The Nile valley of Egypt is characteristically an endemic area of iodine deficiency goiter [21, 22]. The endemic nature of the region casts certain features on the thyroid cancer profile in our locality. At our University, follicular carcinoma constituted 12.6% of thyroid cancer patients . Papillary carcinoma remained the most common variant with a modest frequency of 74.1%. It is widely believed that iodine repletion increases the incidence of both papillary carcinoma of the thyroid as well as Hashimoto`s thyroiditis. In iodine-replete regions, both diseases are prevalent [3-5]. The association between the two thyroid disease entities has been elaborately discussed based on retrospective analysis of patient populations in these iodine-sufficient regions. In our cohort, thyroiditis-associated cancer showed many of the features described in the literature. In others, Egyptian patients significantly deviated from that description.
Hashimoto-associated thyroid cancer is almost always of the papillary type. Papillary carcinoma on top of Hashimoto`s thyroiditis is known to be a less aggressive disease. Several markers of good prognosis of PTC are specifically associated with the presence of Hashimoto`s thyroiditis. In patients with HT, papillary carcinoma tends to be a disease of younger age and the primary tumor is often small. Although multifocality of PTC is characteristic in thyroid with Hashimoto`s thyroiditis, lymph node involvement and extra-thyroidal extension are infrequently observed. These features have been consistently described in several large retrospective studies and meta-analyses [3, 7,8,9,10, 12,13,14,15,16, 19]. Lee et al. analyzed the data of 38 published studies addressing PTC with HT . The meta-analysis included a total of 10,648 patients. Major findings of this meta-analysis reciprocated the generally observed trend in the English literature and were used to compare our Egyptian patients with the global pattern.
In our and others’ experience, PTC is the predominant form of cancer in Hashimoto`s thyroids. In our practice, papillary carcinoma constituted 96.2% of cancer in HT patients while this form of cancer accounted for 74.1% of all thyroid cancer cases. In the meta-analysis published by Lee and colleague, HT was associated with PTC more than any other form of thyroid cancer (OR = 2.432; 95% CI = 1.614–3.665; p = 0.001) . Similarly, our data corroborated the findings of Lee and colleagues regarding female preponderance, multifocality, and lack of association with young age. In their data, being a female and having a multifocal tumor was significantly associated with the presence of HT (OR = 2.678; 95% CI = 1.755–4.087; p = 0.001 and OR = 1.467; 95% CI = 1.096–1.964; p = 0.010; respectively) .
In contrast to the published literature, we observed some characteristic features of aggressive behavior of thyroid carcinoma associated with Hashimoto’s disease. Our patients had similar risk of lymph node involvement and extra-thyroidal extension whether they had associated HT or not. This is in contrast to the generally held idea of HT-associated PTC being a disease of low risk of nodal and extra-thyroidal involvement. Similar to several other authors, Lee and colleagues reported that PTC with HT was related to the absence of lymph node metastases and the lack of extra-thyroidal extension (OR = 1.287; 95% CI = 1.010–1.639; p = 0.041 and OR = 1.295; 95% CI = 1.098–1.527; p = 0.002; respectively) .
Some histological clues also pointed that HT association with PTC may portend aggressive behavior in Egyptian patients. We observed a high prevalence of Hürthle cell metaplasia and several incidences of aggressive histological variants of PTC associated with lymphocytic thyroiditis. Oncocytic cell, tall columnar cell, and follicular and de-differentiated variants are established markers of aggressive papillary carcinoma behavior that were observed in our cohort of Hashimoto-associated papillary carcinoma.
Although few recent reports pointed to some aggressive features of thyroid carcinoma in pediatric population affected with lymphocytic thyroiditis [23, 24], the generally held concept is that HT predicts a better prognosis of associated thyroid cancer.
In the current study, we clearly identified some peculiar pathologic features of thyroid carcinoma associated with lymphocytic thyroiditis. We suggest these peculiarities may at least in part be attributed to the endemic nature of the locality and the background iodine deficiency. In view of this small retrospective sample and in the absence of survival or mechanistic information, more evidence is required to complete the missing parts of the picture.