**3. Results**

The archiving software (Winsapp vers. 3) of the Pathology Department of Mauriziano Umberto I Hospital was used for patient selection.

Through a search with the query "endometrial hyperplasia" of patients undergoing hysteroscopy, 492 patients with a diagnosis of EH at biopsy were identified.

Of these, 317 were excluded given the diagnosis of EH without atypia. Of the remaining 178, 54 were excluded because they underwent surgery at another center. An additional 32 patients were excluded because a qualitatively inferior and different ultrasound was used compared with the Philips Affiniti 70 model. Two were excluded because of synchronous diagnosis of endometrioid adenocarcinoma of the ovary and inability to establish with certainty the origin of the primary lesion. For seven patients, anamnestic data (abnormal uterine bleeding [AUB], BMI, and comorbidities) could not be found and it was, therefore, decided not to include them in the case series. Our study population included 80 women who were diagnosed with AEH from January 2015 to September 2022 at our center and underwent surgery. Table 1 summarizes the characteristics of this population: most women were post-menopausal (87.0%) with a mean age of 64.9 years; a high prevalence of obesity (45.1%) was seen with a mean BMI 30.7 kg/m<sup>2</sup> ; and in 67.5% of cases, AUB was reported and prompted diagnostic evaluation. Among the tests performed during the work-up, TVUS highlighted a high prevalence of endometrial thickening as sonographic

presentation, with a mean thickness of 16.4 mm which is far above the high-risk cut-off suggested by the literature [7].


**Table 1.** Characteristics of the study population.

BMI, body mass index; VD, vaginal delivery; HRT, hormone replacement therapy; CD, color Doppler; AUB, abnormal uterine bleeding; EH, endometrial hyperplasia; EIN, endometrial intraepithelial neoplasia; patients are classified as obese when their body mass index (BMI) is over 30 kg/m<sup>2</sup> . \*: data are reported as mean ± standard error.

At the histopathological examination of the uterus after surgery, EC was revealed in 53 women, whereas the preoperative diagnosis of EAH was confirmed in 27 patients (Figure 1).

The cases of malignancy were all represented by EC, with coexistent hyperplasia confirmed in 29 out of 53 women (54.7%). Twenty-eight EC cases were histological grade 1 (52.8%), twenty-three cases were classified as grade 2 (43.4%), two cases as grade 3 (3.8%), and lymphovascular invasion was reported in fifteen patients (28.3%). The endometrial invasion was detected in 44 (83%) of the 53 EC. Most EC patients (34 out of 53 women, 66.0%) were classified as stage Ia according to FIGO classification [14].

The group of patients with a postoperative diagnosis of EC was compared with the group of women for whom the diagnosis of AEH was confirmed to analyze potential differences in the variables relating to preoperative presentation.

ure 1).

EH on endometrial polyps (%) 41 (52.6)

EIN (%) 6 (7.7)

Multiple foci of hyperplasia (%) 30 (42.9)

Number of endometrial biopsies \* 1.7 ± 0.07

BMI, body mass index; VD, vaginal delivery; HRT, hormone replacement therapy; CD, color Dop‐ pler; AUB, abnormal uterine bleeding; EH, endometrial hyperplasia; EIN, endometrial intraepithe‐ lial neoplasia; patients are classified as obese when their body mass index (BMI) is over 30 kg/m2. \*:

At the histopathological examination of the uterus after surgery, EC was revealed in 53 women, whereas the preoperative diagnosis of EAH was confirmed in 27 patients (Fig‐

(**c**)

The cases of malignancy were all represented by EC, with coexistent hyperplasia con‐ firmed in 29 out of 53 women (54.7%). Twenty‐eight EC cases were histological grade 1 (52.8%), twenty‐three cases were classified as grade 2 (43.4%), two cases as grade 3 (3.8%), Table 2 shows the results regarding the anamnestic features of the two groups, which appeared to be similar without any statistically significant difference, although patients with EC were on average older (*p* = 0.09).

and lymphovascular invasion was reported in fifteen patients (28.3%). The endometrial

invasion was detected in 44 (83%) of the 53 EC. Most EC patients (34 out of 53 women, **Table 2.** Anamnestic features of the study groups.

data are reported as mean ± standard error.


BMI, body mass index; VD, vaginal delivery; HRT, hormone replacement therapy; AUB, abnormal uterine bleeding; patients are classified as obese when their body mass index (BMI) is over 30 kg/m<sup>2</sup> . \*: data are reported as mean <sup>±</sup> standard error. § : analysis was carried out with a two-tailed *t*-test for independent samples with unequal variances for continuous variables, and with Fisher's test for categorical variables.

In Table 3, the main sonographic characteristics of the two groups are shown, highlighting significantly greater endometrial thickness and size of the lesion measured at TVUS for the women with EC. This difference is also relevant in absolute terms, with measures that are on average double the ones reported in AEH patients (notably, 10.3 vs. 20.3 mm for endometrial thickness). Among the other variables, cases of EC showed a significantly higher proportion of irregularity in the appearance of the endometrial–myometrial junction and the presence of endometrial vascularization, expressed by a color score of 2 or higher in the Doppler study.


**Table 3.** Ultrasound features of the endometrial lesions in the two groups.

CD, color Doppler. \*: data are reported as mean <sup>±</sup> standard error. § : analysis was carried out with a twotailed *t*-test for independent samples with unequal variances for continuous variables, and with Fisher's test for categorical variables.

In Tables 4 and 5, findings at hysteroscopy and histopathological examination of endometrial biopsies are shown: among women with EC, a significantly higher prevalence of necrosis (44.2%) and atypical vascularization (70.6%) was reported. In about half of the cases, a surface or nodular growth was described for the lesion. On the contrary, in patients with AEH, the most common presentation was a polypoid lesion protruding into the uterine cavity (77.8%), with a frequent histopathological report of atypical cells in the context of an endometrial polyp (73.1%). It is noteworthy that in 80.0% of cases of endometrial carcinoma, a subjective assessment of malignancy was provided by the operator performing hysteroscopy, whereas this evaluation was reported just in 12.5% of cases of hyperplasia.

### **Table 4.** Hysteroscopic findings in the two groups.


§ analysis was carried out with a two-tailed *t*-test for independent samples with unequal variances for continuous variables, and with Fisher's test for categorical variables.



EH, endometrial hyperplasia; EIN, endometrial intraepithelial neoplasia. \*: data are reported as mean ± standard error. § : analysis carried out with a two-tailed *t*-test for independent samples with unequal variances for continuous variables, and with Fisher's test for categorical variables.
