In this cohort exposed to 131I as a result of the Chornobyl accident, we have found a very high PPV (97.1%) for malignancy when the cytological interpretation was definite or suspect PTC and a lower, but substantial, one (24.4%) when cytology was definite or suspect FN. The major strengths of our study are screening of the entire cohort according to a standardized protocol irrespective of 131I dose; referral to FNA and surgery according to strictly defined criteria; a high rate of compliance with FNA (98.0%) and surgery (96.5%); a low rate of inadequate cytological specimens (0.7%); and independent review of histopathological specimens by an international panel of experts. All these characteristics make our series unique in terms of interpreting FNA accuracy relative to histopathology. The major limitation of our study is the relatively small number of cases as the present analysis is restricted to patients operated upon as a result of only the first cycle of screening. It should also be noted that we could determine if cellular atypia was a consequence of 131I exposure, since cytological interpretations were performed without regard to dose.
Other studies of radiation-exposed individuals have recorded a high frequency of inadequate specimens (18
) and a large number of small cancers that have escaped cytological diagnosis (19
). Therefore, our protocol specified biopsy of up to three sonographically suspicious nodules as small as 5 mm, immediate assessment of cytological material, and recall visits for those with inadequate specimens (26
). In our previously published series of 45 cancers, 10 (23.3%) were less than or equal to10 mm in greatest dimension and only two (5%) were first detected at final pathologic analysis (10
). By way of comparison, among a group of externally exposed children, 50% of the cancers were less than 10 mm in size and in more than half of the cases the malignant nodule was not the one that was biopsied (19
Our results are similar to those obtained from a general population (13
), where FNA cytology has a predictive value approaching 99% for malignancy (13
) and from 15 to 30% for FN (11
). However, they contrast with those from patients treated externally with between 25 and 40 Gy (17
) or internally with therapeutic doses of 131
), which typically delivers up to 100 Gy to the thyroid (35
). In these cases, severe nuclear and cytoplasmic changes can result in an erroneous cytological conclusion of malignancy and lower the predictive value of FNA. We did not observe these cytological alterations in our cohort, which was exposed to an arithmetic mean dose of only 0.79 Gy (36
Very little has been published concerning thyroid cytology in those exposed to Chornobyl fallout as children (23
). Thyroid cancer, all of the papillary type was found in 2.3% and FN in 6.4% of successful aspirates from a population screened by ultrasound, and the largest cause of nodularity was non-neoplastic, mainly chronic thyroiditis and cysts (23
). Another study of the cytological features in 20 cases of pathologically confirmed PTC concluded that the main diagnostic FNA findings were similar to those in unexposed adult cases, with the exception of more prominent nuclear atypia, which correlated with solid proliferation on histology, and a high prevalence of psammoma bodies on FNAs from the exposed children (24
). Although we are unable to confirm a high prevalence of nuclear atypia and psammoma bodies in our PTCs, it should be noted that our subjects were older at surgery (mean 23.5 years compared to 12 years in the earlier study) and had cancers of longer latency (15.1 years compared to 7.9 years). Since long-latency cancers are potentially more differentiated than those of short latency (9
), a direct comparison of our results with those of the previous study may not be justified.
In our cohort, the PPV for a cytological interpretation of PTC or suspect PTC was 97.1% and for one of definite or suspect FN was 24.4%, similar to what has been reported in unexposed populations (11
). It is also worth noting that sensitivity, specificity, PPV, and NPV varied depending on how a cytological conclusion FN was classified. When we considered FN as a “positive” finding, the overall sensitivity was high (100%) and specificity low (17.6 %), largely due to the absence of false negative results. When FN was regarded as “negative” finding, the sensitivity decreased to 77.3% and specificity increased to 97.1 %. These differences demonstrate that specificity is more affected than sensitivity by how FN is treated and emphasize that in our cohort histopathologically confirmed cancer cases were found less often than non-cancer cases when the cytological conclusion was FN.
Among those exposed to the Chornobyl accident as children and adolescents and evaluated between 1998 and 2000, the sensitivity, specificity, and predictive value of FNA for diagnosing malignancy are similar to that seen in unexposed subjects. Although a cytological conclusion of FN is often incorrect, it is also comparable to that found in a general population. We conclude that exposure to 131I at doses received by our study group has not lowered the accuracy of thyroid cytology for either malignancy or FN in nodules detected 12 to 14 years later.