Objective assessment of tumor infiltrating lymphocytes as a prognostic marker in melanoma using machine learning algorithms.
Abstract Background: The prognostic value of tumor-infiltrating lymphocytes (TILs) assessed by machine learning algorithms in melanoma patients has been previously demonstrated but has not been widely adopted in the clinic. We evaluated the prognostic value of objective automated electronic TILs (eTILs) quantification to define a subset of melanoma patients with a low risk of relapse after surgical treatment. Methods: We analyzed data for 785 patients from 5 independent cohorts from multiple institutions to validate our previous finding that automated TIL score is prognostic in clinically-localized primary melanoma patients. Using serial tissue sections of the Yale TMA-76 melanoma cohort, both immunofluorescence and [...]
Melanoma In Situ: A Critical Review and Re-Evaluation of Current Excision Margin Recommendations.
Abstract Most international clinical guidelines recommend 5-10 mm clinical margins for excision of melanoma in situ (MIS). While the evidence supporting this is weak, these guidelines are generally consistent. However, as a result of the high incidence of subclinical extension of MIS, especially of the lentigo maligna (LM) subtype, wider margins will often be needed to achieve complete histologic clearance. In this review, we assessed all available contemporary evidence on clearance margins for MIS. No randomized trials were identified and the 31 non-randomized studies were largely retrospective reviews of single-surgeon or single-institution experiences using Mohs micrographic surgery (MMS) for [...]
Landscape of mutations in early stage primary cutaneous melanoma: An InterMEL study.
Abstract It is unclear why some melanomas aggressively metastasize while others remain indolent. Available studies employing multi-omic profiling of melanomas are based on large primary or metastatic tumors. We examine the genomic landscape of early-stage melanomas diagnosed prior to the modern era of immunological treatments. Untreated cases with Stage II/III cutaneous melanoma were identified from institutions throughout the United States, Australia and Spain. FFPE tumor sections were profiled for mutation, methylation and microRNAs. Preliminary results from mutation profiling and clinical pathologic correlates show the distribution of four driver mutation sub-types: 31% BRAF; 18% NRAS; 21% NF1; 26% Triple Wild [...]
Clinical Outcomes and Risk Stratification of Early-Stage Melanoma Micrometastases From an International Multicenter Study: Implications for the Management of American Joint Committee on Cancer IIIA Disease.
Abstract Purpose: Indications for offering adjuvant systemic therapy for patients with early-stage melanomas with low disease burden sentinel node (SN) micrometastases, namely, American Joint Committee on Cancer (AJCC; eighth edition) stage IIIA disease, are presently controversial. The current study sought to identify high-risk SN-positive AJCC stage IIIA patients who are more likely to derive benefit from adjuvant systemic therapy. Methods: Patients were recruited from an intercontinental (Australia/Europe/North America) consortium of nine high-volume cancer centers. All were adult patients with pathologic stage pT1b/pT2a primary cutaneous melanomas who underwent SN biopsy between 2005 and 2020. Patient data, primary tumor and SN characteristics, and [...]
Hypofractionated or Conventionally Fractionated Adjuvant Radiotherapy After Regional Lymph Node Dissection for High-Risk Stage III Melanoma.
Abstract Aims: Adjuvant radiotherapy can be beneficial after regional lymph node dissection for high-risk stage III melanoma, as it has been shown to reduce the risk of recurrence in the node field. However, the optimal fractionation schedule is unknown and both hypofractionated and conventionally fractionated adjuvant radiotherapy are used. The present study examined the oncological outcomes of these two approaches in patients treated in an era before effective systemic immunotherapy became available. Materials and methods: This retrospective cohort study involved 335 patients with stage III melanoma who received adjuvant radiotherapy after therapeutic regional lymph node dissection for metastatic melanoma between 1990 [...]
The role of regional chemotherapy for advanced limb melanoma in the era of potentially effective systemic therapies.
Abstract To review the current role of regional chemotherapy in the management of advanced limb melanoma. Articles reporting the results of isolated limb infusion (ILI) were identified by performing a comprehensive literature search using the PubMed database. Keywords included isolated limb infusion, in-transit melanoma and melphalan. No publication date restrictions were applied. ILI data were compared with those from current systemic therapy clinical trials and the previously reviewed isolated limb perfusion (ILP) literature. Regional chemotherapy is today required in fewer patients because effective systemic therapies now provide an alternative treatment for those who develop extensive local melanoma recurrence or [...]
Comprehensive Clinical, Histopathologic, and Molecular Analysis and Long-term Follow-up of Patients With Nodal Blue Nevi
Blue nevi are benign, melanocytic neoplasms that show a range of clinical and morphologic patterns and include common/dendritic, cellular, and atypical cellular subtypes. Like other nevi, they most commonly occur in skin but can occasionally involve lymph nodes where they may be misinterpreted as representing metastatic melanoma. Moreover, whether benign blue nevi can metastasize to lymph nodes and their natural history and prognostic significance has been the subject of great controversy. To date, few cases of nodal blue nevi have been reported in the literature, and those reports have had limited clinical follow-up and supporting molecular data. This study [...]
Treatment of in-transit Merkel cell carcinoma by isolated limb infusion with cytotoxic drugs
Abstract Merkel cell carcinoma of the skin is a rare but aggressive malignancy, which predominantly affects older adults with fair skin. Isolated limb infusion (ILI) using melphalan and actinomycin D was first developed as a minimally invasive treatment option to treat unresectable metastatic melanoma confined to the limb. We report on a 62-year-old male with in-transit metastases (ITMs) treated with ILI to highlight the ongoing role this treatment has when all other therapies have been exhausted. At presentation, the patient had widespread ITMs in the right leg. Positron emission tomography scan demonstrated recurrent disease in the thigh and pelvis, [...]
Do we need to rethink the diagnoses melanoma in situ and severely dysplastic naevus?
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Do we need to rethink the diagnoses melanoma in situ and severely dysplastic naevus?
No abstract available Read Full Paper