Role of sentinel lymph node evaluation during hysterectomy for preoperative pathology diagnosis of endometrial intraepithelial neoplasia in a community hospital setting.

OBJECTIVE: To determine the utility of sentinel lymph node (SLN) evaluation during hysterectomy for endometrial intraepithelial neoplasia (EIN) in a community hospital setting and identify descriptive trends among pathology reports from those diagnosed with endometrial cancer (EC). METHODS: We reviewed patients who underwent hysterectomy from January 2015 to July 2022 for a pathologically confirmed diagnosis of EIN obtained by endometrial biopsy (EMB) or dilation and curettage. Data was obtained via detailed chart review. Statistical testing was utilized for between-group comparisons and multivariate logistic regression modeling. RESULTS: Of the 177 patients with EIN who underwent hysterectomy during the study period, 105 (59.3%) had a final diagnosis of EC. At least stage IB disease was found in 29 of these patients who then underwent adjuvant therapy. Pathology report descriptors suspicious for cancer and initial specimen type obtained by EMB were independently and significantly associated with increased odds of EC diagnosis (aOR 8.192, p < 0.001;3.746, p < 0.001, respectively). Operative times were not increased by performance of SLN sampling while frozen specimen evaluation added an average of 28 min to procedure length. Short-term surgical outcomes were also similar between groups. CONCLUSION: Patients treated for EIN at community-based institutions might be more likely to upstage preoperative EIN diagnoses and have an increased risk of later stage disease than previous research suggests. Given no surgical time or short-term outcome differences, SLN evaluation should be more strongly considered in this practice setting, especially for patients diagnosed by EMB or with pathology reports indicating suspicion for EC.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Should body mass index replace age to drive the decision for endometrial sampling in premenopausal women with abnormal uterine bleeding?

OBJECTIVE: This study aimed to evaluate risk factors for endometrial intraepithelial neoplasia/malignancy in premenopausal women with abnormal uterine bleeding or oligomenorrhea. Specifically, we aimed to elucidate whether body mass index (BMI) or age confers a higher risk. STUDY DESIGN: A retrospective cohort study was performed at a large academic center examining risk factors for endometrial hyperplasia/malignancy in premenopausal women undergoing endometrial sampling. RESULTS: Of the 4170 women ages 18-51 who underwent endometrial sampling from 1987 to 2019, 77 (1.85%) were found to have endometrial intraepithelial neoplasia or malignancy. Clinical predictors of EIN/malignancy in this population included obesity (OR: 3.84, 95%, p < .001), Body mass index [(OR30 vs. 25:2.11, p < .001) and OR35 vs. 30: 1.65, p < .001], Diabetes (OR: 3.6, p-value <.001), hormonal therapy use (OR: 2.93, p < .001), personal history of colon cancer (OR: 9.90, p = .003), family history of breast cancer (OR: 2.65, p < .001), family history of colon cancer (OR: 3.81, p < .001), and family history of endometrial cancer (OR: 4.92, p = .033). Age was not significantly associated with an increased risk of disease. Adjusting for other factors, a model using BMI to predict the risk of EIN/malignancy was more discriminative than a model based on age. CONCLUSIONS: Increased BMI, may be more predictive of endometrial hyperplasia/malignancy than age in premenopausal women with abnormal uterine bleeding. Modification of evaluation guidelines in a contemporary demographic setting could be considered.

Is hemoglobin A1c valuable for predicting concurrent endometrial cancer in diabetic women with endometrial intraepithelial neoplasia?

AIM: The purpose of this study was to determine the predictive value of preoperative hemoglobin A1c (HgA1c) level for endometrial cancer in diabetic women with endometrial intraepithelial neoplasia (EIN). MATERIALS AND METHODS: Six hundred patients with EIN were retrospectively studied in a tertiary referral center in Turkey between January 2014 and December 2021. One hundred and thirteen diabetic patients with EIN who met the inclusion criteria were enrolled in the study and divided into three groups according to the final pathological results: Group 1 with benign findings (n = 29), Group 2 with EIN (n = 34) and Group 3 with endometrial cancer (n = 50). Demographic, clinical and biochemical characteristics were compared among the three groups. Receiver operating characteristic analysis (ROC) was used to evaluate the predictive value of HgA1c for concurrent endometrial cancer in EIN. RESULTS: Mean preoperative HgA1c levels were different among three groups (5.41 ± 0.64, 6.01 ± 0.72, 6.65 ± 1.15, p < 0.001, respectively). The highest value of HgA1c level was found in cancer group and difference within pairs was statistically significant (p < 0.001). Age and duration of menopause were also different among groups (p < 0.005). After adjustment of HgA1c level for age and duration of menopause differences were maintained (p < 0.001), the cutoff value was detected as ≥6.05% for HgA1c and sensitivity, specificity was 60%, 70%, respectively (p < 0.001). CONCLUSIONS: HgA1c could be used in prediction of endometrial cancer. The optimal cutoff value determined in our study could be considered in predicting endometrial cancer in diabetic women with EIN.

New classification system of endometrial hyperplasia WHO 2014 and its clinical implications.

Endometrial hyperplasia (EH) is a pathological condition characterised by hyperplastic changes in endometrial glandular and stromal structures lining the uterine cavity. Endometrial hyperplasia, particularly with atypia, is a significant clinical concern because it can be a precursor of endometrial cancer. Accurate diagnosis of precancerous lesions of the endometrium and exclusion of coexisting endometrial carcinomas are absolutely required for the optimal management of patients. The classification of endometrial hyperplasia has had numerous terminology. According to the classification of WHO94, based on glandular complexity and nuclear atypia, EH is divided into four groups: non-atypical endometrial hyperplasia (simple, complex) and atypical endometrial hyperplasia (simple, complex). Estimated risk of progression of atypical hyperplasia to endometrial cancer is 8-29%. The American College of Obstetricians and Gynaecologists and the Society of Gynaecological Oncology states that endometrial intraepithelial neoplasia (EIN) classification is superior to the World Health Organisation (WHO 94) classification for histology of endometrial hyperplasia. However, the WHO classification system remains the most commonly used and reported in existing literature. The new classification, WHO 2014, accepted by the International Society of Gynaecological Pathologists, divided hyperplasia into two groups: benign hyperplasia and atypical hyperplasia/endometrial intraepithelial neoplasia (EIN). The WHO 2014 schema is more likely to successfully identify precancerous lesions than the WHO94 classification.

Assessing the prognostic value of PAX2 and PTEN in endometrial carcinogenesis.

In order to avoid the consequences of over- and under-treatment of endometrial hyperplasia, diagnostic accuracy and progression risk assessment must be improved. The aim of this study was to assess whether PAX2 or PTEN expression could predict progression-free survival in endometrial intraepithelial neoplasia (EIN) and endometrial endometrioid carcinoma (EEC). Immunohistochemistry for detection of PAX2 and PTEN was performed on 348 endometrial samples; 75 proliferative endometrium (PE), 36 EIN and 237 EEC. Cases classified as PTEN null (1 or more glands negatively stained) were more prevalent in EEC than in PE and EIN (64% EEC vs 11% PE/EIN). A progressive decrease in PAX2 expression was observed from PE to EIN to EEC. Long-term clinical follow-up (6-310 months, median: 126) was available for 62 PE cases, all 36 EIN cases and 178 EEC cases. No patients with PE demonstrated progression to EIN or EEC. Progression of disease was observed in 10 (28%) EIN patients. These patients had significantly lower PAX2 expression than those that regressed (P = 0.005). Progression-free survival analysis revealed that EIN patients with a high-risk PAX2 expression score (H-score ≤75) had a higher probability of progression of disease in comparison to those with a low-risk score (H-score >75). PAX2 expression was not prognostic in EEC nor was PTEN status of prognostic value in either EIN or EEC. PAX2 expression analysis by means of H-score has prognostic potential for the identification of high-risk progression cases in EIN but needs to be validated in a larger cohort.