Trouble-makers in cytologic interpretation of the uterine cervix

Abstract

The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

Keywords: Atrophy; Cytology; Glandular involvement; High grade intraepithelial squamous lesion; Metaplasia; Uterine cervix.

Fig. 1.

Atrophic cervicitis in liquid based preparation. (A) A tissue fragment in atrophic cervicitis, showing small nuclei with scant cytoplasm and high nuclear:cytoplasmic ratio. The tissue fragment is not syncytial, with folding of the edge. (B) Inflammatory debris in the background is evident in liquid based preparation. (C) Atrophic parabasal cells showing apoptotic and inflammatory debris within the cell group. (D) The nuclei in atrophic cervicitis are often pyknotic.

Fig. 2.

Atrophic cervicitis in conventional smear. (A) Atrophic cervicitis showing a tissue fragment composed of uniform cell population with a streaming pattern in the background of cellular and inflammatory debris. (B) A blue blob showing small round to oval, smudged, and densely cyanophilic body with an ill-defined border.

Fig. 3.

Cytologic (A) and histologic (B) pictures of immature squamous metaplasia showing fine chromatin pattern with dense cytoplasmic differentiation. The nuclear:cytoplasmic ratio is increased, but short of that in high grade intraepithelial squamous lesion, and the nuclear membrane is not irregular or thickened.

Fig. 4.

Cytologic (A) and histologic (B) pictures of tubal metaplasia, showing cuboidal or columnar cells with basally oriented nuclei and cilia at the other end of the cytoplasm.

Fig. 5.

The most frequent and helpful cytological features of high grade intraepithelial squamous lesion (HSIL) with glandular extension that are indicative of squamous origin. (A, B) The long axis of the peripheral nuclei are parallel to the longitudinal axis of the cellular cluster, arranged circumferentially rather than radially, with one sided flattening. (C) The nuclei often show horizontal polarity around gland opening. (D) Nuclear grooves in HSIL cells. The differential points from transitional metaplasia are nuclear irregularity, slightly thickened nuclear membrane, loss of polarity (absence of a streaming pattern), and increased nuclear:cytoplasmic ratio.