (anti-PD-1) alone or in combination, followed by adjuvant pembrolizumab, for stage IIIB-D melanoma. Here we report results from the first three arms: pembrolizumab plus vibostolimab (anti-TIGIT), pembrolizumab plus gebasaxturev (coxsackievirus A21) and pembrolizumab monotherapy. Pathologic complete responses occurred in 10 of 26 patients (38%) with pembrolizumab plus vibostolimab, 7 of 25 (28%) with pembrolizumab plus gebasaxturev and 6 of 15 (40%) with pembrolizumab monotherapy. Major pathologic responses occurred in 13 (50%), 10 (40%) and 7 [...]
Long-term survival across Breslow thickness categories: findings from a population-based study of 210 042 Australian melanoma patients.
Abstract The prognosis of a patient with a primary cutaneous melanoma is known to be related to the Breslow thickness of their tumor. This study sought to determine long-term (30-year) survival rates for the 4 American Joint Committee on Cancer 8th edition T categories by analyzing Australian registry data for 210 042 melanoma patients diagnosed from 1982 to 2014. The 30-year incidence rates of death due to melanoma and nonmelanoma (with 95% confidence intervals [CIs]) were 7.1% (95% CI = 6.9% to 7.3%) and 32.8% (95% CI = 32.3% to 33.3%), respectively. For T2 melanomas, the corresponding rates were [...]