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Acta Oto-laryngologica Sep 2020The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study. To analyze data with...
The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study. To analyze data with head and neck mucosal melanoma, and compare the prognosis of patients with and without pigment. The patients of amelanotic melanoma were matched with pigmented type according to age, sex, stage, location of disease, treatment history, tobacco and alcohol history. The Kaplan-Meier and Cox proportional risk regression model was used for analyzation. 46 patients of amelanotic melanoma and 46 of pigmented type were included in this study. The overall survival rate and progression-free survival rate of patients with pigmented melanoma were higher than in patients with amelanotic melanoma (HR = 0.533, = .035, 95% CI = 0.296-0.957; HR = 0.530, = .034, 95% CI = 0.294-0.953, respectively), and the risk of distant metastases in patients with amelanotic melanoma was significantly higher than that in patients with pigmented melanoma (HR = 0.474, = .046, 95% CI = 0.228-0.987). The prognosis and disease-free survival of amelanotic melanoma is worse than for the pigmented type group. More identifying the differences in clinical characteristics will help to further individualized treatment decisions.
Topics: Female; Head and Neck Neoplasms; Humans; Male; Melanoma; Melanoma, Amelanotic; Middle Aged; Mouth Mucosa; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Proportional Hazards Models; Survival Analysis
PubMed: 32449432
DOI: 10.1080/00016489.2020.1763456 -
JAAD Case Reports Jun 2019
PubMed: 31194014
DOI: 10.1016/j.jdcr.2019.04.008 -
Qatar Medical Journal 2020Malignant melanoma (melanoma) is a tumor of melanocytes that usually presents as cutaneous lesions. While melanoma can infrequently appear as a primary tumor elsewhere...
Malignant melanoma (melanoma) is a tumor of melanocytes that usually presents as cutaneous lesions. While melanoma can infrequently appear as a primary tumor elsewhere in the body, it is extremely rare in the urethra and even rarer as amelanotic malignant melanoma. We report the case of a 66-year-old male who presented with painless gross hematuria and lower urinary tract obstructive symptoms in the recent 2 weeks prior to his visit to our clinic. History and physical examination, including external genital examination, abdominopelvic sonography, and urine culture, were not conclusive. Cystourethroscopy revealed a creamy pink fragile mass located in the anterior proximal urethra that extended to the mid portion. Pathological examination of this lesion confirmed the diagnosis of amelanotic malignant melanoma using immunohistochemistry. Radical cystourethrectomy with ileal conduit was subsequently conducted. Although this tumor is extremely rare, urologists and pathologists should consider malignant melanoma as a diagnosis in patients with urethral tumor because of the likelihood of early metastasis and, consequently, poor prognosis. Complete surgical removal of the tumor and use of effective therapies can improve outcomes in these patients.
PubMed: 32274353
DOI: 10.5339/qmj.2020.11 -
Cell Biology and Toxicology Dec 2017The incidence of malignant melanoma, the most aggressive skin cancer, is increasing constantly. Despite new targeted therapies, the prognosis for patients with...
The incidence of malignant melanoma, the most aggressive skin cancer, is increasing constantly. Despite new targeted therapies, the prognosis for patients with metastatic disease remains poor. Thus, there is a need for new combinational treatments, and antineoplastic agents potentially valuable in this approach are inhibitors of the ubiquitin-proteasome system (UPS). In this work, we analyze the cytotoxicity mechanisms of proteasome inhibitors (MG-132, epoxomicin, and lactacystin) in a specific form of melanoma which does not synthesize melanin-the amelanotic melanoma (Ab cells). We found that the most cytotoxic of the compounds tested was epoxomicin. Caspase-9 activation as well as cytochrome C and AIF release from mitochondria indicated that exposure to epoxomicin induced the mitochondrial pathway of apoptosis. Epoxomicin treatment also resulted in accumulation of Bcl-2 family members-proapoptotic Noxa and antiapoptotic Mcl-1, which were postulated as the targets for bortezomib in melanoma. Inhibition of caspases by BAF revealed that cell death was partially caspase-independent. We observed no cell cycle arrest preceding the apoptosis of Ab cells, even though cdk inhibitors p21 and p27 were up-regulated. The cell cycle was blocked only after inactivation of caspases by the pan-caspase inhibitor BAF. In summary, this is the first study exploring molecular mechanisms of cell death induced by epoxomicin in melanoma. We found that Ab cells died on the mitochondrial pathway of apoptosis and also partially by the caspase-independent way of death. Apoptosis induction was fast and efficient and was not preceded by cell cycle arrest.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cricetinae; Male; Melanoma, Amelanotic; Mesocricetus; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Skin Neoplasms
PubMed: 28281027
DOI: 10.1007/s10565-017-9390-0 -
Archivos de La Sociedad Espanola de... Feb 2017
Topics: Adult; Biomarkers, Tumor; Biopsy; Brachytherapy; Female; Gonioscopy; Humans; Iris Neoplasms; Melanoma, Amelanotic; Microscopy, Acoustic; Slit Lamp Microscopy
PubMed: 27665123
DOI: 10.1016/j.oftal.2016.07.006 -
Head and Neck Pathology Jun 2022Oral amelanotic melanoma (OAM) is a rare, non-pigmented mucosal neoplasm representing less than 2% of all melanoma. The present study analyses the available data on OAM... (Review)
Review
Oral amelanotic melanoma (OAM) is a rare, non-pigmented mucosal neoplasm representing less than 2% of all melanoma. The present study analyses the available data on OAM and describes its clinicopathological features, identifying potential prognostic factors. Online electronic databases such as PubMed-Medline, Embase, and Scopus were searched using appropriate keywords from the earliest available date till 31st March 2021 without restriction on language. Additional sources like Google Scholar, major journals, unpublished studies, conference proceedings, and cross-references were explored. 37 publications were included for quantitative synthesis, comprising 55 cases. The mean age of the patients was 59.56 years, and the lesions were more prevalent in males than in females. OAM's were most prevalent in the maxilla (67.2%) with ulceration, pinkish-red color, nodular mass, and pain. 2 patients (3.36%) were alive at their last follow-up, and 25 were dead (45.4%). Univariate survival analysis of clinical variables revealed that age older than 68 years (p = 0.003), mandibular gingiva (p = 0.007), round cells (p = 0.004), and surgical excision along with chemotherapy & radiation therapy (p = 0.001) were significantly associated with a lower survival rate. Oral Amelanotic Melanoma is a neoplasm with a poor prognosis, presenting a 6.25% possibility of survival after 5 years. Patients older than 68 years, lesions in the mandibular gingiva, round cells, and surgical excision along with chemotherapy and radiotherapy, presented the worst prognosis. However, they did not represent independent prognostic determinants for these patients.
Topics: Aged; Female; Humans; Male; Melanoma; Melanoma, Amelanotic; Middle Aged; Prognosis; Skin Neoplasms; Survival Rate; Melanoma, Cutaneous Malignant
PubMed: 34309791
DOI: 10.1007/s12105-021-01366-w -
International Journal of Molecular... Jan 2022Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods...
Malignant melanoma is still a serious medical problem. Relatively high mortality, a still-growing number of newly diagnosed cases, and insufficiently effective methods of therapy necessitate melanoma research. Tetracyclines are compounds with pleiotropic pharmacological properties. Previously published studies on melanotic melanoma cells ascertained that minocycline and doxycycline exerted an anti-melanoma effect. The purpose of the study was to assess the anti-melanoma potential and mechanisms of action of minocycline and doxycycline using A375 and C32 human amelanotic melanoma cell lines. The obtained results indicate that the tested drugs inhibited proliferation, decreased cell viability, and induced apoptosis in amelanotic melanoma cells. The treatment caused changes in the cell cycle profile and decreased the intracellular level of reduced thiols and mitochondrial membrane potential. The exposure of A375 and C32 cells to minocycline and doxycycline triggered the release of cytochrome c and activated initiator and effector caspases. The anti-melanoma effect of analyzed drugs appeared to be related to the up-regulation of ERK1/2 and MITF. Moreover, it was noticed that minocycline and doxycycline increased the level of LC3A/B, an autophagy marker, in A375 cells. In summary, the study showed the pleiotropic anti-cancer action of minocycline and doxycycline against amelanotic melanoma cells. Considering all results, it could be concluded that doxycycline was a more potent drug than minocycline.
Topics: Antineoplastic Agents; Apoptosis; Autophagy; Biomarkers, Tumor; Caspases; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dose-Response Relationship, Drug; Doxycycline; Humans; Melanoma, Amelanotic; Membrane Potential, Mitochondrial; Minocycline
PubMed: 35055021
DOI: 10.3390/ijms23020831 -
PloS One 2020Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism...
Amelanotic/hypomelanotic melanoma is a clinicopathologic subtype with absent or minimal melanin. This study assessed previously reported coding variants in albinism genes (TYR, OCA2, TYRP1, SLC45A2, SLC24A5, LRMDA) and common intronic, regulatory variants of OCA2 in individuals with amelanotic/hypomelanotic melanoma, pigmented melanoma cases and controls. Exome sequencing was available for 28 individuals with amelanotic/hypomelanotic melanoma and 303 individuals with pigmented melanoma, which were compared to whole exome data from 1144 Australian controls. Microarray genotyping was available for a further 17 amelanotic/hypomelanotic melanoma, 86 pigmented melanoma, 147 melanoma cases (pigmentation unknown) and 652 unaffected controls. Rare deleterious variants in TYR/OCA1 were more common in amelanotic/hypomelanotic melanoma cases than pigmented melanoma cases (set mixed model association tests P = 0.0088). The OCA2 hypomorphic allele p.V443I was more common in melanoma cases (1.8%) than controls (1.0%, X2 P = 0.02), and more so in amelanotic/hypomelanotic melanoma (4.4%, X2 P = 0.007). No amelanotic/hypomelanotic melanoma cases carried an eye and skin darkening haplotype of OCA2 (including rs7174027), present in 7.1% of pigmented melanoma cases (P = 0.0005) and 9.4% controls. Variants in TYR and OCA2 may play a role in amelanotic/hypomelanotic melanoma susceptibility. We suggest that somatic loss of function at these loci could contribute to the loss of tumor pigmentation, consistent with this we found a higher rate of somatic mutation in TYR/OCA2 in amelanotic/hypomelanotic melanoma vs pigmented melanoma samples (28.6% vs 3.0%; P = 0.021) from The Cancer Genome Atlas Skin Cutaneous Melanoma collection.
Topics: Albinism; Genetic Variation; Germ-Line Mutation; Humans; Melanoma; Membrane Transport Proteins; Monophenol Monooxygenase; Point Mutation; Polymorphism, Single Nucleotide; Skin Neoplasms; Exome Sequencing
PubMed: 32966289
DOI: 10.1371/journal.pone.0238529 -
Journal of the European Academy of... Jun 2018Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumours, improving their ability to detect skin cancer and better... (Review)
Review
Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumours, improving their ability to detect skin cancer and better recognize benign moles. However, dermoscopically 'false-positive' and 'false-negative' tumours do exist. False-positive diagnosis usually leads to unnecessary excisions. False-negative diagnosis is much more dangerous, as it might result in overlooking a cancer, with severe undesirable consequences for the patient and the physician. Therefore, management strategies should mainly focus on addressing the risk of dermoscopically false-negative tumours. The most frequent benign tumours that might acquire dermatoscopic characteristics suggestive of malignancy are seborrhoeic keratosis (SK), including solar lentigo, melanoacanthoma, irritated, clonal and regressive SK, angioma (mainly thrombosed angioma and angiokeratoma), dermatofibroma, benign adnexal tumours and naevi (Clark, Spitz, recurrent, combined, sclerosing). The most useful clues to recognize these tumours are the following: solar lentigo - broad network; melanoacanthoma - sharp border; irritated SK - regularly distributed white perivascular halos; clonal SK - classic SK criteria; regressive SK - remnants of SK; targetoid haemosiderotic haemangioma - dark centre and reddish periphery; thrombosed angioma - sharp demarcation; angiokeratoma - dark lacunae; atypical dermatofibromas - palpation; follicular tumours - white colour; sebaceous tumours - yellow colour; Clark naevi - clinical context; Spitz/Reed naevi - age; combined naevi - blue central area; recurrent naevi - pigmentation within the scar; sclerosing naevi - age and location on the upper back; blue naevi - history. Malignant tumours that might mimic benign ones and escape detection are melanoma (in situ, nevoid, spitzoid, verrucous, regressive, amelanotic), squamous cell carcinoma (mainly well-differentiated variants) and rarely basal cell carcinoma (non-pigmented variants). The most useful clues to recognize the peculiar melanoma subtypes are as follows: melanoma in situ - irregular hyperpigmented areas; nevoid melanoma - history of growth; spitzoid melanoma - age; verrucous melanoma - blue-black sign; regressive melanoma - peppering or scar-like depigmentation; amelanotic melanoma - pink colour, linear irregular vessels, dotted vessels. In this article, we summarized the most frequent dermoscopic variations of common skin tumours that are often misinterpreted, aiming to assist clinicians to reduce the number of false diagnoses.
Topics: Dermoscopy; Diagnostic Errors; False Negative Reactions; False Positive Reactions; Humans; Skin Diseases; Skin Neoplasms
PubMed: 29314288
DOI: 10.1111/jdv.14782 -
International Journal of Molecular... Jan 2023Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of...
Melanoma is one of the fastest-growing cancers worldwide. Treatment of advanced melanoma is very difficult; therefore, there is growing interest in the identification of new therapeutic agents. Pterostilbene is a natural stilbene that has been found to have several pharmacological activities. The aim of this study was to evaluate the influence of pterostilbene on the proliferation and apoptosis of human melanoma cells. Proliferation of pterostilbene-treated amelanotic (C32) and melanotic (A2058) melanoma cells was determined by BRDU assay. Flow cytometric analyses were used to determine cell cycle progression, and further molecular investigations were performed using real-time RT-qPCR. The expression of the p21 protein and the DNA fragmentation assay were determined by the ELISA method. The results revealed that pterostilbene reduced the proliferation of both amelanotic and melanotic melanoma cells. Pterostilbene induced apoptosis in amelanotic C32 melanoma cells, and this effect was mediated by an increase in the expression of the , , and genes; induction of caspase 3 activity; and DNA degradation. Pterostilbene did not affect the activation of apoptosis in the A2058 cell line. It may be concluded that pterostilbene has anticancer potential against human melanoma cells; however, more studies are still needed to fully elucidate the effects of pterostilbene on amelanotic and melanotic melanoma cells.
Topics: Humans; Skin Neoplasms; Stilbenes; Melanoma, Amelanotic; Apoptosis; Cell Proliferation; Cell Line, Tumor; Melanoma, Cutaneous Malignant
PubMed: 36674631
DOI: 10.3390/ijms24021115