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Cancer Apr 2017Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic...
Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma.
BACKGROUND
Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers.
METHODS
In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel.
RESULTS
In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B-Raf proto-oncogene serine/threonine kinase (BRAF) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (P = .008). In BRAF-mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The KIT mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (P < .001) and 8.8% in mucosal (P = .05) melanoma subtypes. NRAS mutations were rare in VVMs compared with cutaneous (25.9%; P = .009) and acral (40.6%; P = .002) melanoma subtypes. PD-L1 (56%) and PD-1 (75%) were frequently expressed in VVM, whereas PI3KCA pathway mutations and estrogen receptor/progesterone receptor expression were rare. Compared with VVMs that had KIT mutations, wild-type KIT VVMs were more likely to express molecular markers suggestive of platinum resistance (ERCC1), alkylating sensitivity (MGMT), and anthracycline sensitivity (TOP2A).
CONCLUSIONS
The unique molecular features of VVM render this disease a distinct subtype of melanoma. Gene-based molecular therapy and immunotherapies may be promising and should be evaluated in clinical trials. Cancer 2017;123:1333-1344. © 2016 American Cancer Society.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Female; Gene Expression Profiling; High-Throughput Nucleotide Sequencing; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Melanoma; Middle Aged; Mucous Membrane; Mutation; Neoplasm Staging; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins c-kit; Vaginal Neoplasms; Vulvar Neoplasms; Young Adult
PubMed: 28026870
DOI: 10.1002/cncr.30473 -
International Journal of Hyperthermia :... 2018Thermography-controlled, water-filtered infrared-A (wIRA) is a novel, effective and approved heating technique listed in the ESHO quality assurance guidelines for... (Review)
Review
Thermography-controlled, water-filtered infrared-A (wIRA) is a novel, effective and approved heating technique listed in the ESHO quality assurance guidelines for superficial hyperthermia clinical trials (2017). In order to assess the special features and the potential of wIRA-hyperthermia (wIRA-HT), detailed and updated information about its physical and photobiological background is presented. wIRA allows for (a) application of high irradiances without skin pain and acute grade 2-4 skin toxicities, (b) prolonged, therapeutically relevant exposure times using high irradiances (150-200 mW/cm) and (c) faster and deeper heat extension within tissues. The deeper radiative penetration depth is mainly caused by forward Mie-scattering. At skin surface temperatures of 42-43 °C, the effective heating depth is 15 mm (T ≥ 40 °C) and 20 mm (T ≥ 39.5 °C). Advantages of wIRA include its contact-free energy input, easy power steering by a feed-back loop, extendable treatment fields, real-time and noninvasive surface temperature monitoring with observation of dynamic changes during HT, and - if necessary - rapid protection of temperature-sensitive structures. wIRA makes the compliant heating of ulcerated and/or bleeding tumors possible, allows for HT of irregularly shaped and diffusely spreading tumors, is independent of individual body contours, allows for very short 'transits' between HT and RT (1-4 min) or continuous heating between both therapeutic interventions. New treatment options for wIRA-HT may include malignant melanoma, vulvar carcinoma, skin metastases of different primary tumors, cutaneous T-and B-cell lymphoma, large-area hemangiomatosis, inoperable squamous cell, basal cell and eccrine carcinoma of the skin with depth extensions ≤20 mm.
Topics: Humans; Hyperthermia, Induced; Infrared Rays; Neoplasms; Water
PubMed: 29745269
DOI: 10.1080/02656736.2018.1469169 -
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 -
International Journal of Molecular... Apr 2014Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The... (Review)
Review
Vulvar melanoma is the second most common vulvar cancer. Patients with vulvar melanoma usually present with the disease at a late stage and have a poor prognosis. The prognostic predictors reported in the literature are not unequivocal and the role of lichen sclerosus and c-KIT mutations in the aetiology of vulvar melanoma is unclear. Breslow staging currently seems to be the most adequate predictor of prognosis. We thus performed a clinicopathological and literature review to identify suitable predictors of prognosis and survival and investigated the expression of c-KIT (by immunohistochemistry) in patients with vulvar melanoma (n=33) from the Gynaecological Cancer Centres of the Royal Hospital for Women (Sydney, Australia) and John Hunter Hospital (Newcastle, Australia). Our series of 33 patients fitted the expected clinical profile of older women: delayed presentation, high stage, limited response to treatment and poor prognosis. We identified 3 patients (9.1%) with lichen sclerosus associated with melanoma in situ, although no lichen sclerosus was found in the areas of invasive melanoma. No patient had vulvar nevi. We identified a) Breslow's depth, b) an absence of any of the pathological risk factors, such as satellitosis, in-transit metastasis, lymphovascular space invasion (LVSI) and dermal mitosis, c) removal of inguino-femoral lymph nodes, d) lateral margin of >1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow's depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Cell Proliferation; Cohort Studies; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Melanocytes; Melanoma; Middle Aged; Molecular Targeted Therapy; Multivariate Analysis; Prognosis; Proto-Oncogene Proteins c-kit; Risk Factors; Treatment Outcome; Vulvar Neoplasms
PubMed: 24535703
DOI: 10.3892/ijmm.2014.1659 -
BMJ Case Reports Jan 2019We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia...
We report a case of a 51-year-old woman with neurofibromatosis who presented in 2012 with postmenopausal bleeding. Excision biopsy of a pigmented lesion of the labia minora was consistent with an ulcerated vulvar BRAF wild type malignant melanoma (MM). Initial excision was followed by radical vulvectomy and adjuvant interferon. Local recurrence in January 2017 was further resected. Positron emission tomography (PET)-CT in May 2017 identified an FDG avid omental deposit; consistent histologically with MM when resected. Postoperative PET-CT in August 2017 demonstrated local recurrence. In the setting of resected stage IV disease and a third local recurrence, the decision was made to instigate immunotherapy. Vulvar melanoma is rare accounting for 0.2% of all melanoma. Presentation is typically a decade later than cutaneous melanoma with a tendency to late metastases and poorer prognosis. Given their rarity the treatment paradigm is less clearly defined and largely extrapolated from that of cutaneous melanomas.
Topics: Female; Gastrointestinal Stromal Tumors; Humans; Immunotherapy; Melanoma; Middle Aged; Neoplasm Recurrence, Local; Neurofibromatoses; Positron Emission Tomography Computed Tomography; Treatment Outcome; Vulvar Neoplasms
PubMed: 30665926
DOI: 10.1136/bcr-2018-224744 -
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