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Journal of Indian Association of... 2024Granular cell tumors (GCTs) (Abrikossoff's tumors) are rare neoplasms derived from Schwann cells. Immunohistochemistry remains the most useful instrument for diagnosing...
Granular cell tumors (GCTs) (Abrikossoff's tumors) are rare neoplasms derived from Schwann cells. Immunohistochemistry remains the most useful instrument for diagnosing GCTs. Complete surgical excision has been demonstrated to be curative for benign lesions. However, long-term follow-up in these patients is strongly recommended.
PubMed: 38405250
DOI: 10.4103/jiaps.jiaps_182_23 -
International Journal of Molecular... Feb 2024Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative...
Advances in molecular tumor diagnostics have transformed cancer care. However, it remains unclear whether precision oncology has the same impact and transformative nature across all malignancies. We conducted a retrospective analysis of patients with human papillomavirus (HPV)-related gynecologic malignancies who underwent comprehensive molecular profiling and subsequent discussion at the interdisciplinary Molecular Tumor Board (MTB) of the University Hospital, LMU Munich, between 11/2017 and 06/2022. We identified a total cohort of 31 patients diagnosed with cervical (CC), vaginal or vulvar cancer. Twenty-two patients (fraction: 0.71) harbored at least one mutation. Fifteen patients (0.48) had an actionable mutation and fourteen (0.45) received a recommendation for a targeted treatment within the MTB. One CC patient received a biomarker-guided treatment recommended by the MTB and achieved stable disease on the mTOR inhibitor temsirolimus for eight months. Factors leading to non-adherence to MTB recommendations in other patient cases included informed patient refusal, rapid deterioration, stable disease, or use of alternative targeted but biomarker-agnostic treatments such as antibody-drug conjugates or checkpoint inhibitors. Despite a remarkable rate of actionable mutations in HPV-related gynecologic malignancies at our institution, immediate implementation of biomarker-guided targeted treatment recommendations remained low, and access to targeted treatment options after MTB discussion remained a major challenge.
Topics: Humans; Female; Vulvar Neoplasms; Genital Neoplasms, Female; Precision Medicine; Papillomavirus Infections; Retrospective Studies; Biomarkers
PubMed: 38397025
DOI: 10.3390/ijms25042345 -
Indian Journal of Pathology &... Apr 2024Synovial sarcoma (SS) is rarely documented in the female genital tract, especially confirmed by molecular testing for SYT::SSX translocation and TLE1 immunostaining. A... (Review)
Review
Poorly differentiated biphasic synovial sarcoma of the vulva, displaying SS18::SSX1 fusion and weak to absent (mosaic) INI1/SMARCB1 immunostaining: A rare case with literature review.
Synovial sarcoma (SS) is rarely documented in the female genital tract, especially confirmed by molecular testing for SYT::SSX translocation and TLE1 immunostaining. A 62-year-old lady presented with a progressively increasing lump and pain over her right groin, for 6-month duration. Radiologically, a well-defined, solid-cystic mass was seen involving the right labia with necrotic areas, sparing the underlying muscles and the overlying skin. She underwent a biopsy followed by a surgical excision. Histopathologic examination revealed a spindle cell sarcoma, including tumor cells exhibiting a prominent hemangiopericytomatous pattern. There were focal areas of epithelial differentiation (pseudoglandular) along with areas of round cell morphology and increased mitoses (poor differentiation) in the resected specimen. Immunohistochemically, the tumor cells were diffusely positive for TLE1, patchily positive for pan keratin (AE1/AE3) and EMA, the latter more in the areas of epithelial differentiation, while negative for CD34, SMA, desmin, S100P, and SOX10. INI1/SMARCB1 showed a characteristic weak to absent (mosaic) staining pattern. Furthermore, the tumor displayed SS18::SSX 1 fusion by RT-PCR. This constitutes one of the few reported cases of vulvar SS, confirmed by molecular testing and the first documented vulvar SS showing a mosaic pattern of INI1/SMARCB1 immunostaining. A review of the literature and diagnostic implications are presented herewith.
Topics: Humans; Female; Sarcoma, Synovial; Middle Aged; SMARCB1 Protein; Immunohistochemistry; Vulvar Neoplasms; Vulva; Oncogene Proteins, Fusion; Biomarkers, Tumor; Histocytochemistry; Microscopy; Co-Repressor Proteins; Proto-Oncogene Proteins; Repressor Proteins
PubMed: 38391333
DOI: 10.4103/ijpm.ijpm_560_23 -
Acta Obstetricia Et Gynecologica... Jun 2024Differentiated vulvar intraepithelial neoplasia (dVIN) is a high-risk preinvasive vulvar lesion and precursor of human papillomavirus-independent vulvar squamous cell...
INTRODUCTION
Differentiated vulvar intraepithelial neoplasia (dVIN) is a high-risk preinvasive vulvar lesion and precursor of human papillomavirus-independent vulvar squamous cell carcinoma (VSCC). Due to its rarity, literature data on its malignant potential are scant. The aim of the study is to assess the risk of developing VSCC in patients surgically treated for dVIN not associated with VSCC (solitary dVIN) and the risk of VSCC recurrence in patients treated for dVIN associated with VSCC (dVIN-VSCC) at first diagnosis.
MATERIAL AND METHODS
A historical cohort study was performed in a northern Italy referral center for vulvar neoplasms. All consecutive women surgically treated for histologically confirmed dVIN from 1994 to 2021 were collected. Primary outcome was cancer risk or recurrent cancer risk, secondary outcomes were risk factors associated with VSCC development or recurrence. Kaplan-Meier method and log-rank test were used to estimate cancer risk or recurrent cancer risk differences and uni- and multivariate Cox regression analyses to identify risk factors associated with VSCC development in solitary dVIN and recurrence of dVIN-VSCC.
RESULTS
Seventy-six patients with dVIN at preoperative biopsy were included: at excisional specimens 44 were solitary dVIN and 32 were dVIN-VSCC. The absolute risk of VSCC development after solitary dVIN treatment was 43.2% with median time to to VSCC diagnosis of 25.4 months (range 3.5-128.0 months). VSCC recurrence absolute risk in treated dVIN-VSCC patients was 31.3% with median time to VSCC recurrence of 52.9 months (range 6.5-94.8 months). At uni- and multivariate regression analyses, only compliant topical ultrapotent corticosteroid treatment after solitary dVIN excision showed an ability to prevent VSCC development. No protective effect by corticosteroid treatment was shown for VSCC recurrence in dVIN-VSCC patients. Smoking was associated with higher cancer recurrence risk in dVIN-VSCC patients on both uni- and multivariate regression analyses.
CONCLUSIONS
Patients with dVIN have a high risk of developing both primary and recurring VSCC. Early recognition, long-term follow up, and compliant ultrapotent topical corticosteroid treatment are recommended.
Topics: Humans; Female; Vulvar Neoplasms; Carcinoma in Situ; Middle Aged; Neoplasm Recurrence, Local; Carcinoma, Squamous Cell; Prognosis; Follow-Up Studies; Cohort Studies; Adult; Risk Factors; Aged; Italy
PubMed: 38383115
DOI: 10.1111/aogs.14814 -
Canadian Family Physician Medecin de... Feb 2024
Topics: Humans; Female; Skin Neoplasms; Primary Health Care; Vulvar Diseases
PubMed: 38383019
DOI: 10.46747/cfp.7002100 -
Minerva Obstetrics and Gynecology Feb 2024Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical...
Safety and efficacy of a class II medical device based on highly purified and standardized plant extracts in the management of post-menopausal patients with vulvar and vaginal atrophy: a single-center prospective observational study.
BACKGROUND
Despite the gold standard treatment for genitourinary syndrome of menopause (GSM) is based on the use of local or systemic estrogen-containing products, the typical long-term side effects of hormonal treatments and, most importantly, the contraindications in patients with history of breast and endometrial neoplasms do limit in some extent its use. As hyaluronic acid and some highly purified botanicals have clearly demonstrated their anti-inflammatory and mucosa-protecting properties, we have tested, in women with GSM, a class II vaginal medical device containing hyaluronate gel and a mucoadhesive active enriched with purified alkylamides from Zanthoxylum bungeanum, triterpenes from Centella asiatica and high molecular weight polysaccharides from Tamarindus indica.
METHODS
Our single-center, open-label, prospective and observational study was conducted on 50 menopausal women enrolled at the Department of Maternal-Fetal Medicine at Umberto I Polyclinic Hospital in Rome, Italy. Gel administration lasted 150 days and was performed daily for the first 12 days and every 48 hours for the remaining 138 days. Clinical evaluations were performed at baseline and after 12, 57 and 150 days. Besides product safety, main outcomes of our study were: 1) vaginal health (by Vaginal Health Index score [VHI]); 2) sexual quality of life (by Female Sexual Distress Scale [FSDS]); and 3) percentage of women declaring regular sexual activity.
RESULTS
The product was safe with no specific adverse events reported. It significantly improved VHI (about 5% after 57 days and 8% after 150 days), FSDS (about 7% after 57 days and 10% after 150 days), and sexual activity (about 20% after 150 days). It also reduced dryness, dyspareunia, burning, itching, and dysuria incidence, respectively by about 18%, 14%, 14%, 27% and 11% after 150 days.
CONCLUSIONS
In women with GSM, the intravaginal administration of a hyaluronate-based gel enriched with purified botanical actives endowed with anti-inflammatory and mucosal-protecting properties, reduced painful sensation during sexual acts and increased regular sexual activity.
PubMed: 38358384
DOI: 10.23736/S2724-606X.23.05409-X -
Asian Journal of Surgery May 2024
Topics: Humans; Female; Neoplasms, Muscle Tissue; Vulvar Neoplasms
PubMed: 38350781
DOI: 10.1016/j.asjsur.2024.01.182 -
Gynecologic Oncology Jun 2024Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn)...
High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.
OBJECTIVE
Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen.
METHODS
Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate.
RESULTS
Most cases 36/57 (63.2%) belonged to the HPV-independent (p53-abn) molecular subtype, followed by HPV-associated 17/57 (29.8%) and HPV-independent (p53wt) 4/57 (7.0%). The overall accuracy rate on biopsy was 91.2% (52/57): 97.3% for p53-abnormal, 94.1% for p16-overexpression and 50% for p16-neg/p53-wt VSCC. Incorrect interpretation of immunohistochemical p53 staining pattern was the reason for discordant results in molecular subtyping in all five cases. In one case there was an underestimation of p53 pattern (wildtype instead of abnormal/aberrant) and in one case an overestimation of the p53 staining pattern (abnormal/aberrant instead of wildtype). In 3/5 there was a "double positive" staining result (p16 overexpression and abnormal/aberrant p53 staining pattern). In that cases additional molecular workup is required for correct molecular subtyping, resulting in an overall need for molecular examination of 3/57 (3.5%).
CONCLUSIONS
Compared to the final resections specimen, the three-tiered molecular classification of VSCC can be determined on pre-surgical biopsies with a high accuracy rate. This enables more precise surgical planning, prediction of the response to (chemo) radiation, selection of targeted therapies and planning of the optimal follow-up strategy for patients in the age of personalised medicine.
Topics: Humans; Female; Vulvar Neoplasms; Tumor Suppressor Protein p53; Cyclin-Dependent Kinase Inhibitor p16; Carcinoma, Squamous Cell; Biopsy; Middle Aged; Immunohistochemistry; Aged; Aged, 80 and over; Adult; Papillomavirus Infections
PubMed: 38342005
DOI: 10.1016/j.ygyno.2024.02.001 -
Gynecologic Oncology May 2024Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have... (Review)
Review
Over recent years, there has been significant progress in the development of immunotherapeutic molecules designed to block the PD-1/PD-L1 axis. These molecules have demonstrated their ability to enhance the immune response by prompting T cells to identify and suppress neoplastic cells. PD-L1 is a type 1 transmembrane protein ligand expressed on T lymphocytes, B lymphocytes, and antigen-presenting cells and is considered a key inhibitory checkpoint involved in cancer immune regulation. PD-L1 immunohistochemical expression in gynecological malignancies is extremely variable based on tumor stage and molecular subtypes. As a result, a class of monoclonal antibodies targeting the PD-1 receptor and PD-L1, known as immune checkpoint inhibitors, has found successful application in clinical settings. In clinical practice, the standard method for identifying suitable candidates for immune checkpoint inhibitor therapy involves immunohistochemical assessment of PD-L1 expression in neoplastic tissues. The most commonly used PD-L1 assays in clinical trials are SP142, 28-8, 22C3, and SP263, each of which has been rigorously validated on specific platforms. Gynecologic cancers encompass a wide spectrum of malignancies originating from the ovaries, uterus, cervix, and vulva. These neoplasms have shown variable response to immunotherapy which appears to be influenced by genetic and protein expression profiles, including factors such as mismatch repair status, tumor mutational burden, and checkpoint ligand expression. In the present paper, an extensive review of PD-L1 expression in various gynecologic cancer types is discussed, providing a guide for their pathological assessment and reporting.
Topics: Humans; Female; B7-H1 Antigen; Genital Neoplasms, Female; Immune Checkpoint Inhibitors; Ovarian Neoplasms
PubMed: 38295614
DOI: 10.1016/j.ygyno.2024.01.032 -
Obstetrics & Gynecology Science Mar 2024Vulvar intraepithelial neoplasia (VIN) is a noninvasive squamous lesion that is a precursor of vulvar squamous cell cancer. Currently, no screening tests are available...
Vulvar intraepithelial neoplasia (VIN) is a noninvasive squamous lesion that is a precursor of vulvar squamous cell cancer. Currently, no screening tests are available for detecting VIN, and a biopsy is performed to confirm the clinical diagnosis. Despite sharing many risk factors with cervical intraepithelial neoplasia, the diagnosis of VIN is poses challenges, contributing to its increasing prevalence. This study aimed to analyze the underlying risk factors that contribute to the development of VIN, identify specific populations at risk, and define appropriate treatment approaches. Differentiated VIN (dVIN) and usual VIN (uVIN) are the classifications of VIN. While dVIN is associated with other vulvar inflammatory disorders, such as lichen sclerosis, the more prevalent uVIN is associated with an underlying human papillomavirus infection. Patients with differentiated VIN have an increased risk of developing invasive malignancies. Few effective surveillance or management techniques exist for vulvar intraepithelial neoplasia, a preinvasive neoplasm of the vulva. For suspicious lesions, a thorough examination and focused biopsy are necessary. Depending on the specific needs of each patient, a combination of surgical and medical approaches can be used.
PubMed: 38262367
DOI: 10.5468/ogs.23274