OBJECTIVE: Sarcopenia is the generalized loss of muscle strength, mass, and function. The aim was to investigate whether pretherapeutic sarcopenia, as determined by the psoas muscles, affects therapy-mediated toxicity in patients with malignant melanoma undergoing immunotherapy.
METHODS: Measurement of psoas musculature was performed pretherapeutically using computed tomography at the level of the third lumbar vertebra in the axial plane in 75 patients between January 2011 and December 2020. Sarcopenia was defined using the psoas muscle index (PMI). Immune-related toxicity was retrospectively assessed.
RESULTS: Treatment-related toxicity was recorded in 33 of the 75 patients (44%). Of these, 16 patients (36.2%) experienced dose-limiting severe events (DLT). Pretherapeutic sarcopenia was identified in 25 patients (33.3%). Comparative analysis showed that the patients with a DLT had lower PMI values compared with the patient group without a DLT (4.65 ± 1.33 vs. 5.79 ± 1.67 cm2m-2, p = 0.015) (odds ratio = 0.60, 95% confidence interval 0.40-0.92, p = 0.02).
CONCLUSIONS: Pretherapeutic sarcopenia measured based on the psoas muscle is not a significant predictor of immune-mediated toxicity in patients with malignant melanoma treated with immune checkpoint inhibitors. Patients with DLT have lower values for the psoas muscle parameters PMI compared to the group of patients without DLT.
UNASSIGNED: HINTERGRUND: Sarkopenie ist die Verminderung der Muskelkraft und -masse sowie Einschränkung der Funktion. Das Ziel der vorliegenden Studie war es zu untersuchen, ob die anhand der Psoasmuskulatur bestimmte prätherapeutische Sarkopenie die therapievermittelte Toxizität bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition beeinflusst.
UNASSIGNED: Die Vermessung der Psoasmuskulatur erfolgte prätherapeutisch mithilfe der Computertomographie auf der Höhe des 3. Lendenwirbelkörpers (LWK) bei 75 Patienten zwischen Januar 2011 und Dezember 2020. Die Sarkopenie wurde anhand des Psoasmuskelindex (PMI) definiert. Die immunvermittelte Toxizität wurde retrospektiv ermittelt.
UNASSIGNED: Bei 33 der 75 Patienten (44 %) wurde eine behandlungsbedingte Toxizität unter Therapie mit Immuncheckpoint-Inhibitoren registriert. Davon erlitten 16 Patienten (36,2 %) eine dosislimitierende schwere Toxizität (DLT). Eine prätherapeutische Sarkopenie wurde bei 25 Patienten (33,3 %) ermittelt. Die Vergleichsanalyse ergab, dass die Patienten mit einer DLT im Vergleich zu der Patientengruppe ohne DLT niedrigere PMI-Werte aufwiesen (4,65 ± 1,33 vs. 5,79 ± 1,67 cm2m−2, p = 0,015) (OR = 0,60, 95 %-KI: 0,40–0,92, p = 0,02).
UNASSIGNED: Die anhand der Psoasmuskulatur gemessene prätherapeutische Sarkopenie ist kein signifikanter Prädiktor für DLT bei Patienten mit malignem Melanom unter einer Immuncheckpoint-Inhibition. Patienten mit einer DLT weisen jedoch im Vergleich zu der Patientengruppe ohne DLT niedrigere Werte für die Psoasmuskelparameter PMI und Gauge auf.

BACKGROUND: Several cathepsins have been identified as being involved in the development of cancer. Nevertheless, the connection between cathepsins and skin cancers remained highly elusive.
METHODS: A bidirectional Mendelian randomization (MR) analysis was performed to investigate the causal association between cathepsins and skin malignancies. The genome-wide association studies (GWAS) data for cathepsins, malignant melanoma (MM), and basal cell carcinoma (BCC) were obtained from European research. The primary method employed was inverse variance weighted. In addition, MR-Egger, weighted median, weighted mode, and simple mode were also executed. Sensitivity analysis was performed using Cochran\'s Q test, MR-Egger, and MR-PRESSO.
RESULTS: From univariable MR (UVMR), cathepsin H, and S were determined to have a causal relationship with BCC. Additionally, cathepsin H was identified as associated with MM. Multivariable MR (MVMR) showed that after correcting for risk factors of skin carcinoma, cathepsin H was detected to be protective against BCC, whereas cathepsin S has been observed as a risk factor for BCC. No substantial pleiotropy and heterogeneity were identified in the sensitivity analysis.
CONCLUSIONS: This study was the first to establish a direct link between cathepsins and skin malignancies. Cathepsin H and S have the potential to serve as new biomarkers for BCC, offering valuable assistance in the prompt identification, treatment, and prevention of the disease. Nevertheless, additional clinical trials are required to validate our findings.

BACKGROUND: Iris nodules are frequently noted as clinical manifestations of neurofibromatosis type 1 but the other intraocular manifestations are rare. The purpose of this study is to present a patient with a phthisic eye who underwent enucleation for a cosmetic reason after 15-year follow-up and also to review 14 patients with enucleation described in the literature.
METHODS: A 17-year-old man with neurofibromatosis type 1 from infancy underwent the enucleation of phthisic left eye and also had the resection of eyelid subcutaneous mass lesions on the left side for a cosmetic reason. He had undergone four-time preceding surgeries for eyelid and orbital mass reduction on the left side in childhood and had developed total retinal detachment 10 years previously. Pathologically, the enucleated eye showed massive retinal gliosis positive for both S-100 and glial fibrillary acidic protein (GFAP) in the area with involvement of the detached retinal neuronal layer, together with a more fibrotic lesion along the choroid which were, in contrast, negative for both S-100 and GFAP. The choroid, ciliary body, and iris did not show apparent neurofibroma while episcleral neurofibroma was present.
METHODS: In review of enucleated eyes of 14 patients in the literature, buphthalmic eyes with early-onset glaucoma on the unilateral side was clinically diagnosed in 9 patients who frequently showed varying extent of hemifacial neurofibromatosis which involved the eyelid and orbit on the same side. Pathologically, neurofibromas in varying extent were found in the choroid of 12 patients. One patient showed choroidal malignant melanoma on the left side and fusiform enlargement of the optic nerve on the right side suspected of optic nerve glioma. The phthisic eye in another patient showed massive retinal gliosis similar to the present patient.
CONCLUSIONS: In summary of the 15 patients with neurofibromatosis type 1, including the present patient, buphthalmic or phthisic eyes with no vision were enucleated for cosmetic reasons and showed choroidal neurofibroma in most patients and massive retinal gliosis in two patients including the present patient.

Primary melanoma of the oral cavity is extremely rare, accounting for 0.2-8% of all melanomas. Lesions arising from mucosal melanocytes occur most frequently on the gingiva or palate. Mucosal melanomas carry a worse prognosis than cutaneous melanomas. Very few studies have been published due to rarity of disease. 46 year old lady presented with black colored lesion over left side of her tongue for 6 weeks. On examination there was 3 × 2.5 cm black colored patch over left lateral part of tongue in middle 1/3rd, not crossing midline. Tip and base of tongue were free. Biopsy was suggestive of malignant melanoma of tongue. Patient underwent surgery (wide local excision of left lateral border of tongue lesion + left selective neck dissection). Final Histopathological report revealed malignant melanoma of tongue with all margins free, Depth of invasion 3 mm, Lympho-vascular invasion present, and no perineural invasion, left level III cervical lymph node metastases. Patient thus received adjuvant RT. Immunotherapy was also advised in multidisciplinary clinic, but patient was non-compliant. Early diagnosis will be promoted by careful oral examination and early biopsy of pigmented and non-pigmented masses. Early diagnosis and treatment will improve the prognosis of patients with oral malignant melanoma.

Small-cell melanoma masquerading as an adrenal non-Hodgkin lymphoma. The index report illustrates the deceptive cytomorphologic features of a small cell type malignant melanoma metastatic to the adrenal gland. The diagnosis was confirmed by performing immunocytochemistry on the cell block sections. The key cytomorphologic mimics and their distinctive features have also been highlighted.

Malignant melanoma (MM) continues to claim millions of lives around the world due to its limited therapeutic alternatives. Photodynamic therapy (PDT) has gained popularity in cancer treatment due it increased potency and low off-target toxicity. Studies have pointed out that the heterogeneity of MM tumours reduces the efficacy of current therapeutic approaches, including PDT, leading to high chances of recurrences post-treatment. Accumulating evidence suggests that cannabidiol (CBD), a non-psychoactive derivative of cannabis, can synergise with various anticancer agents to increase their efficacy. However, CBD demonstrates low bioavailability, which is attributed to factors relating to poor water compatibility, poor absorption and rapid metabolism. Nanotechnology offers tools that address these issues and enhance the biological efficiency and targeted specificity of anticancer agents. Herein, we highlighted the standard therapeutic modalities of MM and their pitfalls, as well as pointed out the need for further investigation into PDT combination therapy with CBD.

Malignant melanoma (MM) is notorious for its high metastatic potential, with cardiac metastasis being particularly severe as it involves cardiac structures and can lead to significant cardiac functional issues. While there is no standardized treatment approach, early detection and intervention can improve prognosis.

OBJECTIVE: To describe the clinical features surgical technique, early and long-term outcome with or without surgery, and histopathological findings of melanocytic anterior uveal lesions in young dogs.
METHODS: Medical records of dogs at a guide dog facility removed from training due to a pigmented iris lesion were reviewed from 2014 to 2021. Selected dogs had surgical iridectomies performed.
RESULTS: Iridal melanocytic lesions were characterized as well-delineated, pigmented, and flat (nevus) or raised (mass) lesions of the iris. Forty dogs (18 Labrador retrievers, 18 German shepherd dogs, 1 Golden retriever, 3 Labrador/Golden mixes) ranging from 0.5 to 3.1 years of age were affected unilaterally (n = 35) or bilaterally (n = 5). Sector iridectomy was performed in 13 dogs with prominent and well-isolated mass lesion and enucleation was carried out in 2 dogs with extensive lesions, while all other cases were monitored without surgical intervention. Postoperative complications included dyscoria (13/13), focal posterior synechia (9/13) and focal nonprogressive cataract (8/13). All eyes remained visual and comfortable up to 6.2 years post-iridectomy with no clinically identifiable local recurrence. Histopathology was consistent with uveal melanocytoma in all samples obtained surgically. All cases that did not undergo surgery remained free of complications up to 4.5 year post diagnosis.
CONCLUSIONS: Melanocytic anterior uveal lesions may be overrepresented in certain lineages of breeds and be present at a young age. While none of the eyes developed complications when monitored without surgery, early surgical excision of the mass by sector iridectomy yields noteworthy functional outcome and retention of a comfortable globe.

Malignant melanoma (MM) is a highly invasive and therapeutically resistant skin malignancy, posing a significant clinical challenge in its treatment. Programmed cell death plays a crucial role in the occurrence and progression of MM. Sphingolipids (SP), as a class of bioactive lipids, may be associated with many kinds of diseases. SPs regulate various forms of programmed cell death in tumors, including apoptosis, necroptosis, ferroptosis, and more. This review will delve into the mechanisms by which different types of SPs modulate various forms of programmed cell death in MM, such as their regulation of cell membrane permeability and signaling pathways, and how they influence the survival and death fate of MM cells. An in-depth exploration of the role of SPs in programmed cell death in MM aids in unraveling the molecular mechanisms of melanoma development and holds significant importance in developing novel therapeutic strategies.

Background and Objectives: Malignant melanoma (MM) remains one of the most aggressive cancers worldwide, presenting a limited number of therapeutic options at present. Aspirin (ASA), a broadly used non-steroid anti-inflammatory medicine, has recently emerged as a candidate for repurposing in cancer management, due to its therapeutic potential in the treatment of several neoplasms which include MM. Fisetin (FIS) is a flavonoid phytoestrogen instilled with multispectral pharmacological activities, including a potent anti-melanoma property. The present study aimed to assess the potential improved anti-neoplastic effect resulting from the association of ASA and FIS for MM therapy. Materials and Methods: The study was conducted using the A375 cell line as an experimental model for MM. Cell viability was assessed via the MTT test. Cell morphology and confluence were evaluated using bright-field microscopy. The aspect of cell nuclei and tubulin fibers was observed through immunofluorescence staining. The irritant potential and the anti-angiogenic effect were determined on the chorioallantoic membrane of chicken fertilized eggs. Results: The main findings related herein demonstrated that the ASA 2.5 mM + FIS (5, 10, 15, and 20 µM) combination exerted a higher cytotoxicity in A375 MM cells compared to the individual compounds, which was outlined by the concentration-dependent and massive reduction in cell viability, loss of cell confluence, cell shrinkage and rounding, apoptotic-like nuclear features, constriction and disruption of tubulin filaments, increased apoptotic index, and suppressed migratory ability. ASA 2.5 mM + FIS 20 µM treatment lacked irritant potential on the chorioallantoic membrane and inhibited blood-vessel formation in ovo. Conclusion: These results stand as one of the first contributions presenting the anti-melanoma effect of the ASA + FIS combinatorial treatment.