Discussion
ATC, which accounts for about 1 to 4% of thyroid cancers, often develops with rapidly increasing painful cervical mass, and worsens to a fatal condition in a short period of time [1]. It is a disease which is expected to be cured only in a very exceptional case such as a case where it is accidentally found in a tissue after excision. In 70 to 80% of cases, radical surgery is difficult due to peripheral invasion and distant metastasis. For this reason, most cases relapse shortly after the initial treatment, and the life expectancy is about 4 months. Patients die from asphyxiation and hemorrhage due to tumor growth in cervical region in addition to the debilitating effects of systemic disseminated metastasis, therefore they cause unbearable to patients, families, and even medical staff. Unfortunately, treatment and prognosis have not improved significantly in the past decades.
The proportion of cases in which ATC remains in the thyroid gland (stage IVA) is reported to be 6-13 % [2-6]. Even if ATC has developed into the surrounding tissues (stage IVB), invasion into the tracheal, laryngeal, esophageal, recurrent laryngeal nerve, and anterior cervical muscles allows definitive surgery by combined resection and reconstruction [7]. Haymart et al. [8] reviewed the prognosis of 2,742 ATC patients using the National Cancer Database and showed that the median survival of stage IVA patients was 4.3 months (95% Cl 3.1-7.4) with surgery alone, and less than 9.3 months, 6.4 months, 11.2 months in patients with postoperative radiation, chemotherapy, or both as adjuvant therapy. Yoshida et al. [9] reported that the prognosis after radical surgery of 25 cases of ATC accidentally found in postoperative pathological examination, and reported that the 1 year overall survival rate was 50% when treatment was completed only by surgery, which was significantly different from 87% when postoperative radiotherapy or adjuvant chemotherapy was added after surgery. However, all of these are retrospective study, and the type of drug to be administered and the method of administration are unknown, and a bias cannot be denied in which patients who can expect long-term prognosis are selected and adjuvant therapy is added.
Kim et al. [3] analyzed prognosis of 121 multi-center cases and reported that most long-term survivors had been recieved postoperative radiation therapy after surgery. Sugitani et al. [6] also report from the results of 677 cases of ATC research consortium that postoperative radiation therapy after surgery resulted in an insignificant but prolonged prognosis at stage IVA (6.2 vs. 13.0 months p = 0.078). On the other hand, Chen et al. [10] reported from the analysis of 261cases of the Surveillance, Epidemiology, and End Results (SEER) database that there was no difference in prognosis between the administration and non-administration of radiation therapy after surgery at stage IVA. In addition, Sugitani et al. [6] analyzed clinical characteristics, and considered leukocytosis (10000 /μL or more), acute exacerbation (within 1 month), distant metastases, and large tumors (5cm or more) as clinical poor prognostic factors, and proposed to proceed with treatment in consideration of these factors . In the case reported by the present inventors, although acute exacerbation was not observed, since the tumor diameter was as large as 55mm and the tumor was in the stage IVB, it was an unfortunate result despite complete excision and postoperative radiotherapy.
Anaplastic transformation occurs not only from the primary lesion but also from the metastatic lymph nodes or distant sites. Sugitani et al. [6] reported that ATC are classified into 4 types : common type, incidental type, anaplastic change at the neck type, and anaplastic change at the distant site type, and that the common type is 80.8%, the incidental type is 4.3%, the anaplastic change at the neck type is 14.0%, and the anaplastic change at the distant site type is 0.9%. This present case corresponds to the anaplastic change at the neck type described above. Although it is a well-known fact that the prognosis is not good in a case where anaplastic transformation is observed in a metastatic lymph nodes or distant sites in PTC [12.13]. According to Ito et al. [14], radical resection of lymph nodes is expected to have a long-term prognosis.
In molecular biology, the mechanism of the onset of anaplastic transformation has been variously reported to involve BRAF and N-RAS mutation, but has not yet been elucidated [15.16]. Elliott et al.[17] reported that EGFR, Platelet-Derived Growth Factor Receptor (PDGFR), and HER-2 are overexpressed in ATC with PTC, and there is a possibility that they play some role in anaplastic transformation, and an application to targeted therapy marker for ATC patients. In addition, Wiseman et al. [18] reported that 63 elements were examined in the tissue microarray structure of 12 cases of ATC with PTC, and 8 elements, i.e., thyroglobulin, Bcl-2, MIB-1, E-cadherin, p53, β-catenin, topoisomerase Ⅱ-α, and VEGF, were found to be significantly changed, and were also searched for , which was described to be useful as a potential target for molecular biology diagnosis, prognosis, and targeted therapy. However, none of these results fall within speculation. Further molecular biological studies are expected to proceed in the future.