Histopathological appearance of simple hyperplasia includes uniformly rounded glands with marked variation in shape, including several cystically dilated forms. The lining epithelium of the glands reveals pseudostratification or multilayering, but lacks nuclear atypia. This may be associated with tubal metaplasia. The stroma is compact (Fig. 10.1). The differential diagnoses include atrophy, wherein glands are lined by flattened epithelium and benign endometrial polyp, in which the glands are covered by a similar benign-appearing hyperplastic epithelium on three surfaces with hyperplastic glands within the stroma that also contains blood vessels (Fig. 10.2). Simple cystic hyperplasia also should be differentiated from proliferative and disordered endometrium, especially the latter wherein endometrial glands are hyperplastic, but without an increase in volume [5]. Chronic endometritis can lead to an overdiagnosis of atypical hyperplasia, especially when inflammatory cells lead to reactive nuclear atypia noted within the glands. The presence of neutrophils on surface and plasma cells within stroma is indicative of chronic endometritis.

One needs to be careful in such cases, especially while dealing with a biopsy. Clinically, patient history related to intake of hormonal medications and an appraisal of thickness of the endometrium, on imaging, are useful in reinforcing a correct diagnosis in some cases with equivocal histopathological features.

This reveals increase in endometrial glands leading to their fusion and causing a common arch bars between the glands. While lack of atypia is noted in simple and complex hyperplasias without atypia, atypical hyperplasias reveal nuclear and cytoplasmic abnormality in the form of lack of polarity, irregular multilayering, and anisocytosis, accompanied by nuclear enlargement, hyperchromasia, chromatin clumping, and prominent nucleoli [5, 6]. Invariably, atypical hyperplasias are complex, wherein cribriform appearance of glands is noticeable, and in certain such cases, differentiation from grade I endometrioid adenocarcinoma becomes challenging (Fig. 10.3).

These are rather uncommon lesions. Papillary proliferations of the endometrium were initially reported by Lehman and Hart [7], who described nine cases mostly in postmenopausal women, who presented with abnormal vaginal bleeding. Invariably these lesions were found to be associated with intake of hormonal medications. Their cases included five of simple papillary proliferations and four of complex papillary proliferations, all associated with metaplastic changes. In another study [8], 59 cases of papillary proliferations of the endometrium without atypia in patients with similar age and symptomatology were analyzed. They classified their study cases as group I lesions (61 %) with localized simple papillae that were further defined as those with short, predominantly non-branching stalks and group II lesions (39 %) comprising complex papillae and/or those with diffuse and crowded intracystic papillae. Complex papillae were defined as those with both short or long stalks and, invariably, secondary and complex branches. These authors [7, 8] concluded that cases with group 2 features were significantly associated with concurrent or subsequent premalignant lesions (non-atypical and atypical hyperplasia) or carcinoma. Furthermore, they suggested that these lesions are analogous to atypical complex hyperplasia, and they termed these as “complex papillary hyperplasia (CPH)” (Fig. 10.4). Recently, a similar case of complex papillary hyperplasia was reported that was initially misdiagnosed as uterine papillary serous carcinoma [9].

Histopathologically, these are classified as villoglandular, secretory, or ciliated cell carcinoma; endometrioid adenocarcinoma with squamous differentiation; and serous, clear cell, mucinous, “pure” squamous cell, mixed, neuroendocrine, or undifferentiated carcinoma. Noteworthy, malignant mixed müllerian tumor (MMMT)/carcinosarcoma is also classified under the rubric of endometrial adenocarcinomas [6].

The dualistic classification also has a molecular basis along with prognostic and therapeutic relevance. Type I cancers are associated with phosphatase and tensin homolog (PTEN) mutation, microsatellite instability, and K-ras mutation, whereas type II adenocarcinomas are associated with p53 mutation. Type I adenocarcinomas are associated with a relatively good prognosis. In some of these cases, “nonsurgical” treatment is opted, such as progesterone therapy. Contrastingly, type II adenocarcinomas are associated with a relatively poor prognosis. In most of these tumors, adjuvant treatment, in the form of chemotherapy (CT) and/or radiotherapy (RT), is included [6, 10].