Educational Case: Abnormal uterine bleeding.

The authors received no financial support for the research and authorship in this work.

A 35-year-old woman who is nulliparous presents to her physician due to bothersome intermenstrual bleeding for the past 5 months. Menarche occurred at age 13, and she previously had regular 28-day cycles with light bleeding for 4 days but currently has unpredictable spotting throughout her cycle. She takes prenatal vitamins, as she and her partner have been trying to conceive for the past 6 months without success. She does not take any other medications, supplements, or substances. Her past medical history is significant only for obesity. She has no personal or family history of bleeding disorders or cancers. She denies any history of sexually transmitted infections. She is concerned that the cause of her abnormal bleeding may be adversely impacting her fertility.

Objective FU2.4: Abnormal Uterine Bleeding. Discuss the causes of abnormal uterine bleeding, including hormonal disturbances, anovulatory cycle, endometriosis, acute and chronic endometritis, and endometrial polyps. Competency 2: Organ System Pathology; Topic: Female Reproductive–Uterus, Cervix, and Vagina (FU); Learning Goal 2: Nonneoplastic Uterine Disorders.

• The differential diagnosis for abnormal uterine bleeding can be summarized using the PALM-COEIN acronym developed by FIGO. ￮ Polyp ￮ Adenomyosis ￮ Leiomyoma ￮ Malignant (endometrial malignancy/hyperplasia) ￮ Coagulopathies ￮ Ovarian dysfunction ￮ Endometrial dysfunction ￮ Iatrogenic ￮ Not otherwise classified • Symptomatic endometrial polyps often present with intermenstrual bleeding. • Polypectomy in low-risk premenopausal patients is performed to alleviate symptoms and/or promote fertility and to evaluate for an underlying polypoid malignancy, not to reduce the risk of malignant transformation of the polyp itself. • There is a statistically significant association between the risk of endometrioid endometrial carcinoma and obesity in both premenopausal and postmenopausal patients. • Patients with hormonal disturbances causing their abnormal uterine bleeding will often have irregular menstrual cycles secondary to ovulatory dysfunction or disruption of the HPA axis. • Chronic endometritis is diagnosed histologically by the presence of plasma cells within the endometrium, while acute endometritis is defined by the presence of neutrophilic infiltrate and microabscesses. • Postpartum endometritis will present as a fever >24 hours after delivery coupled with purulent lochia and uterine fundal tenderness on physical examination. The differential diagnosis for abnormal uterine bleeding can be summarized using the PALM-COEIN acronym developed by FIGO. ￮ Polyp ￮ Adenomyosis ￮ Leiomyoma ￮ Malignant (endometrial malignancy/hyperplasia) ￮ Coagulopathies ￮ Ovarian dysfunction ￮ Endometrial dysfunction ￮ Iatrogenic ￮ Not otherwise classified Polyp Adenomyosis Leiomyoma Malignant (endometrial malignancy/hyperplasia) Coagulopathies Ovarian dysfunction Endometrial dysfunction Iatrogenic Not otherwise classified Symptomatic endometrial polyps often present with intermenstrual bleeding. Polypectomy in low-risk premenopausal patients is performed to alleviate symptoms and/or promote fertility and to evaluate for an underlying polypoid malignancy, not to reduce the risk of malignant transformation of the polyp itself. There is a statistically significant association between the risk of endometrioid endometrial carcinoma and obesity in both premenopausal and postmenopausal patients. Patients with hormonal disturbances causing their abnormal uterine bleeding will often have irregular menstrual cycles secondary to ovulatory dysfunction or disruption of the HPA axis. Chronic endometritis is diagnosed histologically by the presence of plasma cells within the endometrium, while acute endometritis is defined by the presence of neutrophilic infiltrate and microabscesses. Postpartum endometritis will present as a fever >24 hours after delivery coupled with purulent lochia and uterine fundal tenderness on physical examination.

The patient underwent a hysteroscopic polypectomy, and the tissue removed during the procedure was sent to pathology. A low power histological image is shown in Fig. 1 with a representative higher magnification image in Fig. 2 . Fig. 1 Low magnification image of a pedunculated polyp arising from the uterine endometrium. Hematoxylin and eosin stain. Fig. 1 Fig. 2 High magnification image of the pedunculated endometrial polyp revealing endometrial glands and stroma. Hematoxylin and eosin stain. Fig. 2 Low magnification image of a pedunculated polyp arising from the uterine endometrium. Hematoxylin and eosin stain. High magnification image of the pedunculated endometrial polyp revealing endometrial glands and stroma. Hematoxylin and eosin stain.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The polypectomy specimen grossly exhibited a tan-brown to off-white appearance and was 1.1 cm in greatest dimension with a pedunculated appearance. Palpation of the specimen yielded a firm but fluctuant texture, while coronal sectioning revealed a fibrous cut surface. Low-power microscopic examination revealed a polypoid appearance exhibiting proliferative surface epithelium with areas of surface erosion. High-power examination yielded fibrous stroma associated with scattered areas of hemorrhage admixed with hemosiderin-laden macrophages. Although not present within Fig. 2 , scattered thick-walled blood vessels were observed within the stroma. Irregularly distributed endometrial glands ranging from angular to tubular were accompanied by scattered cystically dilated glands. There was no evidence of malignancy. While endometrial polyps account for 13%–50% of premenopausal abnormal uterine bleeding, malignant transformation is rare. 8 A systematic review and meta-analysis of 51 studies comprised of 35,345 cases of endometrial polyps by Uglietta et al. revealed a rate of malignancy in premenopausal women of 1.12%, while that in postmenopausal women was 4.93%. 24 Though not necessarily arising from an endometrial polyp, the patient's history of obesity is associated with an increased relative risk for endometrial carcinoma ranging from 2 to 5, while nulliparity and infertility are each associated with a relative risk factor of 3. 3 , 14 , 22 While the increased risk associated with obesity in postmenopausal patients is a consequence of adipose tissue derived production of estrone; it is a relative excess of estrogen arising from the reduced progesterone effect of anovulation, which accounts for the increased risk in premenopausal patients. 24 , 25 As opposed to breast and ovarian malignancies, the risk of endometrioid endometrial carcinoma increases by more than 50% for each 5-unit increase in BMI. 22 Treatment options range from conservative observation to hysterectomy, with the most patient-appropriate option being determined by the presence or absence of symptoms, risk of malignancy, and desire for fertility. 8 , 9 Small, asymptomatic endometrial polyps (≤10 mm) often spontaneously regress over a one-year period; however, this seldom occurs in the setting of infertility. 8 As the patient's polyp was 1.1 cm in greatest dimension and associated with abnormal uterine bleeding, surgical intervention was the appropriate treatment in order to alleviate symptoms and promote fertility. 8 , 9 As fertility is desired and the patient's risk of malignancy is relatively low, conservative surgery in the form of hysteroscopic polypectomy is the treatment of choice. 8 , 9 Surgical removal of the endometrial polyp removes the lesion responsible for abnormal uterine bleeding while also addressing the potential morphological and biochemical causes of infertility. In addition, removal of the polyp assists in evaluation of the patient for a possible estrogen-associated malignancy, as some endometrial cancers may present as a polypoid mass. 8 As the myometrium is not incised during the procedure, the risk of intrauterine adhesion formation is negligible and thus does not pose a risk to reproductive outcomes. 9