Introduction
The thyroid gland is a rare site for metastasis. Autopsy case series reports an incidence of 1·9–24% of metastasis to the thyroid gland in patients with a history of non-thyroid malignancies.Reference Papi, Fadda and Corsello1, Reference Wood, Vini and Harmer2 The low rate of metastasis to the gland has been proposed to be a result of the fast arterial blood flow and high oxygen content and iodine found in the gland, creating an inhibitory environment for the seeding and growth of metastases.Reference Willis3, Reference Chung, Tran, Brumund, Weisman and Bouvet4 However, in a patient with a history of malignancy, it must be considered in differential diagnosis with the presentation of a new thyroid nodule. Primary tumours that metastasise to the thyroid gland include most commonly renal cell carcinoma, as well as colorectal, lung, breast and sarcoma.Reference Chung, Tran, Brumund, Weisman and Bouvet4 Here we report a case of small-cell lung cancer (SCLC), treated and in clinical remission, followed by the identification of a solitary thyroid nodule found to be metastatic disease.
Case report
A 38-year-old woman with a history of 20 pack-years of smoking (one pack per day for 20 years) presented with sudden shortness of breath and chest tightness in 2007. Imaging [computed tomography (CT) scan] revealed a large mediastinal mass (14·2 × 11·5 cm) occupying the right hemithorax and compressing the heart and central structures of the chest. Biopsy of the mass was consistent with small-cell lung carcinoma, positive for pancytokeratin, synaptophysin, neural cell-adhesion molecule (CD56) and thyroid transcription factor (TTF-1) on immunohistochemical studies (IHC). She received two fractions of palliative chest radiation (600 cGy) and cisplatin and etoposide chemotherapy at an outside institution. A subsequent brain magnetic resonance imaging (MRI) and CT scan showed no metastatic disease and decrease in the size of the mass to 9·2 × 7·4 cm. Subsequently, she received 6,120, 180 cGy per fraction, over 7 weeks’ duration, using intensity-modulated radiation therapy (IMRT) to the gross disease in the right lower lobe and the mediastinum and a total of six cycles of chemotherapy (cisplatin 60 mg/m2 day 1 and etoposide 100 mg/m2 day 1, 2 and 3, 21-day cycle) with the last two chemotherapy cycles concurrent with chemoradiation therapy (CRT). Owing to the lack of metastatic diseases and excellent response, the patient was given prophylactic cranial irradiation, 3,000 cGy in 15 fractions over 3 weeks. Over the course of the following 2 years with serial imaging studies, she remained disease free without evidence of metastatic diseases.
In February 2010, a new 1 cm left thyroid nodule was found on the CT scan. Ultrasound showed multiple thyroid nodules. The dominant nodule on the left side was complex cystic, measuring 1·8 × 1·0 × 1·5 cm, and the dominant nodule on the right side was a heterogeneous solid nodule. Given the heterogeneous and solid appearance of the right nodule, it was biopsied showing follicular cells and colloid consistent with a hyperplastic nodule. Follow-up CT scan (after 3 months) showed interval growth of the left nodule from 1 to 3 cm and the patient began to report throat pain, difficulty in swallowing and hoarseness. Ultrasound showed a 3 cm hypoechoic mass in the left lobe of the thyroid. Ultrasound guided that fine needle aspiration of the left nodule was positive for small-cell carcinoma. Positron emission tomography (fluorodeoxy-glucose, 18FDG-PET) scan showed a solitary left thyroid nodule, measuring 2·5 cm with standardised update value (SUV) of 9·0 and two supraclavicular lymph nodes, 1·5 cm with SUV of 6·6 and other 1·8 cm with SUV of 8 (Figure 1). There was no activity in the primary lesion in the right lower lung lobe or evidence of other metastatic diseases. The patient was offered definitive treatment and received concurrent CRT with two cycles of cisplatin and etoposide and 5,000, 200 cGy per fraction, one fraction per day over 5 weeks’ duration to the left thyroid lobe using IMRT. Later, she received two additional cycles, completing four cycles. Follow-up PET/CT imaging showed no active lesions consistent with a complete response to therapy (Figure 2). The patient continues follow-up and remains free of metastatic diseases for 2 years after completing CRT.
(a) Pre-treatment FDG-PET scan showing metabolic activity in both the left lobe of thyroid and the supraclavicular lymph node, (b) CT scan showing the left thyroid nodule.
(a) Post-treatment imaging FDG-PET scan showing complete response to treatment with no traces of metabolic activity and (b) no residual thyroid nodule seen.
Discussion
Lung cancer is the second most common cancer in both men and women and the leading cause of cancer deaths in the United States. SCLC represents 13% of all lung cancers and is more common in elderly and in patients with a history of smoking andReference van Meerbeeck, Fennell and De Ruysscher5 patients present with distinct clinical features such as central bulky disease, paraneoplastic syndromes. Early metastasis to the brain, liver, adrenals, bone and bone marrow is known with SCLC. Widespread metastatic dissemination of SCLC is a presenting feature in about two-thirds of patients.Reference van Meerbeeck, Fennell and De Ruysscher5 SCLC is extremely sensitive to chemotherapy, and even an extensive, disseminated disease can have rapid responses to therapy. Despite responses to chemotherapy, prognosis in patients with SCLC remains poor. Induction chemotherapy with cisplatin and etoposide followed by concurrent CRT has been shown to increase survival and local control in SCLC.Reference Kosmidis, Samantas, Fountzilas, Pavlidis, Apostolopoulou and Skarlos6 The brain is the most common site for SCLC metastasis, with 80% of patients diagnosed with brain metastases within 2 years of diagnosis.Reference Slotman, Faivre-Finn and Kramer7 Prophylactic intracranial irradiation is now offered to SCLC patients without evidence of a disseminated disease and has been shown to increase the 3-year survival.Reference Slotman, Faivre-Finn and Kramer7
The thyroid gland is an unusual site of metastatic disease compared with primary thyroid neoplasms.Reference Papi, Fadda and Corsello1, Reference Chung, Tran, Brumund, Weisman and Bouvet4 However, studies have proposed that metastasis may be more common in diseased thyroid glands with thyroiditis, goitre and neoplasm, possibly altering the blood supply and microenvironment in favour of metastasis.Reference Heffess, Wenig and Thompson8 In the most recent review of the literature, 44·2% of metastases occurred in thyroid glands with preexisting abnormalities.Reference Chung, Tran, Brumund, Weisman and Bouvet4 Lung cancer metastasis to the thyroid is the most common adenocarcinoma in small reported case series.Reference Papi, Fadda and Corsello1 Symptoms may include dysphagia, hoarseness and airway obstruction due to compression and occasionally altered thyroid function tests. If the initial evaluation is non-diagnostic but clinical suspicion is high, repeat biopsies may be indicated. Specific IHC markers, such as CD56 and TTF-1, in SCLC are useful in differentiating primary tumour from metastasis from other sites. This case is one of the few isolated reports of SCLC metastasis to the thyroid gland.Reference Osawa, Takigawa and Kiura9, Reference Katsenos, Vaias and Skoulikaris10 Unlike the few previous case reports, our patient presented with an isolated thyroid nodule without evidence of further disease dissemination. She responded well to treatment and remains in clinical remission for 2 years after chemotherapy and CRT.
Conclusions
There should be a high suspicion of thyroid metastasis in patients with a history of previous malignancy presenting with a new thyroid nodule. Immunohistochemical analysis is important to differentiate primary tumour from metastatic lesions. Although metastasis to the gland is rare, the primary tumour may be from any number of other sites.
Acknowledgements
None.
Disclosures
None.
