On the benign end of the spectrum, AIS must be distinguished from regenerative/inflammatory changes, tuboendometrioid metaplasia, and endometriosis.
The nuclei in tuboendometrioid metaplasia are larger and more hyperchromatic than the nuclei of endocervical epithelium; in addition, the cytoplasm may be scant, resulting in a high nuclear to cytoplasmic ratio, and therefore such glands may appear suspicious for neoplasia.
For comparison, the average proliferative index in reactive/ regenerating endocervical epithelium with a history of recent biopsy, or in tuboendometrioid metaplasia during the proliferative phase is 7% (range, 0%-32%) and 5% (range, 0%-31%), respectively.
Cervical endometrioid ADC is a rare tumor variant thought to develop from cervical tuboendometrioid metaplasia or endometriosis.
Tubal/Tuboendometrioid Metaplasia.--Tubal/tuboendometrioid metaplasia (TEM) is characterized by replacement of preexisting endocervical-type epithelium by cells closely resembling those seen in the fallopian tube (tubal metaplasia) or, less commonly, endometrium (tuboendometrioid metaplasia) (Figure 3, A through E).
(203,204) Histologically it has a deceptively benign appearance with (1) disorderly distributed irregular glands and cysts (uncommonly may be closely packed with cribriforming or have villous papillae); (2) glands and cysts lined by simple or stratified epithelium comprising cuboidal cells with scant cytoplasm, some with cilia or apical snouts (mucin is absent); (3) mild to moderate cellular atypia; (4) infrequent mitoses; (5) at least focally desmoplastic response (in most cases); and (6) occasional association with tuboendometrioid metaplasia (Figure 9, A-C).
Minimal Deviation Adenocarcinoma Endometrioid Type Versus Benign Mimics.--Even though tuboendometrioid metaplasia (TEM) and endometriosis pose typically more problems in the differential diagnosis with AIS, on occasion, these benign glandular proliferations may cause concern for minimal deviation adenocarcinoma of endometrioid type, as glands and cysts in the latter are often lined by benign-appearing cells, occasionally containing cilia and lacking diffuse stromal desmoplastic reaction.
is essentially tubal metaplasia without ciliated cells, although it commonly displays more pseudostratification and higher nuclear to cytoplasmic ratios than other tubal metaplasia lesions; it lacks the architectural complexity, mitoses, apoptosis, and nuclear irregularity of AIS (Figure 4).