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Dermatology Practical & Conceptual Apr 2024
PubMed: 38810052
DOI: 10.5826/dpc.1402a116 -
Dermatology Practical & Conceptual Apr 2024
PubMed: 38810035
DOI: 10.5826/dpc.1402a131 -
Medicina (Kaunas, Lithuania) May 2024The CDKN2A gene remains understudied in melanoma compared to BRAF alterations. Inactivation of this tumor suppressor gene through homozygous deletions in the 9p21... (Review)
Review
The CDKN2A gene remains understudied in melanoma compared to BRAF alterations. Inactivation of this tumor suppressor gene through homozygous deletions in the 9p21 chromosomal region leads to cellular proliferation and disrupts pro-apoptotic pathways. Genetic changes in CDKN2A are linked to multiple primary melanomas (MPM), with patients diagnosed with melanoma facing an elevated risk of developing additional primaries. We present the rare case of a 72-year-old Caucasian woman with nine metastasizing melanomas across diverse anatomical sites, posing a diagnostic challenge. Initial diagnosis in 2022 revealed ulcerated superficial spreading melanomas, progressing to intradermal and papillary dermal populations with neurotropism and angiotropism by early 2023. Lymph node metastases were identified, classifying the condition as pT3b N3b. Subsequent assessments in April 2023 revealed clinically suspicious melanocytic lesions diagnosed as intradermal and traumatized junctional nevi. In late 2023, cutaneous pigmented lesions and subcutaneous metastases were confirmed as nodular nevoid low-CSD multiple melanomas. Fluorescence in situ hybridization testing revealed homozygous CDKN2A deletion, necessitating close multidisciplinary collaboration for an optimized care plan for effective monitoring and intervention in this intricate clinical scenario. In summary, this case report highlights the diagnostic challenges of MPM in a single patient. Stressing the importance of immuno-histochemistry and CDKN2A genetic testing, our findings underscore the crucial role of these tools in accurately distinguishing malignant melanocytic proliferations from nevi and characterizing MPM cases.
Topics: Humans; Melanoma; Female; Aged; Cyclin-Dependent Kinase Inhibitor p16; Skin Neoplasms; Mutation; Neoplasms, Multiple Primary
PubMed: 38792946
DOI: 10.3390/medicina60050763 -
Wounds : a Compendium of Clinical... Apr 2024Leg ulcers have various etiologies, including malignancy, although vascular issues are the most frequent cause. Malignant wounds present diagnostic challenges, with a...
BACKGROUND
Leg ulcers have various etiologies, including malignancy, although vascular issues are the most frequent cause. Malignant wounds present diagnostic challenges, with a reported prevalence rate ranging from 0.4% to 23%. This significant variability in reported prevalence appears to be due to the different settings in which data are collected, which suggests potential influence by medical specialty. Consequently, the misdiagnosis of neoplastic ulcers (eg, ulcerated melanoma) as vascular wounds is relatively common, leading to delayed diagnosis, inadequate treatment, and a dramatic worsening of the patient's prognosis. Identifying malignancy in nonresponsive wounds involves recognizing signs such as hypertrophic granulation tissue, bleeding, unusual pigmentation, and raised edges. The appearance of the perilesional skin, together with dermoscopic observation, is also crucial to differentiation. Ultimately, a biopsy may provide valuable diagnostic clarification.
CASE REPORT
A case is presented of lower limb melanoma that for years was misdiagnosed as a vascular wound by multiple specialists, with delayed referral to a dermatologist and resulting recognition and diagnosis, at which time nodular satellite metastases were found. Dermoscopy and biopsy confirmed the diagnosis. The disease was already advanced, with in-transit and distant site metastases, and the prognosis was regrettably poor.
CONCLUSION
This case underscores the importance of early detection and accurate diagnosis of malignant wounds, emphasizing the need to refer patients with suspicious nonresponsive ulcers to a dermatologist.
Topics: Humans; Melanoma; Skin Neoplasms; Leg Ulcer; Diagnosis, Differential; Dermoscopy; Male; Female; Fatal Outcome; Biopsy; Aged
PubMed: 38743857
DOI: No ID Found -
Cancers Apr 2024Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in...
BACKGROUND
Cutaneous melanoma (CM) is one of the most lethal tumors among skin cancers and its incidence is rising worldwide. Recent data support the role of microRNAs (miRNAs) in melanoma carcinogenesis and their potential use as disease biomarkers.
METHODS
We quantified the expression of miR-146a-5p and miR-21-5p in 170 formalin-fixed paraffin embedded (FFPE) samples of CM, namely 116 superficial spreading melanoma (SSM), 26 nodular melanoma (NM), and 28 lentigo maligna melanoma (LMM). We correlated miRNA expression with specific histopathologic features including Breslow thickness (BT), histological subtype, ulceration and regression status, and mitotic index.
RESULTS
miR-146a-5p and miR-21-5p were significantly higher in NM compared to SSM and LMM. The positive correlation between miR-146a-5p and miR-21-5p expression and BT was confirmed for both miRNAs in SSM. Considering the ulceration status, we assessed that individual miR-21-5p expression was significantly higher in ulcerated CMs. The increased combined expression of the two miRNAs was strongly associated with ulceration ( = 0.0093) and higher mitotic rate (≥1/mm) ( = 0.0005). We demonstrated that the combination of two-miRNA expression and prognostic features (BT and ulceration) can better differentiate cutaneous melanoma prognostic groups, considering overall survival and time-to-relapse clinical outcomes. Specifically, miRNA expression can further stratify prognostic groups among patients with BT ≥ 0.8 mm but without ulceration. Our findings provide further insights into the characterization of CM with specific prognostic features. The graphical abstract was created with BioRender.com.
PubMed: 38730639
DOI: 10.3390/cancers16091688 -
Dermatology Reports Mar 2024
PubMed: 38623373
DOI: 10.4081/dr.2023.9682 -
Laboratory Investigation; a Journal of... May 2024Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in...
Yes-associated protein (YAP), an effector molecule of the Hippo signaling pathway, is expressed at high levels in cutaneous melanoma. However, the role of YAP in melanoma progression according to cellular localization is poorly understood. Tissues from 140 patients with invasive melanoma were evaluated by immunohistochemistry. Flow cytometry, western blotting, viability assays, wound healing assays, verteporfin treatment, and xenograft assays were conducted using melanoma cell lines B16F1 and B16F10 subjected to Yap transfection and siYap knockdown. Nuclear YAP localization was identified in 63 tumors (45.0%) and was more frequent than cytoplasmic YAP in acral lentiginous and nodular subtypes (P = .007). Compared with cytoplasmic YAP melanomas, melanomas with nuclear YAP had higher mitotic activity (P = .016), deeper invasion (P < .001), and more frequently metastasized to lymph nodes (P < .001) and distant organs (P < .001). Patients with nuclear YAP melanomas had poorer disease-free survival (P < .001) and overall survival (P < .001). Nuclear YAP was an independent risk factor for distant metastasis (hazard ratio: 3.206; 95% CI, 1.032-9.961; P = .044). Proliferative ability was decreased in siYapB16F1 (P < .001) and siYapB16F10 (P = .001) cells and increased in YapB16F1 (P = .003) and YapB16F10 (P = .002) cells. Cell cycle analysis demonstrated relative G1 retention in siYapB16F1 (P < .001) and siYapB16F10 (P < .001) cells and S retention in YapB16F1 cells (P = .008). Wound healing assays showed that Yap knockdown inhibited cell invasion (siYapB16F1, P = .001; siYapB16F10, P < .001), whereas nuclear YAP promoted it (YapB16F, P < .001; YapB16F1, P = .017). Verteporfin, a direct YAP inhibitor, reduced cellular proliferation in B16F1 (P = .003) and B16F10 (P < .001) cells. Proliferative effects of nuclear YAP were confirmed in xenograft mice (P < .001). In conclusion, nuclear YAP in human melanomas showed subtype specificity and correlated with proliferative activity and proinvasiveness. It is expected that YAP becomes a useful prognostic marker, and its inhibition may be a potential therapy for melanoma patients.
Topics: Skin Neoplasms; Humans; YAP-Signaling Proteins; Melanoma; Animals; Adaptor Proteins, Signal Transducing; Female; Male; Middle Aged; Cell Line, Tumor; Transcription Factors; Cell Nucleus; Mice; Adult; Aged; Disease Progression; Mice, Nude; Phosphoproteins; Cell Proliferation; Melanoma, Cutaneous Malignant
PubMed: 38490470
DOI: 10.1016/j.labinv.2024.102048 -
Journal For Immunotherapy of Cancer Mar 2024Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study... (Randomized Controlled Trial)
Randomized Controlled Trial
Pembrolizumab versus placebo as adjuvant therapy in resected stage IIB or IIC melanoma: Outcomes in histopathologic subgroups from the randomized, double-blind, phase 3 KEYNOTE-716 trial.
BACKGROUND
Adjuvant pembrolizumab significantly improved recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) versus placebo in the phase 3 KEYNOTE-716 study of resected stage IIB or IIC melanoma. At the prespecified third interim analysis (data cut-off, January 4, 2022), the HR for RFS in the overall population was 0.64 (95% CI, 0.50 to 0.84) and the HR for DMFS was 0.64 (95% CI, 0.47 to 0.88). We present a post hoc analysis of efficacy by subtypes defined by histopathologic characteristics.
METHODS
Patients aged ≥12 years with newly diagnosed, resected stage IIB or IIC melanoma were randomly assigned (1:1) to pembrolizumab 200 mg every 3 weeks (2 mg/kg up to 200 mg for pediatric patients) or placebo. The primary end point was RFS per investigator review; DMFS per investigator review was secondary. Subgroups of interest were melanoma subtype (nodular vs non-nodular), tumor thickness (≤4 mm vs >4 mm), presence of ulceration (yes vs no), mitotic rate (<5 per mm (median) vs ≥5 per mm), and presence of tumor-infiltrating lymphocytes (TILs; absent vs present).
RESULTS
Between September 23, 2018, and November 4, 2020, 976 patients were assigned to pembrolizumab (n=487) or placebo (n=489). Median follow-up was 27.4 months (range, 14.0-39.4). The HR (95% CI) for RFS was 0.54 (0.37 to 0.79) for nodular and 0.77 (0.53 to 1.11) for non-nodular melanoma; 0.57 (0.37 to 0.89) for thickness ≤4 mm and 0.69 (0.50 to 0.96) for >4 mm; 0.66 (0.50 to 0.89) for ulceration and 0.57 (0.32 to 1.03) for no ulceration; 0.57 (0.35 to 0.92) for mitotic rate <5 per mm and 0.57 (0.40 to 0.80) for ≥5 per mm; and 0.89 (0.52 to 1.54) for TILs absent and 0.51 (0.34 to 0.76) for TILs present. DMFS results were similar. In a Cox multivariate analysis, treatment arm, tumor thickness, and mitotic rate were significant independent factors for RFS, and treatment arm and mitotic rate were significant independent factors for DMFS.
CONCLUSIONS
In this post hoc analysis, the benefit of pembrolizumab was largely consistent with the overall study population regardless of histopathologic characteristics. These results support the use of adjuvant pembrolizumab in patients with resected stage IIB or IIC melanoma.
TRIAL REGISTRATION NUMBER
ClinicalTrials.gov, NCT03553836.
Topics: Humans; Child; Melanoma; Skin Neoplasms; Antibodies, Monoclonal, Humanized; Combined Modality Therapy; Adjuvants, Immunologic
PubMed: 38485189
DOI: 10.1136/jitc-2023-007501 -
World Neurosurgery: X Apr 2024Melanoma metastases to the CNS rank third in frequency, just after lung and breast metastases. There is controversy regarding the factors predisposing to developing CNS...
BACKGROUND
Melanoma metastases to the CNS rank third in frequency, just after lung and breast metastases. There is controversy regarding the factors predisposing to developing CNS metastases in patients with cutaneous melanoma and their survival with conventional treatments.
METHODS
We carried out a retrospective analysis in a third-level hospital in Mexico to determine epidemiological aspects of melanoma metastases to the central nervous system, factors related to its appearance, clinical presentation, and survival in three treatment groups: surgery, radiotherapy, and conservative management.
RESULTS
We found that the nodular variant has the most significant association with CNS metastases. In addition, the superficial spreading variant has the highest risk of presenting a more substantial number of lesions, up to seven for each case and predominantly in the infratentorial space. On the other hand, we found more remarkable survival in patients treated only with surgery than those treated with radiotherapy or conservatively.
CONCLUSIONS
This study lays the foundations for future prospective survival analysis of the different current treatment modalities for metastatic melanoma in the brain and spine. It also highlights the clinical risk factors for metastatic brain and spine tumors of melanoma.
PubMed: 38455253
DOI: 10.1016/j.wnsx.2024.100306 -
Indian Journal of Dermatology 2023Skin malignancies are the most common form of malignant disease in the western world, predominantly affecting older age groups. The majority of skin cancers are basal...
BACKGROUND
Skin malignancies are the most common form of malignant disease in the western world, predominantly affecting older age groups. The majority of skin cancers are basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and malignant melanoma, which account for more than 95% of total skin malignancies. However, in India, these constitute only 1-2% of all cancers. There is an increase in incidence in India over 10 years of period. There is scarcity of data on the clinico-pathological profile of these tumours from this geographical region.
MATERIALS AND METHODS
This was a retrospective study conducted in a tertiary care teaching hospital in which archival records and histopathology sections of all patients of skin carcinomas diagnosed over a period of 5 years (January 2016 to December 2020) were analysed. The clinical parameters and histopathological features of the cases were analysed and correlated for any possible association.
RESULTS
Out of the 230 skin malignancies studied, SCC constituted the most common type ( = 148), followed by BCC ( = 70) and malignant melanoma ( = 12). The tumour commonly presented in the 6 decade of life with slightly higher male preponderance (M: F =1.6:1). Sun-exposed areas were the most common sites, and the common presentations included non-healing ulcer, fungating/cauliflower/polypoidal growth, and hyperpigmented or nodular plaque. In SCC, previous history of diabetes and burns was noted in 10% and 3.4% of the patients, respectively.
CONCLUSION
SCC is likely the most common histological type of skin malignancies in India. The clinico-pathological profile of skin malignancies of patients depends on multiple factors, notably the skin colour and the geographical location.
PubMed: 38371551
DOI: 10.4103/ijd.ijd_401_23