Gut Mycobiota Dysbiosis Is Associated with Melanoma and Response to Anti-PD-1 Therapy.

Recent research indicates that gut microbiota may be vital in the advancement of melanoma. In this study, we found that melanoma patients exhibited a distinct gut mycobiota structure compared with healthy participants. Candida albicans, Candida dubliniensis, and Neurospora crassa were more abundant in samples from patients with melanoma, whereas Saccharomyces cerevisiae and Debaryomyces hansenii were less abundant. During anti-PD-1 treatment, the relative amount of Malassezia restricta and C. albicans increased. A higher level of Saccharomyces paradoxus was associated with a positive response to anti-PD-1 treatment, whereas a higher level of Tetrapisispora blattae was associated with a lack of clinical benefits. High levels of M. restricta and C. albicans, elevated serum lactate dehydrogenase, and being overweight were linked to increased risk of melanoma progression and poorer response to anti-PD-1 treatment. Thus, this study has revealed melanoma-associated mycobiome dysbiosis, characterized by altered fungal composition and fungi species associated with a higher risk of melanoma progression, identifying a role for the gut mycobiome in melanoma progression.

The association between skin cancer and HIV infection.

Background People affected by Human Immunodeficiency Virus (HIV), are burdened by a higher risk of developing malignancies including non-melanoma skin cancer (NMSC) and melanoma skin cancer. Objective To evaluate the association of HIV with melanoma and NMSC at a University Hospital. Methods This is a cross-sectional retrospective study of HIV-infected and a matched comparison group, analyzing the associations between skin cancer and HIV infection. Results Compared to the HIV-uninfected, HIV-infected had 80% association with skin cancer (CI 95%: 1.3-2.4, P = 0.001) The risk was 45-fold higher by patients" age (CI 95%: 3.3-15.9: P = 0.001). When adjusted for patient age, sex and race, the risk was 6.4 fold ligher of having cancer if compared to the others (CI 95%: 49-84, P = 0.001). Melanoma was not found in HIV-infected. Conclusion With this study, we have demonstrated that HIV-infected patients have an increased risk of BCC and SCC. Preventive dermatologic management is pivotal in the care of immunosuppressed patients. These patients must undergo the dermatological examination annually and should receive extensive counseling regarding sun avoidance, use of sunscreens,and sun-protective clothing.

Melanoma growth in non-chemically modified translucid bacterial nanocellulose hollow and compartimentalized spheres.

BACKGROUND: Bacterial nanocellulose (BNC) has been used as cell support in numerous tissue engineering studies. Its use can be explained based on the fact its structure allows the creation of a required microenvironment for an ideal material, which supports 3D cell culture. Its structure and interconnected pores lead to animal cells adhesion and proliferation, also allowing oxygen and nutrients transportation. METHODS: We developed a new methodology to produce spherical platforms synthesized by Komagataebacter hansenii (ATCC 23769) under dynamic culture conditions in minimal medium. The chemical composition and physical properties of the platforms were evaluated. Then, human melanoma cells (SK-MEL-28) were encapsulated into the platforms and evaluated by metabolic activity, morphology and their ability on adhering to the Hollow Translucid BNC Spheres (BNC-TS-H) and Compartmentalized Translucid BNC Spheres (BNC-TS-C) up to 3 days. RESULTS: BNC-TS-H and BNC-TS-C platforms were produced as translucid spheroid platforms with distinct microenvironment under dynamic fermentation. The chemical and physical characterizations confirmed the platforms composition as BNC. The produced internal microenvironments in spherical platforms are relevant to determine tumor cell fate. In the first 12 h of culture, cells could adhere to nanocellulose microfibers assuming their typical tumorous phenotype in 72 h of culture. CONCLUSION: The dynamic fermentation in minimal medium produced distinct microstructured platforms of BNC-TS-H and BNC-TS-C. The platforms microstructure resulted in microenvironments that enabled distinct cell-cell and cell-matrix interactions. This behavior suggests several applications in tissue engineering. GENERAL SIGNIFICANCE: The method produced translucid BNC sphere platforms with distinct microenvironments for 3D cell culture.

Cross-sectional study of acral melanoma awareness in a group of South African final phase medical students.

BACKGROUND: Acral melanoma refers to melanoma arising on the palms, soles and nail unit, which are sun-protected areas and ultraviolet exposure is not a risk factor. Acral melanoma is associated with a poorer prognosis than other melanoma subtypes most likely due to the high rates of delayed diagnosis. Acral melanoma affects all skin types equally. There is a misconception that people with more pigmented skin types (Fitzpatrick 4-6) do not develop melanoma, due to the protective effect of melanin. OBJECTIVES: The aim of the study was to determine acral melanoma knowledge and awareness of a group of South African, final phase medical students. METHODS: This was a quantitative and cross-sectional study. A questionnaire consisting of 20 clinical images of skin lesions requiring a diagnosis and management plan was distributed. Responses to six images of melanomas were analysed. Further questions to measure acral melanoma knowledge and related issues were included in the study. A biostatistician appropriately managed statistical analysis. RESULTS: Hundred and one final phase medical students' answers were gathered and analysed. Only 7.9% of the participants diagnosed all six melanomas correctly; 61.4% correctly diagnosed ≥50% of the melanomas. While 77.2% of the participants identified all non-acral cutaneous melanoma correctly, only 8.9% identified all acral melanomas. However, of all participants making the correct diagnosis, >90% selected the appropriate management plan (urgent referral). LIMITATIONS: This study examined a small sample of trainee healthcare workers. The results cannot be assumed to apply to all South African healthcare workers. Responses given in a questionnaire may not reflect actual behaviour. The dermatology division in question has made acral melanoma a research priority, thus acral melanoma knowledge in this group may in fact be better than in other institutions. CONCLUSION: The present study demonstrates that groups of imminent doctors have low rates of recognition of melanoma, particularly acral melanoma. This is consistent with high levels of primary misdiagnosis of acral melanoma reported in the literature. Fortunately, these participants managed the melanomas they diagnosed appropriately in >90% of cases. This confirms that the deficit in the participant group is awareness and knowledge. Those aware of the disease immediately acknowledged the need for urgent referral.

Human leukocyte antigen Class II alleles associated with acral lentiginous melanoma in Mexican Mestizo patients: A case-control study.

Background Melanoma is an aggressive cutaneous cancer. Acral lentiginous melanoma is a melanoma subtype arising on palms, soles, and nail-units. The incidence, prevalence and prognosis differ among populations. The link between expression of major histocompatibility complex Class II alleles and melanoma progression is known. However, available studies report variable results regarding the association of melanoma with specific HLA Class II loci. Aims The aim of the study was to determine HLA Class II allele frequencies in acral lentiginous melanoma patients and healthy Mexican Mestizo individuals. Methods Eighteen patients with acral lentiginous melanoma and 99 healthy controls were recruited. HLA Class II typing was performed based on the sequence-specific oligonucleotide method. Results Three alleles were associated with increased susceptibility to develop acral lentiginous melanoma, namely: HLA-DRB1*13:01; pC = 0.02, odds ratio = 6.1, IC95% = 1.4-25.5, HLA-DQA1*01:03; pC = 0.001, odds ratio = 9.3, IC95% = 2.7-31.3 and HLA-DQB1*02:02; pC = 0.01, odds ratio = 3.7, IC95% = 1.4-10.3. Limitations The small sample size was a major limitation, although it included all acral lentiginous melanoma patients seen at the dermatology department of Dr. Manuel Gea González General Hospital during the study period. Conclusion HLA-DRB1*13:01, HLA-DQB1*02:02 and HLA-DQA*01:03 alleles are associated with increased susceptibility to develop acral lentiginous melanoma in Mexican Mestizo patients.

Need to restage Korean melanoma patients following publication of the 8th edition of the American Joint Committee on Cancer staging manual.

BACKGROUND: The tumor, nodes and metastasis (TNM) classification and stage grouping have been updated in the 8th edition of the American Joint Committee on Cancer (AJCC) melanoma staging manual. However, restaging all the previous cases are not recommended. AIMS: The aims of the study were to investigate the necessity of restaging Korean melanoma patients staged by the previous edition of the AJCC manual. METHODS: Differences in the staging criteria of the 7th and 8th editions of the AJCC manual were identified. The staging of 276 primary melanomas from January 2011 to December 2018 was classified by both 7th and 8th editions of the manual and their differences were compared. RESULTS: Staging by 7th and 8th edition of the AJCC manual differed in 64 cases (23.2%). The pathological prognostic staging changed in 35 (12.7%), and 29 (10.5%) had changes in only TNM classification but not the pathological staging. None of the patients needed additional sentinel lymph node biopsy or systemic treatment as a result of restaging. Additional counseling was needed for the patients, because melanoma-specific survival was increased in the 8th edition. LIMITATIONS: This is a retrospective study with relatively small number of patients at a single tertiary center in Korea. CONCLUSION: Assessment of the need for additional sentinel lymph node biopsy or systemic treatment is recommended because of the latest changes in the AJCC melanoma staging manual. Although the restaging of previously staged melanomas is not significantly needed in our patients, still the differences in TNM classification and/or pathological prognostic staging suggest the need to separately recognize the patients previously staged by 7th edition and recently staged by 8th edition. Careful counseling about melanoma-specific survival is needed for Asian patients.

Different progression pattern between acral and nonacral melanoma: A retrospective, comparative, clinicoprognostic study of 492 cases of primary cutaneous melanoma according to tumor site.

BACKGROUND: There are limited data regarding the difference in progression pattern between acral melanoma and nonacral melanoma. AIMS: The objectives of this study were to compare the progression pattern between acral and nonacral melanoma and evaluate its impact on clinical outcomes. METHODS: Clinical and histopathological features, survival outcomes and prognostic factors of 492 patients with acral melanoma or nonacral melanoma were retrospectively evaluated using the Asan Medical Center database. RESULTS: The male-to-female ratio and the mean age was 1:0.92 and 60.2 years for acral melanoma (n = 249), and 1:0.85 and 58.4 years for nonacral melanoma (n = 243), respectively. The demographic difference was not significant. Although prediagnosis duration was longer and the advanced stage was more common in acral melanoma than that in nonacral melanoma, the vertical growth phase was more common in nonacral melanoma than that in acral melanoma, whereas, the horizontal diameter is longer in acral melanoma than that in nonacral melanoma. Dissemination to lymph nodes was more common in acral melanoma than that in nonacral melanoma. Lymph node involvement was associated with deeper Breslow thickness in nonacral melanoma but not in acral melanoma. The degree of correlation of prediagnosis duration with horizontal diameter was remarkable in acral melanoma, but with Breslow thickness in nonacral melanoma. Overall survival was worse in acral melanoma than that in nonacral melanoma. The prognostic value of Breslow thickness was more remarkable in nonacral melanoma than that in acral melanoma. LIMITATIONS: This study is a retrospective, single-center design. CONCLUSION: Acral melanoma has a longer radial growth phase compared with nonacral melanoma. However, acral melanoma is commonly associated with lymph node dissemination which contributed to worse survival in acral melanoma than nonacral melanoma.

Malignant melanoma: Underlying epigenetic mechanisms.

Although malignant melanoma is not the most common type of skin cancer, it is the most aggressive and fatal type as it can spread out and metastasize progressively. Early diagnosis and interventions lead to improved patient survival. The incidence rate of melanoma is dramatically increasing, with a few newer therapeutic options available. Therefore, establishing a reliable genetic or epigenetic-based diagnostic and prognostic tool is really important. In this review, we highlight the underlying epigenetic mechanisms involved in melanoma. Furthermore, the epigenetic-based therapeutic options will be also discussed. One of the key areas of discussion will be microRNA which is a small, single-stranded RNA molecule that serves as a regulatory element and found to regulate nearly a third of human genes. MicroRNAs play a role in a wide range of diseases including cancer. In malignant cells, it regulates cell proliferation, invasion, and metastasis.

A descriptive observational study on clinical and dermoscopic features of benign melanocytic neoplasms.

BACKGROUND: Benign melanocytic neoplasms have nests of melanocytic cells and show characteristic dermoscopic features. Clinical and dermoscopic features have not been studied previously in the Indian population. AIMS: To study the clinical, epidemiological and dermoscopic patterns of benign melanocytic neoplasms. METHODS: This was a descriptive, observational, single centre study. In 107 patients with melanocytic neoplasms, 167 lesions were clinically examined and studied under the dermoscope and histopathological examination was done when indicated. The lesions were broadly divided as acquired and congenital. Five main dermoscopic patterns were seen-globular, homogenous, reticular, parallel and streaks. If there were two of these patterns in a particular lesion, it was termed 'mixed pattern'. The presence of three or more patterns was called 'multicomponent pattern'. Various other features were also observed. RESULTS: The majority of patients belonged to the third decade with a female preponderance. History of increased UV exposure and family history was significant in acquired nevi. The dermoscopic pattern progressed from predominantly reticular in junctional nevi to predominantly globular in compound nevi and lesser pigment in intradermal nevi, with more vascular structures. The congenital melanocytic nevi showed additional features of comedo- like lesions, milia- like cysts, perifollicular pigmentary changes and increased colour variation. Even though colour variation was observed in both acquired and congenital lesions, no signs of dysplasia were seen on histopathology. LIMITATIONS: A larger sample size is required, with follow up of lesions. No parallel studies in brown skinned population were found for exact comparison. CONCLUSION: Benign melanocytic proliferations are often neglected in our country. This study will help in understanding the course, clinical features and dermoscopic patterns of various benign melanocytic neoplasms, and will be a step forward towards research in our population. To the best of our knowledge, this is the first study of its kind in India.