Introduction


Thyroid cancer is among the most common of endocrine malignancies. Despite the incidence of differantiated thyroid carcinoma has increased over the past 3 decades, the outcome remains excellent with cancer specific survivals of  98.6%, 94.7% and 87.4% at 5, 10 and 15 years respectively (1). The papillary histotype, being the most frequent (nearly 80%). Papillary thyroid microcarcinoma (PTM) is defined by the WHO as a PTC 1.0 cm in diameter or smaller (2). Although most PTM are good clinical course, distant metastases and mortality can be occasionally seen (3). At the time of diagnosis, PTM  is more often intrathyroid or spread only to cervical lymph nodes because of its typical slow-growing pattern. Metastases are mainly to regional lymph nodes and, less frequently, to the lung and bone [4]. We report the case of a 35-year-old woman with lung and bone metastases of a multifocal PTM, detected with a whole body iodine scan (WBS), computed tomography (CT) and magnetic resonance imaging (MRI).

 

 

Case Presentation

A 35-year-old woman consulted our outpatient clinic of endocrinology. She was clinically asymptomatic. She had undergone a subtotal thyroidectomy due to euthyroide multinodular goitre without fine needlle aspiration biopsy. The histological examination demonstrated multifocal PTM (follicular variant, maximum diameter 0.7 cm). There was no vascular or capsule invasion, or extrathyroideal extention. (Figure 1-2) Her serum thyroglobulin level (Tg) was 1000 ng/ml (0.2-70) when thyroid-stimulating hormone (TSH) level was 38 uIU/ml (0.34-5.6). Thyroglobulin antibodies were negative (0.8 IU/ml, normal range: 0-4). Thyroid and neck ultrasonography showed residual thyroid tissue and lymphadenopathy. Iodine-131-whole body scan showed markedly iodine retention in the neck, lung and pelvis (Figure 3).  Chest CT showed multiple metastases in the lung (Figure 4). Pelvic MRI demonstrated a 5 cm mass in the ischium pubis (Figure 5). Ischium pubis metastases confirmed with bone scintigraphy (Figure 6). She underwent completion thyroidectomy and bilateral neck dissection. Lymph node (LN) metastases were  determined only at santral lenph node compartment. She is going to have high dose radioactive iodine ablation therapy after resection of bone metastases.

Discussion

Papillary thyroid microcarcinoma is defined as papillary carcinoma measuring  1 cm in greatest dimension according to the World Health Organization classification system for thyroid tumors (2). Papillary thyroid microcarcinomas are slow-growing tumours; distant metastasis are very rare, mainly because of the predominantly lymphogenic metastasizing pattern observed in this tumor type. Papillary thyroid carcinoma have a good overall prognosis after total thyroidectomy, radioiodine ablation and levothyroxine suppression therapy. Several studies revealed zero mortality (5-6). In a meta analysis published in 2008 mortality rate associated with cancer was only 0.34% (7). But, PTM can be lethal, because small numbers of patients develop locoregional recurrences and distant metastases (3,7,8). In a meta analysis with 9379 patients local/lenf node recurrens rate was 2.4% and distant  metastasis rate was 0.27%  (7). We reported an unusual case of PTM associated with metastases to the lung and ischium pubis at the time of the diagnosis.
Poor prognostic factors of PTM include that LN involvement at presentation, large tumor size, older age, male sex, multifocality and the presence of extrathyroidal extension (7-9). However, these factors are not entirely reliable in predicting the tumor recurrence, metastasis, or cancer-related death. Our patient have distant metastases and multifocality she have PTM, female sex, and younger age. Presence of metastases in distant sites other than lungs, such as bones, brain or liver, is an important unfavorable prognostic factor (9-10). Distant metastases of a PTM is very rare (3). For metastatic diseases from differentiated thyroid cancer (DTC), a 10-year survival was reported as 13%-61% (9,10) whereas DTC shows a 10-year overall survival rate %74-93 (11). Distant metastases usually involves the lung or the bones. Patients with lung metastasis have three major prognostic factors: the size of lung metastases, lung capability of uptaking radioiodine and the presence of metastatic foci in distant sites other than lungs (12). The increase in size of lung metastatic foci and their loss of capability in uptaking radioiodine were responsible for an evident worsening in prognosis (12). Bone is the second most common site of metastasis resulting from thyroid cancer after lung. Multisite metastasis is generally considered to be associated with decreased survival (13,14). Our patient have single bone lesion and multiple nodular lung metastases. But, the markedly iodine retention in the lung of WBS. This is a positive prognostic condition in our patient.

Conclusions

Papillary thyroid microcarcinoma can rarely show agressive clinic. Therefore all patients who will undergo surgery for nodular guatr should be evaluated by US and FNAB preoperatively to detect the optimal surgical procedure.

References

1. Sciuto R, Romano L, Rea S, Marandino F, Sperduti I, Maini CL. Natural history  and clinical outcome of differentiated thyroid carcinoma: a retrospective analysis of 1503 patients treated at a single institution. Ann Oncol 2009;20:1728-35.
2. Hedinger C, Williams ED. Histological typing of thyroid tumors. In: WHO International Histological Classification of Tumours. Edited by Williams ED. Berlin Springer; 1988;9-10.
3. Mercante G, Frasoldati A, Pedroni C, Formisano D, Renna L, Piana S, Gardini G, Valcavi R, Barbieri V. Prognostic factors affecting neck lymph node recurrence and distant metastasis in papillary microcarcinoma of the thyroid: results of a study in 445 patients. Thyroid. 2009;19:707-16.
4. Pelizzo MR, Boschin IM, Toniato A, Pagetta C, Piotto A, Bernante P, Casara D, Pennelli G, Rubello D. Natural history, diagnosis, treatment and outcome of papillary thyroid microcarcinoma (PTMC): a mono-institutional  12- year experience. Nucl Med Commun 2004;25:547-52.
5. Appetecchia M, Scarcello G, Pucci E, Procaccini A. Outcome after treatment of papillary thyroid microcarcinoma. J Exp Clin Cancer Res  2002;21:159-64.
6. Furlan JC, Bedard Y, Rosen IB. Biologic basis for the treatment of microscopic, occult well-differentiated thyroid cancer. Surgery 2001;130:1050-4.
7. Roti E, degli Uberti EC, Bondanelli M, Braverman LE. Thyroid papillary microcarcinoma: a descriptive and meta-analysis study. Eur J Endocrinol 2008;159:659-73.
8. Besic N, Pilko G, Petric R, Hocevar M, Zgajnar J. Papillary thyroid microcarcinoma: prognostic factors and treatment. J Surg Oncol 2008;97:221-5.
9. Pelizzo MR, Boschin IM, Toniato A, Piotto A, Bernante P, Pagetta C, Rampin L, Rubello D: Papillary thyroid microcarcinoma (PTMC): prognostic factors, management and outcome in 403 patients.   Eur J Surg Oncol 2006;32:1144-8.
10. Ruegemer JJ, Hay ID, Bergstralh EJ, Ryan JJ, Offord KP, Gorman Ca. Distant metastases in differentiated thyroid carcinoma: a multivariate analysis of prognostic variables. J Clin Endocrinol Metab 1988;67:501-8.
11. Rossi RL, Cady B, Silverman ML, Wool MS, ReMine  SG, Hodge MB, Salzman FA. Surgically incurable  well-differentiated thyroid carcinoma. Prognostic factors and results of therapy. Arch Surg 1988;123:569-74.
12. Casara D, Rubello D, Saladini G, Masarotto G, Favero A, Girelli ME, Busnardo B Different features of pulmonary metastases in differentiated thyroid cancer: natural history and multivariate statistical analysis of prognostic variables. J Nucl Med 1993;34:1626-31.
13. Do MY, Rhee Y, Kim DJ, Kim CS, Nam KH, Ahn CW, Cha BS, Kim KR, Lee HC, Park CS, Lim SK. Clinical features of bone metastases resulting from thyroid cancer: a review of 28 patients over a 20-year period. Endocr J 2005;52:701-7.
14. Orita Y, Sugitani I, Matsuura M, Ushijima M, Tsukahara K, Fujimoto Y, Kawabata K. Prognostic factors and the therapeutic strategy for patients with bone metastasis from differentiated thyroid carcinoma. Surgery 2010;147:424-31.