J Pathol Transl Med.  2024 Nov;58(6):283-290. 10.4132/jptm.2024.10.17.

Cervical intraepithelial neoplasia and cervical cytology in pregnancy

Affiliations
  • 1Department of Pathology, CHA University School of Medicine, CHA Gangnam Medical Center, Seoul, Korea

Abstract

Cervical cancer screening during pregnancy presents unique challenges for cytologic interpretation. This review focuses on pregnancy-associated cytomorphological changes and their impact on diagnosis of cervical intraepithelial neoplasia (CIN) and cervical cancer. Pregnancy-induced alterations include navicular cells, hyperplastic endocervical cells, immature metaplastic cells, and occasional decidual cells or trophoblasts. These changes can mimic abnormalities such as koilocytosis, adenocarcinoma in situ, and high-grade squamous intraepithelial lesions, potentially leading to misdiagnosis. Careful attention to nuclear features and awareness of pregnancy-related changes are crucial for correct interpretation. The natural history of CIN during pregnancy shows higher regression rates, particularly for CIN 2, with minimal risk of progression. Management of abnormal cytology follows modified risk-based guidelines to avoid invasive procedures, with treatment typically deferred until postpartum. The findings reported in this review emphasize the importance of considering pregnancy status in cytological interpretation, highlight potential problems, and provide guidance on differentiating benign pregnancy-related changes from true abnormalities. Understanding these nuances is essential for accurate diagnosis and proper management of cervical abnormalities in pregnant women.

Keyword

Cytology; Papanicolaou test; Uterine cervical dysplasia; squamous intraepithelial lesions; Uterine cervical neoplasms; Pregnancy

Figure

  • Fig. 1. (A) Navicular cells (arrows) are intermediate squamous epithelial cells with glycogen-rich cytoplasm and a boat-like (navicular) shape. (B) Navicular cells should be differentiated from koilocytes (arrows) of low-grade squamous intraepithelial lesion (ThinPrep, Papanicolaou stain).

  • Fig. 2. (A) Endocervical fragments in pregnancy in a regular honeycomb structure showing clear cytoplasm filled with mucin. (B) Glandular fragments of adenocarcinoma in situ showing stratified pencil-like, hyperchromatic nuclei with feathering at the edge of the cluster (conventional smear, Papanicolaou stain).

  • Fig. 3. (A) Immature metaplastic cells in pregnancy (arrows) showing ample glossy cytoplasm with slightly increased nuclear-cytoplasmic (N/C) ratio. (B) Atypical squamous cells - cannot exclude high grade squamous intraepithelial lesion cells with higher N/C ratio and hyperchromatic nuclei with irregular nuclear membrane and coarse chromatin (ThinPrep, Papanicolaou stain).

  • Fig. 4. (A) Cluster of glandular cells showing the Arias-Stella reaction. The cells have low nuclear-cytoplasmic (N/C) ratio and ample lacy cytoplasm. The nuclei are dull and opaque with fuzzy outlines. (B) A few scattered glandular cells in the Arias-Stella reaction (arrows). Although the nuclei are enlarged with prominent nucleoli, the N/C ratio remains low, and the chromatin is smudged rather than coarse (ThinPrep, Papanicolaou stain).

  • Fig. 5. (A) Decidual cells in pregnancy (arrowheads). These cells usually have ample thick cytoplasm. The nuclear-cytoplasmic ratio is low with smooth round nuclei. (B) Trophoblastic villi (arrow) and single or multinucleated trophoblasts (arrowheads) in pregnancy. A few decidual cells is observed in the background (empty arrow) (ThinPrep, Papanicolaou stain).

  • Fig. 6. (A) A case of persisting high-grade squamous intraepithelial lesion (HSIL). The cellular cluster shows enlarged hyperchromatic nuclei, irregular nuclear membrane, and rather coarse chromatin discernible at the periphery of the cluster. (B) Another case of persisting HSIL. A sheet-like cluster of cells with high nuclear-cytoplasmic ratio and hyperchromatic nuclei (ThinPrep, Papanicolaou stain).

  • Fig. 7. (A) A case of regressed high-grade squamous intraepithelial lesion (HSIL). HSIL cluster showing enlarged hyperchromatic nuclei. Cytological differences from persisting HSIL cases are not obvious. (B) Another case of regressed HSIL. The loosely cohesive HSIL cells show high nuclear-cytoplasmic ratio and hyperchromatic nuclei with irregular nuclear membrane and coarse chromatin. Specific differences were not observed in cytomorphological features between persisting and regressed cases of HSIL (ThinPrep, Papanicolaou stain).

  • Fig. 8. 2019 American Society for Colposcopy and Cervical Pathology (ASCCP) management guideline. The figure shows how the patient is managed. If the calculated risk of immediate CIN3+ is ≥ 4%, immediate management via colposcopy or treatment is indicated. Reprinted from Nayar et al. J Am Soc Cytopathol 2020; 9: 291-303 [36], with permisison of Elsevier.


Reference

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