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Heliyon Sep 2023Endometrial carcinoma (EC) is a disease that predominantly affects peri- and post-menopausal women and its incidence has continued to rise over recent years. Since the...
BACKGROUND
Endometrial carcinoma (EC) is a disease that predominantly affects peri- and post-menopausal women and its incidence has continued to rise over recent years. Since the gold standard for EC diagnosis-hysteroscopic biopsy-is invasive, expensive, and unsuitable for wide use, there is an urgent need for a non-invasive method that exhibits both high sensitivity and high specificity. We therefore investigated the efficacy of UterCAD (the uterine exfoliated cell chromosomal aneuploidy detector) using tampon-collected specimens for the early detection of EC.
METHODS
We prospectively recruited 51 patients with a history of abnormal bleeding and who planned to undergo hysteroscopic examination or hysterectomy between March 2020 and January 2021. Before executing an invasive procedure, a tampon was inserted into the patient's vagina for 6 h to collect exfoliated cells from the uterine cavity. Total DNA was extracted and low-coverage whole-genome sequencing was performed on an Illumina HiSeq X10, and we analyzed the differences in chromosomal status between women with EC and those bearing benign lesions using UterCAD.
RESULTS
Thirty EC patients-including 26 with endometrioid carcinoma (EEC) and four with uterine serous carcinoma (USC), as well as 14 benign cases-were enrolled in our final analysis. Copy-number variations (CNVs) were detected in tampon specimens collected from 26 EC patients (83.3%), including 21 with EEC (80.7%) and four with USC (100%). In the benign group, only one woman with focal atypical hyperplasia presented with a 10q chromosomal gain ( < 0.001). In the EC group, the most common CNVs were copy gains of 8q (N = 14), 2q (N = 4), and 10q (N = 3); and copy losses of 2q (N = 3) and 17p (N = 2). When we stratified by FIGO stage, the CNV rates in stages IA, IB, and II/III were 83.3% (15/18), 85.7% (6/7), and 80.0% (4/5), respectively. At the optimal cutoff (|Z| ≥ 2.3), UterCAD discriminated 83.3% of EC cases from benign cases, with a specificity of 92.9%.
CONCLUSIONS
We initially reported that UterCAD could serve as a non-invasive method for the early detection of EC, especially in the rare and aggressive USC subtype. The use of UterCAD might thus avoid unnecessary invasive procedures and thereby reduce the treatment burden on patients.
PubMed: 37662762
DOI: 10.1016/j.heliyon.2023.e19323 -
La Radiologia Medica Jan 2024Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a...
BACKGROUND
Vulvar carcinoma is a rather uncommon gynecological malignancy affecting elderly women and the treatment of loco-regional advanced carcinoma of the vulva (LAVC) is a challenge for both gynecologic and radiation oncologists. Definitive chemoradiation (CRT) is the treatment of choice, but with disappointing results. In this multicenter study (OLDLADY-1.1), several institutions have combined their retrospective data on LAVC patients to produce a real-world dataset aimed at collecting data on efficacy and safety of CRT.
METHODS
The primary study end-point was 2-year-local control (LC), secondary end-points were 2-year-metastasis free-survival (MFS), 2-year-overall survival (OS) and the rate and severity of acute and late toxicities. Participating centers were required to fill data sets including age, stage, histology, grading as well as technical/dosimetric details of CRT. Data about response, local and regional recurrence, acute and late toxicities, follow-up and outcome measures were also collected. The toxicity was a posteriori documented through the Common Terminology Criteria for Adverse Events version 5 scale.
RESULTS
Retrospective analysis was performed on 65 patients with primary or recurrent LAVC treated at five different radiation oncology institutions covering 11-year time interval (February 2010-November 2021). Median age at diagnosis was 72 years (range 32-89). With a median follow-up of 19 months (range 1-114 months), 2-year actuarial LC, MFS and OS rate were 43.2%, 84.9% and 59.7%, respectively. In 29 patients (44%), CRT was temporarily stopped (median 5 days, range 1-53 days) due to toxicity. The treatment interruption was statistically significant at univariate analysis of factors predicting LC (p: 0.05) and OS rate (p: 0.011), and it was confirmed at the multivariate analysis for LC rate (p: 0.032). In terms of toxicity profile, no G4 event was recorded. Most adverse events were reported as grade 1 or 2. Only 14 acute G3 toxicities, all cutaneous, and 7 late G3 events (3 genitourinary, 3 cutaneous, and 1 vaginal stenosis) were recorded.
CONCLUSION
In the context of CRT for LAVC, the present study reports encouraging results even if there is clearly room for further improvements, in terms of both treatment outcomes, toxicity and treatment interruption management.
Topics: Humans; Female; Aged; Adult; Middle Aged; Aged, 80 and over; Vulvar Neoplasms; Retrospective Studies; Constriction, Pathologic; Vagina; Chemoradiotherapy; Carcinoma, Squamous Cell; Italy
PubMed: 37700153
DOI: 10.1007/s11547-023-01712-8 -
Cancers Sep 2023(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is...
(1) Background: Vaginal intraepithelial neoplasia (VaIN) is a rare premalignant disease caused by persistent human papillomavirus (HPV) infection. Diagnosing VaIN is challenging; abnormal cytology and positive HPV tests are usually the first signs, but published data on their accuracy for detecting it are rare and contradictory. The aim of this study is to compare the results of hrHPV and cytology co-testing with the histological findings of the vagina. (2) Methods: In the certified Dysplasia Unit at Erlangen University Hospital, cytology and HPV samples from the uterine cervix or vaginal wall after hysterectomy were obtained between 2015 and 2023 and correlated with histological findings in biopsies from the vaginal wall. Women without vaginal biopsy findings or concomitant cervical disease were excluded. (3) Results: In all, 279 colposcopies in 209 women were included. The histological results were: benign ( = 86), VaIN I/vLSIL ( = 116), VaIN II/vHSIL ( = 41), VaIN III/vHSIL ( = 33), and carcinoma ( = 3). Accuracy for detecting VaIN was higher in women with previous hysterectomies. Positive HPV testing during colposcopy increased the likelihood for VaIN II/III/vHSIL threefold. The detection rate for VaIN III/vHSIL was 50% after hysterectomy and 36.4% without hysterectomy. (4) Conclusions: Women with risk factors for VaIN, including HPV-16 infection or prior HPV-related disease, need careful work-up of the entire vaginal wall. Hysterectomy for HPV-related disease and a history of cervical intraepithelial neoplasia (CIN) also increased the risk for VaIN II/III/vHSIL.
PubMed: 37760600
DOI: 10.3390/cancers15184633 -
Cureus Jul 2023Primary small cell neuroendocrine carcinoma of the vagina is a very rare disease. We present a case study of a 52-year-old female who presented to the hospital with...
Primary small cell neuroendocrine carcinoma of the vagina is a very rare disease. We present a case study of a 52-year-old female who presented to the hospital with complaints of urinary dribbling, burning micturition, pain, and per vaginal bleeding for three to four months. A firm globular mass of approximately 5-6 cm was felt in the anterior vaginal wall per speculum examination. Diagnosis of small cell neuroendocrine carcinoma was made with tissue biopsy and immunohistochemistry. Diagnostic imaging (MRI, positron emission tomography (PET)-CT) plays a vital role in reaching the diagnosis and understanding the treatment response. The patient received six cycles of chemotherapy with cisplatin and etoposide and radiotherapy, achieving a complete response, with complete regression of the lesion. The patient had no sign of tumor recurrence and locoregional or distant metastases after six months of follow-up. Nowadays, there is no need for surgery in the treatment of vaginal small cell neuroendocrine carcinoma, rather radiotherapy and chemotherapy are the treatment of choice. We report a case of neuroendocrine cancer of the vagina treated at our institution.
PubMed: 37621790
DOI: 10.7759/cureus.42387 -
The Journal of Investigative Dermatology Dec 2023The epidermis, the keratinized stratified squamous epithelium surrounding the body surface, offers a valuable framework to investigate how terrestrial animals overcome...
The epidermis, the keratinized stratified squamous epithelium surrounding the body surface, offers a valuable framework to investigate how terrestrial animals overcome environmental stresses. However, the mechanisms underlying epidermal barrier function remain nebulous. In this study, we examined genes highly expressed in the human and mouse upper epidermis, the outer frontier that induces various barrier-related genes. Transcriptome analysis revealed that the messenger RNA level of hemoglobin α (HBA), an oxygen carrier in erythroid cells, was enriched in the upper epidermis compared with that in the whole epidermis. Immunostaining analysis confirmed HBA protein expression in human and mouse keratinocytes (KCs) of the stratum spinosum and stratum granulosum. HBA was also expressed in hair follicle KCs in the isthmus region; its expression levels were more prominent than those in interfollicular KCs. HBA expression was not observed in noncutaneous keratinized stratified squamous epithelia of mice, for example, the vagina, esophagus, and forestomach. HBA expression was upregulated in human epidermal KC cultures after UV irradiation, a major cause of skin-specific oxidative stress. Furthermore, HBA knockdown increased UV-induced production of ROS in primary KCs. Our findings suggest that epidermal HBA expression is induced by oxidative stress and acts as an antioxidant, contributing to skin barrier function.
Topics: Humans; Female; Animals; Mice; Hair Follicle; Epidermis; Keratinocytes; Hemoglobins; RNA, Messenger; Carcinoma, Squamous Cell
PubMed: 37981423
DOI: 10.1016/j.jid.2023.08.008 -
Asian Journal of Surgery Feb 2024
Topics: Female; Humans; Carcinoma, Squamous Cell; Vagina; Pelvis
PubMed: 38008629
DOI: 10.1016/j.asjsur.2023.11.012 -
Frontiers in Oncology 2024Primary vaginal cancer is a rare condition. Some studies have revealed an increased risk of vaginal cancer among patients who have undergone hysterectomy for... (Review)
Review
BACKGROUND
Primary vaginal cancer is a rare condition. Some studies have revealed an increased risk of vaginal cancer among patients who have undergone hysterectomy for premalignant and malignant cervical disease. However, there is limited literature available on primary vaginal cancer following hysterectomy for benign conditions.
OBJECTIVES
This review aimed to investigate available evidence on clinical characteristics, treatments, and outcomes of primary vaginal cancer following hysterectomy for benign diseases. Additionally, we provide a case of a patient who developed primary vaginal cancer 10 years after undergoing hysterectomy for abnormal uterine bleeding.
SEARCH STRATEGY
We conducted a comprehensive literature search on PubMed, Scopus, Web of Science using a combination of title and abstract represented by "hysterectomy", and "vaginal cancer"; "vaginal neoplasm"; and "cancer of vagina". No article type restrictions were applied.
MAIN RESULTS
Eight studies with a total of 56 cases were included in this review. The main symptom observed was vaginal bleeding. Squamous cancer was found to be the most common type, followed by adenocarcinoma. The majority of vaginal cancer cases occurred approximately 10 years after undergoing hysterectomy. The most common location of the tumor was in the vaginal apex. The management approaches varied and details were available in 25 cases. Among these, 7 cases were treated with radiotherapy alone, 1 case received concurrent chemoradiation therapy, and the of rest of the cases underwent surgery as the primary treatment, with or without additional adjuvant therapy. Data of follow-up was available for 15 cases, with 2 cases resulting in death and 2 cases experiencing recurrence. The other cases were alive and well at the time of considered follow up.
CONCLUSION
Primary vaginal cancer after hysterectomy for benign conditions is an extremely rare condition. It is essential to have high-level evidence to guide the screening and treatment strategy for this rare condition. A part of women who have undergone hysterectomy for benign disorders can benefit from vaginal cytology evaluation. It is reasonable to postpone the initial screening after surgery and to extend the interval between subsequent screenings. Further retrospective case-control trials are expected to determine which specific subgroups of patients mentioned above might most potentially benefit from screening. The treatment decision for vaginal cancer after hysterectomy is more favorable to radiotherapy-based management rather than surgery. Vaginal endometrioid adenocarcinoma may arise from the malignant transformation of endometriosis. More studies are expected to investigate the correlation between these two diseases.
PubMed: 38347832
DOI: 10.3389/fonc.2024.1334778 -
Turk Patoloji Dergisi Mar 2024Approximately 95% of cervical squamous cell carcinomas are associated with high-risk HPV, with a small number of HPV-independent tumors. However, low-risk HPV types have...
A Low-Risk HPV-Associated Well-Differentiated Squamous Cell Carcinoma of the Cervix with Low-Grade Squamous Intraepithelial Lesion Morphology: Clinical and Pathologic Diagnostic Difficulties and Review of the Literature.
Approximately 95% of cervical squamous cell carcinomas are associated with high-risk HPV, with a small number of HPV-independent tumors. However, low-risk HPV types have also been detected in rare cervical squamous cell carcinomas. Low-grade squamous intraepithelial lesion-related changes are a rare morphologic finding in cervical squamous cell carcinoma. We present the case of a 30-yr-old woman who presented with pelvic pain and foul-smelling vaginal discharge showing an exophytic lesion protruding from the cervix. Repeated superficial biopsies showed a low-grade squamous intraepithelial lesion (LSIL) characterized by binucleation and koilocytosis. Chromogenic in-situ hybridization revealed the presence of HPV6/11. The absence of high-risk HPV was confirmed by PCR. After following the patient for nine months without intervention, type III hysterectomy and bilateral pelvic paraaortic lymphadenectomy were performed. Microscopic examination showed well-differentiated squamous cell carcinoma with solid epithelial islands and extensive eosinophilic cytoplasm without pleomorphism. HPV 6 and 11 were also detected with chromogenic in-situ hybridization. Neoplasm invaded the full-thickness of the cervical wall and infiltrated the vagina, parametrium, the proximal ureter and bladder. The patient who received chemoradiotherapy is disease-free at 36 months follow-up. Low-risk HPV-related well-differentiated invasive squamous lesions exist, and such lesions could be a diagnostic pitfall for gynecologists and pathologists; in these cases, radiologic-pathologic correlation and radiologic guided biopsy are mandatory.
PubMed: 38530111
DOI: 10.5146/tjpath.2024.13189 -
Urology Case Reports Sep 2023A 74-year-old transgender female presented with urinary difficulty and a painful lesion at her neo-vagina, 47 years after undergoing gender-affirming vaginoplasty....
A 74-year-old transgender female presented with urinary difficulty and a painful lesion at her neo-vagina, 47 years after undergoing gender-affirming vaginoplasty. Initial biopsy reported Low-Grade Squamous Intraepithelial Lesion (LGSIL), while MRI revealed no inguinal or pelvic lymphadenopathy. Patient underwent partial neo-vaginectomy with wide local excision and formal urethroplasty. Pathology revealed verrucous carcinoma of the neovagina, a rare neoplasm in transgender female patients. This case highlights the importance of considering squamous cell carcinoma in the differential diagnosis of patients presenting lesions at neo-vagina and the need of screening methods for early detection of such neoplasms.
PubMed: 37719184
DOI: 10.1016/j.eucr.2023.102488