In this case, we present the history of a patient suffering from an oxyphilic variant of a minimally invasive FTC, now known as HCTC. HCTC was long considered as an aggressive variant or subtype of FTC. In 2016, the World Health Organization reclassified HCTC as a separate pathological entity, although histological distinction of FTC and HCTC is particularly difficult [
6]. Clinically, the HCTC is regarded as more aggressive and lethal than FTC, especially in older research articles. However, more recent work contradicts these assumptions. Nagar
et al. were able to demonstrate that HCTC and FTC have a similar mortality [
4]. It should be mentioned that the strict separation between FTC, PTC, and HCTC has only established itself internationally over the last 5–10 years. In the work of Cipriani
et al., the histopathologic results of more than 60 FTC-cases from 1965 to 2007 were reviewed retrospectively by three pathologists [
15]. The majority of the original classifications had to be corrected. Similar findings were reported by a Japanese workgroup after reviewing more than 440 FTC cases. Only 45% of the originally as FTC classified thyroid cancers were confirmed as such on the basis of current diagnostic criteria and genetic and histological techniques [
16]. In summary, much of the early work on both FTC and HCTC has to be interpreted with caution since a reliable discrimination of both entities seems uncertain [
17]. In our patient, we observed metastases in different organs and soft tissue (that is, lung, heart, kidney, pancreas, and skeletal muscle) over a period of more than 14 years. Retrospective analyses have reported that 1–3% of all DTC display distant disease [
13,
18]. Although reports of patients experiencing more than three metastatic sites are scarce, Hugen
et al. reported that over 60% of all patients with metastasized DTC have multiple metastases, corroborating our findings [
19]. However, this was an autopsy study, and some of the included patients were not diagnosed with a thyroid malignancy during their lifetime, limiting the applicability of these results. In most cases, multiple metastases can be found within the lung and the bones [
20]. Distant metastases and especially the involvement of multiple organs are risk factors for increased mortality [
12,
21]. Although we also observed recurrent pulmonary metastases, the majority of the lesions represented rather unusual metastatic sites such as the pancreas, the heart, or the kidney [
22‐
24]. A South Korean study investigated 38,772 patients with DTC, which were further divided into three groups: no metastases (38,361 patients; 97.94%), usual site metastases (392 patients; 1.01%), and unusual site metastases (19 patients; 0.05%). Contrary to our report, only six patients of the latter group experienced lesions in more than one unusual metastatic site. Furthermore, most of these patients were diagnosed with PTC, and the median survival (68 months) was markedly inferior to the observed survival of our patient (more than 168 months) [
13]. A meta-analysis by Paspala
et al., which included 11 patients with pancreatic metastases from thyroid carcinoma revealed an even worse median overall survival of only 37.6 months as opposed to the data presented in our report [
22]. Stojadinovic
et al. reported on a cohort of 260 patients with metastasized DTC in which one-third of all patients displayed multisite metastases [
25], confirming data reported by Yoon
et al. [
13]. Prognostic factors for favorable outcome were female gender, radiological detection of metastases without clinical symptoms, a long disease-free interval between primary diagnosis and metachronous metastases, and young age. Apart from the latter, all of these factors were observed in our patient, partially explaining the excellent long-term survival. In a Japanese study of 106 individuals with metastasized FTC, disease-specific survival after 15 years was only 23.9%. Patient age was reported to be the most significant predictive factor for survival [
26]. In contrast, despite the advanced age of our patient, she was able to withstand her disease for more than 14 years.
Furthermore, the presented case serves as an example of a structured interdisciplinary concept: Over the years, six different departments (radiology, nuclear medicine, cardiothoracic surgery, urology, trauma and orthopedic surgery, and visceral and endocrine surgery) participated in diagnostics and treatment. Experienced endocrine surgeons together with nuclear medicine practitioners should preside over such concepts as they are most familiar with the course of disease, possible changes in tumor biology and behavior, and surgical and conservative treatment modalities. A vital part in their cooperation is a lively discussion. Over the past few years, tumor boards became a strong and valid tool in tumor therapy. They improved the optimization of therapeutic decision-making and helped us to conquer different cancers, including thyroid malignomas, more sufficiently. Our report shows that recurrent disease in patients with HCTC does not preclude long-term survival if modern concepts of tumor aftercare and therapy are ensured.
The strength of this case report lies in the long follow-up of over 14 years and the durability in the treatment team. The patient was continuously cared for by the same experienced endocrine surgeon and nuclear practitioner. Furthermore, the patient showed a high level of compliance and adhered to the prescribed aftercare plans as well as the treatment suggestions. The limitation of this case report typically lies in the exclusive consideration of only one case. Additionally, the diagnostic uncertainty between the different thyroid carcinoma entities is an important fact.