The uterus, an inverted triangular shaped muscular organ with a central mucosal lined cavity, is divided into regions: the fundus, the corpus, the isthmus or lower uterine segment, and the endocervical canal and the exocervix (Fig. 3.1). The fallopian tubes enter the uterine cavity at the cornua of the uterus. Distally, the cervix merges with the vagina. The internal os marks the boundary between the corpus and the endocervix. In the nulliparous woman, the cervix usually measures 3–4 cm in diameter and is approximately the same length as the corpus, but following childbearing the ratio of cervical length to corpus is approximately 1–2. Deep clefts created by invaginations of the endocervical epithelium into the stroma create the rugae characteristic of the endocervical canal. The clefts appear as glands on histologic sections but are not true glands. The endocervical canal transforms to the exocervix at the external os.

The exocervix or ectocervix protrudes into the vagina and is known as the portio vaginalis. The exocervix is covered by non-cornified stratified squamous epithelium identical to the squamous epithelium covering the vagina (Fig. 3.2). A sharp demarcation between the squamous epithelium of the exocervix and the glandular epithelium of the endocervix is present either on the exocervix or in the endocervical canal depending on the reproductive age. Shortly after birth the squamo-columnar junction is found in the endocervical canal. At puberty, the squamo-columnar junction shifts to the exocervix where the exposed endocervical mucosa appears red and is known as ectropion. Gradually the exposed, more fragile glandular covering of the ectropion is replaced by more robust squamous epithelium through the process of squamous metaplasia, creating a new, functional squamo-columnar junction. The region between the original squamo-columnar junction and the functional squamo-columnar junction, where the surface endocervical epithelium has been replaced by squamous epithelium, is known as the transformation zone and on histology can be recognized by the endocervical glands or clefts beneath the surface squamous epithelium (Fig. 3.3). The transformation zone is the region in which cervical squamous metaplasia arises from the reserve cells (Fig. 3.4). On histologic sections these immature metaplastic cells appear to undermine the residual endocervical epithelium. After menopause the functional transformation zone recedes into the endocervical canal.

The endocervical epithelium, comprises a single layer of predominantly mucin-secreting cells with small, usually basally placed nuclei, lines both the surface of the endocervical canal and the clefts or glands (Fig. 3.5). The cytoplasm of the cells is filled with fine mucin droplets and has a characteristic pale blue hue with the hematoxylin and eosin stain. Scattered nonsecretory ciliated cells are interspersed among the more numerous mucinous cells, presumably to propel the mucus expelled by the mucinous cells. The nuclei of the endocervical cells are round to slightly elongate with inapparent nucleoli when the cells are in the resting state. Injury or other stimuli will cause nucleoli to become prominent in enlarged nuclei. Mitotic figures are uncommon in nonneoplastic endocervical cells, but can be present in regenerative states.

On cytology slides, normal endocervical glandular epithelium shows variable appearances depending on several factors: patient age and hormonal status, the level sampled within the endocervical canal, the sampling device, and the cytology preparation. Endocervical cells most commonly present as columnar cells, either singly or in variably sized groups, without attached stroma (Fig. 3.6). When displayed in profile, the single endocervical cell is recognized by the approximately twice longer than wide shape. The nucleus is round with a smooth or slightly irregular nuclear membrane contour and is located at the basal pole of the columnar cells. Small nucleoli may be identified within finely dispersed chromatin. The nuclear size can vary from slightly larger than a red blood cell to greater than the size of a polymorphonuclear leukocyte. Multinucleated endocervical cells are commonly encountered. Small dark knuckles protruding from the nuclear membrane into the cytoplasm have been described in association with ovulation or the secretory, postovulatory phase of the menstrual cycle [1–3]. The significance of the protrusions has never been firmly established. Usually the cytoplasm is filled with fine, almost transparent mucin or small vacuoles, or may have a larger vacuole resembling a goblet cell, but in some cells the cytoplasm may be dense. Most commonly the cytoplasm stains blue-gray with the Papanicolaou stain. A string of endocervical cells in profile will be aligned in the so-called picket fence or palisade arrangement. If the view is rotated 90°, the cells will appear in a geometric arrangement reminiscent of a honeycomb. In the latter case, varying the microscopic focus will bring either the nuclear pole or the mucin-filled cytoplasmic pole into view (Fig. 3.7). Ciliated endocervical cells are common, especially when the sample has been obtained by vigorous brushing of the upper endocervical canal where ciliated cells are present in increased numbers. A terminal bar anchoring the cilia is often identified (Fig. 3.8). Both the cilia and terminal bar stain either blue or pink with the Papanicolaou stain. The height of the endocervical cell, the opacity of the cytoplasm, and the position of the nucleus have been reported to vary with the phase of the menstrual cycle and the geographic location within the canal [4].