Chronic interstitial ectopic pregnancy presenting with a negative urine pregnancy test.

The ampulla portion of the fallopian tube is the most common site of ectopic pregnancy (70%), with approximately 2% of pregnancies implanted in the interstitial portion. In general, an interstitial ectopic pregnancy (IEP) is difficult to diagnose and is associated with a high rate of complications-most patients with an IEP present with severe abdominal pain and haemorrhagic shock due to an ectopic rupture. Chronic tubal pregnancy (CTP) is an uncommon condition with an incidence of 20%. The CTP has a longer clinical course and a negative or low level of serum beta-human chorionic gonadotropin due to perished chorionic villi. This study presents a case of a woman who was diagnosed with a chronic IEP (CIEP) which was successfully treated by surgery. This case also acts as a cautionary reminder of considering a CIEP in women of reproductive age presenting with amenorrhea, vaginal bleeding and a negative pregnancy test.

Depot medroxyprogesterone acetate and endometrial cancer: A multicenter case-control study.

OBJECTIVE: To assess the associations between depot medroxyprogesterone acetate (DMPA) and endometrial cancer. METHODS: This multicenter case-control study was conducted among tertiary hospitals in Thailand. Patients were women with endometrial cancer. Controls were women admitted for other conditions, matched for age within 5 years of the patients' age. The controls had to have no abnormal vaginal bleeding, history of hysterectomy, or cancers of the other organs. A standardized questionnaire was used to gather information. Conditional logistic regression was applied to calculate adjusted odds ratio (aORs) and 95% confidence intervals (CIs). RESULTS: During 2015 to 2021, 378 patients and 1134 controls were included. Ever use of DMPA was associated with a 70% decreased overall risk of endometrial cancer (aOR, 0.30 [95% CI, 0.21-0.42]). Endometrial cancer risk declined by 3% (aOR, 0.97 [95% CI, 0.96-0.98]) for every 3 months of DMPA use. The magnitude of the decline in endometrial cancer risk did not vary appreciably by cancer subtypes (aOR, 0.26 [95% CI, 0.17-0.41] and 0.38 [95% CI, 0.22-0.65] for low-grade and high-grade tumors, respectively). CONCLUSIONS: Depot medroxyprogesterone acetate use was inversely associated with endometrial cancer risk in a duration-dependent manner. This association was independent of cancer subtype.

Mathematical Modelling of Cervical Precancerous Lesion Grade Risk Scores: Linear Regression Analysis of Cellular Protein Biomarkers and Human Papillomavirus E6/E7 RNA Staining Patterns.

The current practice of determining histologic grade with a single molecular biomarker can facilitate differential diagnosis but cannot predict the risk of lesion progression. Cancer is caused by complex mechanisms, and no single biomarker can both make accurate diagnoses and predict progression risk. Modelling using multiple biomarkers can be used to derive scores for risk prediction. Mathematical models (MMs) may be capable of making predictions from biomarker data. Therefore, this study aimed to develop MM-based scores for predicting the risk of precancerous cervical lesion progression and identifying precancerous lesions in patients in northern Thailand by evaluating the expression of multiple biomarkers. The MMs (Models 1-5) were developed in the test sample set based on patient age range (five categories) and biomarker levels (cortactin, p16INK4A, and Ki-67 by immunohistochemistry [IHC], and HPV E6/E7 ribonucleic acid (RNA) by in situ hybridization [ISH]). The risk scores for the prediction of cervical lesion progression ("risk biomolecules") ranged from 2.56-2.60 in the normal and low-grade squamous intraepithelial lesion (LSIL) cases and from 3.54-3.62 in cases where precancerous lesions were predicted to progress. In Model 4, 23/86 (26.7%) normal and LSIL cases had biomolecule levels that suggested a risk of progression, while 5/86 (5.8%) cases were identified as precancerous lesions. Additionally, histologic grading with a single molecular biomarker did not identify 23 cases with risk, preventing close patient monitoring. These results suggest that biomarker level-based risk scores are useful for predicting the risk of cervical lesion progression and identifying precancerous lesion development. This multiple biomarker-based strategy may ultimately have utility for predicting cancer progression in other contexts.

An in vitro carcinogenesis model for cervical cancer harboring episomal form of HPV16.

Deregulated expression of viral E6 and E7 genes often caused by viral genome integration of high-risk human papillomaviruses (HR-HPVs) into host DNA and additional host genetic alterations are thought to be required for the development of cervical cancer. However, approximately 15% of invasive cervical cancer specimens contain only episomal HPV genomes. In this study, we investigated the tumorigenic potential of human cervical keratinocytes harboring only the episomal form of HPV16 (HCK1T/16epi). We found that the HPV16 episomal form is sufficient for promoting cell proliferation and colony formation of parental HCK1T cells. Ectopic expression of host oncogenes, MYC and PIK3CAE545K, enhanced clonogenic growth of both early- and late-passage HCK1T/16epi cells, but conferred tumor-initiating ability only to late-passage HCK1T/16epi cells. Interestingly, the expression levels of E6 and E7 were rather lower in late-passage than in early-passage cells. Moreover, additional introduction of a constitutively active MEK1 (MEK1DD) and/or KRASG12V into HCK1T/16epi cells resulted in generation of highly potent tumor-initiating cells. Thus an in vitro model for progression of cervical neoplasia with episomal HPV16 was established. In the model, constitutively active mutation of PIK3CA, PIK3CAE545K, and overexpression of MYC, in the cells with episomal HPV16 genome were not sufficient, but an additional event such as activation of the RAS-MEK pathway was required for progression to tumorigenicity.

P16/Ki-67 Dual Staining in Positive Human Papillomavirus DNA Testing for Predictive Diagnosis of Abnormal Cervical Lesions in Northeastern Thai Women.

OBJECTIVE: Cervical cancer screening can effectively reduce new cervical cancer cases, including in Thailand. The abnormal results are subsequently referred for colposcopy. To avoid unnecessary colposcopy, an efficient triage is still needed for validation. This study aimed to investigate the overall positivity of cytology-based screening, HPV detection, and p16/Ki-67 dual staining and evaluate different triage strategies for predictive diagnosis of abnormal cervical lesions in northeastern Thailand. METHODS: Cervical cells were collected from 191 women who came for cervical screening in the gynecological outpatient department during March 2019-February 2020. Pap smear samples were classified into 6 groups including 17 atypical glandular cells (AGC), 21 atypical squamous cells of undetermined significance (ASC-US), 7 atypical squamous cells - cannot exclude HSIL (ASC-H), 26 low-grade squamous intraepithelial lesions (LSILs), 19 high-grade SILs (HSILs) and 101 no squamous intraepithelial lesion (noSIL). Polymerase chain reaction (PCR) was performed for HPV DNA detection. HPV genotyping was determined by reverse line blot hybridization. P16/Ki-67 dual staining was performed by using CINtec PLUS Cytology kit. Biopsies from abnormal screening were collected for surgical pathology classification. RESULTS: High-risk HPV (HR-HPV) infection was 2.97%, 29.41%, 38.10%, 57.14%, 46.15% and 84.21% in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL cytology respectively. P16/ Ki-67 in noSIL, AGC, ASC-US, ASC-H, LSIL and HSIL was 0.99%, 5.88%, 9.52%, 42.86%, 26.92% and 63.16%, respectively (P-value < 0.001). Among p16/Ki-67 positive cases, 96.15% (25/26) were infected with HPV and 84.62% (22/26) were HR-HPV. The overall positivity of each and co-testing between cytology or HPV DNA testing or p16/Ki-67 dual staining was evaluated. In each cervical lesion, primary HPV DNA testing showed the highest sensitivity, but low specificity. The combined all HPV/HR-HPV with p16/Ki-67 detection increased the specificity of abnormal cervical lesions. CONCLUSION: P16/Ki-67 dual stain cytology in HPV-positive women performs well for diagnosis of abnormal cervical lesions and should be considered for management of HPV-positive women to avoid unnecessary colposcopy referrals.

Predictive value of 'Smartscopy' for the detection of preinvasive cervical lesions during the COVID-19 pandemic: a diagnostic study.

OBJECTIVE: To evaluate the performance of "Smartscopy" in diagnosing preinvasive cervical lesions among patients with abnormal cervical cancer screening results obtained during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: This diagnostic study enrolled non-pregnant women with abnormal cervical cancer screening results obtained at the colposcopy clinic at Srinagarind Hospital (Khon Kaen, Thailand) between September 2020 and March 2021. Two colposcopists independently evaluated the uterine cervix using a smartphone and colposcopy. Cervical biopsies and endocervical curettage were performed in accordance with standard procedures. The diagnostic performance of a smartphone in detecting low-grade squamous intraepithelial lesions or worse plus (LSIL+) and high-grade squamous intraepithelial lesions plus (HSIL+) was assessed. RESULTS: In total, 247 patients were included. There was high agreement between the two colposcopists (κ=0.88; 95% confidence interval [CI], 0.82-0.93). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the smartphone to detect LSIL+ were 96.6% (95% CI, 91.6-99.1), 12.9% (95% CI, 8.06-19.2), 46.2% (95% CI, 39.7-52.4), 83.3% (95% CI, 62.6-95.3), and 0.49% (95% CI, 0.43-0.55), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of smartscopy in diagnosing HSIL+ were 67.6% (95% CI, 55.2- 78.5), 85.4% (95% CI, 79.9-90.0), 60.5% (95% CI, 48.6-71.6), 88.9% (95% CI, 83.7-92.9), and 81.0% (95% CI, 0.75-0.85), respectively. CONCLUSION: Smartscopy demonstrated a remarkable correlation with colposcopy and a high diagnostic performance value for the detection of preinvasive cervical lesions. Therefore, smartscopy may be an alternative tool for detecting abnormal cervical lesions in low to medium medical resource settings. Smartscopy may be applied in telemedicine during the COVID-19 pandemic.

Clinical outcomes of immunohistochemistry of the p53 Staining pattern in high-grade serous ovarian carcinoma.

OBJECTIVE: To investigate the prevalence of p53 mutations and associated factors between immunohistochemistry (IHC) and p53 staining patterns among patients with high-grade serous ovarian carcinoma (HGSOC). METHODS: This study is a retrospective review. A total of 62 patients with HGSOC underwent surgery at Srinagarind Hospital between January 2016 and December 2020. Histological examination was performed based on a combination of morphology and IHC staining with p53. The p53 immunostaining pattern was interpreted as a missense mutation, nonsense mutation, or a wild-type pattern. Missense (p53 overexpression pattern) and nonsense (null expression p53 pattern) mutations were considered p53 mutations. A wild-type pattern was defined as a p53 non-mutation. RESULTS: p53 mutations were identified in 93.6% of the patients. Subgroup analysis of the p53 mutation group between the p53 overexpression pattern and the p53 null expression pattern in terms of clinicopathological characteristics and initial treatment was performed. Patients with the p53 overexpression pattern had significantly more omental metastases than those with the p53 null expression pattern (87.8% vs. 64.7%, P=0.042). There were no statistically significant differences in median progression-free survival (PFS) (9 vs. 10 months, P=0.813) or median overall survival (OS) (12 vs. 17 months, P=0.526) between the two groups. CONCLUSION: The prevalence of p53 mutations in HGSOC patients in this study was 93.6%. Omental metastasis is a significant pathological factor in predicting overexpression p53 pattern in HGSC. However, IHC analysis of the p53 staining pattern did not affect OS or PFS among patients with HGSOC.

Endometriosis-Associated Massive Ascites in an Asian Woman: A Case Report of a Rare Clinical Entity.

Massive ascites as a presentation of endometriosis is a rare clinical entity that is most commonly seen in black nulliparous females. Herein, we describe a case of a 32-year-old multiparous Thai woman who presented with a two-year history of abdominal distension. Computerized tomography of the abdominopelvic region showed an infiltrative enhancing lesion involving the cul-de-sac and perirectal region with massive loculated ascites, suggesting carcinomatosis peritonei. Abdominal paracentesis was performed to yield fluid samples for evaluation, which revealed no malignant cells, and polymerase chain reaction (PCR) was negative for tuberculosis. The patient underwent exploratory laparotomy which revealed a large amount of serosanguinous ascites, thickened matted bowel loops, and necrotic debris covering the entire surface of the peritoneum and visceral organs. The surgical procedures included drainage of 6.5 liters of ascites, lysis adhesion, biopsy of the peritoneum, and right salpingo-oophorectomy. Histologic examination revealed benign endometrial glands with stroma at the peritoneum tissue and broad ligament. Other causes of ascites were excluded. The ascites responded to drainage and hormonal suppression. A final diagnosis of endometriosis was made based on these findings. Endometriosis should therefore be considered in differential diagnosis in women of childbearing age who present with ascites.

Extragastrointestinal stromal tumor in the rectovaginal septum associated with acute arterial occlusion.

Extragastrointestinal stromal tumors (EGISTs) arise from atypical sites, such as the omentum, mesentery, retroperitoneal space, urinary bladder, or rectovaginal septum, and account for fewer than 10% of gastrointestinal stromal tumors (GISTs). Most EGISTs are asymptomatic at the time of diagnosis, due to the fact that they rarely cause symptoms until they grow to greater than 10 cm in diameter. Common presenting symptoms are a feeling of vaginal fullness and increased urinary frequency. Cases described in previous reports have been treated with surgery with or without targeted therapy. Here we report an unusual case of an EGIST at the rectovaginal septum presenting with excessive vaginal bleeding and acute arterial occlusion. This rectovaginal mass was successfully removed using the abdominoperineal approach and did not require targeted therapy.

Rate of Significant Endometrial Pathology in Women at Low Risk for Endometrial Hyperplasia or Cancer Presenting with Abnormal Uterine Bleeding.

BACKGROUND AND OBJECTIVES: To determine the rate of significant endometrial abnormalities in premenopausal women at low risk for endometrial hyperplasia and cancer presenting with abnormal uterine bleeding (AUB). PATIENTS AND METHODS: This descriptive study was conducted from January 1, 2016 to March 31, 2019. The inclusion criteria were premenopausal women, 35-50 years, presenting with AUB, low risk for endometrial hyperplasia or endometrial cancer, and having undergone endometrial sampling or uterine curettage. Nulliparous, obesity, diabetes mellitus, polycystic ovary syndrome, chronic anovulation, infertility, tamoxifen therapy and/or a family history of uterine, ovarian, breast and colon cancer were excluded. Data regarding baseline characteristics were collected, and histopathology reports were reviewed. RESULTS: During the study period, 644 subjects were recruited, 557 of whom had adequate endometrial tissue for histopathology study. The pathology demonstrated benign in most cases (96%). The rate of significant abnormal endometrial pathology was 4% (23 cases) including 19 cases of endometrial hyperplasia without atypia (3.3%), and 4 cases of endometrial cancer (0.7%). CONCLUSION: The rate of significant abnormal endometrial pathology in premenopausal women at low risk for endometrial hyperplasia or endometrial cancer presenting with AUB was very low. This information should be incorporated into the counseling process regarding the risks and benefits of endometrial sampling.

Sexual behavior and infection with cervical human papillomavirus types 16 and 18.

OBJECTIVE: This study assessed whether sexual behavior, including engaging in early sexual intercourse and having had multiple sexual partners, can predict the risk of infection with cervical human papillomavirus (HPV) types 16 and 18. METHODS: Records were reviewed of women who underwent cervical cancer screening and were found to be infected with high-risk HPV. The genotypes of high-risk HPV were categorized as HPV 16, HPV 18, and other than 16 or 18. Early sexual intercourse was defined as first sexual intercourse at the age of 19 years or younger. Multiple sexual partners was defined as having more than three lifetime sexual partners. Associations between sexual behavior and HPV 16/18 infection were presented as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 349 women included in the study, 72 (20.6%) and 30 (8.6%) were infected by HPV 16 and 18, respectively. Eighty-two women (26.0%) reported having engaged in early sexual intercourse, and 33 (10.4%) reported having had multiple sexual partners. After adjustment for age, parity, and smoking habits, we found that women who had engaged in early sexual intercourse tended to have a higher risk of HPV 16 (OR 1.74; 95% CI 0.93-3.29), and those who had had multiple sexual partners were found to be at a significantly higher risk for HPV 18 (OR 4.58; 95% CI 1.44-14.58). CONCLUSION: Sexual behavior was associated with an increased risk of HPV 16/18 infection. Engaging in early sexual intercourse increased the risk of HPV 16 infection, and having had multiple sexual partners increased that of HPV 18.

Association of Abnormal Pap Smear with Occult Cervical Stromal Invasion in Patients with Endometrial Cancer.

Objective: The purpose of this study was to determine the association between abnormal preoperative Pap smear results and occult cervical stromal invasion in endometrial cancer patients. Methods: Medical records were reviewed of patients with endometrial cancer who had undergone surgical staging at Srinagarind Hospital. Patients with gross cervical involvement, with an unsatisfactory Pap smear, without available Pap smear results, with no cervical intraepithelial lesion/invasive cervical cancer, or who had previously undergone pelvic radiation therapy were excluded. The patients were assigned to one of two groups according their Pap smear results (negative and epithelial cell abnormalities). Logistic regression was used to determine the independent association between an abnormal Pap smear and the risk of cervical stromal invasion. Results: All cervical smears in this study were performed as conventional Pap smears. Smears were abnormal in 50 (21.0%) of the 238 patients enrolled and normal in the remaining 188 (79.0%). The types of Pap smear abnormalities included adenocarcinoma (n=22); atypical endometrial cells (n=2); atypical glandular cells (n=17); high-grade squamous intraepithelial lesions (n=4); atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (n=2); and atypical squamous cells of undetermined significance (n=3). After controlling for type of endometrial cancer, abnormal Pap smear results were found to be a significant independent factor that indicated cervical stromal invasion (adjusted OR 2.65; 95% CI 1.35 to 5.21). Conclusion: Endometrial cancer patients with abnormal Pap smears were strongly and independently associated with histopathologically diagnosed cervical stromal invasion.

Programmed Death Ligand 1 (PD-L1) Expression in Epithelial Ovarian Cancer: A Comparison of Type I and Type II Tumors

Objective: To examine the expression of programmed death ligand 1 (PD-L1) in type I and type II epithelial ovarian cancers (EOC) and its associations with outcomes. Methods: Records of 132 women with EOC were reviewed. Immunostaining of PD-L1 was performed with formalin-fixed, paraffin-embedded specimens. Expression of PD-L1 was classified into four categories (0; 1+; 2+; 3+) according to intensity of expression. Expression of PD-L1 ≥2+ was deemed to be high. Results: Of the 132 women, 75 (56.8%) and 57 (43.2%) women had type I and type II tumors, respectively. Approximately 70% of cases exhibited high PD-L1 expression. There was no significant difference in the rate of high PD-L1 expression between the two EOC types (65.3% versus 59.6%). In type I tumors, high PD-L1 expression was associated with more advanced stages (51.0% versus 34.6%), greater recurrence (46.9% versus 26.9%), and shorter median progression-free survival (27 months versus 62 months) than low expression. In type II tumors, there were no apparent differences between high and low expression of PD-L1 in terms of the percentage of advanced-stage tumors (82.6% versus 79.4%), recurrence (56.5% versus 58.8%), and median progression-free survival (21 months versus 24 months). Conclusion: high PD-L1 expression is associated with worse oncological outcomes in type I EOC. This finding emphasizes the merit of further studies to confirm this promising result and to determine the potential role of PD-L1 blockade therapy in type I EOC.

Impact of Coexisting Uterine Adenomyosis on the Survival Outcome of Patients with Endometrial Cancer: A Retrospective Cohort Study

Objective: To determine the effects of uterine adenomyosis on endometrial cancerrecurrence rates. Methods: This retrospective cohort study reviewed all consecutive patients diagnosed with endometrial cancerwho underwent total hysterectomy-based surgical staging at Srinagarind Hospital between January, 2010 and January, 2016. The patientswere divided into two groups:a uterine adenomyosisgroup and a non-adenomyosis group. Patient demographics, type of surgery, histopathology, stage of endometrial cancer, adjuvant treatment, and survival outcomes were compared. Results: A total 350 patients were enrolled, with 132 (37.71%) in the adenomyosis group and 218 (62.29%) in the nonadenomyosis group. Deep myometrial invasion and lymphovascular space invasion (LVSI) were more commonly found among patients who had no adenomyosis compared to those with adenomyosis(52.8% vs 39.4%, P=0.02 and 53.2% vs. 38.6%, P=0.01). There were no significant differences in terms of five-year recurrence-free survival (HR=1.47; 95%CI 0.88-2.44) and five-year overall survival (HR=0.81; 95%CI 0.43-1.53) between the two comparison groups. Conclusion: Coexisting uterine adenomyosis in endometrial cancer wasassociated withdeep myometrial invasion and LVSI but did not have significant impact on survival.

Histopathology of Women with "Atypical Squamous Cells Cannot Exclude High-Grade Squamous Intraepithelial Lesion" (ASC-H) Smears

Objectives: To evaluate prevalence of underlying significant pathologies among women with cervical smears rated as 'atypical squamous cells cannot exclude high grade squamous intraepithelial lesion (ASC-H)', as well as associated risk factors. Methods: Medical records were reviewed of all consecutive women with ASC-H smears who had undergone colposcopy at Srinagarind Hospital from January 2008 to July 2016. Significant pathology results included cervical intraepithelial neoplasia (CIN) 2-3, adenocarcinoma in situ (AIS), endometrial hyperplasia, and cancer of any original site. Result: During the study period, 133 women with ASC-H were reviewed. The mean age was 45.3 years (range 21-72). The histopathologic results for the 133 women were as follows: no lesions (58; 43.6%), CIN 1 (34; 25.6%), CIN 2-3 (33; 24.8%), AIS (2; 1.5%), and cervical cancer (6; 4.5%). The overall rate of significant pathology was 30.8% (95% confidence interval, 22.9%-38.8%). Women younger than 40 years old carried a higher risk of harboring significant lesions when compared to older women (41.7% versus 27.8%, respectively). There was no significant impact of parity and menopausal status on the risk of significant pathology results. Conclusion: The rate of significant histopathologies among women with ASC-H smears in this study was approximately 31% and the associated risk factor was patient age.

Suppression of miR-22, a tumor suppressor in cervical cancer, by human papillomavirus 16 E6 via a p53/miR-22/HDAC6 pathway.

MicroRNAs (miRNAs) are small non-coding RNAs that function to down-regulate gene expression involving in various cellular processes related to carcinogenesis. Recently, miR-22 was identified as a tumor-suppressing miRNA in many human cancers. However, the regulatory mechanism and the specific function of this miRNA in cervical cancer remain unclear. In the present study, we carried out gene transfection, western blot and quantitative RT-PCR to explore the regulatory mechanism and the functional role of miR-22 in cervical cancer. We verified that miR-22 was down-regulated in cervical cancer tissues and cervical cancer cell lines relative to matched non-tumor tissues and normal human cervical keratinocyte line (HCK1T). By contrast, histone deacetylase 6 (HDAC6) was inversely correlated with miR-22 in both cervical tissues and cancer cell lines. Mechanically, HDAC6 was down-regulated by miR-22 at the post-transcriptional level, via a specific target site within the 3'UTR, identified by a luciferase reporter assay. Moreover, we also showed that the correlation between miR-22 and HDAC6 expression was regulated by an E6/p53 pathway in HCK1Ts expressing HPV16 E6. For functional study, an ectopic expression of miR-22 could inhibit cell proliferation and migration, and could induce apoptosis of cervical cancer cell lines. These findings demonstrated that miR-22 was down-regulated in cervical cancer and inversely collated with its downstream target HDAC6. MiR-22 acts as tumor suppressor by inhibiting proliferation and migration, and by inducing apoptosis of cervical cancer cell lines by targeting the 3'UTR of HDAC6. This newly identified E6/p53/miR-22/HDAC6 regulatory network might be a candidate therapeutic target for cervical cancer.

Incidence and risk factors for insufficient endometrial tissue from endometrial sampling.

OBJECTIVE: To assess the incidence of and factors that predict insufficient tissue after endometrial sampling. METHODS: This study reviewed the records of women undergoing endometrial sampling at Khon Kaen University's Srinagarind Hospital between June 2014 and June 2015. It excluded cases in which the device could not be inserted into the uterine cavity due to pain intolerance or equipment failure. The criterion for diagnosing insufficient endometrial tissue was a lack of any intact tissue fragments containing both glands and stroma. RESULTS: Medical records of 233 women were reviewed. Insufficient tissue following endometrial sampling was noted in 67 cases (28.8%; 95% confidence interval [CI]=23.0-35.0). Histologic results in the remaining 166 women included normal pathological endometrium (121, 51.9%), endometrial polyps (7, 3.0%) endometrial hyperplasia (27, 11.6%), and endometrial cancer (11, 4.7%). According to multivariable analysis, menopausal status (odds ratio [OR] =3.60, 95% CI=1.84-7.05) and endometrial thickness of less than 8 mm (OR=3.91, 95% CI=1.49-10.21) were significant independent predictors for insufficient endometrial tissue after endometrial sampling. CONCLUSION: The incidence of insufficient tissue following endometrial sampling was 28.8%. Significant independent factors associated with an increased risk of insufficient tissue were menopausal status and endometrial thickness of less than 8 mm.

Clear Cell Carcinoma Arising in Vulvar Endometriosis.

We report a case of vulvar clear cell adenocarcinoma in a woman presenting with a lump and pain in the right side of the labia majora. Three years prior to this visit, she underwent a total abdominal hysterectomy with bilateral salpingooophorectomy and excision of a labial mass. Pathological examination revealed adenomyosis and multiple leiomyomas in the uterus, endometriotic cysts in both ovaries, and foci of atypical endometriosis in the labial mass. The results of an incision biopsy performed before referral indicted only apocrine hidrocystoma. Physical examination revealed a hard mass at the right labia majora extending to the right groin. The mass seemed to be in continuity with the pubic symphysis that would require pubic bone excision and reconstruction with flap surgery to achieve complete resection. However, the patient refused such extensive surgery. Based on previous diagnosis of vulvar endometriosis, she had been treated with GnRH agonists and depot medroxyprogesterone acetate. However, the mass developed into an ulcer and increased in size. A second biopsy of the mass was undertaken, and the pathological diagnosis was clear cell carcinoma with coexisting atypical endometriosis. Computed tomography of the abdominopelvic region showed an ulcerative mass at the right labia majora and nodal metastasis at the external iliac and inguinal regions. Systemic chemotherapy was administered. The growth of the tumors stabilized during the first two cycles of chemotherapy but rapidly progressed thereafter. At 17 months after her initial presentation, the patient passed away due to the progression of the disease.

Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

A Case Report of High-Grade Endometrial Stromal Sarcoma: A Rare Cause of Abnormal Uterine Bleeding in a Young Woman.

High-grade endometrial stromal sarcoma (HG-ESS) is a rare clinical entity, particularly among young women, and only few cases have been reported in the literature. Herein, we describe the case of a 21-year-old woman who presented with a four-month history of excessive bleeding per vagina. Endometrial curettage and cervical biopsy revealed a malignant round cell tumor suggestive of metastatic sarcoma of uterine origin. Computed tomography of the abdominopelvic region showed an enlarged uterus with diffused thickening throughout the entire endometrial cavity. Intraabdominal lymphadenopathy and ascites in the pelvic cavity were noted. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, resections of the enlarged pelvic nodes, omentectomy, and biopsy of the peritoneal nodules in the cul-de-sac. Histological examination revealed a tumor with a permeative growth pattern composed of uniformly high-grade round cells with brisk mitotic activity and extensive lymphovascular space invasion. Sections of the pelvic lymph nodes on both sides and the peritoneal nodule revealed multiple metastatic foci. Immunohistochemical studies showed positive diffuse staining for vimentin, CD 10, and cyclin D1. The pathological diagnosis was HG-ESS stage IIIC. The patient experienced rapid progression of the disease while receiving adjuvant treatment and succumbed eight months after the operation. HG-ESS is a rare cause of AUB in adolescents and young women but should be considered in the differential diagnosis.