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Fulltext Malignant conjunctival melanoma. A case report

Kandiah R, Sukumaran K, Chandran S, Jayalakshmi P

Med J Malaysia, 1988 Jun;43(2):178-80.
PMID: 3237135
Matched MeSH terms: Melanoma/pathology*
Primary anorectal malignant melanoma: A clinical, radiology and pathology correlation

Bohan S, Ramli Hamid MT, Poh KS, Chow TK, Chan WY

Malays J Pathol, 2020 Dec;42(3):461-467.
PMID: 33361730

INTRODUCTION: Primary gastrointestinal melanomas are mucosal malignancies that arise from melanocytes in the oropharynx, rectum, and anus. Anorectal malignant melanoma (ARMM) are exceedingly rare, accounting for less than 1% of all melanomas, 0.1% of all rectal malignancies and 4% of anal malignancies. Diagnosis is frequently delayed as these lesions are often mistaken for haemorrhoids. Histological evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Due to the aggressive nature, 61% of patients with ARMM would already have lymph node involvement or distant metastases, by the time of diagnosis. Prognosis is usually poor with 5-year survival rate of <20%. We report a case of metastatic ARMM in an elderly lady who presented with symptoms and signs mimicking a haemorrhoid.
CASE REPORT: A 69-year-old lady presented with one year history of intermittent rectal bleed and an anorectal mass that was initially treated as haemorrhoid. Colonoscopy showed a hyperpigmented mass in the anorectal region which was confirmed as malignant melanoma on histopathological examination. Imaging with CT and MRI demonstrated locally advanced tumour with distant metastases to the liver and lung. Patient was referred for palliative management.
CONCLUSION: ARMM is a rare malignancy and often presented with non-specific clinical signs. Diagnosis is frequently delayed without high index of suspicion. MRI pelvis is the imaging of choice to assess local extent of disease. Histologic evaluation with special immunohistochemical stains is often necessary for definitive diagnosis. Prognosis is poor despite surgical and chemotherapeutic interventions.

Matched MeSH terms: Melanoma/pathology*
Fulltext Acral melanoma of the extremities: a study of 33 cases Sarawakian patients

Zainal AI, Zulkarnaen M, Norlida DK, Syed Alwi SA

Med J Malaysia, 2012 Feb;67(1):60-5.
PMID: 22582550

Acral melanoma involve the non-pigmented palmoplantar and subungual areas and are commonly seen among Asians. Patients commonly display advanced stage of disease at presentation. It may appear unnoticed and mimic benign lesions.

Matched MeSH terms: Melanoma/pathology*
Fulltext Sinonasal malignant melanocytic melanoma: a rare case report

Pathma L, Philip R, Harvinder S, Manjit S

Med J Malaysia, 2008 Jun;63(2):152-3.
PMID: 18942306 MyJurnal

Malignant melanocytic melanoma is a rare sinonasal malignancy. We present a case report of an elderly lady who presented with epistaxis and intranasal polyps. Computed tomography revealed soft tissue mass in the oropharynx, nasopharynx, left ethmoid and entire maxillary sinus. The mass was removed via endoscopic medial maxillectomy. Histopathology examination revealed sinonasal melanocytic malignant melanoma. At present 17 months postoperatively she is symptom free with no recurrence and under regular follow up.

Matched MeSH terms: Melanoma/pathology*
Fulltext Cyclin D1 expression in acral melanoma: a case control study in Sarawak

Ibrahim ZA, Narihan MZ, Ojep DN, Soosay AE, Pan KL

Malays J Pathol, 2012 Dec;34(2):89-95.
PMID: 23424770 MyJurnal

Acral melanoma has been reported to have distinctive clinical presentation and ethnic distribution compared to other histological types of malignant melanoma. Acral melanoma also exhibits distinctive focused gene amplifications, including cyclin D1 overexpression. We reviewed archived histological material of malignant melanoma in the Sarawak General Hospital from year 2004 to 2010. 43 tumours, comprising 28 acral melanoma and 15 non-acral melanoma, had sufficient material to be included in the study. The majority (36%) of acral melanoma tumours occurred in the heel. The tumours were analyzed for cyclin D1 expression by immunohistochemistry. 68% of acral melanoma were cyclin D1 positive compared to a positivity of 33% in non-acral tumours. This difference was statistically significant (p < 0.05). This finding may improve the histological diagnosis of acral melanoma and detection of positive resection margins.

Matched MeSH terms: Melanoma/pathology*
Fulltext Mucosal malignant melanoma of the maxillary sinus

Norhafizah M, Mustafa WM, Sabariah AR, Shiran MS, Pathmanathan R

Med J Malaysia, 2010 Sep;65(3):218-20.
PMID: 21939172

Mucosal malignant melanoma (MMM) is an aggressive tumour occurring in the upper respiratory tract. It is rare compared to malignant melanoma of the skin. We report a case of a 53-year-old man with left paranasal swelling. A biopsy showed high-grade spindle cell tumour. Subsequently a subtotal maxillectomy was performed. Histopathological examination revealed a hypercellular tumour composed of mixed spindle and epitheloid cells with very occasional intracytoplasmic melanin pigment. The malignant cells were immunopositive for vimentin, S-100 protein and HMB-45. It was diagnosed as mucosal malignant melanoma (MMM). This article illustrates a rare case of MMM where the diagnosis may be missed or delayed without proper histopathological examination that include meticulous search for melanin pigment and appropriate immunohistochemical stains to confirm the diagnosis. Malignant melanoma can mimic many other types of high-grade malignancy and should be considered as a differential diagnosis in many of these instances.

Matched MeSH terms: Melanoma/pathology*
Primary malignant melanoma of the oesophagus

Gul YA, Prasannan S, Hairuszah I

Acta Chir. Belg., 2003 Aug;103(4):420-2.
PMID: 14524166

Primary malignant melanoma arising in the oesophagus is a rare condition with a dismal prognosis. The diagnosis is often made following surgical resection even though the endoscopic features may be pathognomonic. The classical treatment is oesophagectomy even though the advanced disease stage at the time of presentation and aggressive biological behaviour of the tumour usually results in a fatal outcome. We report the case of a male patient initially diagnosed with squamous oesophageal carcinoma and treated with conventional neo-adjuvant chemo-radiotherapy. Poor clinical and radiological response resulted in a review of the original histology confirming a diagnosis of primary malignant melanoma of the oesophagus. The subsequent alteration in management conferred the patient an improved quality of life. A short review of the literature on primary malignant melanoma of the oesophagus supplements this case report.

Matched MeSH terms: Melanoma/pathology*
Anorectal melanoma

Jalleh RP, Pathmanathan R, Krishnan MM, Mukherjee A

Postgrad Med J, 1988 Sep;64(755):669-71.
PMID: 3251217

Four cases of anorectal melanoma are presented. The authors believe that this is the first report of the occurrence of this tumour in Malays. Advanced disease at initial presentation accounts for the poor prognosis observed in this series. Surgery remains the principal treatment modality, although controversy exists regarding optimal extent of resection.

Matched MeSH terms: Melanoma/pathology
A deadly hidden nodule

Lim JA

Am J Obstet Gynecol, 2018 11;219(5):502.
PMID: 29678504 DOI: 10.1016/j.ajog.2018.04.021
Matched MeSH terms: Melanoma/pathology*
Fulltext Viability and Antioxidant Effects of Traditional Cooling Rice Powder (bedak sejuk) Made from Oryza sativa ssp. Indica and Oryza sativa ssp. japonica on UVB-Induced B164A5 Melanoma Cells

Ghazali AR, Muralitharan RV, Soon CK, Salyam T, Ahmad Maulana NN, Mohamed Thaha UAB, et al.

Asian Pac J Cancer Prev, 2020 Nov 01;21(11):3381-3386.
PMID: 33247699 DOI: 10.31557/APJCP.2020.21.11.3381

BACKGROUND: Traditional cooling rice powder (bedak sejuk) is a fermented rice-based cosmetic that is applied topically on one's skin, as an overnight facial mask. According to user testimonies, bedak sejuk beautifies and whitens skin, whereby these benefits could be utilised as a potential melanoma chemopreventive agent.
OBJECTIVE: Hence, this study aimed to determine the effects of bedak sejuk made from Oryza sativa ssp. indica (Indica) and Oryza sativa ssp. japonica (Japonica) on UVB-induced B164A5 melanoma cells, and also identify the antioxidant capacities of both types of bedak sejuk.
METHODS: The optimum dose of Indica and Japonica bedak sejuk to treat the cells was determined via the MTT assay. Then, the antioxidant capacities of both types of bedak sejuk were determined using the FRAP assay.
RESULTS: From the MTT assay, it was found that Indica and Japonica bedak sejuk showed no cytotoxic effects towards the cells. Hence, no IC50 can be obtained and two of the higher doses, 50 and 100 g/L were chosen for treatment. In the FRAP assay, Indica bedak sejuk at 50 and 100 g/L showed FRAP values of 0.003 ± 0.001 μg AA (ascorbic acid)/g of bedak sejuk and 0.004 ± 0.0003 μg AA/g of bedak sejuk. Whereas Japonica bedak sejuk at 50 g/L had the same FRAP value as Indica bedak sejuk at 100 g/L. As for Japonica bedak sejuk at 100 g/L, it showed the highest antioxidant capacity with the FRAP value of 0.01 ± 0.0007 μg AA/g of bedak sejuk which was statistically significant (p < 0.05) when compared to other tested concentrations.
CONCLUSION: In conclusion, Japonica bedak sejuk has a higher antioxidant capacity compared to Indica bedak sejuk despite both being not cytotoxic towards the cells. Regardless, further investigations need to be done before bedak sejuk could be developed as potential melanoma chemoprevention agents.

Matched MeSH terms: Melanoma/pathology
Fulltext Germline variants are associated with increased primary melanoma tumor thickness at diagnosis

Mangantig E, MacGregor S, Iles MM, Scolyer RA, Cust AE, Hayward NK, et al.

Hum Mol Genet, 2021 01 06;29(21):3578-3587.
PMID: 33410475 DOI: 10.1093/hmg/ddaa222

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P melanoma growth and invasion.

Matched MeSH terms: Melanoma/pathology*
5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave

Khan NR, Wong TW

Artif Cells Nanomed Biotechnol, 2018;46(sup1):568-577.
PMID: 29378453 DOI: 10.1080/21691401.2018.1431650

This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.

Matched MeSH terms: Melanoma/pathology*
Fulltext Malignant melanoma of the gastrointestinal tract presenting as a bleeding gastric ulcer

Noraidah M, Jasmi AY

Malays J Pathol, 2003 Jun;25(1):57-61.
PMID: 16196379

Malignant melanoma involving the gastrointestinal tract is diagnosed antemortem in only a small percentage of patients with the disease. Presenting symptoms are often non-specific, causing a diagnostic problem. The vast majority of such melanomas are metastatic from a cutaneous primary, however there is evidence that the tumour can arise de novo in the gastrointestinal system. We report a 74-year-old man with malignant melanoma with an unusual presentation simulating a symptomatic gastric ulcer. He presented with epigastric pain, haematemesis and melaena. Explorative laparotomy revealed a large ulcerated tumour with several pigmented satellite nodules in the proximal stomach, multiple ileal nodules and widespread nodal and liver metastases. Proximal gastrectomy and limited small bowel resection was performed. Histology revealed the tumour to be composed of nests of epithelioid cells with melanin pigment. The tumour cells showed immunohistochemical positivity for S100 protein and HMB45 antibodies. This report emphasizes that melanoma should be a diagnostic consideration in patients with gastric ulcer.

Matched MeSH terms: Melanoma/pathology
Emphysematous gastritis after metastatic malignant melanoma: a radiological surprise

Ng CY, Hayati F, Nadarajan C

BMJ Case Rep, 2020 Sep 09;13(9).
PMID: 32912885 DOI: 10.1136/bcr-2020-235174

Malignant melanoma is cancer of the skin which commonly metastasises to the stomach. There have been no reported cases of emphysematous gastritis secondary to metastasis of malignant melanomas, to date. However, a 61-year-old woman with metastatic malignant melanoma of the left great toe presented to us with symptoms of severe left hypochondrium pain associated with high-grade fever, gross abdominal distension and recurrent vomiting. Two months earlier, metastasis was observed to have spread to the stomach and inguinal lymph nodes. At this stage, the patient opted for traditional medication instead of definitive surgery and chemotherapy. Radiological imaging revealed an emphysematous change to the stomach which was radiologically consistent with gastric malignant melanoma. Unfortunately, the patient succumbed to this rare condition.

Matched MeSH terms: Melanoma/pathology*
Multidisciplinary Approach for Management of a Patient with Oral Mucosal Malignant Melanoma

Eachempati P, Aggarwal H, Shenoy VK, Baliga M

J Coll Physicians Surg Pak, 2018 Sep;28(9):S187-S189.
PMID: 30173693 DOI: 10.29271/jcpsp.2018.09.S187

Oral mucosal melanoma is rare and more aggressive than cutaneous melanoma. Hard palate and maxillary alveolar crest are most commonly involved. Multidisciplinary team approach is necessary for successful management of this tumor. The main treatment modality is surgical resection, which usually results in impaired mastication, deglutition, speech, oral competence and significant cosmetic deformity. Here, a rare case of oral mucosal melanoma of mandibular gingiva in a 44-year man is reported, who was treated by en-block mandibular resection followed by adjuvant therapy with high dose interferons (IFN) - 2b. Following two weeks of healing period, prosthetic rehabilitation of the patient was done with an interim removable denture prosthesis, which effectively limited the unfavourable effects of surgery and helped him in resocialisation.

Matched MeSH terms: Melanoma/pathology*
Fulltext The Role of PPARβ/δ in Melanoma Metastasis

Lim JCW, Kwan YP, Tan MS, Teo MHY, Chiba S, Wahli W, et al.

Int J Mol Sci, 2018 Sep 20;19(10).
PMID: 30241392 DOI: 10.3390/ijms19102860

BACKGROUND: Peroxisome proliferator⁻activated receptor (PPAR) β/δ, a ligand-activated transcription factor, is involved in diverse biological processes including cell proliferation, cell differentiation, inflammation and energy homeostasis. Besides its well-established roles in metabolic disorders, PPARβ/δ has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPARβ/δ's role in tumour progression and metastasis remains controversial.
METHODS: In the present studies, the consequence of PPARβ/δ inhibition either by global genetic deletion or by a specific PPARβ/δ antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models.
RESULTS: Our study showed that 10h promotes epithelial-mesenchymal transition (EMT), migration, adhesion, invasion and trans-endothelial migration of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell extravasation in the lungs of wild-type mice subjected to 10h treatment and in Pparβ/δ-/- mice in an experimental mouse model of blood-borne pulmonary metastasis by tail vein injection. This observation was further supported by an increased tumour burden in the lungs of Pparβ/δ-/- mice as demonstrated in the same animal model.
CONCLUSION: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.

Matched MeSH terms: Melanoma/pathology
Fulltext Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin

Dorasamy MS, Ab A, Nellore K, Wong PF

Biomed Pharmacother, 2019 Feb;110:29-36.
PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010

Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.

Matched MeSH terms: Melanoma/pathology
Malignant melanoma of the choroid in a naevus of Ota

Singh M, Kaur B, Annuar NM

Br J Ophthalmol, 1988 Feb;72(2):131-3.
PMID: 3349013

A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye.

Matched MeSH terms: Melanoma/pathology*
Fulltext Inhibition of MAPKs, Myc/Max, NFκB, and hypoxia pathways by Phyllanthus prevents proliferation, metastasis and angiogenesis in human melanoma (MeWo) cancer cell line

Tang YQ, Jaganath IB, Manikam R, Sekaran SD

Int J Med Sci, 2014;11(6):564-77.
PMID: 24782645 DOI: 10.7150/ijms.7704

Melanoma is the most fatal form of skin cancer. Different signalling pathways and proteins will be differentially expressed to pace with the tumour growth. Thus, these signalling molecules and proteins are become potential targets to halt the progression of cancer. The present works were attempted to investigate the underlying molecular mechanisms of anticancer effects of Phyllanthus (P.amarus, P.niruri, P.urinaria and P.watsonii) on skin melanoma, MeWo cells.

Matched MeSH terms: Melanoma/pathology*
Panduratin A induces protective autophagy in melanoma via the AMPK and mTOR pathway

Lai SL, Mustafa MR, Wong PF

Phytomedicine, 2018 Mar 15;42:144-151.
PMID: 29655680 DOI: 10.1016/j.phymed.2018.03.027

BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma.
PURPOSE: Our previous proteomics analysis revealed that treatment with PA resulted in the upregulation of an autophagy marker, LC3B in melanoma cells. Therefore, the present study sought to investigate the role of PA-induced autophagy in melanoma cells.
METHODS: Transmission electron microscopy was performed for examination of autophagic ultra-structures in PA-treated A375 cells. Cytoplasmic LC3B and p62/SQSMT1 punctate structures were detected using immunofluorescene staining. Expression levels of LC3B II, p62/SQSMT1, ATG 12, Beclin 1, phospho S6 (ser235/236), phospho AMPK (Thr172) and cleaved PARP were evaluated by western blotting.
RESULTS: Autophagosomes, autolysosomes and punctuates of LC3 proteins could be observed in PA-treated A375 cells. PA-induced autophagy in A375 melanoma cells was found to be mediated through the inhibition of mTOR signaling and activation of AMPK pathway. Furthermore, we showed that PA-induced apoptosis was increased in the presence of an autophagy inhibitor, signifying the cytoprotective effect of PA-induced autophagy in melanoma cells.
CONCLUSION: Taken together, results from the present study suggest that the inhibition of autophagy by targeting mTOR and AMPK could potentiate the cytotoxicity effects of PA on melanoma cells.

Matched MeSH terms: Melanoma/pathology

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