Epidermal Melanoma Research Articles

Diagnosis of metastatic melanoma by fine-needle aspiration biopsy and primary melanoma by using the skin and mucousa imprints

BACKGROUND: Determination of the cytogenetic origin and morphological type of metastatic or primary tumor determines the prescription of therapy and affects the efficiency of patient’s treatment. Currently, a number of publications evaluate the potential of cytological diagnostics of melanoma. AIM: To evaluate the significance of diagnosing metastatic melanoma by fine-needle aspiration biopsy and primary melanoma by using the skin and mucosa imprints. METHODS: In a retrospective study, a comparative analysis of cytological melanoma samples, in comparison with clinical and anamnestic information and the results of histological, immunohistochemical, and molecular genetic studies, was carried out. Information about 109 patients from the cancer registry of the Altai Regional Oncology Dispensary (Barnaul, Russia) for 2022 was used in the study. Traditional and liquid-based methods for preparing samples were used. The samples were stained using Pappenheim and Papanicolaou methods. In some observations, cytological material was used for molecular genetic studies. Using the cancer registry data of the dispensary, the results of histological and of molecular genetic studies, and a final conclusion was given about each patient. RESULTS: Fine-needle aspiration biopsy was carried out in 80 patients. Tumor smears were obtained from 29 patients. The cytological diagnose “melanoma” was consistent with the data of histological and immunohistochemical studies (p 0.001) for all 109 patients. Melanoma was diagnosed for the first time in 66 (60.5%) patients. In other cases, the process of progression was noted within the period from one year to 20 years. Epidermal melanoma was noted in 101 (92.7%) cases, including 9 patients with acral melanoma, and 2 cases with localization on the vulva. Melanomas of mucosa were found in 5 cases (4.5%): in the rectum and anal canal, vagina, and in 2 cases on the hard palate. Non-epidermal (uveal) melanomas metastases were diagnosed in liver by fine-needle aspiration biopsy in 3 patients (2.8%). Based on the cellular composition, epithelioid cell melanoma was determined in 81 (74.3%) patients, mixed cell in 14 (12.8%) cases, spindle cell in 9 (8.2%), pigmentless in 2 (1.8%) cases and nevoid melanoma in 1 (0.9%) case. The mutation status was determined in 96 patients (88.1%). Of these, in 8 patients it was determined using cytological material. In epidermal melanomas, mutations in codon 600 of exon 15 of the BRAF gene were found in 43 (44.8%) patients, including 2 cases of acral melanoma. Mutations V600K, V600E/Ec were found in one patient each. In mucousal melanomas: Q61R mutation was found in exon 3 of the NRAS gene (vaginal melanoma), G12C mutation was identified in exon 2 of the NRAS gene (anal canal melanoma). In uveal melanomas, the assessed mutations were absent (it is necessary to determine mutation is GNAQ11 and BAP1 genes). CONCLUSION: Cytological diagnosis of melanoma by fine-needle aspiration biopsies and imprints from the tumor mass is a highly informative method that allows diagnosing melanoma and verifying the tumor subtype. The obtained results indicate tumor heterogeneity and differences in mutational status depending on the location of melanomas. The molecular classification of melanoma is important when choosing individualized therapy.

Epidermal melanoma prognostic factors: a link to paracrine transforming growth factor-β signalling.

Linked Article: Cosgarea et al. Br J Dermatol 2022; 186:694–704.

Selective cytotoxicity of PAMAM G5 core–PAMAM G2.5 shell tecto-dendrimers on melanoma cells

BackgroundThe controlled introduction of covalent linkages between dendrimer building blocks leads to polymers of higher architectural order known as tecto-dendrimers. Because of the few simple steps involved in their synthesis, tecto-dendrimers could expand the portfolio of structures beyond commercial dendrimers, due to the absence of synthetic drawbacks (large number of reaction steps, excessive monomer loading, and lengthy chromatographic separations) and structural constraints of high-generation dendrimers (reduction of good monodispersity and ideal dendritic construction due to de Gennes dense-packing phenomenon). However, the biomedical uses of tecto-dendrimers remain unexplored. In this work, after synthesizing saturated shell core–shell tecto-dendrimers using amine-terminated polyamidoamine (PAMAM) generation 5 (G5) as core and carboxyl-terminated PAMAM G2.5 as shell (G5G2.5 tecto-dendrimers), we surveyed for the first time the main features of their interaction with epithelial cells.MethodsStructural characterization of G5G2.5 was performed by polyacrylamide gel electrophoresis, matrix-assisted laser desorption time-of-flight mass spectrometry, and microscopic techniques; their hydrodynamic size and Z-potential was also determined. Cellular uptake by human epidermal keratinocytes, colon adenocarcinoma, and epidermal melanoma (SK-Mel-28) cells was determined by flow cytometry. Cytotoxicity was determined by mitochondrial activity, lactate dehydrogenase release, glutathione depletion, and apoptosis/necrosis measurement.ResultsThe resultant 60%–67% saturated shell, 87,000-dalton G5G2.5 (mean molecular weight) interacted with cells in a significantly different fashion in comparison to their building blocks and to its closest counterpart, PAMAM G6.5. After being actively taken up by epithelial cells, G5G2.5 caused cytotoxicity only on SK-Mel-28 cells, including depletion of intracellular glutathione and fast necrosis that was manifested above 5 μM G5G2.5. It cannot be discounted that traces of LiCl within G5G2.5 were involved in such deleterious effects.ConclusionThese preliminary results suggest that at concentrations that do not damage healthy keratinocytes, G5G2.5 could display antimelanoma activity.

Malignant melanoma presenting as an intrathymic tumor: a primary thymic melanoma?

The identification of malignant melanoma in a visceral organ of nonepidermal origin is not an uncommon occurrence. Frequently, these cases are solitary metastases that present years after a thin epidermal melanoma has been diagnosed (and sometimes forgotten). However, primary visceral melanomas have been reported that have not been preceded by an epidermal lesion. We describe herein a unique case of melanoma presenting as a primary intrathymic tumor. The patient had no previous history of epidermal melanoma, and extensive workup did not reveal evidence for an alternative primary site. The tumor exhibited histologic features characteristic of melanoma, including an abundance of large pleomorphic cells with eosinophilic cytoplasm, prominent nucleoli, and S100 protein and ultrastructural analysis revealed stage II and stage III melanosomes. The patient remained free of disease until intrathoracic recurrence was detected on a computed tomographic scan 14 months later. The lack of clinical history and physical findings of melanoma at presentation, the intrathymic location of the tumor, and the pattern of recurrence suggest that this case likely represents a primary thymic melanoma, a previously unreported entity.

Melanoma in situ (MIS) adjacent to an invasive nodular melanoma ("SSM/NM") and its metastases--DNA-cytophotometry, mitotic index, and anisokaryosis.

Malignant melanomas of the superficial spreading type usually have an intraepidermal tumour component in their periphery which frequently displays the morphological features of a melanoma in situ (adjacent MIS). It is thus comparable to exclusively epidermal melanomas; melanoma in situ (MIS). Taking 10 superficial melanomas with a nodular component ("SSM/NM") 31 adjacent MIS regions and 36 nodular melanoma components were analysed in serial tissue slides. Planimetric estimation of the nuclear areas was employed as a measure of anisokaryosis. DNA-Feulgen-cytophotometry was applied to obtain an objective variable in judging malignancy in the DNA-histographs (paraffin material). Furthermore we investigated 8 metastases of one of the malignant melanomas applying the methods described. A comparison of the epidermal with the invasive tumour components revealed an increase in the nuclear area which, however, decrease from the superior to the inferior nodular regions and which are further reduced in melanoma metastases. Anisokaryosis is evidently less in metastases compared with all primary melanomas. The nuclear DNA-content increases from the epidermal to the invasive tumour compartments and is lower in the inferior nodular regions when compared with the superior ones. No further significant differences are, however, established in the metastases. The coefficients of variability of the DNA-contents, being a potential indicator of DNA-heterogeneity reflect higher values in the epidermal tumour components compared with the nodular regions, decreasing from the superior to the inferior nodular parts of the tumour. All metastases have smaller values than the respective primary melanoma. In the DNA-histographs 75% of the intraepidermal tumour components have obvious signs of malignancy including tumour cell stem lines in 19% of the cases. 85% of the nodular regions investigated have clear signs of malignancy, 33% of which also have aneuploid stem lines. All metastases have obvious signs of malignancy and tumour cell stem lines in 50% of the cases observed. The following conclusions can be drawn from our findings: DNA-Feulgen-cytophotometry and nuclear planimetry are additional feasible methods for judging the epidermal component of a melanocytic lesion as malignant (adjacent melanoma in situ) on paraffin material. Furthermore these methods give different results in invasive nodular versus epidermal (in situ) melanoma components. Both the DNA-histographs and our immunohistochemical investigations (monoclonal antibody P 3.58) indicate the malignant potential of adjacent MIS.(ABSTRACT TRUNCATED AT 400 WORDS)