This is the most common type of CGIN, although the term usual or endocervical type is not generally used in the pathology report. CGIN usually occurs at or close to the transformation zone and there is coexistent CIN in a high proportion of cases. It was previously considered that both skip lesions and extension high up the endocervical canal were common in CGIN but, although these sometimes occur, both are relatively uncommon [25, 26]; tangentional sectioning may result in an impression of skip lesions. However, there have been occasional reports of CGIN with extension to the endometrium [27, 28]. Some of these cases have been misdiagnosed as a primary adenocarcinoma of the uterine corpus or have resulted in ovarian metastasis, sometimes even in the absence of obvious invasion within the cervix [27]. Those cases with ovarian metastases have not generally been associated with an adverse outcome and the ovarian disease is likely secondary to transuterine and transtubal spread [27].

CGIN is first identified on low power examination, which is the initial clue to diagnosis, given the contrast to the normal endocervical glands; it is not necessary to examine every endocervical gland under high power to look for CGIN. In high grade CGIN, the abnormal glands are confined to the pre-existing “normal” endocervical glandular field which, in itself, may be quite complicated. In some cases, there is accentuation of the normal lobular endocervical glandular architecture (Fig. 3.1). There is often an abrupt transition between normal and abnormal epithelium both within and between glands (Fig. 3.2). Usually both the surface and crypt epithelium is involved with mucin depletion, nuclear stratification (often with the long axis of the cells perpendicular to the base), atypia, hyperchromasia with coarse clumped chromatin and loss of polarity. There are usually easily identifiable mitotic figures, especially on the luminal aspect of the glands, sometimes with atypical mitoses; however, in some cases mitoses are relatively sparse. Apoptotic bodies are a characteristic and relatively constant feature and are usually seen in the non-luminal aspect of the glands (Fig. 3.3) [29–31]; sometimes they are numerous. In general, apoptotic bodies are more commonly seen and are more numerous in high grade CGIN than in invasive cervical adenocarcinomas. The combination of luminal mitoses and basal apoptotic bodies is a characteristic feature of high grade CGIN. Focal intraglandular papillae and a cribriform architecture may be seen in high grade CGIN (Fig. 3.4) but when these features are prominent and widespread, this should result in consideration of invasive adenocarcinoma; in those cases of CGIN with a cribriform architecture, the glandular outlines should be round and not irregular. There may be inflammation of the stroma surrounding the glands in CGIN but there is no desmoplastic reaction. Since CGIN is confined to the pre-existing endocervical glandular field, it may also involve dilated crypts. Occasionally, CGIN involves a pre-existing benign endocervical glandular lesion such as papillary endocervicits, microglandular hyperplasia or tunnel clusters and this may result in diagnostic problems and consideration of adenocarcinoma for obvious reasons. The immunophenotype of high grade CGIN is discussed below (section on “Immunohistochemistry of premalignant endocervical glandular lesions”).

As discussed, low grade CGIN is a much more uncommon and subtle lesion. The morphological features are similar to those of high grade CGIN but the cytological abnormalities are less marked. There is usually nuclear hyperchromasia but there is only mild atypia, mucin depletion, nuclear stratification and loss of polarity (Fig. 3.5). Mitotic figures are usually present but not numerous. The presence of apoptotic bodies may be a useful diagnostic clue.

Superficial CGIN (superficial AIS) has been used as a term for CGIN which is confined to the surface mucosa and crypt openings (Fig. 3.6) [32]. It has been speculated that this represents an early form of CGIN occurring in a younger age group than more established CGIN. In contrast to the latter, in superficial CGIN there is usually only mild nuclear atypia with rare to absent apoptotic bodies. Given its superficial nature, the lesion may not be obvious at low power and may be overlooked, especially since the cytological abnormalities can be subtle; immunohistochemical staining for p16 and MIB1 may assist in diagnosis (see below).

A scoring system for non-invasive endocervical glandular lesions to be used primarily in research practice has been proposed [33]. Using this system, a final numerical score is based on the summation of three individual scores given for nuclear atypia, stratification and the sum of mitoses and apoptoses [33]. While this scoring system may be useful in a research setting, it is of limited value in routine pathological practice.

After the usual type, the most common variant of CGIN is the intestinal type where goblet cells are present (Fig. 3.7). Paneth cells and/or neuroendocrine cells also occur more uncommonly [26, 34]. Intestinal type CGIN is usually associated with usual type; in one study, intestinal differentiation was present in 29 % of cases of CGIN, always in association with usual type [26]. When intestinal type epithelium with goblet cells is present in the cervix, this almost always indicates a premalignant or malignant endocervical glandular lesion, although the nuclear features of malignancy may be subtle because of compression by intracytoplasmic mucin globules (Fig. 3.8). “Benign” intestinal metaplasia (unassociated with CGIN) rarely exists in the cervix, although it is occasionally seen in association with lobular endocervical glandular hyperplasia and other forms of gastric metaplasia (see Chap.​ 2, section on “Lobular endocervical glandular hyperplasia”) [35, 36]. One study found that intestinal type CGIN is more likely than the usual type to be associated with early invasion [34].

Most cases of intestinal type CGIN are HPV-associated [37]. However, it has been suggested that a minority of examples of intestinal type CGIN are not HPV-associated [37]. In one study, cases of intestinal type CGIN which were not HPV-associated occurred in an older age group than HPV-associated CGIN, were less likely to express p16 diffusely and exhibited a lower MIB1 proliferation index [37].

An endometrioid variant of CGIN (AIS) has been described. However, this is likely to merely represent usual type CGIN with marked depletion of intracytoplasmic mucin resulting in a pseudoendometrioid appearance. As such, it is doubtful whether a true endometrioid variant of CGIN exists or whether it could be distinguished from usual type.

Occasional examples of CGIN contain cilia and are referred to as being of tubal or ciliated type (Fig. 3.9) [38]. This uncommon variant of CGIN usually occurs in association with usual type. The main differential diagnosis is tuboendometrial metaplasia with a degree of nuclear atypia. Apoptotic bodies are a useful diagnostic clue in favour of CGIN but these should not be mistaken for the intraepithelial lymphocytes surrounded by a halo which are commonly seen in tuboendometrial metaplasia. It has been suggested that tubal type CGIN may arise from tuboendometrial metaplasia or atypical tuboendometrial metaplasia but there is no firm evidence for this. p16 may be useful in the distinction from tuboendometrial metaplasia in that CGIN is diffusely positive while tuboendometrial metaplasia is usually negative or exhibits patchy immunoreactivity. However, the immunophenotype of tubal type CGIN has not been studied given the rarity of the lesion. Given its rarity, caution should be exercised before making a diagnosis of tubal type CGIN. The nuclear features should unequivocally be those of a malignant lesion since tuboendometrial metaplasia may exhibit a significant degree of nuclear atypia.