Original Investigation

Differentiated Thyroid Carcinoma: Distant Metastasis as an Unusual Sole Initial Manifestation


  • Rahim Dhanani
  • Muhammad Faisal
  • Mahir Akram
  • Osama Shakeel
  • Muhammad Toqeer Zahid
  • Aamna Hassan
  • Raza Hussain

Received Date: 12.02.2021 Accepted Date: 25.05.2021 Turk Arch Otorhinolaryngol 2021;59(3):188-192 PMID: 34713003


The objective of this study was to identify the characteristic features of patients with distant metastasis as the only manifestation of well-differentiated thyroid cancers and to analyze the treatment outcomes


A retrospective review of all patients with well-differentiated thyroid cancers and distant metastasis as the sole initial presentation was carried out. Data regarding age, gender, tumor histology, site, symptoms, and treatment outcomes were collected.


There were 10 patients who presented with distant metastasis as the only presentation. The mean age was 56.1 years. Eight (80%) patients had osseous metastasis, one (10%) had pulmonary and one (10%) had both. Follicular thyroid carcinoma was more common and seen in six (60%) patients. Seven (77.8%) out of nine patients had demised within five years of initial presentation.


Distant metastases without a neck lump as the initial presentation of well-differentiated thyroid cancers are extremely rare. No specific guidelines are available to manage such patients due to lack of relevant data in the literature.

Türkçe Özet


Bu çalışmanın amacı, tek belirti olarak uzak metastaz görülen iyi diferansiye tiroid kanseri hastalarının karakteristik özelliklerini belirlemek ve tedavi sonuçlarını analiz etmektir.


İlk belirti olarak tek başına uzak metastaz görülen iyi diferansiye tiroid kanseri tüm hastalar geriye dönük olarak incelendi. Yaş, cinsiyet, tümör histolojisi, yerleşim yeri, semptomlar ve tedavi sonuçlarına ilişkin veriler toplandı.


Tek belirti olarak uzak metastaz olan 10 hastanın olduğu belirlendi. Hastaların ortalama yaşı 56,1 yıldı. Sekiz (%80) hastada kemik metastazı, bir (%10) hastada pulmoner metastaz, bir (%10) hastada ise her ikisi vardı. Foliküler tiroid karsinomu daha sıktı ve altı (%60) hastada görüldü. Dokuz hastanın yedisi (%77,8) metastazın görülmesini izleyen beş yıl içinde hayatını kaybetmişti.


İyi diferansiye tiroid kanserlerinin ilk belirtisi olarak boyunda kitle olmadan gelişen uzak metastazlar oldukça enderdir. Literatürde bu konudaki veri eksikliği nedeniyle bu tip hastaların tedavisine yönelik özel kılavuzlar bulunmamaktadır.

Anahtar Kelimeler:

Diferansiye tiroid kanseri, tümör metastazı, uzak metastaz, prognoz, cerrahi, radyoaktif iodin, sağkalım

Keywords: Differentiated thyroid cancer, neoplasm metastasis, distant metastasis, prognosis, Cite this article as: Dhanani R, Faisal M, surgery, radioactive iodine, survival


Thyroid cancers account up to 1% to 5% of all cancers worldwide (1). The most common endocrine malignancy is thyroid carcinoma which presents as an enlarging lump in the neck (2). The bulk of thyroid malignancies, including papillary and follicular thyroid cancers, have a well-differentiated form, and usually are clinically indolent with good prognosis (3). The overall survival for 10 years in well-differentiated thyroid cancers (WDTC) ranges from 85% to 95% and drops to 50% in patients with distant metastasis (4).

One of the key factors for poor prognosis is distant metastasis; although patients who have WDTC with distant metastasis have comparatively better survival rates than other forms of thyroid cancers (2). Studies have reported 53% and 58% five-year survival rates, respectively, in patients with differentiated thyroid cancers with distant metastasis (5, 6). This is due to the use of multimodality treatment including surgery, radioactive iodine, radiotherapy and surgical removal of metastatic deposit depending on the type and site of the metastasis (5, 7). Most of the times, thyroid carcinoma metastases remain asymptomatic and are only discovered on surveillance or whole-body metastatic work up (2). However, symptomatic distant metastasis can rarely present as an unusual and sole initial presentation of WDTC without any swelling in the neck (2, 8).

Because of the rarity of such cases, there is limited data available on this subject in literature and the course of disease as well as the treatment outcomes in these patients are not well documented. Therefore, we decided to describe the treatment outcomes of such patients treated at our center; hence, the objective of our study was to report and identify the characteristic features of the patients who presented with distant metastasis as the only manifestation of WDTC and analyze the treatment outcomes.


A retrospective review of all patients treated for WDTC at a dedicated cancer center between 1995 to 2015 was carried out. Approval was obtained from the Institutional Review Board (IRB) of the Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, Pakistan with IRB number EX-15-07-20-01 and written informed consent was taken from all the patients. All patients with cytologically or histologically proven diagnosis of WDTC and presenting with distant metastasis as the sole initial presentation without any complaint of neck swelling or goiter were included. Patients with simultaneous distant metastasis and thyroid or neck swelling, or those with missing data were excluded. Cervical lymph node metastasis was not considered as distant metastasis. Data regarding age, gender, tumor histology, site, symptoms and treatment outcomes were collected. The data were analyzed using SPSS software v25.0.


The total number of patients with WDTC managed between 1995 to 2015 were 886 (papillary thyroid cancer = 689, follicular thyroid cancer = 114 and medullary thyroid cancer = 83). Out of these, 76 (8.6%) patients presented with metastasis at presentation. Ten patients were identified to fulfill the inclusion criteria of presenting with distant metastasis as the only presentation without any prior history of thyroid or neck lump (Figures 1 and 2). The mean age at presentation was 56.1±10.6 years (range: 36–78 years). There were seven (70%) female and three (30%) male patients.

All patients were symptomatic at the time of presentation, examinations, including fine needle aspiration cytology (FNAC) or incisional biopsies of the metastatic lesion were performed, led to the final diagnosis of differentiated thyroid cancer with distant metastasis. The most common initial presentation was bone pain or fracture, seen in five (50%) patients, followed by mass or swelling seen in three (30%) patients. Two (20%) patients presented with more than one symptom, one of them presented with hoarseness and difficulty in breathing whereas the other presented with difficulty in breathing along with pain in sternal bone. Eight (80%) patients had osseous metastasis, one (10%) had pulmonary and one (10%) had both pulmonary and osseous metastasis. In nine patients with osseous involvement, the appendicular skeleton was more commonly involved and seen in six (66.7%) patients whereas osseous metastasis was in the axial skeleton in three (33.3%) patients.

Regarding histology, follicular thyroid carcinoma was seen in six (60%) patients of whom five had extracapsular extension and angioinvasion. The remaining four (40%) patients were diagnosed with papillary thyroid carcinoma, two of which were follicular variant. There were six (60%) patients who underwent surgery. Five (50%) patients underwent total thyroidectomy. Of these, one patient also underwent lateral neck dissection. There was one patient who underwent wide excision of sternal mass. Adjuvant radioactive iodine (RAI) was given to six (60%) patients (200 mci in three patients and 150 mci in the other three patients); out of these, four (66.7%) patients received multiple sessions of RAI (200 mci in two patients and 150 mci in two patients). Post therapy thyroglobulin and antithyroglobulin levels were raised in four patients. Eight (80%) patients received radiation therapy and majority of them (n=5, 62.5%) were given radiation with a palliative intent.

All patients were followed up regularly, except for one patient who was lost to follow-up. Mean follow-up period was 41.7 months (minimum one month and maximum 156 months). Seven (77.8%) out of nine patients died within the five years after initial presentation. Except for one case, all deaths were related to the disease process. The characteristics of all patients included in the study are provided in Table 1.


WDTCs limited to thyroid gland have an excellent survival outcome, with a 10-year disease-specific survival outcome reported up to 90% (9). Even in the presence of distant metastasis, it has a better survival outcome compared to the other malignancies with distant metastasis (5, 6). WDTCs are more often limited to thyroid gland only, and distant metastasis is rare, with rates reported from 1% to 15% in the literature (10, 11, 12). The prevalence of distant metastasis in WDTC was reported up to 2.2% in a comprehensive Surveillance, Epidemiology, and End Results (SEER) database study (13). The most common sites of distant metastasis are the bones and the lungs, although involvement of other organs is also reported in the data, at a rate less than 5% (4, 8, 12). In our series, eight (80%) patients had osseous metastasis, one (10%) had pulmonary and one (10%) had combination of pulmonary and osseous metastasis, these findings are similar to the data reported in the literature (2, 8).

Distant metastasis at the time of initial presentation has a significant prognostic implication as the 10-year survival rate falls significantly to 50%. Factors including age, gender and distant metastasis are associated with survival outcomes in patients with WDTC (12, 14, 15). Metastasis to organs other than the bones and the lungs is not well understood and usually missed in clinical settings because of the rarity of such cases. Shaha et al. (11) reported a case series of 44 patients, over a period of more than half a century, with distant metastases as the only initial presenting symptom. Since then, the literature regarding this topic has remained scarce.

Shaha et al. (11) reported that acceptable long-term survival outcomes were achieved after adequate treatment of primary tumor and aggressive RAI for metastatic disease. Similar management approach is reported in our series and in the literature (2, 8).

See et al. (2) found that follicular thyroid carcinoma, which has hematogenous spread, was most frequently associated with patients with distant metastasis followed by papillary thyroid carcinoma which has lymphatic spread. Also, they found that papillary thyroid carcinoma was more frequently associated with multiple foci of distant metastasis as compared to follicular thyroid carcinoma. In our series we had similar findings that were found comparable with data available in the literature (11, 16).

Mazzaferri (17) took 40 years of age as cut-off and found that patients younger than 40 had a significantly lower risk of developing distant metastasis compared to patients older than 40. Similar findings were noted in our study. The mean age of our patients at the time of their presentation was 56.1 years and only one patient was younger than 40. Comparable results are seen in studies reported in the literature (2, 8, 18).

Patients with swelling in the neck, an easily noticeable and palpable region of the body, would normally seek early medical advice. In our series, patients did not present to head and neck surgeons due to the atypical initial presentation and usually sought medical advice from other specialty departments for complaints such as bone pain, bone fracture and difficulty in breathing, leading to delays and providing the disease the opportunity to metastasize further and thereby adversely affecting the survival outcomes. Studies in the literature also reported similar trends of presentation, with patients being referred to head and neck surgeons by other specialty departments (2, 8).

The American Thyroid Association (ATA) guidelines are widely accepted and used in the management of non-metastatic WDTC (2). There is, however, lack of consensus as to which management protocols should be opted for patients with metastatic thyroid cancer because of the paucity of data on thyroid cancers with distant metastasis. The management plan for all the patients included in our study was discussed and decided by the Multidisciplinary Tumor Board and we advocate that a similar approach is adopted for all patients with rare and atypical presentation.

Our study has several limitations, namely the small sample size, single institution experience and retrospective study design. We were not able to identify the prognostic and risk factors because of our smaller sample size. Nonetheless, the findings of our study on the characteristic features of a rare entity can help further investigations on the risk and prognostic factors in patients diagnosed with WDTC, a condition which generally is regarded as a relatively favorable condition but may have a poor clinical outcome.


We conclude that distant metastases without a neck mass as the sole initial presentation of WDTC is extremely rare. While follicular thyroid carcinoma is the most common etiology, osseous metastases are seen more commonly. Its prognosis is low. Due to the paucity of data, there are still no guidelines available for the treatment of such patients. We recommend further studies in order to better understand the natural course of the disease and subsequently to formulate the guidelines that will help clinicians devise a correct management plan when dealing patients with thyroid cancers with distant metastases.

Main Points

• The incidence of thyroid cancers is on a rising trend, mainly as a result of the advancement in diagnostic modalities.

• Distant metastasis in well-differentiated thyroid cancers is rarely seen and its presentation without any neck mass is even rarer.

• Here, we report an interesting investigation on the characteristic features of the patients who had presented with distant metastasis as the only manifestation of well-differentiated thyroid cancers, and their treatment outcomes.

• These patients have low prognosis. Due to paucity of data, there are still no guidelines available to treat such patients.

Ethics Committee Approval: Approval from Institutional Review Board (IRB) of Shaukat Khanum Memorial Cancer Hospital and Research Centre was taken. IRB number: EX-15-07-20-01.

Informed Consent: Written informed consent was taken from all the patients included in the study.

Peer-review: Externally peer-reviewed.

Authorship Contributions

Surgical and Medical Practices: A.H., R.H., Concept: R.D., M.F., A.H., R.H., Design: R.D., M.F., O.S., M.T.Z., Data Collection and/or Processing: R.D., M.A., O.S., M.T.Z., Analysis and/or Interpretation: R.D., M.F., O.S., M.T.Z., A.H., R.H., Literature Search: R.D., M.F., M.A., O.S., M.T.Z., Writing: R.D., M.F., M.A., A.H., R.H.

Conflict of Interest: The authors declare no conflict of interest.

Financial Disclosure: The authors declare that this study received no financial support.


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