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If a cell appears almost too bizarre, it may be due to radiation atypia.

A bizarre multinucleated cell with abundant cytoplasm and prominent cytoplasmic vacuolization is a good example of radiation atypia.

More typical reparative changes are seen here. Note the cohesive sheet of cells with enlarged nuclei, open chromatin pattern and prominent nucleoli. Repair is common after radiation therapy.

Multinucleated cells (center) indicative of radiation atypia are seen admidst parabasal cells.

Vesicular chromatin, prominent nucleoli and cytoplasmic vacuolization are features of radiation atypia. Note that although cytomegaly may be present, the N:C ratio remains normal or only slightly elevated.

A multinucleated giant cell is seen here. A good internal litmus test for radiation atypia is that the cells seem almost too bizarre for malignancy.


Radiation is commonly employed in the treatment of cervical cancer. Pap smears remain a good method of assessing treatment efficacy and recurrence of cancer. It is very important to recognize radiation atypia so one does not overcall these cells as cancerous or vice versa, mistake cancerous cells for radiation change.1,2

The microscopic features of radiation atypia include cytomegaly (although the N/C ratio is normal or only slightly increased as both nuclei and cytoplasm enlarge proportionally), polychromasia (two-toned staining), prominent nucleoli, multinucleation and cytoplasmic vacuolization.

Radiation change is broadly divided into two stages, acute and chronic. Acute changes (4-8 weeks post-radiation) include necrosis, robust inflammation, presence of debris as well as degenerating and/or viable tumor cells. Pap smears performed soon after radiation are not diagnostic. However, at 6 to 8 weeks post-treatment, a pap may be performed to assess for the presence of tumor cells and the presence of a vigorous radiation reaction. Persistence of viable tumor cells and lack of radiation change are poor prognostic factors indicating resistance to therapy.1

Chronic changes may be present for years or even the lifetime of the patient. Features of chronic radiation change are similar to those of acute changes (polychromasia, pleomorphism, cytomegaly, etc), however, the inflammatory component is generally lacking.


Cervix : Reparative Atypia

Cervix : Squamous Atrophy

Cervix : Reactive Atypia

Cervix : Reparative Atypia


1 DeMay RM. The Art and Science of Cytopathology. Chicago, IL: ASCP Press; 1996; 118-119.

2 Shield PW, Daunter B, Wright RG. Post-irradiation cytology of cervical cancer patients. Cytopathology. 1992;3(3):167-82.

Last updated: 2011-04-27
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