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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 -
BMC Cancer Jun 2021Malignant melanoma of the female genital tract is relatively uncommon and accounts for 3-7% of all melanoma localizations. This study aimed to identify driver genes in...
BACKGROUND
Malignant melanoma of the female genital tract is relatively uncommon and accounts for 3-7% of all melanoma localizations. This study aimed to identify driver genes in melanoma of the female genital tract with the purpose of enhancing understanding of disease pathogenesis and identifying potential new therapeutic targets to develop effective therapies.
METHODS
KIT (CD117) and BRAF expression were detected immunohistochemically. Polymerase Chain Reaction (PCR) and Sanger sequencing techniques were performed to identify the mutational status of BRAF, NRAS, KRAS, NF1, KIT, PDGFRA and SF3B1 on 19 melanomas of the female genital tract, paired with 25 cutaneous melanomas, 18 acral melanomas and 11 melanomas of nasal cavity.
RESULTS
Somatic variant analysis identified KRAS (6/19; 32%) as the most commonly mutated gene, followed by KIT (4/19; 21%), SF3B1 (3/19; 16%) and NRAS (1/19; 5%). None of the cases were found to harbor BRAF, NF1 and PDGFRA mutations in melanomas of the female genital tract. However, none of the cases were found to harbor SF3B1 and KIT mutations in cutaneous melanomas, acral melanomas and melanomas of nasal cavity. Recurrent KIT mutations, as well as mutations in the less frequently mutated genes NRAS and SF3B1, were exclusively detected in vulvovaginal melanomas, but not in tumors arising in the cervix. However, recurrent KRAS mutations were detected in similar frequencies in tumors of the vulva, vagina, and cervix. Additionally, recurrent KRAS and KIT mutations occurred predominantly in polygonal and epithelioid cell types of melanoma in the female genital tract. Immunohistochemistry revealed moderate or strong cytoplasmic CD117 expression in 6 of the 19 cases (31.6%).
CONCLUSIONS
We observed that gynecologic melanoma harbored distinct mutation rates in the KIT, BRAF, SF3B1, KRAS, and NRAS genes. Our findings support the notion that gynecologic melanoma is a distinct entity from non-gynecologic melanoma, and these findings offer insights into future therapeutic options for these patients.
Topics: Adult; Aged; Female; Genital Neoplasms, Female; High-Throughput Nucleotide Sequencing; Humans; Melanoma; Middle Aged; Mutation; Phosphoproteins; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins p21(ras); RNA Splicing Factors
PubMed: 34102999
DOI: 10.1186/s12885-021-08427-x -
Seminars in Nuclear Medicine Nov 2019Gynecologic cancers are one of the most important causes of women death worldwide. The sentinel lymph node concept was introduced by Cabanas in 1977 for the penile... (Review)
Review
Gynecologic cancers are one of the most important causes of women death worldwide. The sentinel lymph node concept was introduced by Cabanas in 1977 for the penile cancer. This technique was proven safe and feasible in selected cancers such as breast cancer, melanoma, or some gynecologic cancers. Sentinel lymph node mapping is increasingly used in early stages of cervical or vulvar cancer in particular due to the safety, high detection rate, and sensitivity of the technique. In this review, we will discuss in depth the most recent evidence of nuclear medicine and other techniques used to determine the status of the sentinel lymph node in women affected by gynecologic neoplasms. Although significant efforts have been already done in order to address several issues, there are still determined questions without a clear answer, in particular for endometrial, ovarian, and vaginal neoplasms.
Topics: Female; Genital Neoplasms, Female; Humans; Sentinel Lymph Node Biopsy
PubMed: 31630736
DOI: 10.1053/j.semnuclmed.2019.06.012 -
Human Pathology Oct 2020Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50%... (Comparative Study)
Comparative Study
Vulvar malignant melanoma (VMM), although uncommon, comprises 5-10% of all vulvar malignancies. Local control is notoriously poor in VMM with recurrence rates of 30-50% compared with approximately 3% in cutaneous melanomas. We studied clinicopathologic features of 37 women with VMM, after reviewing three decades of clinical follow-up data in our institutional databases. Most patients were Caucasian (n = 35) with an average age at diagnosis of 60.6 years (range 23-83). The most common subtype was mucosal lentiginous melanoma (n = 25). We compared Kaplan-Meier survival curves of 31 patients defined by clinical and microscopic attributes using exact log-rank tests. Younger patients at diagnosis (23-64 years), those with thin melanomas (≤1 mm), and those with Clark's level II or III tumors had better 5-year survival rates than older patients (65-83 years) and those with thick melanomas (>1 mm) and those with Clark's level IV or V (P ≤ 0.05), respectively, by exact log-rank test. Local recurrence of melanoma occurred in 15 patients. Nine patients (24%) had eventual urethral involvement by malignant melanoma, and this feature was associated with significantly shorter survival (P = 0.036). Patients with urethral involvement had shorter median time to death and worse 5-year survival rates. Given that spread to the urethra is common in VMM and urethral recurrence is also associated with mortality, pathology excision specimens should be carefully reviewed with attention to urethral involvement as a potentially important prognostic factor.
Topics: Adult; Age Factors; Aged; Aged, 80 and over; Databases, Factual; Female; Humans; Melanoma; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Philadelphia; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Urethra; Urethral Neoplasms; Vulvar Neoplasms; Young Adult
PubMed: 32702401
DOI: 10.1016/j.humpath.2020.07.017 -
American Journal of Clinical Dermatology Apr 2020Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment.
BACKGROUND
Vulvar melanoma (VuM) and vaginal melanoma (VaM) represent a unique subgroup of malignant melanomas with important differences in biology and treatment.
OBJECTIVE
The objective of this study was to describe the epidemiology and prognosis of VuM and VaM in a large representative cohort.
METHODS
Women with invasive VuM or VaM were identified from the Surveillance, Epidemiology and End Results-18 population representing 27.8% of the US population. Data on age, ethnicity, stage, location, histopathology, primary surgery, and lymphadenectomy were collected. The Kaplan-Meier method was used to analyze disease-specific and overall survival. Univariate and multivariate regression models were used to identify factors with a significant association with disease-specific survival.
RESULTS
A total of 1400 VuM and 463 VaM were included for further analysis; 78.6% and 49.7% of women with VuM and VaM underwent surgery, but only 52.9% of women with non-metastatic VuM and 42.9% of women with non-metastatic VaM undergoing surgery had lymph node assessment; one third of these had positive nodes. Superficial spreading was the most common subtype in VuM, and nodular melanoma in VaM (p < 0.001). The median disease-specific survival was 99 months (95% confidence interval 60-138) and 19 months (95% confidence interval 16-22), respectively. Survival was significantly associated with age at diagnosis, ethnicity, stage, surgery, lymph node metastases, histologic subtype, ulceration, mitotic count, and tumor thickness in VuM, and stage, surgery, and lymph node involvement in VaM. In the Cox model, lymph node status and number of mitoses remained independent predictors of outcome in VuM; in VaM, only lymph node status remained significant.
CONCLUSIONS
The overall prognosis of VuM and VaM remains poor. The American Joint Committee on Cancer staging system is applicable and should be used for VuM; however, lymph node status and mitotic rate are the most important predictors of survival. Lymph node status should be assessed and patients with positive nodes may be candidates for adjuvant treatment.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Cohort Studies; Female; Humans; Melanoma; Middle Aged; SEER Program; United States; Vagina; Vaginal Neoplasms; Vulva; Vulvar Neoplasms; Young Adult
PubMed: 31784896
DOI: 10.1007/s40257-019-00487-x -
Surgical Pathology Clinics Jun 2021Primary anogenital mucosal melanomas (AGMs) are rare aggressive malignancies that are typically diagnosed at an advanced stage. Ulceration is a common feature in AGMs... (Review)
Review
Primary anogenital mucosal melanomas (AGMs) are rare aggressive malignancies that are typically diagnosed at an advanced stage. Ulceration is a common feature in AGMs and may not correlate with outcome. Therefore, staging of AGMs similar to primary cutaneous melanomas, based on tumor thickness and ulceration, may not robustly predict outcome. Derivation of site-specific staging systems is essential for prognostication and optimal management of these patients. To this end, recent retrospective studies have revealed tumor thickness (TT) and mitotic rate (MR) as features of most prognostic significance as follows: in anorectal (TT only) and vulvar (TT and MR) melanomas.
Topics: Humans; Melanoma; Neoplasm Staging; Prognosis; Retrospective Studies; Skin Neoplasms
PubMed: 34023102
DOI: 10.1016/j.path.2021.01.003 -
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 -
International Journal of Gynecological... Mar 2020To characterize our institutional experience with sentinel lymph node (SLN) biopsy in patients with vulvar cancer. We describe the oncologic outcomes of these patients...
OBJECTIVES
To characterize our institutional experience with sentinel lymph node (SLN) biopsy in patients with vulvar cancer. We describe the oncologic outcomes of these patients and the utilization of SLN detection techniques over time.
METHODS
A retrospective analysis of all patients who underwent inguinofemoral SLN biopsy as part of their treatment for vulvar cancer at Memorial Sloan Kettering Cancer Center from January 1, 2000 to April 1, 2019. Patients were included in this analysis if they underwent inguinofemoral SLN biopsy for vulvar cancer, irrespective of presenting factors such as histology, tumor size or laterality. An "at-risk groin" was defined as either the right or left groin for which SLN biopsy of inguinofemoral lymph nodes was performed.
RESULTS
A total of 160 patients were included in our analysis, representing 265 at-risk groins. 114 patients had squamous cell histology representing 195 at-risk groins. Of the 169 negative groins in patients with squamous cell carcinoma, the 2 year isolated groin recurrence rate was 1.2%. SLN detection rate, irrespective of modality, was 96.2%. Technetium-99 (TC-99) + blue dye detected SLNs in 91.8% of groins; TC-99 + indocyanine green detected SLNs in 100% of groins (p0.157). Among the 110 groins that underwent mapping with TC-99 and blue dye, 4 patients had failed mapping with blue dye and mapped with TC-99 alone (3.6%). Among the 96 groins that underwent mapping with TC-99 and ICG, 14 patients failed to map with TC-99 and mapped with indocyanine green alone (14.6%).
CONCLUSIONS
SLN mapping in vulvar cancer is reliable and oncologically effective. The utilization of indocyanine green for mapping has increased over the past decade and is associated with high rates of SLN detection.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Female; Humans; Lymph Node Excision; Lymph Nodes; Middle Aged; Retrospective Studies; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Vulvar Neoplasms; Young Adult
PubMed: 32075896
DOI: 10.1136/ijgc-2019-000936 -
International Journal of Gynecological... Sep 2020This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer.
OBJECTIVE
This study aimed to analyze the prognostic factors for overall and progression-free survival in patients with vulvar cancer.
METHODS
This international, multicenter, retrospective study included 2453 patients diagnosed with vulvar cancer at 100 different institutions. Inclusion criteria were institutional review board approval from each collaborating center, pathologic diagnosis of invasive carcinoma of the vulva, and primary treatment performed at the participating center. Patients with intraepithelial neoplasia or primary treatment at non-participating centers were excluded. Global survival analysis and squamous cell histology subanalysis was performed.
RESULTS
After excluding patients due to incomplete data entry, 1727 patients treated for vulvar cancer between January 2001 and December 2005 were registered for analysis (1535 squamous, 42 melanomas, 38 Paget's disease and 112 other histologic types). Melanomas had the worse prognosis (p=0.02). In squamous vulvar tumors, independent factors for increase in local recurrence of vulvar cancer were: no prior radiotherapy (p<0.001) or chemotherapy (p=0.006), and for distant recurrence were the number of positive inguinal nodes (p=0.025), and not having undergone lymphadenectomy (p=0.03) or radiotherapy (p<0.001), with a HR of 1.1 (95% CI 1.2 to 1.21), 2.9 (95% CI 1.4 to 6.1), and 3.1 (95% CI 1.7 to 5.7), respectively. Number of positive nodes (p=0.008), FIGO stage (p<0.001), adjuvant chemotherapy (p=0.001), tumor resection margins (p=0.045), and stromal invasion >5 mm (p=0.001) were correlated with poor overall survival, and large case volume (≥9 vs <9 cases per year) correlated with more favorable overall survival (p=0.05).
CONCLUSIONS
Advanced patient age, number of positive inguinal lymph nodes, and lack of adjuvant treatment are significantly associated with a higher risk of relapse in patients with squamous cell vulvar cancer. Case volume per treating institution, FIGO stage, and stromal invasion appear to impact overall survival significantly. Future prospective trials are warranted to establish these prognostic factors for vulvar cancer.
Topics: Aged; Female; Humans; Prognosis; Retrospective Studies; Survival Analysis; Vulvar Neoplasms
PubMed: 32571891
DOI: 10.1136/ijgc-2019-000526 -
British Gynaecological Cancer Society (BGCS) vulval cancer guidelines: Recommendations for practice.European Journal of Obstetrics,... Sep 2020The purpose of this guideline is to collate evidence and propose evidence-based guidelines for the diagnosis and management of adult patients with vulva carcinoma... (Review)
Review
The purpose of this guideline is to collate evidence and propose evidence-based guidelines for the diagnosis and management of adult patients with vulva carcinoma treated in the UK. Malignant melanoma may present via similar routes and will be discussed. The reader is referred to the Ano-uro-genital Mucosal Melanoma Full Guideline [1] for more detailed recommendations. The management of vulval sarcoma is outside of the scope of this guideline. For further information, including details of guideline development and GRADE of recommendations, please see BGCS website for details (https://www.bgcs.org.uk/professionals/guidelines-for-recent-publications/).
Topics: Adult; Female; Humans; Melanoma; Skin Neoplasms; Vulvar Neoplasms
PubMed: 32620514
DOI: 10.1016/j.ejogrb.2020.05.054