Rarity of fetal cells in exocervical samples for noninvasive prenatal diagnosis

Objectives The possibility to isolate fetal cells from pregnant women cervical samples has been discussed for five decades but is not currently applied in clinical practice. This study aimed at offering prenatal genetic diagnosis from fetal cells obtained through noninvasive exocervical sampling and immuno-sorted based on expression of HLA-G. Methods We first developed and validated robust protocols for cell detection and isolation on control cell lines expressing (JEG-3) or not (JAR) the HLA-G antigen, a specific marker for extravillous trophoblasts. We then applied these protocols to noninvasive exocervical samples collected from pregnant women between 6 and 14 weeks of gestational age. Sampling was performed through insertion and rotation of a brush at the ectocervix close to the external os of the endocervical canal. Finally, we attempted to detect and quantify trophoblasts in exocervical samples from pregnant women by ddPCR targeting the male SRY locus. Results For immunohistochemistry, a strong specific signal for HLA-G was observed in the positive control cell line and for rare cells in exocervical samples, but only in non-fixative conditions. HLA-G positive cells diluted in HLA-G negative cells were isolated by flow cytometry or magnetic cell sorting. However, no HLA-G positive cells could be recovered from exocervical samples. SRY gene was detected by ddPCR in exocervical samples from male (50%) but also female (27%) pregnancies. Conclusions Our data suggest that trophoblasts are too rarely and inconstantly present in noninvasive exocervical samples to be reliably retrieved by standard immunoisolation techniques and therefore cannot replace the current practice for prenatal screening and diagnosis.

Mesonephric Like-Carcinoma (MLCA) of the Uterus with a Predominant Spindled Morphology: A Case Report

Introduction/Objective Mesonephric-like carcinoma of the uterus is an increasingly recognized carcinoma with mesonephric differentiation, but without association with mesonephric remnants. We present a case of a 60-year-old woman presented with postmenopausal bleeding. Methods/Case Report Pelvic MRI showed possibly a cervical lobulated lesion (4.4cm) extending into the endocervical canal. Initial biopsy of this mass showed a spindle cell neoplasm raising possibility of an endometrial stromal sarcoma. On subsequent radical hysterectomy, there was a mass arising in the lower uterine segment (LUS) with circumferential cervical involvement. The tumor was comprised of sheets of epithelioid to spindle cells with scant cytoplasm and indistinct cell borders. Abundant mitotic figures and foci of necrosis were identified. Focal areas showed dense sclerosis with cords of cells, and only rare areas showed tubule formation with scant secretions. By immunohistochemistry (IHC), the tumor cells were positive for keratin AE1/AE3 (strong, diffuse), TTF-1, p63, p16, CD10 (with luminal accentuation); PAX8, desmin and caldesmon showed focal/rare positivity. Other markers were negative, including GATA3 (patchy, weak), ER and PR. Mismatch repair proteins were intact. Next-generation sequencing (NGS) revealed a KRAS mutation. Considering strong expression of epithelial markers, focal tubule formation with positive TTF-1 and negative GATA-3 labeling, and absence of identified mesonephric remnants, the tumor was classified as a high-grade mesonephric-like carcinoma of the uterus (LUS). Pelvic lymph nodes were negative (pT2 N0), and the patient is receiving cisplatin and external beam radiation. Results (if a Case Study enter NA) NA Conclusion MLCA with a prominent spindled/sarcomatoid component can be difficult to diagnose. Ancillary testing including a broad IHC panel with TTF-1, GATA-3 and NGS may be useful to aid in the diagnosis.

Human Papillomavirus Types Associated with Cervical Dysplasia among HIV- and Non-HIV-Infected Women Attending Reproductive Health Clinics in Eastern Kenya

Background. Human papillomavirus (HPV) causes over 99% of all cervical cancer globally. In 2019, it was responsible for 3286 deaths in Kenya. Data on the epidemiological distribution of HPV genotypes by cervical dysplasia and HIV-infected women which is important in designing prevention strategy monitoring treatment and management of cervical cancer is lacking in Eastern Kenya. Objective. To determine HPV genotype prevalence and their association with cervical dysplasia among HIV-infected (cases) and noninfected (control) women aged 18-48 years seeking reproductive healthcare. Methods. A cervical broom was softly rotated 360 degrees five times to exfoliate cells from the region of the transformation zone, squamocolumnar junction, and endocervical canal for HPV genotyping. Social-demographic and risk factors responsible for HPV acquisition were collected using a questionnaire. Laboratory outcome and questionnaire data statistical relationships were computed using Pearson chi-square test. Results. 317 women (cases: 161 (50.8%), control 156 (49.2%), mean age: 34.3, SD ± 10.4 , range 18-46 years) were recruited from Embu (85/317 (26.8%)), Isiolo (64/317 (20.2%)), Kirinyaga (56/317 (17.7%)), Meru (81/317 (25.6%)), and Tharaka-Nithi (31/317 (9.8%)). The frequency HPV genotypes detected by cervical dysplasia were CIN1 (cases: HPV81 (12/317 (3.8%)), HPV11 (2/317 (0.6%)); control: HPV53 and 66 coinfection (1/317 (0.3%)), CIN2 (cases: HPV11, HPV16, HPV66 ((1/317 (0.3%) each), HPV81 (6/317 (1.9%)), and single case (1/317 (0.3%)) of HPV11 and 66, HPV81 and 44, HPV81 and 88, HPV9 and 53, and HPV16 and 58 coinfection; control: HPV81 (2/317 (0.6%)) and invasive cervical cancer (cases: HPV16 (1/317 (0.3%)) and HPV81 (3/317 (0.9%)); control: HPV16 and 66 (1/317 (0.3%))).Conclusions. There was a higher frequency of both high-risk and low-risk HPV genotypes associated with cervical dysplasia among HIV-infected than HIV-uninfected women seeking reproductive health care. This study provides epidemiological data on the existence of nonvaccine HPV types associated with cervical dysplasia in the region.

Giant hamartomatous polyp of the uterine cervix with heterologous mesenchymal tissue in a child: a case report

Background Polyps of the uterine cervix are one of the most common benign hyperplastic lesions occurring in the female genital tract that usually arise from the endocervical canal and are believed to be the result of reactive changes due to long-standing chronic inflammation, multiparty, and foreign bodies. Cervical polyps are usually small in size (less than 4 cm) that are commonly found in adult women; however, a few cases of giant polyps and the rare occurrence of these lesions in children have also been reported. Heterotopias and malignant transformation in cervical polyps are considered to be very rare. Case presentation We present the case of a 10-year-old Afghan girl with a giant pedunculated mass protruding out of the uterine cervix that was accompanied by abdominal pain and mass sensation. The mass was completely excised by surgical intervention and the specimen was submitted for histopathological evaluation. Upon gross and microscopic examination, the characteristic findings of a hamartomatous polyp with heterologous mesenchymal tissue in the form of mature cartilage were seen. To the best of our knowledge, this is the first case of a giant (17.5 cm) hamartomatous polyp of the uterine cervix in this age group. Conclusion Giant hamartomatous cervical polyps rarely occur in patients below 10 years of age. The majority of these lesions are benign; however, a few cases with malignant transformation are also reported, which demands elaborate investigations into the etiopathogenesis and nature of the lesions.

Diagnostic Three Slides Pap Test Compared to Punch Biopsy and Endocervical Curettage in Confirmed HSIL+ Diagnosis

Objective: The aim of the study was to evaluate the accuracy of the diagnostic Pap test (DPT) on three slides and punch biopsy and endocervical curettage (PB/ECC) compared with the final biopsy material in the detection of high-grade squamous intraepithelial lesion (HSIL). Materials and methods: Patients treated with conization after previous DPT and PB/ECC were analyzed. The findings of the DPT and PB/ECC as well as of the endocervical brush cytology and ECC were compared with the final conus histology. Results: 150 patients were analyzed, and final histology verified 145 cases of HSIL and 3 cancers. The percentage of confirmed HSIL cytology was 97%, while for PB/ECC it was 79% with 30/145 false negative results. The correlation between Pap test and PB/ECC showed that the diagnostic accuracy of DPT is significantly higher (p < 0.0001). Endocervical brush cytology confirmed HSIL+ in the endocervical canal in 83% and ECC in 35% of cases (p < 0.0001). Conclusion: The DPT on three slides enables better detection of HSIL compared to PB/ECC, particularly for lesions localized in the endocervical canal sampled with a cytobrush. A high quality DPT could represent a surrogate for PB/ECC and open the possibility of direct access to therapeutic procedure.

Bleeding cervical varices in pregnancy: A case report and review of the literature

BACKGROUND: Venous varicosities are a relatively common finding during pregnancy. Rarely, varices can arise in the cervix and cause life-threatening maternal hemorrhage. This article offers an example of a patient who was diagnosed with bleeding cervical varices during pregnancy and summarizes the diagnosis and treatment strategies for the 20 other reported cases in the literature. METHODS: A PubMed literature search using the following terms was performed to gather data for the literature review: “bleeding” or “hemorrhage” and “cervical varices” or “cervical varix” or “cervical varicosities” and “pregnancy” or “obstetric” or “maternal.” Individual references cited in each article were also evaluated for inclusion in this review. RESULTS: A 50-year-old gravida 7 para 1 presented at 12 4/7 weeks with vaginal bleeding. Endo-vaginal ultrasound showed enhanced color Doppler signal in the endocervical canal. During a speculum exam, she was found to have active bleeding from ruptured cervical varicosities and required blood and fresh frozen plasma transfusion. Hemostasis was achieved with interrupted suture ligation. A McDonald cerclage was subsequently placed. She continued pregnant until delivery via cesarean section at 37 2/7 weeks. To date, there have only been 20 other reported cases of bleeding cervical varices during pregnancy. CONCLUSIONS: This case report and review of the literature highlight the importance of including bleeding cervical varices in the differential diagnosis of maternal hemorrhage and offer a treatment strategy if cervical varicosities are discovered during pregnancy.

A uterine cervix supporting device (Con-CapTM) for reducing canal stenosis after Loop Electrosurgical Excisional Procedure

BACGROUND: Cervical stenoses are one of the main long-term consequences after conization of the uterine cervix. OBJECTIVE: The purpose of this study was to evaluate the safety and efficacy of a uterine cervix supporting device (Con-CapTM) in reducing uterine cervical stenosis after Loop Electrosurgical Excisional Procedure (LEEP). METHODS: We enrolled 112 patients who underwent LEEP between March 2017 to May 2019. Con-CapTM was inserted into the uterine endocervical canal for 4 weeks after LEEP. Laboratory values and clinical symptoms were evaluated. The presence of uterine cervical narrowing was determined at 2 weeks after removal of the Con-CapTM. Data were analyzed using the two-sample t test and χ2 test. RESULTS: A total of 78 women completed the 6-week study period. Thirty-four patients did not complete the study period. The diameter of the uterine cervical canal was significantly greater at postoperative 6 weeks than preoperatively (Hegar dilator No, 2.10 ± 0.56 vs. 3.21 ± 0.71, P< 0.01). The complications were acceptable. CONCLUSIONS: Con-CapTM can be used to reduce uterine cervical stenosis safely and effectively after conization of uterine cervix.

P16INK4a Expression of Uterine Cervical Biopsy Specimen in SBMCH

Introduction: The cervix is the lower portion of the uterus which connects this organ to the vagina through the endocervical canal. It is divided into the vagina (portiovaginalis) and one that lies above the vaginal vault (supravaginal portion). The outer surface of the portiovaginalis is known as the ectocervix or exocervix and the portion related to the endocervical canal corresponds to the endocervix. Carcinoma cervix accounts for the most common form of cancer by 13% of all the women affected cancers. The P16INK 4a is a tumour suppressor protein which is a CDKN2A gene product, an inhibitor of cyclin dependent kinase (CDK) 4 and 6 which is encoded by tumour suppressor gene INK 4a. Objective: The present study is to evaluate the P16INK 4a expression in cervical biopsy specimens and to correlate it with the histopatholgical findings. Materials and Methods: Cervical biopsy specimens were processed using rotary microtome and tissue blocks cut in sections of 3-5 μm was taken. Results: P16INK4a expression on cervical biopsy specimen showed that those with inflammatory cervical histology, benign lesions of the cervix along with premalignant lesions of cervix are negative for P 16INK4a and all malignant lesions are P 16INK4a positive. Conclusion: Hence P16INK4a immunoreactivity may be used for the diagnosis of neoplastic lesions of the cervix. But in our study, only a small size sample was positive. So, P16INK4a is used as one of the valuable markers for diagnosing neoplastic lesions of the cervix.

An Algorithm for Treatment of Cervical Pregnancy: Report of a Series of Eight Patients

Being considered as an important life-threatening condition, Cervical Pregnancy (CP) is defined as the implantation and growth of the gestational sac in the endocervical canal. Due to high maternal mortality and morbidity expectant management is not recommended. There is no definite treatment for this complication. During this case series study, we usedan algorithm for CP treatment according to gestational age, presence of fetal heart activity, hemodynamic stability, and patients desire for future fertility in 8 patients. We used a combination of several modalities such as fetal heart reduction, systemic methotrexate, and uterine artery embolization to successfully treat all of them. Reproductivity ability of all patients has been reserved and 3 pregnancies including 2 terms and 1 preterm occurred during the follow-up period.