INTRODUCTION: Papillary thyroid carcinoma (PTC) typically carries an excellent prognosis, in part due to its propensity to remain localized to the thyroid and regional lymph nodes. Although metastatic disease most commonly involves the lungs, pleural effusions are rare, and pleural metastases are even more uncommon without concomitant parenchymal disease. We report the case of a patient with previously treated PTC presenting with isolated pleural metastases and a large pleural effusion.
CASE PRESENTATION: A 65 year old male presented to his primary care physician with a complaint of dyspnea. He had a history of PTC, which was diagnosed seven years prior. Nuclear imaging at that time revealed spread to regional lymph nodes but no distant metastases. Despite treatment with total thyroidectomy, neck dissection, and Iodine 131 ablation, FDG-PET remained positive in cervical lymph nodes and thyroglobulin levels remained elevated. A chest x-ray was performed, showing a large right sided pleural effusion. Computed tomography (CT) of the chest revealed a large unilateral pleural effusion but no parenchymal nodules or infiltrates. Laboratory analysis of pleural fluid revealed an exudative effusion with a leukocyte differential comprised mainly of lymphocytes (49%). Cytologic examination revealed metastatic carcinoma in a papillary configuration (graphic 1) with special staining positive for Thyroid Transcription Factor (TTF-1) and negative for thyroglobulin. Pleural fluid re-accumulated rapidly despite serial large volume thoracentesis and the patient was referred for pleurodesis. During video assisted thoracoscopic surgery, numerous small nodules were noted on the parietal pleura (graphic 2). Histologic examination confirmed metastatic PTC. The patient responded well symptomatically to talc pleurodesis and is currently enrolled in a clinical trial for metastatic PTC, refractory to Iodine 131 radioablation.
DISCUSSIONS: Despite its benign reputation, PTC presents with metastatic disease in 5% of patients. Common sites of metastasis include bone (25%) and lung (67%). Malignant pleural effusions are rare, found in only 0.6% of patients with PTC in a large case series over a period of 47 years1. All of these patients had either prior or simultaneous documentation of pulmonary metastases. A pleural effusion may be present at the time of initial presentation but also has been reported to occur as much as 28 years later. Typically, the presence of a pleural effusion carries a dismal prognosis, with a reported median survival of 11 months. A long disease free interval preceding the pleural effusion, along with non-specific cytologic features, make the diagnosis challenging. In such cases special stains are useful. Thyroid Transcription Factor-1 (TTF-1) is a nuclear protein expressed normally in thyroid tissue and type II pneumocytes. It has diagnostic value in distinguishing primary lung from extrathoracic adenocarcinomas presenting in serous fluid2. However, metastatic thyroid cancer will also stain immunopositive for TTF-1. Moreover, lung adenocarcinoma can display a papillary architecture in cytologic specimens, indistinguishable from PTC. While a positive thyroglobulin stain would help distinguish the two, up to 50% of metastatic thyroid malignancies will stain negative, as in this case.
CONCLUSION: When faced with a malignant pleural effusion, it is important to consider PTC in the differential diagnosis. Without high clinical suspicion this diagnosis may be missed given the considerable overlap in pathologic features between primary lung cancer and metastatic thyroid carcinoma. Although rare, malignant effusions can develop years after the initial diagnosis of PTC, and, as seen in this unique case, can be seen even in the absence of known parenchymal metastases.
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