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American Journal of Obstetrics and... Apr 2023
Topics: Female; Humans; Immune Checkpoint Inhibitors; Dermatitis; Skin Diseases; Vulva; Vulvar Diseases; Vulvar Neoplasms
PubMed: 36084703
DOI: 10.1016/j.ajog.2022.08.052 -
Journal of Lower Genital Tract Disease Jan 2023Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they...
OBJECTIVES
Neoplasms arising from the vulva are uncommon and comprise various subtypes. Given the recent advancements in the molecular aspects of oncologic pathology and how they have impacted cancer treatment, an understanding of recent innovations in the molecular features of vulvar lesions is important.
MATERIALS AND METHODS
Systematic literature search was performed on PubMed, Google Scholar, and Scopus databases for molecular and genetic characteristics of vulvar neoplasms. Peer-reviewed literature published in English is included.
RESULTS
Squamous cell carcinoma (SCC) and its precursors are the predominant neoplasm at this site. Human papillomavirus (HPV) plays a crucial role in the pathogenesis of some of these lesions. Human papillomavirus-associated SCC follows the carcinogenic pathway driven by viral proteins E6 and E7 while HPV-independent SCC shows a high incidence of mutation of TP53 and CDKN2A genes. Mutations in the genes involving the PI3K-Akt pathway play an important role in the pathogenesis of both types of SCC. Among other vulvar malignancies, melanoma, and vulvar Paget disease (VPD) pose a significant clinical challenge and have unique molecular characteristics. Compared with dermal cutaneous melanoma, vulvar melanoma shows a higher rate of mutation of cKIT and NRAS genes and a lower rate of mutations in BRAF . Less than 20% of VPD shows amplification of ERBB2 and seldom shows mutation in genes involving the PI3K-Akt pathway.
CONCLUSIONS
Several potentially targetable molecular pathways have emerged as they have been shown to be involved in the tumorigenesis of SCC, melanoma, and VPD.
Topics: Female; Humans; Carcinoma, Squamous Cell; Human Papillomavirus Viruses; Melanoma; Papillomavirus Infections; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36083687
DOI: 10.1097/LGT.0000000000000701 -
International Journal of Cancer Jan 2023South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have...
South Africa's HIV epidemic has evolved over time in terms of numbers of people living with HIV, access to antiretroviral treatment (ART) and age. These changes have profoundly influenced local cancer patterns. The Johannesburg Cancer Study has, over a period of 22 years (1995-2016), recruited over 20 000 incident black cancer patients who consented to provide answers to a questionnaire and blood samples (serum, DNA). This has presented a unique opportunity to examine the evolving association of HIV with cancer in Africa. We used logistic regression models to explore case-control associations between specific cancers and HIV, using participants with non-infection related cancers as controls. Using data of 20 835 cancer patients with confirmed HIV status, we found the following cancers to be associated with HIV: Kaposi's sarcoma (OR ; 95%CI): (99.1;72.6-135.1), non-Hodgkin lymphoma (11.3;9.3-13.6), cervical cancer (2.7;2.4-3.0), Hodgkin lymphoma (3.1;2.4-4.2), cancer of the eye/conjunctiva (18.7;10.1-34.7), anogenital cancers (anus [2.1;1.4-3.2], penis [5.4;2.7-10.5], vulva [4.8;3.5-6.4], vagina [5.5;3.0-10.2]), oropharyngeal cancer (1.6;1.3-1.9), squamous cell carcinoma of the skin (3.5;2.4-4.9), melanoma (2.0;1.2-3.5) and cancer of the larynx (1.7;1.3-2.4). Kaposi's sarcoma odds ratios increased from the pre-ART (1995-2004) to the early ART (2005-2009) period but declined in the late ART (2010-2016) period. Odds ratios for cancers of the eye/conjunctiva, cervix, penis and vulva continued to increase in recent ART periods. Our study confirms the spectrum of HIV-associated cancers found in other African settings. The odds ratios of conjunctival and HPV-related cancers continue to rise in the ART era as the HIV positive population ages.
Topics: Humans; Female; Male; HIV Infections; South Africa; Sarcoma, Kaposi; Black People; Anti-Retroviral Agents; Uterine Cervical Neoplasms
PubMed: 36054877
DOI: 10.1002/ijc.34236 -
Modern Pathology : An Official Journal... Dec 2022Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions,...
Though uncommon in melanoma, gene fusions may have therapeutic implications. Next generation sequencing-based clinical assays, designed to detect relevant gene fusions, mutations, and copy number changes, were performed on 750 melanomas (375 primary and 375 metastases) at our institution from 2014-2021. These included 599 (80%) cutaneous, 38 (5%) acral, 11 (1.5%) anorectal, 23 (3%) sinonasal, 27 (3.6%) eye (uveal/ conjunctiva), 11 (1.5%) genital (vulva/penile), and 41 (5.5%) melanomas of unknown primary. Sixteen fusions (2%) were detected in samples from 16 patients: 12/599 (2%) cutaneous, 2/38 (5%) acral, 1/9 (11%) vulva, 1/23(4.3%) sinonasal; and 12/16 (75%) fusions were potentially targetable. We identified two novel rearrangements: NAGS::MAST2 and NOTCH1::GNB1; and two fusions that have been reported in other malignancies but not in melanoma: CANT1::ETV4 (prostate cancer) and CCDC6::RET (thyroid cancer). Additional fusions, previously reported in melanoma, included: EML4::ALK, MLPH::ALK, AGAP3::BRAF, AGK::BRAF, CDH3::BRAF, CCT8::BRAF, DIP2B::BRAF, EFNB1::RAF1, LRCH3::RAF1, MAP4::RAF1, RUFY1::RAF1, and ADCY2::TERT. Fusion positive melanomas harbored recurrent alterations in TERT and CDKN2A, among others. Gene fusions were exceedingly rare (0.2%) in BRAF/RAS/NF1-mutant tumors and were detected in 5.6% of triple wild-type melanomas. Interestingly, gene rearrangements were significantly enriched within the subset of triple wild-type melanomas that harbor TERT promoter mutations (18% versus 2%, p < 0.0001). Thirteen (81%) patients were treated with immunotherapy for metastatic disease or in the adjuvant setting. Six of 12 (50%) patients with potentially actionable fusions progressed on immunotherapy, and 3/6 (50%) were treated with targeted agents (ALK and MEK inhibitors), 2 off-label and 1 as part of a clinical trial. One patient with an AGAP3::BRAF fusion positive melanoma experienced a 30-month long response to trametinib. We show that, detecting fusions, especially in triple wild-type melanomas with TERT promoter mutations, may have a clinically significant impact in patients with advanced disease who have failed front-line immunotherapy.
Topics: Male; Female; Humans; Proto-Oncogene Proteins B-raf; Melanoma; Gene Fusion; Mutation; Receptor Protein-Tyrosine Kinases; Nerve Tissue Proteins
PubMed: 35871080
DOI: 10.1038/s41379-022-01138-z -
Journal of Lower Genital Tract Disease Jul 2022The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of...
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) Consensus Statements on Pre-invasive Vulvar Lesions.
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
Topics: Carcinoma in Situ; Colposcopy; Female; Humans; Imiquimod; Melanoma; Paget Disease, Extramammary; Pregnancy; Skin Neoplasms; Squamous Intraepithelial Lesions; Vulvar Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35763611
DOI: 10.1097/LGT.0000000000000683 -
Minerva Obstetrics and Gynecology Dec 2022This paper summarizes the position of the Italian Society of Vulvology on the clinical approach to vulval disease. A thorough history (general medical, gynaecological,...
This paper summarizes the position of the Italian Society of Vulvology on the clinical approach to vulval disease. A thorough history (general medical, gynaecological, and vulval history) is essential for a successful and fruitful vulvological examination. Characteristics of pruritus (itch) and pain, that are the two main vulval symptoms, should be collected and reported with precision, according to duration, temporal course, location, provocation, and intensity. Physical examination must consider both the general condition of the patient and the specific vulval region, that must be examined following a standardized methodology. The physical examination of the vulva is carried out with naked eye and adequate natural or halogen lighting. The subsequent use of instrumental magnification can be considered on particular parts of skin/mucosa, already highlighted with the first inspection. Also, palpation is essential, allowing to appreciate physical features of vulval lesions: consistency, surface, soreness, adherence to underlying plans. Finally, the five-step approach of the International Society for the Study of Vulvo-vaginal Disease about Terminology and Classification of Vulvar Dermatological Disorders (2012) is summarized. A vulval biopsy may be useful in the following situations: when clinical diagnosis is uncertain, lesion not responding to treatment; histologic confirmation for a clinical diagnosis and exclusion or confirmation of a suspected neoplastic intraepithelial or invasive pathology.
Topics: Female; Humans; Vulvar Diseases; Vulva; Mucous Membrane; Biopsy
PubMed: 35758091
DOI: 10.23736/S2724-606X.22.04944-2 -
International Journal of Gynecological... Jul 2022The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of...
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD) and the European Federation for Colposcopy (EFC) consensus statements on pre-invasive vulvar lesions.
The European Society of Gynaecological Oncology (ESGO), the International Society for the Study of Vulvovaginal Disease (ISSVD), the European College for the Study of Vulval Disease (ECSVD), and the European Federation for Colposcopy (EFC) developed consensus statements on pre-invasive vulvar lesions in order to improve the quality of care for patients with vulvar squamous intraepithelial neoplasia, vulvar Paget disease in situ, and melanoma in situ. For differentiated vulvar intraepithelial neoplasia (dVIN), an excisional procedure must always be adopted. For vulvar high-grade squamous intraepithelial lesion (VHSIL), both excisional procedures and ablative ones can be used. The latter can be considered for anatomy and function preservation and must be preceded by several representative biopsies to exclude malignancy. Medical treatment (imiquimod or cidofovir) can be considered for VHSIL. Recent studies favor an approach of using imiquimod in vulvar Paget's disease. Surgery must take into consideration that the extension of the disease is usually wider than what is evident in the skin. A 2 cm margin is usually considered necessary. A wide local excision with 1 cm free surgical margins is recommended for melanoma in situ. Following treatment of pre-invasive vulvar lesions, women should be seen on a regular basis for careful clinical assessment, including biopsy of any suspicious area. Follow-up should be modulated according to the risk of recurrence (type of lesion, patient age and immunological conditions, other associated lower genital tract lesions).
Topics: Carcinoma in Situ; Cidofovir; Colposcopy; Female; Genital Neoplasms, Female; Humans; Imiquimod; Melanoma; Paget Disease, Extramammary; Pregnancy; Skin Neoplasms; Vulvar Neoplasms; Melanoma, Cutaneous Malignant
PubMed: 35728950
DOI: 10.1136/ijgc-2021-003262 -
Clinical Oncology (Royal College of... Aug 2022
Topics: Female; Humans; Melanoma; Rare Diseases; Skin Neoplasms; Vagina; Vulvar Neoplasms
PubMed: 35660065
DOI: 10.1016/j.clon.2022.05.013 -
Dermatology Practical & Conceptual May 2022
PubMed: 35646426
DOI: 10.5826/dpc.1202a50 -
Current Oncology (Toronto, Ont.) Apr 2022In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer... (Review)
Review
In order to identify the molecular pathways governing melanoma and track its progression, the next-generation sequencing (NGS) approach and targeted sequencing of cancer genes were employed. The primary tumor, as well as metastatic tissue, of an 84-year-old patient diagnosed with vulvar melanoma (VM), were investigated. The primary tumor specimen showed multiple somatic mutations in gene, suggesting its major contribution to melanoma origin. The metastatic sample showed additional alterations, including other melanoma-related genes. Clinical relevancy is postulated to juxtamembrane region instability of gene (c-KIT). We did not identify or alterations, which are typical for the most common melanoma pathway-MAPK cascade. However, it should be noted that this is the first report evidencing in melanoma, although its role in triggering VM needs to be further elucidated.
Topics: Aged, 80 and over; Humans; MAP Kinase Signaling System; Melanoma; Mutation; Proto-Oncogene Proteins B-raf; Skin Neoplasms
PubMed: 35621644
DOI: 10.3390/curroncol29050254