• Radiation can lead to cytologic features affecting any organ following radiotherapy (commonly those of the female reproductive, GI and GU tracts), which may be mistaken for neoplastic or preneoplastic conditions
• Cervical changes due to radiation are discussed below

Contributed by Carlos Parra-Herran, M.D.

Contributed by Erika Baardsen, D.O.


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A 69 year old woman with a remote history of cervical adenocarcinoma presents with chief complaint of pelvic pain. On pelvic exam, the clinician notes nodularity of the vaginal cuff. A vaginal Pap smear is performed and shows rare atypical cells with large pleomorphic nuclei, prominent nucleoli and abundant vacuolated polychromatic cytoplasm. The remainder of the specimen is comprised of scattered squamous cells of varying maturation and inflammation. Which is the most likely diagnosis?

1. Adenocarcinoma
2. Atypical glandular cells of undetermined significance (AGUS)
3. Glandular cells status posthysterectomy
4. Reactive cellular changes associated with radiation
5. Squamous cell carcinoma

D. Reactive cellular changes associated with radiation

Invasive cervical adenocarcinoma is typically treated with simple or radical hysterectomy with radiation therapy or chemotherapy. It is assumed this patient received standard treatment, including radiation therapy. The cytologic features described are most representative of cellular changes seen after radiation therapy, which may persist for many years. Additionally, the background reflects a nonneoplastic process, further supporting the diagnosis.

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Reference: Radiation atypia

Which of the following is the appropriate management of this lesion seen on cervical Pap smear from a 32 year old woman?

1. Colposcopy with endocervical sampling
2. Immediate loop electrosurgical excision (LEEP)
3. No HPV testing should be performed; routine screening with Pap smear only at 1 year
4. Observation with colposcopy and cytology at 6 month intervals for 12 months
5. Perform HPV cotesting; if negative, repeat cotesting at 5 years

E. Perform HPV cotesting; if negative, repeat cotesting in 5 years

In the absence of an intraepithelial lesion or malignancy (NILM), reactive cellular changes associated with radiation (radiation atypia) should be managed according to the American Society for Colposcopy and Cervical Pathology (ASCCP) Consensus Guidelines. Per the Cytology NILM algorithm, women 30 years and older with negative cytology should undergo HPV cotesting (preferred):

• If negative, continue routine screening (cotesting at 5 years or cytology alone at 3 years)
• If positive, repeat cotesting at 1 year or genotyping is indicated
• If HPV status is unknown / cannot be performed, repeat cytology at 3 years

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Reference: Radiation atypia