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INTRODUCTION
The thyroid nodule is a discrete lesion within the thyroid gland that is radiologically distinct from the surrounding parenchyma 1. Its prevalence in the population depends on the method of detection, varying from 5% by palpation, to 65% by ultrasonography. Only about 5 to 10% of thyroid nodules are malignant 2. Metastatic disease to the thyroid corresponds to 2% of thyroid malignancies. In a clinical series, 25 to 50% are due to renal cell carcinoma (Ree) 3.
Ree is the third most common neoplasm of the urogenital tract. The most frequent sites of metastasis are the lung (45.2%), bone (29.5%), lymph nodes (21.8%), liver (20.3%), adrenal glands (8.9%), and brain (8.1%) 4. At the neck level, the thyroid is the second most frequent site after the lymph nodes 5. Metastases can occur several years after diagnosis or nephrectomy. We present the case of a patient with isolated relapse in the thyroid gland, following a prolonged asymptomatic course after an initial nephrectomy.
Clinical Case Presentation
We present a 68-year-old woman with a history of renal cell carcinoma managed with nephrectomy and retroperitoneal lymphadenectomy (2012). She had a history of arterial hypertension, type 2 diabetes mellitus, dyslipidemia, and hyperuricemia. She had no relevant family or psychosocial history.
After 7 years free of symptoms, she noticed the appearance of a mass over the thyroid region, accompanied by a sensation of discomfort when swallowing. On physical examination, a thyroid nodule was palpated in the right lobe. No adenopathies were palpable.
Ultrasonography reported bilateral thyroid nodules: 2.5 x 1.5 cm in the right thyroid lobe, and 1.1 x 0.6 cm in the left thyroid lobe. The fine needle aspiration biopsy (ultrasound guided) report of the larger lesion was BETHESDA I. Due to the oncologic history and the affirmation of symptoms during swallowing, a full thyroidectomy was performed.
Histopathology showed a non-encapsulated neoplastic lesion separated from the thyroid tissue by a fibrotic area (see figure 1), positive for anhydrase (see figure 2), Ree, PAX8, CD10, and CAM 5.2; negative for TTF-1 (see figure 3), thyroglobulin (see figure 4), synaptophysin, calcitonin, chromogranin, GATA-3 or CD4. Cell proliferation index is given by Ki-67 of 15%. No other lesions were identified in the rest of the gland. It was concluded that it was compatible with Ree. Positron emission tomography with 18-Fluorodeoxyglucose and other radiological studies did not document synchrony with other lesions until 4 months after thyroidectomy.
About 8 months later, she presented local recurrence in the pancreas, nivolumab and ipilimumab were started, and the latter was suspended after 3 months due to suspicion of pneumonitis. After 10 months, pulmonary metastases were identified, and treatment was changed to axitinib.
Discussion
Despite its high vascularity, metastases to the thyroid gland are not common. It has been suggested that the thyroid microenvironment with high concentrations of oxygen and iodine limits the anchorage and subsequent growth of circulating tumor cells 6. In a clinical series, the main primary site of malignancy reported is the kidney, followed by the lung. The latter is the most frequent site in an autopsy series 3.
Metastases are usually multifocal by autopsy and solitary in clinical series with sizes of <15 mm. Metastases of renal origin are usually >15 mm in size, unilateral, and unifocal 7. In our patient, two suspicious lesions were identified by ultrasonography, with corroboration of a metastatic neoplasm of renal origin in the larger one with a longitudinal diameter of 25 mm.
The literature shows that the average time for thyroid metastasis in patients with Ree is 8.8 years (5.0 to 10.3 years), close to the time described for our patient (7 years). Identification of metastases can occur up to 20 years of follow-up after initial diagnosis. Most patients are asymptomatic or report a palpable painless mass 8. Dysphagia, dysphonia, cervical pain, cough, wheezing, and dyspnea have also been described 9,10. Rapidly growing masses that raise suspicion of primary high-grade thyroid lesions such as anaplastic carcinoma 11 have been described.
Ultrasonography does not allow for distinguishing the origin of the lesion, usually characterized as a hypoechogenic nodule in a euthyroid patient 12. Preoperative diagnosis by fine needle aspiration biopsy leads to the correct diagnosis in 73.7% of evaluated metastases. In the remaining 24% of cases, the diagnosis may erroneously correspond to primary thyroid malignancy, benign follicular nodules, normal and indeterminate. In Ree, misdiagnosis may occur in 28.6% of cases. As in our case, surgical management in the presence of non-diagnostic biopsies and a history of malignancy 13 is recommended.
Metastatic lesions to the thyroid can be identified as isolated or immersed in primary thyroid lesions. Metastases of Ree have been identified in lesions such as follicular adenoma, papillary carcinoma, oncocytic adenoma, and carcinoma 14. This situation of coexistence difficults the preoperative diagnosis of the lesions. In our patient, no concomitant lesions were documented.
Immunohistochemistry becomes the main tool in the correct identification of the lesion. TTF-1 is used to identify tumors of pulmonary and thyroid origin. The joint staining for TTF-1 and Thyroglobulin allows confirming or excluding the origin in the thyroid follicles of the neoplastic lesion 15. In the patient, both stains were negative in the neoplastic lesion and positive in the surrounding thyroid tissue. The specific complementary positivity for Ree marker, CD10 and carbonic anhydrase in the neoplastic lesion allowed for establishing the origin in renal cells.
Total thyroidectomy is recommended to prevent disease progression, although, in unilateral involvement, hemithyroidectomy can be considered. After surgery, survival is estimated at 3.4 to 5.2 years 8,16. Survival without thyroidectomy can be as short as 12 months 17. The main cause of mortality is a generalized metastatic disease with a worse prognosis if there is extra-thyroid involvement of the identified lesion 18.
