Atypical Polypoid Adenomyoma Research Articles

Stromal p16 and SATB2 Expression Does Not Distinguish Atypical Polypoid Adenomyoma (APA) From its Benign Mimics.

Atypical polypoid adenomyoma (APA) is a polypoid biphasic lesion of low malignant potential that arises in the lower uterine segment and uterine corpus. The diagnosis of APA is often challenging on biopsy and curettage specimens, and both benign and malignant processes need to be considered in the differential. Stromal expression of p16 and SATB2 have recently been shown to distinguish APA from myoinvasive endometrioid carcinoma. The authors hypothesized that p16 and SATB2 immunohistochemistry could also aid in the distinction of APA from benign adenomyomatous polyp and endometrioid adenomyoma. The study comprised 10 APAs, 7 adenomyomatous polyps, 11 endometrioid adenomyomas, and 10 myoinvasive endometrioid carcinomas. The majority of APAs showed moderate to strong, diffuse p16 and stromal expression. However, most adenomyomatous polyps and endometrioid adenomyomas also exhibited moderate to strong, focal to diffuse p16 stromal expression. SATB2 showed weak to moderate, focal to diffuse expression in the majority of APAs, adenomyomatous polyps and endometrioid adenomyomas. In contrast, p16 and SATB2 were negative to weak and focal in 90% of myoinvasive endometrioid carcinomas. Our findings demonstrate that p16 and SATB2 may be helpful in the differential diagnosis of myoinvasive endometrioid carcinoma and APA while not useful in separating APA from adenomyomatous polyp and endometrioid adenomyoma.

Clinicopathological characteristics and fertility preserving treatment of atypical polypoid adenomyoma.

Atypical polypoid adenomyoma (APA) is a rare benign tumor frequently diagnosed in young women that may coexist with or progress to atypical endometrial hyperplasia (EAH) or endometrioid endometrial carcinoma (EEC). This study aimed to investigate which subset of patients with APA are prone to concurrent or subsequent EAH or EEC, evaluate the necessity of progestin treatment in patients with APA only after achieving a complete response (CR) through hysteroscopic lesion resection, and assess the impact of concurrent APA on the fertility-preserving treatment of EAH or EEC. This retrospective single-center study analyzed 86 patients with APA treated at the Obstetrics and Gynecology Hospital of Fudan University between January 2010 and October 2021. Patients with EAH or EEC only who underwent fertility-preserving treatment during the same period were matched in a 2:1 ratio with patients with concurrent APA and EAH or EEC. The clinicopathological characteristics, treatments, and prognosis were analyzed. The median patient age was 31 years (range 21-47 years). Among the 86 included patients, nine underwent total hysterectomy, 62 received conservative treatment, and the remaining 15 were lost to follow-up. A comparison of the 16 patients with APA only versus the 58 patients with APA and concurrent or subsequent EAH or EEC revealed that a homeostasis model assessment of insulin resistance (HOMA-IR) of > 2.2 (P = 0.047) and high-density lipoprotein (HDL) concentration of < 1.2 mmol/L (P = 0.028) were independent risk factors for EAH or EEC in patients with APA. Among the 17 patients with APA only who received conservative treatment and achieved a CR after hysteroscopic lesion resection, 13 received hormone treatment for a median duration of 6.3 months. The median follow-up time for these 17 patients was 49.0 months, during which no recurrence of APA was observed, but six patients developed endometrial hyperplastic diseases. Regarding the impact of concurrent APA on fertility-preserving treatment for EAH or EEC, the median time to achieve a CR was 24.0 weeks (95% confidence interval [CI]: 23.0-40.4) in the APA group and 26.0 weeks (95% CI: 24.3-32.3) in the non-APA group (P = 0.424). There were no significant differences between the two groups in the outcomes of fertility-preserving treatment. Patients with APA only may still develop endometrial hyperplastic diseases after complete resection of the lesion under hysteroscopy to achieve a CR, particularly those with a HOMA-IR of > 2.2 or HDL concentration of < 1.2 mmol/L. Concurrent APA did not affect the efficacy of fertility-preserving treatment in patients with EAH or EEC.

Endometrioid Squamous Proliferations of the Endometrium Express Alpha-Methylacyl-CoA Racemase (P504s).

Squamous morular metaplasia is closely associated with endometrioid proliferative lesions such as endometrial intraepithelial neoplasia, whereas endometrioid adenocarcinoma may also demonstrate squamous differentiation (morular or nonmorular). Alpha-methylacyl-CoA racemase (AMACR; P504s) is an immunohistochemistry marker expressed in many tumors, including prostate adenocarcinoma, renal cell carcinoma, and in a subset of gynecologic carcinomas, predominantly of clear cell histology. In small biopsy samples, the distinction between cervical high-grade squamous intraepithelial lesions (HSILs) involving endocervical glands from endometrioid squamous proliferations can be challenging, given their anatomic vicinity and some degree of morphologic overlap. Following the observation of AMACR positivity by immunohistochemistry within squamous morules in an index case, 35 endometrial samples containing squamous morular metaplasia (25) and nonmorular squamous metaplasia (10), and 32 cases of cervical HSIL involving endocervical glands were stained with AMACR. The endometrial cohort consisted of 2 benign anovulatory endometrium, 7 endometrial polyps, 7 endometrial intraepithelial neoplasia, 4 atypical polypoid adenomyomas, and 15 endometrioid adenocarcinomas. Positive cases were scored as diffuse (≥50%) or focal (<50%). AMACR staining was present in 96.7% of endometrial squamous lesions, including 14 (93.3%) of endometrioid carcinomas, and in all cases of endometrial intraepithelial neoplasia, endometrial polyps, atypical polypoid adenomyomas, and anovulatory endometrium with squamous morular metaplasia or nonmorular squamous metaplasia. In comparison, only 2 cases (5.8%) of cervical HSIL demonstrated positivity for AMACR. In conclusion, AMACR can reliably differentiate the cervical versus endometrial origin of squamous lesions in small biopsy specimens.

Utility of a PAX2, PTEN, and β-catenin Panel in the Diagnosis of Atypical Hyperplasia/Endometrioid Intraepithelial Neoplasia in Endometrial Polyps.

The diagnosis of atypical hyperplasia/endometrioid intraepithelial neoplasm (AH/EIN) within endometrial polyps (EMPs) often poses a diagnostic conundrum. Our previous studies demonstrated that a panel of immunohistochemical (IHC) markers consisting of PAX2, PTEN, and β-catenin can be effectively utilized for the identification of AH/EIN. A total of 105 AH/EIN within EMP were analyzed using the 3-marker panel. We also evaluated these cases for the presence of morules. Benign EMP (n=90) and AH/EIN unassociated with polyp (n=111) served as controls. Aberrant expression of PAX2, PTEN, or β-catenin was observed in AH/EIN in EMP in 64.8%, 39.0%, and 61.9% of cases, respectively. At least 1 IHC marker was abnormal in 92.4% of cases. Overall, 60% of AH/EIN in EMP demonstrated abnormal results for≥2 IHC markers. The prevalence of PAX2 aberrancy was significantly lower in AH/EIN in EMP than in nonpolyp AH/EIN (64.8% vs. 81.1%, P =0.007), but higher than in benign EMP (64.8% vs. 14.4%, P <0.00001). The prevalence of β-catenin aberrancy was significantly higher in AH/EIN in EMP than in nonpolyp AH/EIN (61.9% vs. 47.7%, P =0.037). All control benign EMP demonstrated normal expression of PTEN and β-catenin. Morules were present in 38.1% of AH/EIN in EMP versus 24.3% in nonpolyp AH/EIN, and absent in benign EMP. A strong positive association was found between β-catenin and morules (Φ=0.64). Overall, 90% cases of atypical polypoid adenomyoma (n=6) and mucinous papillary proliferation (n=4) showed IHC marker aberrancy. In conclusion, the 3-marker IHC panel (PAX2, PTEN, and β-catenin) is (1) a useful tool in the diagnosis of AH/EIN in EMP; (2) PAX2 loss should be interpreted with caution and in combination with morphology and other markers.

A Clinicopathological Review of 203 Cases of Atypical Polypoid Adenomyoma of the Uterus.

To provide a reference for the diagnosis and treatment of atypical polypoid adenomyoma (APA). This was a retrospective study of 203 APA patients from 2011 to 2021. The clinicopathological characteristics, treatments, and prognosis were analyzed. The average age at diagnosis of APA patients was 39.30 ± 11.01 years, and premenopausal women accounted for 81.3%. Abnormal uterine bleeding or menorrhagia were the most common clinical manifestations of APA. The uterine fundus (78.3%), followed by the lower segment of the uterus (11.8%), was the most common location of the APA lesions. Abnormal blood vessels were seen on the surface of 28 APA tumors. APA can coexist with atypical endometrial hyperplasia (18.2%) and endometrial cancer (10.8%). Immunohistochemical analysis was performed on 99 samples. In the glandular component, ER (94.8%), PR (94.8%), Ki-67 (51.5%), p53 (45.6%), PTEN (18.8%), and mismatch repair proteins (96.4%) were positively expressed. Stromal immunophenotype expression was exhibited as follows: CD10-(89.5%), p16+(86.9%), h-caldesmon-(66.7%), Desmin+(75%), and Vimentin+(88.9%). Fifty-five APA patients received TCR, and 33 of them received adjuvant therapy after the operation. The postoperative recurrence rate (9.1% vs. 36.4%, p < 0.05) and malignant transformation rate (3.0% vs. 18.2%, p < 0.05) of the treated group were significantly lower than the untreated group. APA usually occurs in women of childbearing age, and the diagnosis is based on pathological morphology. APA has a low malignant potential, and those who have fertility requirements can undergo conservative TCR treatment, supplemented by progesterone treatment after surgery and close follow-up. Total hysterectomy is the treatment of choice for APA patients with atypical endometrial hyperplasia around the lesion.

Atypical Polypoid Adenoma – A Histopathological Enigma

Atypical polypoid adenomyoma is an infrequent intrauterine polypoidal lesion. As per WHO classification of female genital tumors published in 2020, APA is classified as a mixed epithelial and mesenchymal tumor. The epithelial component comprises endometrioid-type glands with complex architecture, mild cytological atypia and fibromyomatous stroma with morular metaplasia. We present a case of a 32-year-old female with primary infertility; hysteroscopy showed a smooth polypoidal lesion over anterior wall of uterus. Complete transcervical resection of the lesion was done. Histopathology showed all the prementioned features of atypical polypoid adenomyoma and there was no other associated pathology. Since the patient desired fertility preservation, a conservative management plan with follow up was done. This lesion mostly involves women of fertile age group, hence differentiation from pre-malignant/malignant lesions is of utmost importance as fertility preservation can be done for this lesion. In older patients where fertility preservation is not required hysterectomy is advised in view of risk of recurrence.

Serous endometrial intraepithelial carcinoma coexistence with atypical polypoid adenomyoma in a young woman: a rare case

Serous endometrial intraepithelial carcinoma coexistence with atypical polypoid adenomyoma in a young woman: a rare case

Clinical analysis of 44 cases of atypical polypoid adenomyoma of the uterus

BackgroundAtypical polypoid adenomyoma (APA) is a rare intrauterine polypoid lesion that occurs predominantly in premenopausal women. Although APA was previously considered a benign lesion and treated conservatively, an increasing number of cases show that APA has a high rate of recurrence or residual disease and that it precedes the development of carcinoma. The clinical management of APA remains to be established. The aim of this study was to analyse the clinicopathological features of APA and discuss its diagnosis and prognosis.MethodsForty-four patients with APA were admitted to Beijing Obstetrics and Gynecology Hospital from 2005 to 2019, and their clinical and histopathologic features were evaluated. B-ultrasound was performed, and all the patients (n = 44) underwent hysteroscopy. Endometrium excision was performed by means of the four-step diagnosis and treatment method. Hysteroscopic transcervical resection (TCR) was performed in 5 patients with APA-H and 11 with APA-L. Except for one patient who underwent transcervical endometrial resection, all the patients underwent hysterectomy and salpingectomy or salpingo-oophorectomy. Data from a median follow-up of 42 months (ranging from 3 to 174 months) were available for these patients.ResultsPathological diagnosis were made according to the degree of abnormality of the APA surface glands, resulting in APA-L in 36 patients and APA-H in 8 patients. Among these patients, 28 (25 APA-L and 3 APA-H) were treated conservatively. The effect of the four-step diagnosis and treatment method as an APA therapy was excellent. During the follow-up, no evidence of recurrence was found.ConclusionsFor patients with intracavitary lesions > 1 cm, the hysteroscopic four-step diagnosis and treatment method and pathological diagnosis are the basis of clinical treatment. More than 30% of APA surface glands have complex structures characterized by branching and budding or other high-risk factors, such as endometrial hyperplasia, which are indications for hysterectomy. For patients who desire to become pregnant or to preserve the uterus, hysteroscopy with complete excision of the lesions should be the preferred treatment method. The patients should be treated and followed up closely with regular hysteroscopy and endometrial biopsy.

Oncologic outcomes of conservative treatment of atypical polypoid adenomyoma of the uterus: A two-center experience.

Atypical polypoid adenomyoma (APA) is a rare uterine premalignant lesion mainly occurring in premenopausal and nulliparous women. Although hysteroscopic resection (HR) has showed promising results, the conservative management of APA in young women is not standardized, and few data are available in the literature. We aimed to assess oncologic outcomes of the conservative treatment of APA. A multicenter observational retrospective cohort study was performed including all patients with APA who underwent conservative treatment from January 2006 to June 2020. Rates of each oncologic outcome (i.e. initial complete response, persistence, progression to cancer, recurrence, long-term treatment success, and treatment failure) were calculated for all conservative treatment together and separately. Twenty-five patients were included. Conservative treatments consisted of HR alone (n=14) and HR+progestin (n=11). Overall, 24 (96%) patients showed initial complete response, of which 21 (84%) showed long-term treatment success; four (16%) patients had progression to cancer, of which two (8%) first recurred as APA. Long-term treatment success was achieved in 13 of 14 (92.9%) patients with HR alone and 8 of 11 (72.3%) with HR+progestin. Conservative treatment appears to be a safe option in women with APA. The four-steps HR might be considered as the first-line conservative approach, while the addition of progestin does not seem to improve oncologic outcomes. However, the risk of progression to cancer highlights the need for a close and long-term follow up with ultrasonography and hysteroscopic biopsies, and for hysterectomy in patients not desiring pregnancy.

An Unusual Imaging of Atypical Polypoid Adenomyoma in a 21-Year-Old Woman

A 21-year-old woman was admitted with a 9-month history of irregular vaginal bleeding, anemia, and an enlarged abdominal mass on examination. The MRI scan showed an intracavitary mass measuring 95 × 45 × 63 mm (Fig. 1A). Hysteroscopy revealed multiple cauliflower-like lesions (Fig. 1B), with biopsies demonstrating an atypical polypoid adenomyoma (APA). Following 3 months of GnRHa treatment, the lesion size decreased to 69 × 49 × 70 mm, and hysterotomy at laparotomy was undertaken to remove the lesion (Fig.

A clinicopathological study of 39 cases of atypical polypoid adenomyoma of the uterus

ObjectiveTo clarify the clinical and pathological characteristics of atypical polypoid adenomyoma (APA) in order to improve the criteria used to diagnose and treat this disease. Study designIn 39 cases of APA, retrospective analysis was performed of theclinical data, pathological characteristics, and the follow-up findings in patients admitted to the Peking University People's Hospital from 2007 to 2019. ResultsThe median age was 39.6 years (range 24–60 years). Thirty seven patients were premenopausal (i.e.94.9 ​%) and eighteen patients were nullipara (i.e. 46.2 ​%). Abnormal uterine bleeding was the most common presenting symptom. Hysteroscopic transcervical resection (i.e.TCR) identified lesions in 35 cases whereas: a) hysterectomy identified them in 3 cases; b) dilatation and curettage (D&C) identified them in 1 case. Immunohistochemical analysis was performed on 24 samples. In the glandular component, hormone receptors were positively expressed. In all cases, Ki67 expression was detectable in approximately 50 ​% of the cases. In those samples, its presence was definitive in eighteen of the nineteen cases (94.7 ​%,18/19), p53 positive expression was present in most cases (68.8 ​%,11/16), and PTEN positive expression was detected in 40 ​% (4/10). Stroma immunophenotype expression was exhibited as follows: a)CD10-(12/12), Desmin +(6/7); b) Vimentin +(4/4); c) α-SMA+ (3/3) and; d) p16 positve staining in of 80 ​%(4/5).The concurrent amount of atypical endometrial hyperplasia with atypical polypoid adenomyoma was 23.1 ​%(9/39), while its concurrent level of endometrial carcinoma with atypical polypoid adenomyoma was 7.7 ​% (3/39). Fertility preserving treatments were performed in 20 patients with strong childbearing desires. Their pregnancy success was 15 ​%(3/20) and the live birth frequency was 10 ​%(2/10). Follow-up findings were available in 36 cases (92.3 ​%) with a medial follow-up of 48.1 months (range 4–122 months). Its pathological recurrence and frequency of progression into endometrial carcinoma were both 5 ​%(1/20). One case died of another type of malignancy, while the other patients were alive. ConclusionsAPA occurs mostly during the years of a women's reproductive period. Its diagnosis is based on the analysis of pathological and immunohistochemical findings. Individuals diagnosed with APA are at risk to coexist with endometrial carcinoma and atypical endometrial hyperplasia. For those individuals who desire retaining fertility, the treatment strategy involves performing TCR completely remove the lesions and close follow-up for surveillance of possible progressive APA recurrence. For those individuals who have no fertility desire, hysterectomy may be a preferred option.

Patterns of SATB2 and p16 reactivity aid in the distinction of atypical polypoid adenomyoma from myoinvasive endometrioid carcinoma and benign adenomyomatous polyp on endometrial sampling.

Atypical polypoid adenomyoma (APAM) is an uncommon uterine lesion composed of complex endometrioid glands with frequent squamous morular metaplasia and fibromuscular stroma. On endometrial curettage, biopsy or polypectomy specimens, the admixture of endometrioid glands and smooth muscle raises the differential diagnosis of myoinvasive endometrioid carcinoma. Reproductive-age APAM patients may opt for fertility preservation, whereas myoinvasive carcinoma is treated surgically. One previous study reported an incidental finding that the stroma of APAM, in contrast to that of other polypoid lesions, was SATB2-positive. APAM has also been reported to show increased stromal p16 staining. We aimed to assess whether SATB2 and p16 are useful stains for the distinction of APAM from myoinvasive carcinoma and benign adenomyomatous polyps. Cases of 'atypical polypoid adenomyoma' (n=32), 'adenomyomatous polyp' (n=39) and 'myoinvasive endometrioid carcinoma' (n=30) were identified. Morphological features were assessed, along with the intensity and extent of SATB2 and p16 staining in the stromal component of each lesion. SATB2 expression was seen in the stromal components of 30 of 32 (94%) APAMs, versus none of 39 (0%) benign adenomyomatous polyps and five of 30 (17%) myoinvasive endometrioid carcinomas. Stromal p16 expression was seen in 31 of 31 (100%) APAMs, versus 20 of 39 (51%) benign adenomyomatous polyps and 12 of 30 (40%) myoinvasive endometrioid carcinomas. Patchy to diffuse SATB2 and block-type p16 staining of fibromuscular stroma separating atypical endometrioid glands is more consistent with APAM than with myoinvasive endometrioid carcinoma. These stains are potentially useful adjuncts to careful morphological evaluation of endometrial biopsies/curettings.

Atypical polypoid adenomyoma

Atypical polypoid adenomyoma is an uncommon polypoid lesion, located in the lower uterine segment or endometrial cavity, often diagnosed on biopsy or curettage.[1][1] It is characterized by endometrial glands, often...

Lesion-targeted cytology to improve cytological sampling for atypical polypoid adenomyomas of the uterus: A case series and review of the literature.

Atypical polypoid adenomyomas (APAs) are uncommon tumours consisting of atypical endometrioid glands and fibromyomatous stroma. Identifying the biphasic nature of atypical glandular components and spindle mesenchymal components without atypia is crucial for the cytological diagnosis of APA. We investigated the utility of lesion-targeted cytology (LTC) to directly collect firm spindle components. We recruited seven consecutive surgical patients who underwent cytological examinations before surgery and were diagnosed with APA on postoperative histological examinations. Cytological smears were obtained by routine sampling in five cases and by targeted sampling using transvaginal ultrasonography, that is, LTC, in two cases. We retrospectively analysed the cytological findings from our cases and compared them to those of APA cases previously reported in the English literature. Among 5/7 cases that involved routine cytological sampling, normal cytological findings were found in 2 and atypical glandular cells were found in 3, but spindle cells from mesenchymal components were not detected. In contrast, among 2/7 cases in which sampling involved LTC, spindle cells without atypia, in addition to atypical glandular cells were found. Lesion-targeted cytology is useful to assess mesenchymal components of APAs and may improve the cytological diagnosis of APA.

Atypical polypoid adenomyoma follow-up and management: Systematic review of case reports and series and meta-analysis.

Atypical polypoid adenomyoma (APA) is a rare uterine tumor typically found in fertile age and associated with infertility. Among young nullipara women, conservative treatment is proposed despite the high recurrence rate and the association with endometrial cancer.Our aim was to assess the risk of recurrence with different conservative treatments in fertile ages and the prevalence of malignant or pre-malignant associated lesions to better address an adequate patient counselling when treatment modalities are discussed. This study is a systematic review and meta-analysis of case reports and case series about APA management and follow-up. A literature search was carried from Medline and Scopus for studies published from January 1, 1980 to December 31, 2018. We included 46 observational studies and 296 cases in fertile women. The prevalence of APA relapse was 44% (CI.95 33-57%) and was lower in cases treated with operative hysteroscopy (22%; CI.95 11-39%) than in cases treated with blind curettage and polypectomy (38%; CI.95 15-67%). The prevalence of the concomitant or during the follow-up diagnosis of endometrial carcinoma was 16% (CI.95 9-29%). The risk of cancer development during follow-up was significantly less in cases treated with histeroscopy (10.56% new cumulative diagnosis at 5 years follow up; CI.95 0-23.7%) than blind curettage and polypectomy (35.5% new cumulative diagnosis at 5 years; CI.95 11.65-52.92%; P < .05). Medical treatment with medroxyprogesterone acetate after surgery does not reduce APA recurrence. Pregnancy was observed in 79% cases in which the desire was expressed. This review suggests that conservative treatment performed by operative hysteroscopy is the optimal choice because it lowers the risk of recurrence, improves the accuracy of concomitant carcinoma or hyperplasia diagnosis, and leaves the possibility of future pregnancies.

18F-FDG PET/CT imaging in uterine atypical polypoid adenomyoma: a case report

18F-FDG PET/CT imaging in uterine atypical polypoid adenomyoma: a case report

Case report of successful live birth in an infertile couple with male idiopathic hypogonadotropic hypogonadism/azoospermia and atypical polypoid adenomyoma of the uterus

Case report of successful live birth in an infertile couple with male idiopathic hypogonadotropic hypogonadism/azoospermia and atypical polypoid adenomyoma of the uterus

Stromal p16 Expression Helps Distinguish Atypical Polypoid Adenomyoma From Myoinvasive Endometrioid Carcinoma of the Uterus.

Atypical polypoid adenomyoma (APA) is a polypoid lesion that is comprised of atypical endometrial glands and fibromuscular stroma, which pathologists often confuse with myoinvasive endometrioid carcinoma. Here, we characterized the immunohistochemical and molecular features of the stromal components of APA to find distinct markers between APA and myoinvasive endometrioid carcinoma. First, we examined the immunohistochemical expression and gene mutations that were previously investigated in uterine and breast fibroepithelial lesions using 12 cases of APA. α-smooth muscle actin was diffusely positive in the stromal component in all cases, whereas desmin and h-caldesmon were focally expressed in 8 cases. Positive expression was also observed in 9 cases for CD10, 12 cases for estrogen receptor, 3 cases for HMGA2, and 3 cases for MDM2. All cases showed normal p53 expression and negative staining of HMGA1 and nuclear β-catenin. No mutations in MED12 exon 2 and the TERT promoter were found in any cases. p16 was positive in all cases and showed diffuse expression in 10 cases. We assessed stromal p16 expression in 84 cases of myoinvasive endometrioid carcinoma. The stromal p16 status was negative in all myoinvasive carcinomas, but there was 1 case with focal staining. There was a significant difference in stromal p16 expression between APA and myoinvasive endometrioid carcinoma (P<0.001). Stromal p16 expression was more suggestive of APA than myoinvasive endometrioid carcinoma among endometrial fibroepithelial lesions.

Mutations of RAS genes in endometrial polyps.

Endometrial polyps are common, yet the molecular mechanisms underlying their formation and progression remain unclear. We examined gene mutations possibly related to the pathogenesis of endometrial polyps, as well as to their clinical features. Four premenopausal patients with endometrial polyps, who were not under drug treatment, were recruited. Whole exomes of endometrial polyps and peripheral blood lymphocytes were analyzed by next-generation sequencing, and somatic mutations were derived by subtraction. Then, 35 samples of endometrial polyps and 12 samples of atypical polypoid adenomyoma were newly recruited to validate the identified mutations by polymerase chain reaction-reverse sequence specific oligonucleotide method. The mutations were also analyzed in separate stromal and glandular components of the polyps after laser-capture microdissection. Whole exome sequencing revealed that KRAS mutations were the only type of mutation detectable in multiple cases (2/4). Targeted mutation analysis revealed that 16 of 35 samples (45.7%) of endometrial polyps harbored RAS mutations. Mutation-positive cases exhibited a significantly higher number of endometrial polyps (3.25±2.70 vs. 1.74±0.87, P=0.045). Laser-capture microdissection in NRAS-mutated endometrial polyps revealed that both stromal and glandular components harbored RAS mutations. There was no RAS mutation in 12 samples of atypical polypoid adenomyoma. This is the first report demonstrating that pathogenic RAS mutations are frequent in non-treated endometrial polyps. RAS mutations may have an important role in tumorigenesis and in the formation of multiple endometrial polyps.

SATB2 is Consistently Expressed in Squamous Morules Associated With Endometrioid Proliferative Lesions and in the Stroma of Atypical Polypoid Adenomyoma.

So-called squamous morules are closely associated with endometrioid proliferative lesions, in the endometrium and the ovary. Morules have an unusual immunophenoptype, typically exhibiting nuclear staining with β-catenin, positivity with CDX2, CD10, and p16 and are negative with hormone receptors and p63. We report the previously undescribed occurrence of consistent SATB2 nuclear positivity within morules. Nuclear positivity was present in 38/43 (88%) cases of morules (24 focal; 14 diffuse) while all cases of nonmorular squamous metaplasia in endometrioid proliferative lesions (n=13) were SATB2 negative, except for occasional positive nuclei in 1 case. We also observed that the stromal cells of atypical polypoid adenomyoma typically exhibited diffuse nuclear immunoreactivity with SATB2 while the stromal cells of other endometrial polypoid lesions (endometrial polyp, adenomyoma, adenosarcoma) were usually negative, although there was focal weak staining in occasional cases. Pathologists should be aware of this previously undescribed phenomenon which represents a further example of the unusual immunophenotype of so-called squamous morules. The reasons underlying SATB2 nuclear positivity in squamous morules and the stroma of atypical polypoid adenomyoma are unknown.