What does the presence of parabasal cells on a Pap smear indicate?

Parabasal Cells on Pap Smear: Clinical Significance

Parabasal cells on a Pap smear indicate atrophic changes in the cervical and vaginal epithelium, most commonly due to hypoestrogenic states such as menopause, postpartum period, or exogenous hormone effects, and do not represent a pathologic finding requiring treatment unless accompanied by inflammation or epithelial abnormalities.

What Parabasal Cells Represent

Parabasal cells are the deepest layer of squamous epithelial cells that become visible on cytology when the superficial and intermediate cell layers are absent due to lack of estrogen stimulation. 1

• In reproductive-age women with adequate estrogen, the cervical epithelium is thick with predominantly intermediate and superficial cells, while parabasal cells remain in the basal layer and are not typically shed 2
• When estrogen levels drop, the epithelium becomes thin and atrophic, causing parabasal cells to predominate on cytology 1, 2
• The maturation index shifts dramatically from intermediate:superficial cells to predominantly parabasal cells in hypoestrogenic states 2

Common Clinical Scenarios

Postmenopausal Women

• 98% of postmenopausal women demonstrate predominantly parabasal cells with some intermediate cells on Pap smears 2
• This represents normal physiologic atrophy and does not indicate disease 1
• Parabasal cells in elderly postmenopausal women may undergo degeneration, forming cyanophilic bodies that can be mistaken for cancer cells 3

Hormonal Contraception Effects

• Depot-medroxyprogesterone acetate (Depo-Provera) users show predominantly intermediate cells (86% of cases), not parabasal cells, regardless of duration of use 2
• Combined oral contraceptives similarly show mostly intermediate and superficial cells (93% of cases) 2
• The presence of predominantly parabasal cells in contraceptive users should prompt evaluation for other causes of atrophy 2

Testosterone Therapy in Transgender Patients

• Female-to-male transgender patients on testosterone therapy demonstrate atrophic changes with "small cells" (82.4% of cases) representing atrophic parabasal cells 4
• These patients also show transitional cell metaplasia (88.2%) alongside parabasal cells 4
• The cytomorphologic pattern differs from typical postmenopausal atrophy and should not be misinterpreted as abnormal 4

Critical Distinction: Atrophic Pattern vs. Atrophic Vaginitis

The presence of parabasal cells alone should be reported as "atrophic pattern," not "atrophic vaginitis," unless significant inflammation is present. 1

• Atrophic pattern indicates predominantly parabasal cells with low numbers of neutrophils (0-5 per high-power field) 1
• Atrophic vaginitis indicates parabasal cells with abundant neutrophils (>10 per high-power field) and represents true inflammation 1
• This distinction is clinically important because atrophic pattern does not require treatment, while atrophic vaginitis may warrant evaluation for infection or consideration of estrogen therapy 1

Impact on Specimen Adequacy

Potential Misinterpretation Issues

• Goblet-like cells may appear between clusters of parabasal cells in atrophic smears and can be mistaken for endocervical cells 5
• These goblet-like cells occur in 19.2% of atrophic smears and originate from the upper layer of atrophic squamous epithelium 5
• Misidentifying these cells as endocervical cells can lead to false assessment of specimen adequacy 5

When Parabasal Cells Indicate Unsatisfactory Specimen

• If a Pap smear is reported as unsatisfactory due to insufficient cellularity, the specimen should be repeated within 6-12 weeks 6
• A negative HPV result does not eliminate the need for repeat Pap testing when the specimen is unsatisfactory, because HPV tests lack confirmatory measures for adequate squamous cellularity 7
• Underlying infection should be treated before obtaining the subsequent cytology if indicated 6

Management Approach

When Parabasal Cells Are the Only Finding

• No intervention is required for atrophic pattern (parabasal cells without inflammation) in asymptomatic postmenopausal women 1
• Resume routine age-appropriate screening intervals 6
• Patient education should emphasize this is a normal finding related to hormonal status, not disease 7

When Accompanied by Inflammation

• Evaluate for infectious processes including trichomoniasis, bacterial vaginosis, candidiasis, chlamydia, and gonorrhea 8
• Treat identified infections appropriately 9, 8
• Re-evaluate with repeat cytology 2-3 months after treatment 9, 8

When Accompanied by Epithelial Abnormalities

• Any epithelial cell abnormalities (ASC-US, ASC-H, LSIL, HSIL, AGC) require standard management protocols regardless of the presence of parabasal cells 6
• Atrophic changes do not alter the management algorithm for squamous or glandular abnormalities 9, 8

Common Pitfalls to Avoid

• Do not assume parabasal cells indicate an inadequate specimen—they represent a valid cytologic finding of atrophy 1, 5
• Do not treat asymptomatic atrophic pattern with estrogen therapy based solely on cytology findings 1
• Do not misinterpret degenerating parabasal cells (cyanophilic bodies) as malignant cells in elderly patients 3
• Do not confuse goblet-like cells in atrophic smears with endocervical cells when assessing specimen adequacy 5
• Never delay evaluation of epithelial abnormalities because of concurrent atrophic changes—manage the abnormality according to standard guidelines 9, 8