The simultaneous occurrence of MTC and PTC in the same thyroid is a rare phenomenon that can be observed in two main settings: a mixed tumor showing dual differentiation [
15] or a collision tumor (that is, a tumor with two separate and different components) [
2‐
8]. Our case belongs to the latter category since lesions with features of MTC and PTC were detected in two different locations and separated by normal thyroid tissue.
Histopathology and immunohistochemical findings of the first nodule suggested that it was a small-cell variant of MTC. Histopathology and immunohistochemical findings of these nodules were small-cell variants of MTC and papillary microcarcinoma according to the current World Health Organization classification of thyroid tumors.
Our strategy in the treatment of thyroid carcinoma is similar to guidelines used in Western countries [
16]. All patients were routinely examined by preoperative ultrasonography to estimate intrathyroid spread of the tumor. In patients with clinically involved lateral cervical lymph nodes detected by ultrasonography or computed tomography, a modified radical neck dissection was performed. For evaluation of bone and distant metastases, radioactive iodine whole-body scanning was done. Before radioactive iodine scanning, any thyroxin treatments were discontinued for four weeks and patients were placed under strict restriction of iodine-containing food for two weeks. Postoperative radioiodine therapy and thyroid-stimulating hormone suppressive therapy were performed. During follow-up, the serum levels of thyroglobulin, anti-Tg Ab, and calcitonin were routinely checked.
The coexistence of PTC and MTC has been reported in the literature [
1‐
11]. These tumors occurred together more frequently in women, presented with a palpable neck mass, and were treated with surgery. Metastatic foci of either PTC or MTC were detected in few patients [
4,
6,
7]. These lymph node metastases show pure tumor cell populations of one or two components or an admixture of both components within the same lymph node [
9,
17]. Distant metastases were described mostly in the mediastinum, lung, liver, and bone [
18]. Fugazzola and colleagues [
3] reported the familial clustering for these types of tumors, but the exact pathogenesis of these thyroid malignancies is completely unknown. Genetic analysis of RET oncogene in reported cases had conflicting results. Brauckhoff and colleagues [
19] and Papi and colleagues [
20] reported that germline point mutation of the RET gene had a potential role in the development of both MTC and PTC. However, according to Cerrato and colleagues [
21], half of sporadic MTCs do not carry RET mutations and other genes, such as RB (retinoblastoma) and TP53 tumor suppressor pathways, may be involved in MTC formation. Rossi and colleagues [
1] reported that both the RET and BRAF genes had a role in the genesis of the medullary-papillary collision tumors. The RET proto-oncogene plays a key role in the development of MTC. Vantyghem and colleagues [
10] reported 11 cases of familial MTC-PTC according to clinical, histologic, or family features (or a combination of these features), but no RET defects were present. The authors suggested that another gene or uncommon abnormality of the RET gene was responsible for tumorgenesis. A recent animal study by Miller and colleagues [
22,
23] suggested that the PI3K or Ras signaling cascade alone was unable to transform thyroid follicular cells but that simultaneous activation had invasive and metastatic potential. Overall, the molecular evidence suggested that the two components of these heterogeneous groups of tumors were not derived from a common stem cell [
23,
24]. The origin of each carcinoma is embryologically different because the C cells stem from an ultimobranchial body that derived from the fourth pharyngeal pouch, whereas the thyroglobulin and thyroid hormone-producing cells come from the follicular epithelial cells derived from a median endodermal anlage from the tongue.