-
Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe.Cancers Feb 2022Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but...
BACKGROUND
Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma's mutational profile can help to develop target therapies in advanced disease or adjuvant settings.
METHODS
We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994-2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel.
RESULTS
Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found.
CONCLUSION
Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials.
PubMed: 35159047
DOI: 10.3390/cancers14030780 -
PloS One 2023Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that...
Melanomas from gynecologic sites (MOGS) are rare and have poor survival. MicroRNAs (miRs) regulate gene expression and are dysregulated in cancer. We hypothesized that MOGS would display unique miR and mRNA expression profiles. The miR and mRNA expression profile in RNA from formalin fixed, paraffin embedded vaginal melanomas (relative to vaginal mucosa) and vulvar melanomas (relative to cutaneous melanoma) were measured with the Nanostring Human miRNA assay and Tumor Signaling mRNA assay. Differential patterns of expression were identified for 21 miRs in vaginal and 47 miRs in vulvar melanoma (fold change >2, p<0.01). In vaginal melanoma, miR-145-5p (tumor suppressor targeting TLR4, NRAS) was downregulated and miR-106a-5p, miR-17-5p, miR-20b-5p (members of miR-17-92 cluster) were upregulated. In vulvar melanoma, known tumor suppressors miR-200b-3p and miR-200a-3p were downregulated, and miR-20a-5p and miR-19b-3p, from the miR-17-92 cluster, were upregulated. Pathway analysis showed an enrichment of "proteoglycans in cancer". Among differentially expressed mRNAs, topoisomerase IIα (TOP2A) was upregulated in both MOGS. Gene targets of dysregulated miRs were identified using publicly available databases and Pearson correlations. In vaginal melanoma, suppressor of cytokine signaling 3 (SOCS3) was downregulated, was a validated target of miR-19b-3p and miR-20a-5p and trended toward a significant inverse Pearson correlation with miR-19b-3p (p = 0.093). In vulvar melanoma, cyclin dependent kinase inhibitor 1A (CDKN1A) was downregulated, was the validated target of 22 upregulated miRs, and had a significant inverse Pearson correlation with miR-503-5p, miR-130a-3p, and miR-20a-5p (0.005 < p < 0.026). These findings support microRNAs as mediators of gene expression in MOGS.
Topics: Humans; Female; Melanoma; Skin Neoplasms; MicroRNAs; Genes, cdc; Vulvar Neoplasms; Suppressor of Cytokine Signaling Proteins
PubMed: 37384650
DOI: 10.1371/journal.pone.0285804 -
JAMA Dermatology Nov 2020Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of...
IMPORTANCE
Vulvar melanosis is a common pigmentary change that accounts for most pigmented vulvar lesions. It presents as single or multiple asymptomatic macules or patches of varying size and color that may be asymmetric with poorly defined borders. The differential diagnosis of melanocytic lesions includes melanoma, which creates anxiety for patients and the physicians who diagnose the condition and treat the patients.
OBJECTIVE
To evaluate the clinical and dermoscopic features of vulvar melanosis and their changes over time.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study, patients with vulvar melanosis were recruited and followed up in the Department of Dermatology, University of Florence, Florence, Italy, between January 1, 1998, and June 30, 2019. Data on patient characteristics and on both the clinical and dermoscopic features of the vulvar lesions were collected. Each lesion was photographed clinically and dermoscopically at initial evaluation and at annual follow-up visits.
MAIN OUTCOMES AND MEASURES
The clinical, dermoscopic, and histopathologic features of vulvar melanosis and their changes over time.
RESULTS
This cohort study included 129 women (mean age at diagnosis, 46 years [range, 19-83 years]) with vulvar melanosis. A total of 87 patients (67%) with vulvar melanotic lesions were premenopausal, and 84 patients (65%) had received some type of hormone therapy. The most frequent location for vulvar melanosis was the labia minora (55 [43%]), followed by the labia majora (33 [26%]). In 39 of 129 cases (30%), the lesions increased in size and changed color after initial evaluation but ultimately stabilized. No malignant evolution was documented in any patient during a median follow-up of 13 years (range, 5-20 years).
CONCLUSIONS AND RELEVANCE
This study suggests that vulvar melanosis was a benign entity, and changes in lesions over time did not signify malignant transformation. An association between hormonal status and vulvar melanosis may be hypothesized.
Topics: Adult; Aged; Aged, 80 and over; Biopsy; Color; Dermoscopy; Diagnosis, Differential; Disease Progression; Female; Follow-Up Studies; Hormone Replacement Therapy; Humans; Italy; Melanoma; Melanosis; Middle Aged; Mucous Membrane; Photography; Retrospective Studies; Vulva; Vulvar Diseases; Vulvar Neoplasms; Young Adult
PubMed: 32785609
DOI: 10.1001/jamadermatol.2020.2528 -
Gynecologic Oncology Apr 2021To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM).
OBJECTIVE
To identify clinicopathological characteristics, treatment patterns, clinical outcomes and prognostic factors in patients with vulvar melanoma (VM).
MATERIALS & METHODS
This retrospective multicentre cohort study included 198 women with VM treated in eight cancer centres in the Netherlands and UK between 1990 and 2017. Clinicopathological features, treatment, recurrence, and survival data were collected. Overall and recurrence-free survival was estimated with the Kaplan-Meier method. Prognostic parameters were identified with multivariable Cox regression analysis.
RESULTS
The majority of patients (75.8%) had localized disease at diagnosis. VM was significantly associated with high-risk clinicopathological features, including age, tumour thickness, ulceration, positive resection margins and involved lymph nodes. Overall survival was 48% (95% CI 40-56%) and 31% (95% CI 23-39%) after 2 and 5 years respectively and did not improve in patients diagnosed after 2010 compared to patients diagnosed between 1990 and 2009. Recurrence occurred in 66.7% of patients, of which two-third was non-local. In multivariable analysis, age and tumour size were independent prognostic factors for worse survival. Prognostic factors for recurrence were tumour size and tumour type. Only the minority of patients were treated with immuno- or targeted therapy.
CONCLUSION
Our results show that even clinically early-stage VM is an aggressive disease associated with poor clinical outcome due to distant metastases. Further investigation into the genomic landscape and the immune microenvironment in VM may pave the way to novel therapies to improve clinical outcomes in these aggressive tumours. Clinical trials with immunotherapy or targeted therapy in patients with high-risk, advanced or metastatic disease are highly needed.
Topics: Aged; Cohort Studies; Disease-Free Survival; Female; Humans; Immune Checkpoint Inhibitors; Melanoma; Middle Aged; Molecular Targeted Therapy; Neoplasm Staging; Netherlands; Prognosis; Retrospective Studies; Survival Rate; United Kingdom; Vulvar Neoplasms
PubMed: 33514483
DOI: 10.1016/j.ygyno.2021.01.018 -
Gynecologic Oncology Reports Jun 2023Primary vulvar melanoma is a rare but highly aggressive malignant neoplasm accounting for 1-2 % of all malignant melanoma and 5-10 % of all vulvar cancers in females....
Primary vulvar melanoma is a rare but highly aggressive malignant neoplasm accounting for 1-2 % of all malignant melanoma and 5-10 % of all vulvar cancers in females. Here we report a case of 32 years old female diagnosed with primary vulvar melanoma during the evaluation of a two cm growth in the inner labia minora on the right side. She underwent wide local excision with excision of the distal one cm of the urethra and bilateral groin node dissection. The final histopathology was vulvar malignant melanoma with 1 out of 15 groin nodes involved but all resected margins were free of tumor. The final surgical stage was T4bN1aM0 (8th AJCC TNM) and IIIC (FIGO). She received adjuvant radiotherapy followed by 17 cycles of Pembrolizumab. To date, she is both clinically and radiologically disease free with a progression-free survival of 9 months.
PubMed: 37293352
DOI: 10.1016/j.gore.2023.101206 -
JID Innovations : Skin Science From... Sep 2022Cases of vulvar melanocytic lesions in juveniles are rarely reported. We analyze the evidence regarding vulvar melanocytic lesions in juveniles with or without vulvar...
Cases of vulvar melanocytic lesions in juveniles are rarely reported. We analyze the evidence regarding vulvar melanocytic lesions in juveniles with or without vulvar lichen sclerosus to help decision making by clinicians and pathologists. A scoping review on vulvar melanocytic lesions with or without vulvar lichen sclerosus, including malignant vulvar melanomas, in females up to age 18 years was performed. In addition, the histopathology records of the cohort of all such lesions in The Netherlands from 1991 through 2020 were investigated, and a structured analysis of tissue samples of the subset of cases with lichen sclerosus was performed. The literature study performed confirms that vulvar melanomas in juveniles are extremely rare and that published case reports are often disputed. In The Netherlands, there are no cases of malignant vulvar melanomas up to age 18 years recorded from 1991 through 2020. Atypical histopathological features are often found in biopsies of vulvar nevi in juveniles, especially with concomitant lichen sclerosus, confirming earlier case studies in the literature. We conclude that even with atypical findings, vulvar melanocytic lesions in juveniles have a benign course. To avoid unnecessary and possibly mutilating procedures, we advise referral to an expert center and adaption of existing guidelines for vulvar melanocytic lesions in juveniles.
PubMed: 36105669
DOI: 10.1016/j.xjidi.2022.100140 -
Cells May 2020Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well...
INTRODUCTION
Mucosal melanoma is rare and associated with poorer prognosis in comparison to conventional melanoma subtypes. Little is known about the prognostic significance as well as possible associations between PARP1 and immunologic response in mucosal melanoma.
METHODS
PARP1, PD-L1 and IDO1 immunostains were performed on 192 mucosal melanomas including 86 vulvar, 89 sinonasal, and 17 anorectal melanomas.
RESULTS
By Kaplan-Meier analyses, high PARP1 expression correlated with worse overall and melanoma-specific survival (log-rank values = 0.026 and 0.047, respectively). Tumors with combined PARP1 and IDO1 high expression correlated with worse overall and melanoma-specific survival ( = 0.015, 0.0034 respectively). By multivariate analyses, high PARP1 expression remained a predictor of worse survival independent of stage. By Fisher's exact test, high PARP1 expression correlated with highly mitogenic tumors ( = 0.02). High tumoral PD-L1 and IDO1 expression were associated with ulcerated primary tumors ( = 0.019, 0.0019, respectively). By linear regression analyses, correlations between PARP1 expression versus IDO1 expression ( = 0.0001) and mitotic index ( = 0.0052) were observed.
CONCLUSION
Increased expression of PARP1 is an independent negative prognostic marker in mucosal melanomas. The association between PARP1 and IDO1 and their combined adverse prognostic role raise the potential of combined therapy in mucosal melanoma.
Topics: Adult; Aged; Aged, 80 and over; B7-H1 Antigen; Gene Expression Regulation, Neoplastic; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Kaplan-Meier Estimate; Linear Models; Melanoma; Middle Aged; Mucous Membrane; Multivariate Analysis; Poly (ADP-Ribose) Polymerase-1; Proportional Hazards Models; Skin Neoplasms; Survival Analysis; Ulcer; Up-Regulation; Young Adult
PubMed: 32380691
DOI: 10.3390/cells9051135 -
Cancers May 2023Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D...
Development and Validation of Blood-Based Predictive Biomarkers for Response to PD-1/PD-L1 Checkpoint Inhibitors: Evidence of a Universal Systemic Core of 3D Immunogenetic Profiling across Multiple Oncological Indications.
BACKGROUND
Unprecedented advantages in cancer treatment with immune checkpoint inhibitors (ICIs) remain limited to only a subset of patients. Systemic analyses of the regulatory 3D genome architecture linked to individual epigenetic and immunogenetic controls associated with tumour immune evasion mechanisms and immune checkpoint pathways reveal a highly prevalent molecular profile predictive of response to PD-1/PD-L1 ICIs. A clinical blood test based on a set of eight (8) 3D genomic biomarkers has been developed and validated on the basis of an observational trial to predict response to ICI therapy.
METHODS
The predictive eight biomarker set is derived from prospective observational clinical trials, representing 280 treatments with Pembrolizumab, Atezolizumab, Durvalumab, Nivolumab, and Avelumab in a broad range of indications: melanoma, lung, hepatocellular, renal, breast, bladder, colon, head and neck, bone, brain, lymphoma, prostate, vulvar, and cervical cancers.
RESULTS
The 3D genomic eight biomarker panel for response to immune checkpoint therapy achieved a high accuracy of 85%, sensitivity of 93%, and specificity of 82%.
CONCLUSIONS
This study demonstrates that a 3D genomic approach can be used to develop a predictive clinical assay for response to PD-1/PD-L1 checkpoint inhibition in cancer patients.
PubMed: 37345033
DOI: 10.3390/cancers15102696 -
American Journal of Cancer Research 2020The female lower genital tract melanomas mainly include vulvar, vaginal and cervical melanoma. There is little clinical data on the melanomas thus making them highly... (Review)
Review
The female lower genital tract melanomas mainly include vulvar, vaginal and cervical melanoma. There is little clinical data on the melanomas thus making them highly lethal with their prognosis being worse than for cutaneous melanoma and other gynecological malignancies. Surgery is still the primary treatment for gynecological melanomas with wide local resection (WLE) of tumors with adequate margins being preferred for early-stage vulvar melanoma while complete resection of the primary tumor is the standard treatment for early-stage cervical and vaginal melanoma. Sentinel lymph node biopsy seems to avoid unnecessary complete regional lymphadenectomy. However, it should be chosen cautiously. Recently discovered molecular changes have provided new hopes for effective systemic treatment of female genital tract melanomas. In this review, we summarize the pathogenesis and clinicopathological characteristics of these rare melanomas with particular emphasis on new therapies and clinical management methods that may affect prognosis. The review aims to provide a viable direction for clinicians to diagnose and treat female lower genital tract melanomas.
PubMed: 33414983
DOI: No ID Found -
Journal of the American College of... Jan 2023Inguinal lymph node dissection (ILND) is used for diagnosis and treatment in penile cancer (PC), vulvar cancer (VC), and melanomas draining to the inguinal lymph nodes....
BACKGROUND
Inguinal lymph node dissection (ILND) is used for diagnosis and treatment in penile cancer (PC), vulvar cancer (VC), and melanomas draining to the inguinal lymph nodes. However, ILND is often characterized by its morbidity and high wound complication rate. Consequently, we aimed to characterize wound complication rates after ILND.
STUDY DESIGN
The NSQIP database was queried for ILND performed from 2005 to 2018 for melanoma, PC, or VC. Thirty-day wound complications included wound disruption and superficial, deep, and organ-space surgical site infection. Multivariable logistic regression was performed with covariates, including cancer type, age, American Society of Anesthesiologists score ≥3, BMI ≥30, smoking history, diabetes, operative time, and concomitant pelvic lymph node dissection.
RESULTS
A total of 1,099 patients had an ILND with 92, 115, and 892 ILNDs performed for PC, VC, and melanoma, respectively. Wound complications occurred in 161 (14.6%) patients, including 12 (13.0%), 17(14.8%), and 132 (14.8%) patients with PC, VC, and melanoma, respectively. Median length of stay was 1 day (interquartile range 0 to 3 days), and median operative time was 152 minutes (interquartile 83 to 192 minutes). Readmission rate was 12.7%. Wound complications were associated with longer operative time per 10 minutes (odds ratio 1.038, 95% CI 1.019 to 1.056, p < 0.001), BMI ≥30 (odds ratio 1.976, 95% CI 1.386 to 2.818, p < 0.001), and concomitant pelvic lymph node dissection (odds ratio 1.561, 95% CI 1.056 to 2.306, p = 0.025).
CONCLUSIONS
Predictors of wound complications after ILND include BMI ≥30, longer operative time, and concomitant pelvic lymph node dissection. There have been efforts to decrease ILND complication rates, including minimally invasive techniques and modified templates, which are not captured by NSQIP, and such approaches may be considered especially for those with increased complication risks.
Topics: Male; Humans; Inguinal Canal; Lymph Node Excision; Penile Neoplasms; Melanoma; Lymph Nodes
PubMed: 36519902
DOI: 10.1097/XCS.0000000000000438