British Journal of Radiology (2006) 79, e84-e87
© 2006 British Institute of Radiology
doi: 10.1259/bjr/62250180
Unusual case of well-differentiated papillary thyroid carcinoma lacking thyroglobulin expression while still concentrating radioiodine
B Singh, PhD1,
R Bollmann, MD2,
H Ahmadzadehfar, MD3,
H J Biersack, MD3 and
S Ezziddin, MD3
1 Department of Nuclear Medicine, PGIMER, Chandigarh-160012, India, 2 Institute for Pathology, Heilsbachstr. 15, 53123 Bonn-Duisdorf, Germany, 3 Department of Nuclear Medicine, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
Correspondence: S Ezziddin
 |
Abstract
|
|---|
We present an unusual case of a well-differentiated papillary thyroid carcinoma with bilateral lung metastases. Despite undetectable serum thyroglobulin (Tg) on thyroid stimulating hormone (TSH) stimulation and no immunohistochemical evidence of Tg expression in the primary tumour, the patient showed significant uptake of radioiodine in both lungs. After five cycles of high dose radioiodine therapy, the patient went into complete remission and therefore had an excellent response to radioiodine treatment. This case is a rare exception to the rule of Tg production as a prerequisite for differentiated thyroid cancers to concentrate radioiodine.
|
Introduction
|
|---|
A 74-year-old female patient with a palpable neck swelling in the right thyroid lobe was referred to surgery in a peripheral hospital. Intraoperatively, it was observed that the thyroid tumour mass infiltrated the muscles of the larynx and partial tumour excision was performed. Thereafter, the patient was referred to the University Hospital of Bonn where she underwent neck dissection and complete thyroidectomy. Chest CT showed multiple intrapulmonary lesions in both lungs (Figure 1
). Routine histopathological examination documented a well-differentiated papillary thyroid cancer in the right lobe and immunostaining of the tumour showed an increased proliferative index with Mib-1 nuclear labelling. Subsequently, the patient was recommended for radioiodine therapy. Pre-therapeutic work-up indicated undetectable serum thyroglobulin (Tg) (Tg-S immunoradiometric assay, IRMA, Dynotest) levels. The detection range of this assay was 0.01–500 ng ml–1 (0.01–500 µg l–1). The Tg recovery test and the direct Tg antibody assay were negative. Immunohistochemical staining for Tg revealed an absent Tg expression by the primary tumour (Figures 2 and 3).
View larger version (158K):
[in this window]
[in a new window]
|
Figure 2. Anti-thyroglobulin (Tg) immunostaining showing no evidence of Tg expression in the tumour specimen.
|
|
The first dose of iodine-131 (100 mCi) was administered 1 month after surgery under thyroxine withdrawal with a stimulated thyroid stimulating hormone (TSH) value of 18.30 µIU ml–1 and an undetectable serum Tg. The post-therapeutic whole body scan demonstrated multiple iodine avid focal areas in both the lungs (Figure 4). The second radioiodine therapy (300 mCi) was given to the patient 3 months later (TSH = 76.72 µIU ml–1) and the post-therapeutic scan showed significant resolution of the bilateral lung lesions (Figure 5). Three more radioiodine therapy doses of 300 mCi each were administered to the patient after 3 months, 6 months and 11 months, respectively. The repeat CT scan at the time of the fourth therapy revealed a significant size reduction of the multiple lung lesions (Figure 6). Despite the absence of any detectable serum Tg before initiation of therapy and during the entire course of radioiodine treatment, the patient showed a radiographic and scintigraphic response to each successive therapy, eventually resulting in remission, as demonstrated by the post-therapeutic whole body scan after the fifth therapy (Figure 7). Repeat CT scanning consistently showed fixed residual pulmonary lesions with no further change as shown in Figure 6; also, repeat diagnostic radioiodine application did not depict any pathological tracer accumulation. Altogether, this was interpreted as a complete remission.
View larger version (49K):
[in this window]
[in a new window]
|
Figure 4. First therapeutic(100 mCi) whole body radioiodine scan (anterior view) showing multiple radioiodine avid lesions in both lungs.
|
|
View larger version (74K):
[in this window]
[in a new window]
|
Figure 5. Post-therapeutic whole body radioiodine scan (anterior view) after the second therapy (300 mCi) showing reduction in the size and number of radioiodine avid lesions (left > right) in both lungs.
|
|
View larger version (110K):
[in this window]
[in a new window]
|
Figure 6. Repeat chest CT scan after the third radioiodine therapy showing significant size reduction in the lung lesions.
|
|
|
Discussion
|
|---|
Differentiated thyroid carcinomas (DTC) of follicular origin, i.e. papillary and follicular DTC, most commonly metastasise to the lungs, lymph nodes and bone [1, 2]. Due to early diagnosis and effective initial therapy, the patients with DTC have shown improvement in survival rates over the past four decades [3, 4]. Pacini et al [5] reported that the treatment with therapeutic doses of 131I is effective in patients with lung metastases and, to a lesser extent, in those with lymph node metastases. It is a general observation that poorly differentiated tumours often lack the ability to trap iodine while still retaining the capacity to secrete Tg. Such variants of thyroid cancer are considered aggressive and associated with poor prognosis [6].
In a recent report [7] summarizing the consensus of 15 thyroid cancer experts, the assessment of serum Tg was recognized as part of the routine surveillance of DTC patients. It was highlighted that an undetectable serum Tg measured during TSH suppression is often misleading. This report reviewed eight studies and demonstrated that 21% of 784 patients who primarily had no clinical evidence of tumour with baseline serum Tg levels below 1 µg l–1 during TSH suppressive thyroxine medication exhibited a rise of serum Tg to more than 2.0 µg l–1 after administration of recombinant human TSH (rhTSH). Amongst these, 36% were found to have metastases. It was also stated that diagnostic whole body iodine (dWBI) scanning, after either rhTSH or thyroid hormone withdrawal, identified only 19% of the cases with metastases. Furthermore, 10 studies comprising 1599 patients demonstrated that a TSH-stimulated Tg test using a Tg cut-off of 2 µg l–1 is sufficiently sensitive to be used as the principal test in the follow up management of low risk patients of DTC and that the routine use of dWBI scanning should be discouraged. This report finally concluded and proposed a surveillance guideline based on TSH stimulated Tg levels for patients who have undergone total or near total thyroidectomy and 131I ablation for DTC and have no clinical evidence of residual tumour with a serum Tg below 1.0 µg l–1 during TSH suppression.
A unique property of thyroid follicular cells is the ability to trap and concentrate iodine, which depends on the expression of the sodium/iodide symporter (NIS), thyroglobulin (Tg) and thyroperoxidase (TPO) [8]. Based on iodide trapping and concentration, radioiodine provides a highly effective therapy in the treatment of differentiated thyroid carcinomas [9–11]. NIS mediates iodide uptake in normal and well-differentiated neoplastic thyroid cells. However, in most poorly differentiated and anaplastic tumours, dedifferentiation-induced loss of these functions renders them unresponsive to radioiodine [12]. Rogna et al [2] reported that simple histological classification of DTC into follicular and papillary types is somewhat inadequate in predicting iodine uptake and effectiveness of radioiodine treatment. The identification of histological subtypes could explain in some cases, the biological behaviour of the tumour, but not response to 131I therapy.
It is thus inferred that only those patients with differentiated thyroid cancer having either detectable serum Tg or a subsequent rise in Tg to more than 2.0 µg l–1 in response to rhTSH should be considered for radioiodine treatment. Contrary to this, the present case represents a unique exception from the rule of Tg production as a prerequisite for radioiodine accumulation in thyroid cancer. Despite the negativity of the primary tumour for Tg on immunohistochemical staining and the absence of detectable serum Tg, the lung metastases showed excellent concentration of radioiodine.
Consequently, the patient became disease free as a result of successful radioiodine therapy. In our opinion, this case reveals a unique variant of well-differentiated thyroid cancer lacking Tg expression without loss of radioiodine concentration ability via the existing NIS. Although exceptional, this unusual variant suggests that Tg expression may not be a necessary prerequisite for radioiodine therapy of differentiated thyroid cancer.
B Singh is a temporary UICC-ICRETT fellow at Bonn.
|
Acknowledgments
|
|---|
One of the authors (B Singh) is thankful to UICC, Switzerland for providing him ICRETT fellowship for a period of 2 months, during which this work was complied at Bonn, Germany.
Received for publication May 10, 2005.
Revision received September 30, 2005.
Accepted for publication October 3, 2005.
|
References
|
|---|
- Loureiro MM, Leite VH, Boavida JM, Raposo JF, Henriques MM, Limbert S, et al. An unusual case of papillary carcinoma of the thyroid with cutaneous and breast metastases only. Eur J Endocrinol 1997;137:267–9.[Abstract]
- Ronga G, Filesi M, Montesano T, Di Nicola AD, Pace C, Travascio L, et al. Lung metastases from differentiated thyroid carcinoma – 40 years experience. Q J Nucl Med Mol Imaging 2004;48:12–9.[CrossRef]
- Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller AB, Clegg L, et al. 2000 SEER Cancer Statistics Review, 1973–1977. Bethesda, MD: National Cancer Institute, 2000
- Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A national cancer data base report on 53,856 cases of thyroid carcinoma treated in the US, 1985–1995. Cancer 1998;83:2638–48.[CrossRef][Medline]
- Pacini F, Molinaro E, Lippi F, Castagna MG, Agate L, Ceccarelli C, et al Prediction of disease status by recombinant human TSH-stimulated serum Tg in the postsurgical follow-up of differentiated thyroid carcinoma. J Clin Endocrinol Metab 2001;86:5686–90.[Abstract/Free Full Text]
- O'Doherty MJ, Coakley AJ. Drug therapy alternatives in the treatment of thyroid cancer. Drugs 1998;55:801–12.[CrossRef][Medline]
- Mazzaferri EL, Robbins RJ, Spencer CA, Braverman LE, Pacini F, Wartofsky L, et al. A consensus report of the role of serum thyroglobulin as a monitoring method for low risk patients with papillary thyroid carcinoma. J Clin Endocrinol Metabolism 2003;88:1433–41.[Abstract/Free Full Text]
- DeGroot LJ, Kaplan EL, McCormick M, Straus FH. Natural history, treatment and course of papillary thyroid carcinoma. J Clin Endocrinol Metab 1999;71:414–24.
- Beierwaltes WH. The treatment of thyroid carcinoma with radioactive iodine. Semin Nucl Med 1978;8:79–94.[CrossRef][Medline]
- Schlumberger M, Tubiana M, De Vathaire F, Hill C, Gardet P, Travagli JP, et al. Long term results of treatment of 283 patients with lung and bone metastases from differentiated thyroid carcinoma. J Clin Endocrinol Metab 1986;63:960–7.[Abstract]
- Schlumberger MJ. Papillary and follicular thyroid carcinoma. N Engl J Med 1998;338:297–306.[Free Full Text]
- Furuya F, Shimura H, Suzuki H, Taki K, Ohta K, Haraguchi K, et al. Histone deacetylase inhibitors restore radioiodide uptake and retention in poorly differentiated and anaplastic thyroid cancer cells by expression of the sodium/iodide symporters thyroperoxidase and thyroglobulin. Endocrinology 2004;145:2865–75.[Abstract/Free Full Text]
Top
Abstract
Introduction
