Fig. 2.1
Superficial squamous cells (LBP, ThinPrep). Admixture of superficial and intermediate squamous cells. The superficial cells have smaller condensed (pyknotic) nuclei. Light brown glycogen is present in the cytoplasm of both cell types. The inset reveals a characteristic superficial cell at high magnification. Note the polygonal cytoplasmic profile, cytoplasmic keratohyaline granules, and pyknotic nucleus with a cross-sectional area of approximately 10 μm2. The dense nucleus is opaque to light
2.3.1.2 Intermediate Cell
Generally present in the middle or intermediate layer of the squamous epithelium. In the secretory phase, this cell type may compose both the middle and superficial layers of the normal cervical epithelium. It is particularly prominent in pregnancy and with the use of progestational agents. The nucleus is larger than that of the superficial cell, with a cross-sectional nuclear area of 35 μm2 and a finely granular chromatin pattern. The nucleus is often elongate with a longitudinal nuclear groove (Fig. 2.2). The intermediate cell nucleus serves as the basic size reference for other cells in cervical cytology specimens. Naked intermediate cell nuclei are seen in the second half of the cycle secondary to bacterial cytolysis (Fig. 2.59).
Fig. 2.2
Intermediate squamous cell (LBP, ThinPrep). A typical intermediate cell with a polygonal cytoplasmic profile. The nucleus possesses finely granular chromatin with a longitudinal groove. The cross-sectional area of the intermediate nucleus is approximately 35 μm2 and is generally used as the internal reference for size comparison. Light can pass through the intermediate nucleus due to the chromatin being more open than that of a superficial cell
2.3.1.3 Parabasal Cell
Along with immature squamous metaplastic cells, parabasal cells are the least mature cells in a cervical cytology sample. They are generally not present in specimens from a hormonally mature epithelium as they are derived from deep cell layers not typically sampled in cervical cytology specimens from premenopausal women. In the absence of hormonal stimulation, this cell type comprises layers of a relatively thin and atrophic epithelium. Parabasal cells may predominate in postmenopausal and postpartum states. The nuclei are larger than in intermediate cells with an area of 50 μm2. The cytoplasmic area is smaller and the nuclear to cytoplasmic ratio is higher than in intermediate or superficial cells; and the cytoplasmic texture is more granular and dense (Fig. 2.3).
Fig. 2.3
Parabasal cell (LBP, ThinPrep). A parabasal cell is contrasted with an intermediate cell. The parabasal cell exhibits typical features with an oval nucleus, fine chromatin, and a cross-sectional area of approximately 50 μm2. The cytoplasm is dense relative to the intermediate cell, because the intermediate cell cytoplasm flattens out next to the nucleus, whereas in the parabasal cell, the cytoplasm is heaped up. If the cells were viewed from the side, an intermediate cell would be a flattened saucer with a central nuclear heap. The parabasal cell would resemble a hill with sloping sides
2.3.2 Glandular Cells
2.3.2.1 Endocervical Cell
Endocervical glandular cells have nuclear sizes that are highly variable with a mean of 50 μm2 which is slightly larger than that of an intermediate squamous cell. The nucleus shows a finely granular and evenly distributed chromatin pattern with small nucleoli. The cytoplasm is diffusely vacuolated or granular. Cells exhibit polarity with nuclei at one end of the cytoplasm and mucus present at the opposite end. The cytomorphology will differ depending on the orientation of the cells on the slide: when viewed from the side, there will be a “picket-fence” formation, whereas when viewed en face, they will have a classic “honeycomb” configuration (Fig. 2.4).
Fig. 2.4
Endocervical cells (LBP, ThinPrep). Endocervical cells may be seen en face in a typical “honeycomb” arrangement of benign glandular epithelium (a). Alternatively, endocervical cells when viewed from the side present in a “picket-fence” configuration (b). There is normal nuclear polarity and ample evidence of apical mucin in these columnar cells
2.3.2.2 Endometrial Cell
Spontaneously exfoliated endometrial cells may be of epithelial or stromal origin and can occur as isolated cells or as aggregates. Endometrial glandular cells are typically smaller than endocervical cells, with a nuclear area equal to or slightly smaller than an intermediate cell nucleus (35 μm2) and have a higher nuclear to cytoplasmic ratio. The nuclear chromatin tends to be dense, heterogeneous and may contain apoptotic debris due to degenerative changes. Nucleoli are generally not prominent, but may be observed in liquid-based preparations due to improved fixation. The cytoplasm is scant and may be dense or vacuolated. Exfoliated endometrial stromal cells are typically arranged in dense aggregates which often have a surrounding layer of glandular epithelium – a characteristic formation often referred to as an “exodus” ball because of its presence at the end of menstrual flow. Exfoliated endometrial stromal cells may also be isolated and have spindled tails of wispy cytoplasm. Exfoliated endometrial cells (Figs. 2.5 and 2.6, see Figs. 3.1, 3.2, and 3.4) present differently than do directly sampled lower uterine segment and endometrial cells, which are described below (Figs. 2.7, 2.8, and 2.9, see Fig. 3.5).
Fig. 2.5
Endometrial cells (LBP, SurePath). A tight cluster of endometrial glandular cells with nuclei having cross-sectional areas slightly smaller than the 35 μm2 of intermediate cells. Endometrial cell nuclear to cytoplasmic ratios are high and the cells tend to form three-dimensional groups. The small and monotonous nuclear size should prevent overinterpretation as a squamous, or glandular abnormality
Fig. 2.6
Endometrial cells, exodus (LBP, ThinPrep). Collections of peripheral glandular and central stromal endometrial cells (exodus ball) are typically seen between day 6 and 10 of the menstrual cycle. These clusters are among the last remnants of endometrial shedding and the cells may show degenerative changes. Both images show exodus balls from two different cases. On the left (a) is an intermediate magnification from a conventional preparation. More nuclear structure is observed in cells on the periphery of the exodus ball. In (b), from a liquid based preparation, physical forces have accentuated the rounding up of cells during fixation. The resultant three dimensional cell ball obstructs more light, is darker and may be over interpreted as a glandular abnormality
Fig. 2.7
Lower uterine segment sampling (CP). Lower uterine segment sampling with ill-defined glandular cells near the upper left aspect and stromal cells loosely adherent to the glandular cells. Several blood vessels can be seen protruding from the group. Stromal and glandular components are not always easy to distinguish on cervical cytology
Fig. 2.8
Lower uterine segment sampling (CP). A well-preserved endometrial gland presenting as a tubular structure. A stromal component is also visible at the lower right side of the epithelial tube. The inset shows columnar endometrial glandular cells that have round to oval, variably hyperchromatic nuclei, with moderately coarse but evenly distributed chromatin and smooth nuclear borders (CP)
Fig. 2.9
Lower uterine segment sampling (CP). Endometrial stromal cells adherent to blood vessels and flattened against the slide in a fanlike pattern
Preparation-Specific Criteria for Normal Cellular Elements
Liquid-Based Preparations:
Fixation is generally improved and these preparations remove much of the background bacteria, debris, and inflammatory material that can obscure the cells of interest. Glandular cells may form three-dimensional structures, as cellular fixation occurs during suspension in liquid as opposed to preparations in which fixation occurs after smearing on a slide. Rounded benign groups can be more densely cellular and hyperchromatic. Observation of cells near the borders of the group becomes more important to determine the true origin and nature of such cell groupings. Nucleoli may be better preserved and more prominent.
Conventional Preparations:
Bacteria, inflammatory cells, and debris are more prominent in the background. Degenerative changes, “air-drying artifact”, mechanical artifact, and other limiting factors associated with sample collection and preparation are more common. Cells may be larger as they are flattened out on the slide.
2.3.3 Lower Uterine Segment and Directly Sampled Endometrial Cells (Figs. 2.7–2.9)
2.3.3.1 Criteria
Cells directly sampled from the lower uterine segment or endometrial cavity may present as large, cellular, hyperchromatic groups composed of both endometrial glandular and stromal cells (Fig. 2.7, see Fig. 3.5). Branching glands can be seen in some groups, with surface gland openings and palisading of nuclei in the interior of the fragments (Fig. 2.8). The glands are surrounded by stroma, which may contain small vessels that can appear to protrude from the surface of the groups in a spindled or “feathered” pattern. Smaller fragments may contain only glandular or stromal cells. Nuclear crowding and overlap are present in both epithelial and stromal components.
Directly sampled endometrial and lower uterine segment glandular cells are columnar and have round to oval, variably hyperchromatic nuclei, with moderately coarse but evenly distributed chromatin and smooth nuclear borders (Fig. 2.8). Nucleoli are inconspicuous and mitotic figures may be seen, particularly during the proliferative phase. Ciliated cells may be present in the case of coexistent tubal metaplasia.
Stromal cell groupings are arranged in a disorganized pattern (Fig. 2.9). The cells have oval to elongate nuclei and scant, spindled cytoplasm. Nuclei have smooth contours and an evenly distributed, finely granular chromatin pattern. Nucleoli are inconspicuous and mitotic figures are rare.
Preparation-Specific Criteria
In liquid-based preparations, lower uterine segment and directly sampled endometrium tends to exhibit small dense cellular groups containing only epithelium or stroma (Fig. 2.8). In conventional preparations, large cellular groups may have a “stretched” configuration and glands and blood vessels are more commonly noted (Fig. 2.7, see Fig. 3.5).
2.3.3.2 Explanatory Notes
Sampling of the lower uterine segment and endometrium may occur because of closer proximity to the cervical os following an excisional procedure (loop electrosurgical excision or conization) that shortens the endocervix [11] or a trachelectomy (a fertility-sparing resection of the cervix, upper vagina, and adjacent tissue, for minimally invasive squamous cell carcinoma) [12, 13]. Direct endometrial sampling can occasionally be present in women with an intact cervix secondary to the vigorous use of an endocervical brush or broom sampling device.
Directly sampled endometrial tissue may mimic glandular neoplastic abnormalities or rarely high-grade squamous lesions due to the presence of hyperchromatic crowded groups with nuclear crowding, nuclear overlap, and high nucleus to cytoplasmic ratios. In contrast to spontaneously exfoliated endometrial cells, direct brushing of endometrial tissue may yield large cellular fragments that can recapitulate their native in situ architecture (so-called organoid differentiation). This appearance may include branching tubular glands amid stroma composed of round to spindle-shaped cells. Peripheral palisading may be evident. The low-power recognition of branching glands and glandular-stromal complexes can avoid confusion with atypical glandular cells (AGC) or glandular neoplasia. In liquid-based preparations, smaller rounded groups may have only one visible component. The most helpful clues in this situation are small nuclear size (approximating that of an intermediate nucleus); smooth, regular nuclear contours; and evenly distributed chromatin. In addition, groups of endometrial stromal cells may contain small vessels that protrude from the surface of the organoid groups, a feature not seen in neoplastic epithelial abnormalities.
2.4 Nonneoplastic Cellular Variations
2.4.1 Squamous Metaplasia (Figs. 2.10–2.13)
2.4.1.1 Criteria
Fig. 2.10
Squamous metaplasia (LBP, SurePath). A characteristic metaplastic cell is found in the center of the field. The nucleus is round to oval with fine, evenly distributed chromatin. The nuclear to cytoplasmic ratio is variable, and in this instance, it approaches one to one. These cells should not be overinterpreted as ASC-H or HSIL
Fig. 2.11
Squamous metaplasia (CP). Routine screening from a 27-year-old woman, day 8 of menstrual cycle shows reactive metaplastic cells with “spidery” cytoplasmic processes, a feature that is seen more often in conventional smears. Follow-up cytology was NILM
Fig. 2.12
Squamous metaplasia (histology, H&E). (a, left) Early squamous metaplasia in an endocervical sample. A variety of stimuli can trigger an altered pathway of differentiation in the stem cell population that was committed to generating endocervical cells. The cells underneath the mucus secreting epithelial cells have rounded up, lost their ability to secrete mucin, and assumed a protective role, increasing the thickness of barrier between the stimulus and the underlying tissue. (b, right) A later stage in squamous metaplasia where multiple layers of metaplastic cells are seen under the surface epithelium
Fig. 2.13
Squamous metaplasia (CP). Squamous metaplastic cells show nuclear size similar to parabasal cells. This cohesive group of cells also shows some modest nucleolar prominence that is consistent with reactive/reparative changes
Squamous metaplastic cells which show a range of cytoplasmic differentiation from immature parabasal-like cells to those that approximate the appearance of differentiated intermediate/superficial cells (Fig. 2.10). The mean nuclear area is larger than that of the intermediate cell and similar to the parabasal cell at 50 μm2.
Preparation-Specific Criteria
Cells having spindled cytoplasmic projections (“spider cells”) are often seen in conventional preparations due to disruption of the cohesion of cellular attachments by the force of the smearing procedure (Fig. 2.11).
2.4.1.2 Explanatory Notes
The process of metaplasia represents the replacement of one type of epithelium (in this case endocervical) with another (squamous) as a protective response. Squamous metaplastic cells can exhibit a spectrum of morphology from relatively undifferentiated small round cells to highly differentiated intermediate/superficial squamous cells. In metaplasia, stimuli such as infection, inflammation, or other type of trauma cause an alteration in the pathway of development of new cells replacing those lost by wear and tear. The newly generated cells become progressively more differentiated along the squamous pathway in response to the noxious stimulus. The metaplastic surface epithelium may eventually become indistinguishable from other squamous mucosa; however, the histologic finding of glandular spaces filled by endocervical or metaplastic squamous cells beneath the surface is a marker of the cervical transformation zone and an indication that the overlying epithelium was once glandular (Fig. 2.12).
One of the most difficult tasks in day-to-day cytologic practice is the evaluation of metaplastic cells, especially those with high nuclear to cytoplasmic ratios. Nuclear enlargement without other nuclear abnormalities in squamous metaplastic cells should lead to cautious evaluation, so as not to overinterpret the sample. One should evaluate single nuclei in intact cells. A nuclear to cytoplasmic ratio of less than 50 %, smooth nuclear contours, and even distribution of chromatin all favor benign squamous metaplasia (Fig. 2.13). A higher nuclear to cytoplasmic ratio in conjunction with hyperchromasia and/or nuclear contour irregularities, such as notching or grooving, should prompt consideration of a HSIL or ASC-H designation.
2.4.2 Keratotic Cellular Changes (Figs. 2.14–2.17)
Fig. 2.14
Keratotic cellular changes (LBP, ThinPrep). Intermediate squamous cells showing prominent cytoplasmic keratohyaline granules, a precursor to full keratinization
Fig. 2.15
Keratotic cellular changes (CP). Keratotic cellular changes, “typical parakeratosis.” On the left side (a), note the “squamous pearl” formation in this specimen from a 49-year-old woman being followed up after treatment for SIL. On the right side (b) is a small cluster of miniature squamous cells. Both are examples of “typical parakeratosis” showing miniature squamous cells with small bland, pyknotic nuclei
Fig. 2.16
Keratotic cellular changes. Keratotic cellular changes, “typical parakeratosis”. On the left (a, CP) is an orangeophilic cluster, and on the right (b, LBP, ThinPrep) are more eosinophilic squamous cells with small, opaque nuclei. Human papillomavirus (HPV) testing, performed as part of co-testing on the liquid-based specimen, was negative
Fig. 2.17
Keratotic cellular changes, “hyperkeratosis.” On the left (a, LBP, ThinPrep) is a group of anucleate squames at low power. On the right (b, LBP, ThinPrep) are anucleate, mature polygonal squamous cells with ghostlike “nuclear holes” (“b” is reprinted with permission from Williamson et al. [15])
Normally, the cervix is a nonkeratinizing, stratified squamous epithelium. Keratotic changes usually occur as a protective reactive phenomenon or in association with human papillomavirus (HPV)-induced cell changes. Both of these processes lead to hypermaturation of the native squamous epithelium, more closely approximating the normal appearance of skin. Keratotic changes can be considered a second-order protective reaction for subepithelial tissues with metaplasia being the first-order reaction.
“Keratosis,” “hyperkeratosis,” “parakeratosis,” and “dyskeratosis” are descriptive terms for keratotic cellular changes which have been used inconsistently in the past. These terms are not specifically listed in Bethesda terminology due to lack of consensus definitions. They are included parenthetically for clarification only. Although some cytologists may choose to include such terms to describe a morphologic feature that may correlate with leukoplakia on colposcopy, they should not be used as an interpretive category in cytology reports.
After metaplastic conversion, continued trauma may lead to formation of cytoplasmic keratohyaline granules (Fig. 2.14). In rare examples, the epithelium may come to resemble skin with a granular layer.
2.4.2.1 Typical Parakeratosis (Figs. 2.15 and 2.16)
2.4.2.1.1 Criteria
Miniature superficial squamous cells with dense orangeophilic or eosinophilic cytoplasm. Cells may be seen in isolation, in sheets, or in whorls; cell shape may be round, oval, polygonal, or spindle shaped.
Nuclei are small (approximately 10 μm2 in cross-sectional area) and dense (pyknotic).
If atypical nuclear changes are present, an atypical squamous cell (ASC-US/ASC-H) or SIL interpretation should be considered, but if nuclei are round, regular, and resemble neighboring nuclei, a designation as abnormal is not warranted.
2.4.2.2 Hyperkeratosis (Fig. 2.17)
2.4.2.2.1 Criteria
Anucleate but otherwise unremarkable mature polygonal squamous cells, often associated with mature squamous cells showing keratohyaline granules.
Empty spaces or “ghost nuclei” may be noted.
2.4.2.3 Explanatory Notes
The Bethesda classification and interpretation of such keratotic changes depends on the nuclear alterations present. Miniature squamous cells with small pyknotic nuclei and orangeophilic to eosinophilic cytoplasm (“parakeratosis”) are a nonneoplastic reactive cellular change. However, single cells or cell clusters that demonstrate pleomorphism of nuclear shape and/or increased nuclear size and/or chromasia (“atypical parakeratosis,” “dyskeratosis,” or “pleomorphic parakeratosis”) are representative of an epithelial cell abnormality. Such findings should be categorized as atypical squamous cells (ASC) or as a squamous intraepithelial lesion (SIL), depending on the degree of cellular abnormality identified (see Figs. 4.15, 4.16, 5.8, 5.9, 5.26, 5.42, 5.43, 5.44, 5.56, and 5.59) [14].
Anucleate, but otherwise unremarkable mature, squamous cells (“hyperkeratosis”) constitute a nonneoplastic cellular change. Inadvertent contamination of the specimen with vulvar material may also introduce anucleate squamous cells into the cervical cytology specimen. When extensive hyperkeratosis is present, an underlying neoplastic or nonneoplastic process may be associated and should be considered when evaluating such cytologic preparations [15]. Thick plaques of pleomorphic anucleate squamous cells with irregular contours may rarely be the only clue to an underlying squamous cell carcinoma [16]. Similar to parakeratosis, hyperkeratosis alone does not constitute a specific interpretive category.
2.4.3 Tubal Metaplasia (Figs. 2.18–2.21)
2.4.3.1 Definition
Fig. 2.18
Tubal metaplasia (histology, H&E). Endocervical gland with tubal metaplasia amid cervical stroma. The ciliated cells of tubal metaplasia show prominent terminal bars at the base of the cilia
Fig. 2.19
Tubal metaplasia (CP). Ciliated cells derived from tubal metaplasia. Note terminal bar and cilia at left edge (arrow). Tubal metaplasia shows prominent pseudostratification and can have enlarged nuclei that make it a look-alike for endocervical adenocarcinoma in situ
Fig. 2.20
Tubal metaplasia (LBP, Thin Prep). A linear array of cells showing tubal metaplasia
Fig. 2.21
Tubal metaplasia (CP). Ciliated columnar endocervical cells. A goblet cell is seen at the center with its nucleus closer to the top of the image (arrow)
Tubal metaplasia is a metaplastic phenomenon in which the normal endocervical epithelium is replaced by an epithelium that recapitulates that of the normal fallopian tube. This metaplastic epithelium includes several cell types (ciliated cells, peg cells, and goblet cells) [17] (Fig. 2.18). Tubal metapalsia is a frequent finding in the upper endocervical canal/lower uterine segment.
2.4.3.2 Criteria
Columnar ciliated endocervical cells that may occur in small groups or as pseudostratified crowded groups (Figs. 2.19 and 2.20).
Nuclei are round to oval and may be enlarged, pleomorphic, and often hyperchromatic.
Chromatin is evenly distributed and nucleoli are usually not seen.
Nuclear to cytoplasmic ratio can be high.
The cytoplasm may show discrete vacuoles or goblet cell change (Fig. 2.21).
Presence of cilia and/or terminal bars is characteristic, but single ciliated cells in isolation are not sufficient for the designation.
Mitoses may be present.
2.4.3.3 Explanatory Notes
Tubal metaplasia is among the most common benign processes to be misinterpreted as endocervical atypia or neoplasia. This is due to the tendency toward enlarged nuclei, crowded nuclei, and nuclear stratification. However, terminal bars and cilia establish a benign interpretation (see Figs. 6.12, 6.13, and 6.14).
2.4.4 Atrophy (Figs. 2.22–2.27)
Fig. 2.22
Atrophy (histology, H&E). The cervical squamous epithelium is remarkably thinned and made up entirely of parabasal cells. This is a consequence of waning hormonal support. In such cases, p16 immunostain would be negative
Fig. 2.23
Atrophy (LBP, ThinPrep). Note flat, monolayer sheet of parabasal-type cells, with preserved nuclear polarity
Fig. 2.24
Atrophy with inflammation (“atrophic vaginitis”) (CP). Note the classic finding of granular debris in background, degenerating parabasal cells, and polymorphonuclear leukocytes. (a) “Blue blobs” and pseudoparakeratosis are also seen in atrophic vaginitis, the former being more prominent in conventional preparations (b)
Fig. 2.25
Atrophy with inflammation (atrophic vaginitis) (LBP, ThinPrep). In liquid-based preparations, the granular debris is often clumped and adheres to atrophic cell clusters in a pattern that may mimic “clinging tumor diathesis” (see Fig. 5.58). Attention to cellular features is crucial to avoid overinterpretation
Fig. 2.26
Atrophy (LBP, SurePath). Note more dissociation of parabasal cells in a relatively clean background
Fig. 2.27
Atrophy with multinucleated giant cells (CP). Multinucleated histiocytic giant cells are a nonspecific finding and are often seen in postmenopausal and postpartum specimens. They differ from other giant cells such as syncytiotrophoblast (Fig. 2.29b) and multinucleated cells in herpes infection (Fig. 2.63)
2.4.4.1 Definition
Atrophy is a normal aging phenomenon associated with lack of hormonal stimulation that leads to thinned epithelium consisting of only immature basal/parabasal cells (Fig. 2.22).
2.4.4.2 Criteria
Flat, monolayer sheets of parabasal-like cells with preserved nuclear polarity and little nuclear overlap in individual focal planes (Fig. 2.23).
Dispersed parabasal-type cells may predominate.
Generalized nuclear enlargement may occur with a slight increase in nuclear to cytoplasmic ratio.
Intermediate cells tend to be normochromatic, but parabasal-type cells may have mild hyperchromasia and tend to have more elongated nuclei.
Chromatin is uniformly distributed and nuclear contours are regular.
Autolysis may result in the presence of stripped nuclei.
An abundant inflammatory exudate and basophilic granular background that resembles tumor diathesis may be present in examples of extreme atrophy (atrophic vaginitis) (Figs. 2.24 and 2.25).
Globular collections of basophilic amorphous material (blue blobs) reflect either degenerated parabasal cells or inspissated mucus.
Degenerated orangeophilic or eosinophilic parabasal cells with nuclear pyknosis resembling “parakeratotic” cells may be present (“pseudoparakeratosis”) (Fig. 2.26).
Histiocytes varying in size and shape and containing multiple, round to epithelioid nuclei and foamy or dense cytoplasm may be seen (Fig. 2.27).
Preparation-Specific Criteria
Liquid-Based Preparations:
Less nuclear enlargement than in conventional preparations due to immediate fixation, rounding up, and a lack of flattening on the slide.
Naked nuclei from autolysis may be reduced in number.
Conventional Preparations:
Air-drying artifact may result in more prominent cellular enlargement.
Granular basophilic “dirty” background of debris, with more “blue blobs” (Fig. 2.24).
2.4.4.3 Explanatory Notes
Atrophic changes are due to decreased hormonal support of epithelial tissues. The degree of atrophic change is thus highly variable, reflecting the differing levels of hormonal support that may be present. Cytomorphology can range from intermediate cell predominant to parabasal predominant to deeply atrophic (atrophic vaginitis) patterns in postmenopausal women. These differences may reflect alternate sources of endogenous estrogen or the presence of exogenous estrogenic substances.
Reporting of atrophic changes is variable and poorly reproducible [18]. Atypical cellular changes associated with atrophy warrant an interpretation of atypical squamous cells (ASC). Although cytology should be judged on its own morphologic merits, a patient is more likely to have significant disease in face of a history of previous cervical abnormality or a prior positive high-risk HPV test. In addition, atrophy may coexist with dysplasia or neoplasia, and the diffusely increased nuclear to cytoplasmic ratio of background parabasal/basal squamous cells can make identification of true abnormalities more challenging. As such, these cases should be reviewed with care. “Atrophic” changes may also be seen for weeks after parturition and other situations where estrogen and progesterone levels have decreased.
2.4.5 Pregnancy-Related Cellular Changes (Figs. 2.28–2.30)
