The classification scheme endorsed by the International Society of Gynecological Pathologists is based on architectural and cytologic features and long-term studies that reﬂect the natural history of the lesions (12) (Table 35.2). Architecturally, hyperplasias are either simple or complex; the major differing features are complexity and crowding of the glandular elements. Simple hyperplasia is characterized by dilated or cystic glands with round to slightly irregular shapes, an increased glandular-to-stromal ratio without glandular crowding, and no cytologic atypia. Complex hyperplasia has architecturally complex (budding and infolding) crowded glands, with less intervening stroma without atypia. Atypical hyperplasia refers to cytologic atypia and can be categorized as simple or complex, depending on the corresponding glandular architecture. Criteria for cytologic atypia include large nuclei of variable size and shape that have lost polarity, increased nuclear-to-cytoplasmic ratios, prominent nucleoli, and irregularly clumped chromatin with parachromatin clearing (Fig. 35.1).
Table 35.2 Classification of Endometrial Hyperplasias
Type of Hyperplasia Progression to Cancer (%)
Simple (cystic with atypia)
Complex (adenomatous with atypia)
From Kurman RJ, Kaminski PF, Norris HJ. The behavior of endometrial hyperplasia: a long term study of “untreated” hyperplasia in 170 patients. Cancer 1985;56:403–412, with permission.
Figure 35.1 Atypical hyperplasia (complex hyperplasia with severe nuclear atypia) of endometrium. A: The proliferative endometrial glands reveal considerable crowding and papillary infoldings. The endometrial stroma, although markedly diminished, can still be recognized between the glands. B: Higher magnification demonstrates disorderly nuclear arrangement and nuclear enlargement and irregularity. Some contain small nucleoli. (Provided by Gordana Stevanovic, MD, and Jianyu Rao, MD, Department of Pathology, UCLA.)
Fertility Sparing Treatment of Endometrial Hyperplasia and Cancer
The risk of endometrial hyperplasia progressing to carcinoma is related to the presence and severity of cytologic atypia. Kurman et al. retrospectively studied endometrial curettings from 170 patients with untreated endometrial hyperplasia followed a mean of 13.4 years (13). They found that progression to carcinoma occurred in 1% of patients with simple hyperplasia, 3% of patients with complex hyperplasia, 8% of patients with atypical simple hyperplasia, and 29% of patients with atypical complex hyperplasia. Most of the hyperplasias seemed to remain stable (18%) or regress (74%). The premalignant potential of hyperplasia is inﬂuenced by age, underlying ovarian disease, endocrinopathy, obesity, and exogenous hormone exposure (14,15).
As many as 25% to 43% of patients with atypical hyperplasia detected in an endometrial biopsy or curettage specimen will have an associated, usually well-differentiated, endometrial carcinoma detected during hysterectomy (16). Marked cytologic atypia, a high mitotic rate, and marked cellular stratification are features of atypical endometrial hyperplasia most often associated with the finding of an undiagnosed carcinoma at hysterectomy.