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International Journal of Gynecological... Jun 2024In the last decade, we have witnessed important advances in novel therapeutics in the management of gynecologic cancers. These studies have built on the findings from... (Review)
Review
In the last decade, we have witnessed important advances in novel therapeutics in the management of gynecologic cancers. These studies have built on the findings from preexisting data and have provided incremental contributions leading to changes that have not only impacted the accuracy of cancer detection and its metastatic components but also led to improvements in oncologic outcomes and quality of life. Key landmark trials have changed the standard of care in cervix, uterine, and ovarian cancer. A number of these have been controversial and have generated significant debate among gynecologic oncologists. The main objective of this review was to provide an overview on each of these trials as a reference for immediate and consolidated access to the study aims, methodology, results, and conclusion.
PubMed: 38858104
DOI: 10.1136/ijgc-2024-005471 -
Scientific Reports Jun 2024The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics...
The incidence of vulvar carcinoma varies by race; however, it is a rare disease, and its genomic profiles remain largely unknown. This study examined the characteristics of vulvar squamous cell carcinoma (VSCC) in Japanese patients, focusing on genomic profiles and potential racial disparities. The study included two Japanese groups: the National Cancer Center Hospital (NCCH) group comprised 19 patients diagnosed between 2015 and 2023, and the Center for Cancer Genomics and Advanced Therapeutics group comprised 29 patients diagnosed between 2019 and 2022. Somatic mutations were identified by targeted or panel sequencing, and TP53 was identified as the most common mutation (52-81%), followed by HRAS (7-26%), CDKN2A (21-24%), and PIK3CA (5-10%). The mutation frequencies, except for TP53, were similar to those of Caucasian cohorts. In the NCCH group, 16 patients of HPV-independent tumors were identified by immunohistochemistry and genotyping. Univariate analysis revealed that TP53-mutated patients were associated with a poor prognosis (log-rank test, P = 0.089). Japanese VSCC mutations resembled those of Caucasian vulvar carcinomas, and TP53 mutations predicted prognosis regardless of ethnicity. The present findings suggest potential molecular-targeted therapies for select VSCC patients.
Topics: Humans; Female; Vulvar Neoplasms; Carcinoma, Squamous Cell; Middle Aged; Aged; Mutation; Tumor Suppressor Protein p53; Japan; Aged, 80 and over; Cyclin-Dependent Kinase Inhibitor p16; Class I Phosphatidylinositol 3-Kinases; Prognosis; Adult; Asian People; Genomics; Proto-Oncogene Proteins p21(ras); East Asian People
PubMed: 38844774
DOI: 10.1038/s41598-024-63913-z -
European Journal of Surgical Oncology :... Jul 2024Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of...
INTRODUCTION
Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC).
METHODS
This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC.
RESULTS
We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.
Topics: Humans; Female; Vulvar Neoplasms; Carcinoma, Squamous Cell; Retrospective Studies; Aged; Neoplasm Recurrence, Local; Middle Aged; Tertiary Care Centers; Prognosis; Neoplasm Staging; Lymphatic Metastasis; Survival Rate; Papillomavirus Infections; Aged, 80 and over; Adult; Neoplasm Grading; Margins of Excision; Neoplasm Invasiveness
PubMed: 38843661
DOI: 10.1016/j.ejso.2024.108447 -
International Journal of Gynecological... Jul 2024External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with...
OBJECTIVES
External beam radiation with sensitizing platinum is the recommended therapy for locally advanced vulvar cancers not amenable to curative surgery and is associated with considerable acute and chronic side effects. Radical vulvectomy post-radiation for persistent disease is often compromised with poor wound healing. We describe clinical outcomes for patients who received neoadjuvant chemotherapy plus bevacizumab followed by radical vulvectomy for locally advanced vulvar cancer.
METHODS
We performed retrospective analyses of all patients at our institution who underwent radical vulvectomy from January 2015 to November 2023. Of 113 patients, 13 patients underwent neoadjuvant chemotherapy. Demographics and clinicopathologic data were extracted, and descriptive statistical analyses were performed. Cases with neoadjuvant chemotherapy plus bevacizumab were further evaluated for response, adverse effects, and survival.
RESULTS
Neoadjuvant chemotherapy was administered to 13 patients with stage II-IV disease that involved the urethra, vagina, or anus. Lesion sizes ranged from 4 to 20 cm (median 7 cm). Patients received 2-6 cycles of carboplatin or cisplatin, paclitaxel, and bevacizumab. Nine (69.2%) patients had partial pathologic responses, and four patients had complete responses. All patients had negative surgical margins. Ten (76.9%) patients had radiographic evidence of inguinal lymph node metastasis prior to neoadjuvant chemotherapy, and four had residual nodal disease. Only one patient developed a superficial groin seroma. Three patients developed recurrence, two locally and one distant, and there was one death. The median follow-up was 23 months (range 6-84 months).
CONCLUSIONS
Neoadjuvant chemotherapy using combination platinum/paclitaxel/bevacizumab was efficacious for locally advanced vulvar cancer, resulting in complete resections, negative margins, and excellent wound healing. A multi-institutional phase II trial is warranted to validate these findings.
Topics: Humans; Female; Bevacizumab; Vulvar Neoplasms; Neoadjuvant Therapy; Middle Aged; Retrospective Studies; Aged; Antineoplastic Combined Chemotherapy Protocols; Adult; Paclitaxel; Carboplatin; Cisplatin; Vulvectomy; Aged, 80 and over
PubMed: 38830645
DOI: 10.1136/ijgc-2024-005402 -
Anticancer Research Jun 2024Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation...
BACKGROUND/AIM
Texture analysis is a quantitative imaging technique that provides novel biomarkers beyond conventional image reading. This study aimed to investigate the correlation between texture parameters and histopathological features of lymph nodes in patients with vulvar cancer.
PATIENTS AND METHODS
Overall, nine female patients (mean age 70.1±13.4 years, range=39-87 years) were included in the analysis. All patients had squamous cell carcinomas and underwent upfront surgery with inguinal lymph node resection. Immunohistochemical assessment was performed using several markers of the epithelial-mesenchymal transition. The presurgical magnetic resonance imaging (MRI) was analyzed with the MaZda package.
RESULTS
In discrimination analysis, several parameters derived from T1-weighted images showed statistically significant differences between non-metastatic and metastatic lymph nodes. The highest statistical significance was reached by the texture feature "S(0,3)InvDfMom" (p=0.016). In correlation analysis, significant associations were found between MRI texture parameters derived from both T1-weighted and T2-weighted images and the investigated histopathological features. Notably, S(0,3)InvDfMom derived from T1-weighted images highly correlated with the Vimentin-score (r=0.908, p=0.001).
CONCLUSION
Several associations between MRI texture analysis and immunohistochemical parameters were identified in metastasized lymph nodes of cases with vulvar cancer.
Topics: Humans; Female; Vulvar Neoplasms; Aged; Lymphatic Metastasis; Magnetic Resonance Imaging; Aged, 80 and over; Middle Aged; Adult; Lymph Nodes; Carcinoma, Squamous Cell; Inguinal Canal
PubMed: 38821619
DOI: 10.21873/anticanres.17078 -
Anticancer Research Jun 2024This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC).
BACKGROUND/AIM
This study investigated the clinical impact of resection of pelvic sentinel lymph nodes (PSLNs) in squamous cell vulvar cancer (SCVC).
PATIENTS AND METHODS
Sixty-two groins of 33 patients with SCVC who underwent sentinel lymph node (SLN) resection between 2010 and 2021 at the University Hospital of Cologne, Germany, were analyzed in this retrospective cohort study. The frequency of additionally resectable PSLNs, histological findings, and count rates were analyzed and compared to the findings for inguinal sentinel lymph nodes (ISLNs).
RESULTS
In all patients and in 61 (98%) of the 62 radiolabeled groins, at least one SLN could be resected. Five (8%) of the 62 groins had histologically confirmed lymph node metastases (4/33 patients, 12%). Twenty (33%) of the 62 groins underwent additional PSLN resection. Resection of these PSLNs was feasible without causing an additional burden for the patients. None of the PSLNs showed signs of tumor infiltration. Information on the extent of radioactivity for ISLNs and simultaneously for PSLNs, expressed as count rate of intraoperative measurement with the gamma probe, was available for 20 (32%) groins. In three (15%) of these cases, the highest count rate in a SLN was found in a PSLN and not in an ISLN.
CONCLUSION
Resection of PSLNs is feasible and can be performed without short-term complications. In patients with early SCVC, resection of PSLNs is not necessary, even in those with early infiltration of inguinal lymph nodes. The intraoperative count rate of SLN is not relevant for the decision to perform resection.
Topics: Humans; Female; Vulvar Neoplasms; Sentinel Lymph Node Biopsy; Carcinoma, Squamous Cell; Aged; Middle Aged; Retrospective Studies; Aged, 80 and over; Lymphatic Metastasis; Sentinel Lymph Node; Adult; Pelvis; Lymph Node Excision
PubMed: 38821614
DOI: 10.21873/anticanres.17068 -
Experimental and Molecular Pathology Jun 2024Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS...
BACKGROUND
Shallow whole genome sequencing (Shallow-seq) is used to determine the copy number aberrations (CNA) in tissue samples and circulating tumor DNA. However, costs of NGS and challenges of small biopsies ask for an alternative to the untargeted NGS approaches. The mFAST-SeqS approach, relying on LINE-1 repeat amplification, showed a good correlation with Shallow-seq to detect CNA in blood samples. In the present study, we evaluated whether mFAST-SeqS is suitable to assess CNA in small formalin-fixed paraffin-embedded (FFPE) tissue specimens, using vulva and anal HPV-related lesions.
METHODS
Seventy-two FFPE samples, including 36 control samples (19 vulva;17 anal) for threshold setting and 36 samples (24 vulva; 12 anal) for clinical evaluation, were analyzed by mFAST-SeqS. CNA in vulva and anal lesions were determined by calculating genome-wide and chromosome arm-specific z-scores in comparison with the respective control samples. Sixteen samples were also analyzed with the conventional Shallow-seq approach.
RESULTS
Genome-wide z-scores increased with the severity of disease, with highest values being found in cancers. In vulva samples median and inter quartile ranges [IQR] were 1[0-2] in normal tissues (n = 4), 3[1-7] in premalignant lesions (n = 9) and 21[13-48] in cancers (n = 10). In anal samples, median [IQR] were 0[0-1] in normal tissues (n = 4), 14[6-38] in premalignant lesions (n = 4) and 18[9-31] in cancers (n = 4). At threshold 4, all controls were CNA negative, while 8/13 premalignant lesions and 12/14 cancers were CNA positive. CNA captured by mFAST-SeqS were mostly also found by Shallow-seq.
CONCLUSION
mFAST-SeqS is easy to perform, requires less DNA and less sequencing reads reducing costs, thereby providing a good alternative for Shallow-seq to determine CNA in small FFPE samples.
Topics: Humans; Female; DNA Copy Number Variations; Paraffin Embedding; High-Throughput Nucleotide Sequencing; Formaldehyde; Tissue Fixation; Whole Genome Sequencing; Vulvar Neoplasms; Papillomavirus Infections; Anus Neoplasms
PubMed: 38820761
DOI: 10.1016/j.yexmp.2024.104906 -
Acta Oncologica (Stockholm, Sweden) May 2024Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used,...
BACKGROUND
Electrochemotherapy (ECT) is a combined treatment method based on electroporation and simultaneous chemotherapy. In cases where radiotherapy has previously been used, surgery is often the only treatment option for vulvar cancer recurrence with potential resection of clitoris, vagina, urethra or anal sphincter. The unique advantage of ECT is its selectivity for cancer cells while sparing the surrounding healthy tissue. The aim of the study was to compare the ECT treatment of vulvar cancer recurrence for non-palliative purposes with surgical treatment.
MATERIALS AND METHODS
Eleven patients with single vulvar cancer recurrence were treated with ECT and followed up for 12 months. As a control group, 15 patients with single vulvar cancer recurrence were treated with wide local excision. The following data were collected, analyzed and compared: Age, body mass index, comorbidities, histological type, location and size of vulvar cancer recurrence, treatment history, details of procedures and hospital stay.
RESULTS
The probability curves for local tumor control did not differ between the ECT group and the surgical group (p = 0.694). The mean hospital stay and the mean duration of procedure were statistically significantly shorter in the ECT group (p < 0.001). There were no statistically significant differences between the ECT and surgical groups in terms of mean body mass index, associated diseases, previous treatments, presence of lichen sclerosus, p16 status, gradus, anatomical site of the tumor, and type of anesthesia.
CONCLUSION
In this case-control study, treatment of vulvar cancer recurrence with ECT for non-palliative purposes was comparable to surgical treatment in terms of effectiveness. The results need to be confirmed in larger randomized trials.
Topics: Humans; Female; Vulvar Neoplasms; Electrochemotherapy; Neoplasm Recurrence, Local; Case-Control Studies; Aged; Middle Aged; Aged, 80 and over; Adult; Treatment Outcome; Follow-Up Studies
PubMed: 38770722
DOI: 10.2340/1651-226X.2024.33241 -
European Journal of Obstetrics,... Jul 2024Aggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their...
OBJECTIVE
Aggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age.
STUDY DESIGN
Seventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features.
RESULTS
All seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumors were located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size were 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases.
CONCLUSIONS
AAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence.
Topics: Humans; Female; Adult; Myxoma; Middle Aged; Retrospective Studies; Perineum; Young Adult; Pelvic Neoplasms; Genital Neoplasms, Female; Vulvar Neoplasms; Neoplasm Recurrence, Local; Vaginal Neoplasms; Buttocks
PubMed: 38762952
DOI: 10.1016/j.ejogrb.2024.05.012 -
Annals of Diagnostic Pathology Oct 2024Borderline Brenner tumors (BBT) have a range of morphology that shows considerable overlap with that of malignant Brenner tumors (MBT). In particular, two histological...
Borderline Brenner tumors (BBT) have a range of morphology that shows considerable overlap with that of malignant Brenner tumors (MBT). In particular, two histological patterns of BBT can be particularly challenging: 1) BBT with intraepithelial carcinoma (BBT-IEC) and 2) BBT with a small nested pattern (BBT-SNP). BBT-IEC is characterized by a tumor with the low-power non-infiltrative silhouette of a conventional BBT, but with increased cytological atypia and mitotic activity similar to that of MBT. Conversely, BBT-SNP is characterized by a complex proliferation of small tumor nests that closely resemble the infiltrative growth pattern of MBT, but without the obligate cytologic atypia and mitotic activity of MBT. We suggest that the combination of p16, p53 and Ki-67 may be helpful in distinguishing these 2 patterns of BBT from both conventional BBT and from MBT. While both conventional BBT and BBT-IEC show a null pattern of p16 expression, our case of BBT-IEC showed aberrant p53 overexpression, albeit with a maturation pattern similar to that described for TP53 mutant mucinous ovarian carcinoma and differentiated vulvar intraepithelial neoplasia (dVIN). Similarly, while BBT-SNP shows an infiltrative-like growth pattern similar to that of MBT, our case also showed a wild-type pattern of p53 expression and a Ki-67 proliferative index similar to areas with conventional BBT histology. In conclusion, in our small case series, we show that the use of immunohistochemistry for p53 and Ki-67 may help to distinguish challenging patterns of BBT from MBT. Further studies are needed to validate this finding in a larger case cohort.
Topics: Humans; Female; Immunohistochemistry; Brenner Tumor; Middle Aged; Biomarkers, Tumor; Ki-67 Antigen; Ovarian Neoplasms; Tumor Suppressor Protein p53; Aged; Adult; Cyclin-Dependent Kinase Inhibitor p16; Carcinoma in Situ
PubMed: 38733672
DOI: 10.1016/j.anndiagpath.2024.152324