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Lancet (London, England) Aug 2023Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations. Cutaneous melanoma is typically... (Review)
Review
Cutaneous melanoma is a malignancy arising from melanocytes of the skin. Incidence rates are rising, particularly in White populations. Cutaneous melanoma is typically driven by exposure to ultraviolet radiation from natural sunlight and indoor tanning, although there are several subtypes that are not related to ultraviolet radiation exposure. Primary melanomas are often darkly pigmented, but can be amelanotic, with diagnosis based on a combination of clinical and histopathological findings. Primary melanoma is treated with wide excision, with margins determined by tumour thickness. Further treatment depends on the disease stage (following histopathological examination and, where appropriate, sentinel lymph node biopsy) and can include surgery, checkpoint immunotherapy, targeted therapy, or radiotherapy. Systemic drug therapies are recommended as an adjunct to surgery in patients with resectable locoregional metastases and are the mainstay of treatment in advanced melanoma. Management of advanced melanoma is complex, particularly in those with cerebral metastasis. Multidisciplinary care is essential. Systemic drug therapies, particularly immune checkpoint inhibitors, have substantially increased melanoma survival following a series of landmark approvals from 2011 onward.
Topics: Humans; Melanoma; Skin Neoplasms; Ultraviolet Rays; Sentinel Lymph Node Biopsy; Lymph Node Excision; Melanoma, Cutaneous Malignant
PubMed: 37499671
DOI: 10.1016/S0140-6736(23)00821-8 -
Nature Medicine Nov 2023Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial... (Randomized Controlled Trial)
Randomized Controlled Trial
Patients with resected stage IIB/C melanoma have high recurrence risk, similar to those with resected stage IIIA/B disease. The phase 3, double-blind CheckMate 76K trial assessed 790 patients with resected stage IIB/C melanoma randomized 2:1 (stratified by tumor category) to nivolumab 480 mg or placebo every 4 weeks for 12 months. The primary endpoint was investigator-assessed recurrence-free survival (RFS). Secondary endpoints included distant metastasis-free survival (DMFS) and safety. At 7.8 months of minimum follow-up, nivolumab significantly improved RFS versus placebo (hazard ratio (HR) = 0.42; 95% confidence interval (CI): 0.30-0.59; P < 0.0001), with 12-month RFS of 89.0% versus 79.4% and benefit observed across subgroups; DMFS was also improved (HR = 0.47; 95% CI: 0.30-0.72). Treatment-related grade 3/4 adverse events occurred in 10.3% (nivolumab) and 2.3% (placebo) of patients. One treatment-related death (0.2%) occurred with nivolumab. Nivolumab is an effective and generally well-tolerated adjuvant treatment in patients with resected stage IIB/C melanoma. ClinicalTrials.gov identifier: NCT04099251 .
Topics: Humans; Adjuvants, Immunologic; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Melanoma; Neoplasm Staging; Nivolumab; Skin Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 37845511
DOI: 10.1038/s41591-023-02583-2 -
Surgical Pathology Clinics Mar 2024Pleomorphic dermal sarcoma (PDS) is a rare cutaneous/subcutaneous neoplasm of purported mesenchymal differentiation that exists along a clinicopathologic spectrum with... (Review)
Review
Pleomorphic dermal sarcoma (PDS) is a rare cutaneous/subcutaneous neoplasm of purported mesenchymal differentiation that exists along a clinicopathologic spectrum with atypical fibroxanthoma (AFX). While PDS and AFX share histopathologic and immunohistochemical features, PDS exhibits deeper tissue invasion and has a higher rate of metastasis and local recurrence than AFX. Given its aggressive clinical course, early recognition and clinical management of PDS are essential for optimizing patient outcomes. This review aims to provide a brief overview of the clinicopathologic and molecular features, prognosis, and treatment of PDS.
Topics: Humans; Sarcoma; Histiocytoma, Malignant Fibrous; Skin Neoplasms; Prognosis
PubMed: 38278604
DOI: 10.1016/j.path.2023.06.007 -
Seminars in Diagnostic Pathology Jul 2023Atypical fibroxanthoma (AFX) is an uncommon, primary dermal neoplasm of uncertain histogenesis, typically originating in the sun-damage skin of the head and neck of the... (Review)
Review
Atypical fibroxanthoma (AFX) is an uncommon, primary dermal neoplasm of uncertain histogenesis, typically originating in the sun-damage skin of the head and neck of the elderly. Since first description in 1958, ∼3000 cases have been reported in the literature. However, the disease is underreported as the neoplasm is considered a standard diagnosis in the last decades. On the other hand, many earlier reports likely have included non-AFX mimics or aggressive pleomorphic dermal sarcomas. In contrast to its alarming high-grade histology, AFX behaves indolently with rare recurrences/ metastatic rate of <2%. The overall 10- and 20-year disease-specific survival rates are ∼ 100% and 98%, respectively. Histologically, AFX displays undifferentiated pleomorphic spindle cell morphology akin to undifferentiated pleomorphic sarcoma (UPS), a feature that was the basis of the abandoned historical terminology "MFH of skin". However, in contrast to other undifferentiated sarcomatoid neoplasms, AFX is notorious for its highly variable histology with a plethora of patterns, underlining a wide differential diagnosis. Notably, spindle cell, keloid-like, pleomorphic, epithelioid, rhabdoid, clear cell, foamy cell, granular cell, bizarre cell, pseudoangiomatous, inflammatory, osteoclast-rich, and many others have been recognized with varying frequencies. Immunohistochemically, AFX is characterized by nonspecific profile with block-type expression of CD10 and aberrant p53 pattern and lack of pankeratin and other lineage-specific epithelial, mesenchymal, melanocytic and hematolymphoid markers. Sarcomatoid melanoma, spindle cell carcinoma and cutaneous anaplastic large cell lymphoma are major considerations. Distinction of AFX from pleomorphic dermal sarcoma (PDS) is arbitrary and is based on presence of ≥ 1 of four unfavorable histological features: more than minimal subcutaneous involvement, coagulative necrosis, lymphovascular invasion and perineurial invasion.
Topics: Humans; Aged; Skin Neoplasms; Sarcoma; Melanoma; Histiocytoma, Malignant Fibrous; Diagnosis, Differential; Biomarkers, Tumor
PubMed: 37438163
DOI: 10.1053/j.semdp.2023.06.001 -
Ugeskrift For Laeger Nov 2023Disturbances of the nail apparatus are common and mainly benign. This review aims to investigate the aetiology of these disturbances, which range from more common benign... (Review)
Review
Disturbances of the nail apparatus are common and mainly benign. This review aims to investigate the aetiology of these disturbances, which range from more common benign causes to less common melanomas. Melanonychia may be the most prominent concern and is characterised by brown or black nail plate discoloration. Hence, understanding the most common nail changes, their epidemiology, pathophysiology, and clinical features are imperative to diagnosis and may prevent unnecessary surgical procedures in cases where it is not warranted.
Topics: Humans; Skin Neoplasms; Dermoscopy; Melanoma; Nails; Nail Diseases
PubMed: 38018740
DOI: No ID Found -
The Veterinary Clinics of North... May 2024New knowledge and data can influence the treatment options of dogs and cats affected by neoplasms. Partial limb amputation with the use of a prosthesis is possible in... (Review)
Review
New knowledge and data can influence the treatment options of dogs and cats affected by neoplasms. Partial limb amputation with the use of a prosthesis is possible in dogs. Newer studies attempt to define better and understand the complications and limb function associated with this approach. Limb sparing is an alternative to amputation, and three-dimensional printing allows the manufacturing of personalized endoprostheses. Finally, the recommended approach for the excision of cutaneous mast cell tumors (MCTs) is with proportional margins. In dogs, grade shifting might have occurred when removing a recurrent MCT or soft tissue sarcoma.
Topics: Cats; Animals; Dogs; Skin Neoplasms; Surgical Oncology; Cat Diseases; Neoplasm Recurrence, Local; Dog Diseases; Treatment Outcome
PubMed: 38238221
DOI: 10.1016/j.cvsm.2023.12.010 -
Ceskoslovenska Patologie 2024Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share... (Review)
Review
Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.
Topics: Humans; Skin Neoplasms; Melanoma; Nevus, Pigmented
PubMed: 38697825
DOI: No ID Found -
Journal of Surgical Oncology Jul 2023Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive cutaneous malignancy. Complete resection is the primary treatment but there is debate over the... (Review)
Review
Dermatofibrosarcoma protuberans (DFSP) is an uncommon, locally aggressive cutaneous malignancy. Complete resection is the primary treatment but there is debate over the optimal method. Wide local excision was traditionally the standard of care; however, National Comprehensive Cancer Network guidelines now recommend Mohs micrographic surgery as the preferred approach. Medical therapy with imatinib can be used in advanced or unresectable disease. This review will discuss the current management of DFSP, focusing on optimal surgical approach.
Topics: Humans; Dermatofibrosarcoma; Skin Neoplasms; Neoplasm Recurrence, Local; Skin; Mohs Surgery
PubMed: 36999599
DOI: 10.1002/jso.27258 -
The American Journal of Dermatopathology Nov 2023Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as...
Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.
Topics: Humans; Antigens, Neoplasm; Biomarkers, Tumor; Immunohistochemistry; Melanoma; Nevus; Skin Neoplasms; Transcription Factors; Melanoma, Cutaneous Malignant
PubMed: 37856737
DOI: 10.1097/DAD.0000000000002440 -
Gene fusions in superficial mesenchymal neoplasms: Emerging entities and useful diagnostic adjuncts.Seminars in Diagnostic Pathology Jul 2023Cutaneous mesenchymal neoplasms are diagnostically challenging because of their overlapping morphology, and, often, the limited tissue in skin biopsy specimens.... (Review)
Review
Cutaneous mesenchymal neoplasms are diagnostically challenging because of their overlapping morphology, and, often, the limited tissue in skin biopsy specimens. Molecular and cytogenetic techniques have identified characteristic gene fusions in many of these tumor types, findings that have expanded our understanding of disease pathogenesis and motivated development of useful ancillary diagnostic tools. Here, we provide an update of new findings in tumor types that can occur in the skin and superficial subcutis, including dermatofibrosarcoma protuberans, benign fibrous histiocytoma, epithelioid fibrous histiocytoma, angiomatoid fibrous histiocytoma, glomus tumor, myopericytoma/myofibroma, non-neural granular cell tumor, CIC-rearranged sarcoma, hybrid schwannoma/perineurioma, and clear cell sarcoma. We also discuss recently described and emerging tumor types that can occur in superficial locations and that harbor gene fusions, including nested glomoid neoplasm with GLI1 alterations, clear cell tumor with melanocytic differentiation and ACTIN::MITF translocation, melanocytic tumor with CRTC1::TRIM11 fusion, EWSR1::SMAD3-rearranged fibroblastic tumor, PLAG1-rearranged fibroblastic tumor, and superficial ALK-rearranged myxoid spindle cell neoplasm. When possible, we discuss how fusion events mediate the pathogenesis of these tumor types, and we also discuss the related diagnostic and therapeutic implications of these events.
Topics: Humans; Glomus Tumor; Skin Neoplasms; Histiocytoma, Malignant Fibrous; Gene Fusion; Transcription Factors; Biomarkers, Tumor; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 37156707
DOI: 10.1053/j.semdp.2023.04.014