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Simple Summary: Morphea and eosinophilic fasciitis (EF) are cutaneous autoimmune fibrosing diseases. We conducted a scoping review following PRISMA-ScR guidelines to ascertain the association between cancer and morphea/EF, focusing specifically on the paraneoplastic phenomenon, risk of subsequent cancer and development of morphea/EF as a consequence of cancer treatment. We identified that morphea patients, particularly those with generalized disease, might be at an increased risk of secondary malignancy, notably skin and pancreatic cancer. EF, on the other hand, occurred as a paraneoplastic disease in 10% of patients, primarily associated with hematologic malignancies. While reports of radiotherapy and chemotherapy-induced morphea are numerous, immunotherapy-induced morphea/EF cases are emerging. Interestingly, all immunotherapy-induced cases occurred with PD-1 inhibitors. Morphea is an autoimmune fibrotic skin disease. Eosinophilic fasciitis (EF) is considered to belong to the severe spectrum of morphea. We conducted a scoping review assessing the risk of secondary cancer among morphea/EF patients, paraneoplastic morphea/EF and morphea/EF developing secondary to cancer therapy. The search was conducted using MEDLINE, Embase, Cochrane databases for articles published from inception to September 2022 following the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Scoping Reviews (PRISMA-ScR) guidelines with no language or date restrictions. Two hundred and one studies were included. Of these, 32 studies reported on secondary cancer in morphea/EF patients, 45 on paraneoplastic morphea/EF and 125 on cancer-treatment-induced morphea/EF. While the current evidence remains limited, data suggest an increased risk of secondary cutaneous and possibly pancreatic malignancy in morphea patients, particularly the generalized subtype. There were insufficient data for EF. On the other hand, paraneoplastic morphea was anecdotal, whereas several observational studies suggested that ~10% of EF cases may be paraneoplastic, primarily in the context of hematologic malignancies. Radiotherapy-induced morphea is rare, seen in ~0.2% of treated patients and is usually localized to the treatment site, except in patients with pre-existing autoimmunity. While chemotherapy-induced cases are reported, immunotherapy morphea/EF cases are emerging and are preferentially seen with PD-1 and not CTLA-4 inhibitors. This study is limited by the type of articles included (case reports, case series and observational studies), and hence, additional research on this important topic is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Reflex molecular testing is an emerging concept in oncology that, for a variety of cancers, was demonstrated to reduce the time to treatment initiation, thus potentially impacting survival outcomes. In advanced melanoma, BRAF mutation testing is critical in predicting treatment response with targeted therapy (i.e., BRAF/MEK inhibitors). Certain features were identified in melanomas that harbor BRAF mutations (e.g., primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). For select advanced melanoma patients, delays in determining mutational status present a significant barrier to the prompt initiation of treatment, which can adversely impact patient outcomes, especially in the metastatic setting due to a rapidly progressive disease. Treatment in these cases needs to start promptly by a medical oncologist. Ordering BRAF testing by preceding members of the treating team will allow medical oncologists to initiate treatment at the first visit. According to poor survival outcomes, we propose that patients with thick tumors (>4.0 mm) or >2 mm tumors with ulceration (i.e., stage ≥IIB) should potentially be considered for systemic therapy, thus justifying reflex BRAF testing. We overview current BRAF mutation testing recommendations and methods used in the United States, Canada, and Europe. Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the BRAF oncogene. Certain clinical features have been identified in BRAF-mutated melanomas (primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). While BRAF mutation testing is recommended for stage III–IV melanoma, guidelines differ in recommending mutation testing in stage II melanoma patients. To fully benefit from these treatment options and avoid delays in therapy initiation, advanced melanoma patients harboring a BRAF mutation must be identified accurately and quickly. To achieve this, clear definition and implementation of BRAF reflex testing criteria/methods in melanoma should be established so that patients with advanced melanoma can arrive to their first medical oncology appointment with a known biomarker status. Reflex testing has proven effective for a variety of cancers in selecting therapies and driving other medical decisions. We overview the pathophysiology, clinical presentation of BRAF-mutated melanoma, current guidelines, and present recommendations on BRAF mutation testing. We propose that reflex BRAF testing should be performed for every melanoma patient with stages ≥IIB. [ABSTRACT FROM AUTHOR]