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Cancers Oct 2022Malignant melanoma is a fatal disease that affects all skin sites. Among these, vulvar melanoma (VM) is a rare gynecological condition that accounts for 5% of all vulvar... (Review)
Review
Malignant melanoma is a fatal disease that affects all skin sites. Among these, vulvar melanoma (VM) is a rare gynecological condition that accounts for 5% of all vulvar neoplasms. VM primarily affects older Caucasian women and its relationship to sun exposure is undefined. Diagnosis is defined by biopsy but many clinical, dermatoscopic, and confocal microscopic features can guide doctors. The molecular profile is characterized by the KIT mutation, revealed by all of the technologies that are used (classical sequencing, next-generation sequencing, and immunohistochemical staining). BRAF and NRAS mutations are also common in VM. All of these mutations are possible therapeutic targets. Today, surgery remains the first treatment choice for primary VM. The role of neoadjuvant and adjuvant therapy is scarce and the treatment of relapses is widely debated.
PubMed: 36358637
DOI: 10.3390/cancers14215217 -
Cancers Oct 2022Cutaneous melanoma is a relatively common neoplasm, with fairly well understood pathogenesis, risk factors, prognosis and therapeutic protocols. The incidence of this... (Review)
Review
Cutaneous melanoma is a relatively common neoplasm, with fairly well understood pathogenesis, risk factors, prognosis and therapeutic protocols. The incidence of this disease is increasing every year. The situation is different for rare malignancies such as vulvar melanomas and for the even rarer vaginal melanomas. The risk factors for vulvovaginal tumors are not fully understood. The basis of treatment in both cases is surgical resection; however, other types of treatments such as immunotherapy are available. This paper focuses on comparing the pathogenesis and risk factors associated with these neoplasms as well as the efficacy of two groups of drugs-anti-PD-L1 and anti-CTLA4 inhibitors-against both cutaneous melanoma and melanoma of the lower genital tract (vulva and vagina). In the case of cutaneous melanoma, the situation looks more optimistic than for vulvovaginal melanoma, which has a much worse prognosis and, as it turns out, shows a poorer response to immune therapy.
PubMed: 36291906
DOI: 10.3390/cancers14205123 -
Bladder Cancer (Amsterdam, Netherlands) 2022Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the...
BACKGROUND
Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease.
OBJECTIVE
To describe the clinical, pathological, and molecular characteristics of urethral melanoma.
METHODS
We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT ( = 5) and gene-specific PCR data on , , and/or ( = 8) were compared to genomic data of cutaneous melanomas ( = 143), vulvar/vaginal melanomas ( = 24), and primary non-melanoma urethral tumors ( = 5) from our institutional database.
RESULTS
Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment.Primary urethral melanomas showed a higher frequency of mutations compared to cutaneous (80.0% vs. 18.2%, = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, = 0.04). mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas ( = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, = 0.03).
CONCLUSIONS
Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.
PubMed: 36277327
DOI: 10.3233/BLC-211633 -
Annals of Medicine and Surgery (2012) Sep 2022Vulvar melanoma is a rare malignant tumor of the female genital sphere, representing postmenopausal women's prerogative, the diagnosis is based on immunohistochemicals...
Vulvar melanoma is a rare malignant tumor of the female genital sphere, representing postmenopausal women's prerogative, the diagnosis is based on immunohistochemicals analysis, and treatment requires a multidisciplinary approach. On account of its high metastatic potential as well as the late diagnosis given that it has non-specific clinical signs, the prognosis remains poor. In this study, we report the case of a woman of childbearing who presented a vaginal mass associated to chronic pelvic pain. Paraclinical investigations revealed a right vulvar tumoral process with pathological-looking inguinal adenomegalies on the right side with a necrotic center measuring 16.7 mm on the short axis, micronodules and secondary pulmonary nodules. The patient has been put under palliative chemotherapy, then passed out 8 months later. By this work, we attempt to review the diagnostic circumstances to better understand this delay, also to encourage self-examination and self-screening of abnormal lesions, as well as leveling the awareness of health professionals on this rare disease.
PubMed: 36147087
DOI: 10.1016/j.amsu.2022.104473 -
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 -
Medicine Sep 2022Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of... (Review)
Review
RATIONALE
Vulvar melanoma is a rare and aggressive tumor with a high risk of local recurrence and distant metastasis. The prognosis is poor with a 5-year overall survival rate of only 46.6%. Management of vulvar melanoma remains a clinical challenge. Recent evidences have shown that immune checkpoint inhibitors are effective in the treatment of vulvar melanoma.
PATIENT CONCERNS AND DIAGNOSES
A 63-year-old woman with vulvar malignant melanoma suffered inguinal lymph node metastasis after vulvectomy and chemotherapy. She underwent inguinal lymph node dissection and inguinal radiotherapy. The tumor progressed again and she received immunotherapy.
INTERVENTIONS
The tumor progressed again, and she was admitted to our hospital and received toripalimab combined with apatinib and abraxane.
OUTCOMES
After 6 cycles of immunotherapy, the efficacy achieved partial remission. And with toripalimab as maintenance therapy, the patient achieved durable antitumor efficacy and good safety.
LESSONS
In this rare case, the patient with metastatic vulvar malignant melanoma had durable antitumor efficacy and good safety when receiving toripalimab.
Topics: Antibodies, Monoclonal, Humanized; Female; Humans; Melanoma; Middle Aged; Neoplasms, Second Primary; Skin Neoplasms; Vulvar Neoplasms
PubMed: 36086787
DOI: 10.1097/MD.0000000000030239 -
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 -
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 -
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