OBJECTIVE: To review pregnancy-related changes in cervicovaginal smears and to distinguish them from neoplasia and dysplasia. STUDY DESIGN: One hundred consecutive abnormal cervicovaginal smears from pregnant women obtained during 1992-1993 were reviewed. Corresponding biopsies that were available were also reviewed for cytologic correlation. RESULTS: Sixty-one percent of cases showed inflammation changes, 21% contained low grade squamous intraepithelial lesion, and 9% had high grade squamous intraepithelial lesion. Diagnostic problems were encountered with decidual cells, Arias-Stella reaction and trophoblastic cells. CONCLUSION: Both the clinician and pathologist must be aware of diagnostic pitfalls and false positive diagnoses in pregnancy. Hence, it is extremely important that the clinician notify the pathologist about the pregnancy status of the patient.

A wide spectrum of histologic changes has been described throughout the female genital tract during pregnancy and in the postpartum period. Of these, the endometrial glandular changes referred to as the Arias-Stella reaction have classically been a diagnostic pitfall in histologic sections. Pregnancy-related changes are also reflected in cytologic material obtained from the cervix and vagina. Both glandular and stromal alterations may be seen. The changes involving endocervical glandular epithelium are often alarming enough to cause diagnostic difficulties, especially when the history of pregnancy is not provided. We report 13 cases where marked glandular changes led to diagnostic misinterpretations. These were characterized by cyto- and karyomegaly, a high nuclear to cytoplasmic ratio, round to oval nuclei with smudgy chromatin imparting a ground glass appearance, frequent intranuclear inclusions, and vacuolated to dense variable cytoplasm. The cytologic diagnoses ranged from "glandular atypia" to "suspicious for adenocarcinoma." Follow-up was available in 11/13 cases. In 9/11 cases, subsequent cervical smears on multiple occasions were negative. Cervical biopsies and/or dilatation and curettage in 4/11 cases did not show significant glandular abnormalities. The glandular changes encountered in cytologic material were similar to those described histologically in the Arias-Stella reaction involving the cervix. This similarity and the fact that these changes disappeared upon termination of the pregnancy favors the presumption that they represent the Arias-Stella reaction. Awareness of these changes during pregnancy and postpartum may prevent interpretive errors and unnecessary surgical procedures.

OBJECTIVE: To study the clinical significance of atypical glandular cells of undertermined significance (AGUS) in pregnant and postpartum women. STUDY DESIGN: We evaluated 35 women who were pregnant (30) or within three months postpartum (5) and had a cytologic diagnosis of AGUS. Twenty-seven (77%) patients had follow-up: 17 (63%) patients underwent colposcopic examination and biopsy, and 10 (37%) had repeat Pap smears. Eight patients were lost to follow-up. RESULTS: Five (29.4%) patients had a squamous intraepithelial lesion (SIL), including three high grade and two low grade, on subsequent biopsy. The remaining (70.6%) patients had benign pathology, which included 5 chronic cervicitis, 4 endocervical and/or endometrial polyps, 2 Arias-Stella reaction and 1 microglandular hyperplasia. Among the patients with repeat Pap smears, two had persistent AGUS/atypical squamous cells of undetermined significance, the remaining cases were within normal limits. CONCLUSION: Pregnancy-related changes may present with glandular atypia. In addition, about one-third of pregnant and postpartum women with a diagnosis of AGUS had SIL on subsequent biopsy; that rate is similar to that in nonpregnant women. Therefore, pregnant women with a cytologic diagnosis of AGUS should be followed closely.

Considerable interest has been devoted to cytology in pregnancy, especially the morphologic changes that may cause problems in differential diagnosis. It is surprising that the published discussion of the cytologic appearance of smears from pregnant women has been so limited. This review emphasizes that retained trophoblastic tissue may be a source of highly atypical appearing cells in the cervicovaginal cytology obtained under various clinical conditions. Distinguishing between Arias-Stella cells and cells of glandular abnormalities can be problematic, since the morphologic characterization of the former is poor. This review also emphasizes that a full awareness of the morphology of pregnancy as well as of the patient's clinical history are needed for greater precision in diagnosing cell patterns as pregnancy-related and not malignant.

Pregnancy-related physiologic changes are well recognized. However, the normal range of changes as reflected in the cervical smear have not been adequately described. Review of 278 abnormal cervical smears from 153 pregnant/preabortal and 125 postpartum/ abortal patients revealed the following: 21 high-grade squamous intraepithelial lesion (HGSIL) cases, 46 low-grade squamous intraepithelial lesion (LGSIL) cases, 185 atypical squamous cells of undetermined significance (ASCUS) cases, and 26 atypical glandular cells of undetermined significance (AGUS) cases. Surgical correlation (excluding 18 products of conception and 153 placentas) was available in 98 (35%) of the cases. Dysplasia was confirmed on biopsy of 11 cases cytologically diagnosed as HGSIL (7 CINII/III and 4 CIN I), 19 cases cytologically diagnosed as LGSIL (6 CIN II/III and 13 CIN I), 35 cases of ASCUS (4 CIN II/III and 31 CIN I), and 2 cases of AGUS (1 CIN III and 1 CIN I). Decidualization was present in six cervical and three endometrial biopsies. The remaining 180 cases revealed pregnancy-related changes in most of the atypical groups and a few in the dysplasia groups. With pregnancy, both cervical glands and stroma undergo physiologic changes. These result in squamous metaplasia due to ectropion and cells with hypervacuolated cytoplasm and atypical nuclei reflecting endocervical gland hyperplasia and/or Arias-Stella reaction. The decidual cells are large, with variably staining cytoplasm and a large nucleus. Degenerated decidual or trophoblastic cells can also shed from the endometrium and mimic HGSIL. Despite the caution required in this population, dysplastic changes should not be underestimated.