FIGURE 1.1 Normal squamous epithelium.

FIGURE 1.2 Squamous epithelium rich in glycogen.

The cervical squamous epithelium undergoes changes during the menstrual cycle; during the influence of estrogens, there is a predominance of superficial cells, and after ovulation with the effects of progesterone, there is a predominance of intermediate cells (2).

Endocrine cells, with an unknown function, have been identified by immunohistochemistry in the squamous epithelium (5,6). Langerhans cells, which are involved in antigen presentation to T lymphocytes, are found in the exocervix and transformation zone (7). In addition, melanocytes may be found in the basal layer of the cervix in a small percentage of women (8).

Seldom, the presence of ectodermal elements in the form of sebaceous glands, hair follicle–like structures, or sweat gland–like structures can be found in the exocervix (Fig. 1.3, e-Fig. 1.6). Usually, these ectodermal elements are incidentally found, with a rare case of sebaceous glands in the exocervix being associated with a gross lesion or nodule (9).

FIGURE 1.3 Sebaceous glands and hair follicle–like structure in ectocervix. (Courtesy of Dr. W. Glenn McCluggage)

EPITHELIUM OF THE ENDOCERVIX

The endocervical epithelium is composed of a single layer of mucin-producing columnar cells with small, oval, basally located nuclei with dense chromatin. Nuclear overlapping may be present (Fig. 1.4, e-Fig. 1.7), but mitotic figures are rare. Nuclear enlargement and nucleoli can be seen as part of regenerative changes (2). There are also ciliated cells (Fig. 1.5, e-Fig. 1.8) and subcolumnar reserve cells, which may give rise to glandular cells or differentiate along squamous lines as discussed in the next section. The amount of ciliated cells increases towards the superior part of the endocervical canal, where they can become the only epithelial component. The reserve cells are also variable along the cervical canal not only in their distribution but also in the expression of immunomarkers. At the level of the transformation zone, the reserve cells are positive for p63, bcl-2, and cytokeratins 5, 7, and 17. Moving upward in the endocervical canal, subcolumnar reserve cells maintain expression of p63 and cytokeratins 5 and 7 but the percentage and intensity of staining for bcl-2 and cytokeratin 17 diminishes (10). Neuroendocrine cells have also been described (2).

The endocervical epithelium lines not only the surface of the endocervical canal, but also the endocervical clefts and glands that are contained within the cervical stroma (Fig. 1.6, e-Fig. 1.9), usually up to 5 mm in depth, and on rare occasions up to 1 cm (11). These clefts and glands can be variable in size and shape (Fig. 1.7, e-Fig. 1.10) and may be mistaken for minimal deviation adenocarcinoma. However, comparison of the glands in question with unquestionably benign ones in the vicinity may provide guidance, and attention to the following features should help rule out carcinoma: the absence of cytologic atypia and desmoplastic response, the absence of marked variation in size and shape, and the absence of glands around nerves or medium-sized vessels. This may require the examination of additional tissue (i.e., cervical cone), since some of these features can be focal in minimal deviation adenocarcinoma.

FIGURE 1.4 Normal endocervical epithelium.

FIGURE 1.5 Endocervical epithelium with cilia.

FIGURE 1.6 Endocervical epithelium lining the surface of the endocervical canal, clefts, and glands.

FIGURE 1.7 Endocervical glands with variation in shape; note the claw-shaped gland (arrow).

FIGURE 1.8 Endocervical epithelium with subnuclear vacuoles.

During the menstrual cycle, the endocervical epithelium undergoes minimal changes consisting of displacement of the nuclei towards the mid-portion or apical portion of the cells secondary to subnuclear vacuoles (Fig. 1.8, e-Figs. 1.11–1.14).

EPITHELIUM OF THE TRANSFORMATION ZONE

There are two mechanisms involved in the transformation of endocervical epithelium into squamous epithelium: squamous epithelialization and squamous metaplasia.

In squamous epithelialization, mature squamous cells move underneath the endocervical cells, pushing them off of the basement membrane with the eventual detachment of these cells from the epithelium (2). This process can extend into endocervical clefts/glands and should not be misinterpreted as carcinoma. Although the cells of squamous epithelialization may have enlarged nuclei with prominent nucleoli, they lack the nuclear pleomorphism, chromatin abnormalities, or the abnormal mitotic figures of carcinoma. In addition, these cells conform to the boundaries of the cleft and do not infiltrate the stroma (Fig. 1.9).

Squamous metaplasia entails the proliferation of endocervical “reserve cells” and subsequent differentiation of these reserve cells into squamous cells rather than mucin-producing cells (Fig. 1.9, arrow) (2). The reserve cells initially do not have squamous characteristics, but appear identical to basal and parabasal cells. After they proliferate and stratify, they acquire somewhat more cytoplasm (immature squamous metaplasia; Fig. 1.10, e-Figs. 1.15