Isolated intrathyroidal metastasis revealing an occult lung adenocarcinoma.

Thyroid gland is an uncommon site of tumor metastasis inspite of rich vascular supply. Most of the cases are picked up after the diagnosis or during the work up for the primary. Unexpected involvement of thyroid gland as the first presenting sign in a primary lung adenocarcinoma is an extremely rare, however, clinically significant finding, upstaging the disease. Fine needle aspiration cytology as a primary tool for detecting metastasis in thyroid is a rapid procedure, associated with high accuracy and low morbidity.

Introduction

Metastasis to the thyroid is uncommon and a palpable thyroid tumor is usually assumed to be a primary thyroid tumor. The incidence of clinically significant metastasis appears to be lower than the incidence found at autopsy.[1-3] Most of the thyroid metastasis are detected after the diagnosis or during the work up of the primary tumor.[45] Clinically significant metastatic involvement of thyroid without the clinical evidence of primary tumor is rare. Metastatic involvement of thyroid revealing an occult lung primary is extremely rare and only a handful of cases have been described in the world literature.[35] We report a rare case of metastatic mucinous adenocarcinoma of occult primary lung origin presenting as solitary thyroid nodule.

Case Report

A 58-year-old gentleman with no significant past and family history presented with a solitary thyroid nodule of 6-weeks duration, which was gradually increasing in size. The nodule on clinical examination was found to be 2.2 × 2 × 1.4 cm, involving the isthmus and right thyroid lobe and moved on deglutition. The patient had no history of weight loss, anorexia, hemoptysis or any respiratory complaints. The routine investigations were normal including the thyroid function test. An ultrasonography (USG) of the thyroid was performed, which revealed a hypoechoic lesion measuring 2.7 × 2.4 × 1.9 cm occupying the right lobe and isthmus of thyroid. Rest of the thyroid was unremarkable. The patient underwent an ultrasonogram-guided fine needle aspiration cytology (FNAC) subsequently, which showed a cellular aspirate comprising predominantly of cohesive clusters of atypical epithelial cells having hyperchromatic eccentric nucleus and moderate to abundant amount of vacuolated cytoplasm with occasional scattered thyroid follicular epithelial cell clusters with absence of colloid [Figure 1a]. Intracellular mucin was readily evident imparting signet ring cell appearance [Figure 1b]. Overall features were overshadowing a primary thyroid tumor and were suggestive of a metastasis of a mucinous adenocarcinoma. To reveal the occult primary further work up was performed. Whole body computed tomography (CT) scan was done and CT scan-chest revealed an ill-defined heterogeneously enhancing mass abutting the right main lower lobe bronchus, right pulmonary artery and inseparable from the right hilar confluent lymph nodes. Multiple right paratracheal and subcarinal lymph nodes were also enlarged with nodulocystic changes. Abdominal CT scan was normal. Bronchoscopic-guided biopsy was done, which revealed histopathological features of mucinous adenocarcinoma [Figure 1c]. On immunohistochemistry (IHC), the tumor cells showed immunoreactivity for cytokeratin 7 and thyroid transcription factor-1, [Figure 1d] whereas it was negative for thyroglobulin. Hence, a final diagnosis of mucinous adenocarcinoma of lung, metastasizing to thyroid was established. The studies for epidermal growth factor receptor mutation analysis were negative for exon 18, 19, 20, and 21. The patient received six cycles of pemetrexed and after five months of follow-up is doing well.

Figure 1

(a) Cytological smears from thyroid show neoplastic epithelial cells (yellow arrow) scattered along with thyroid epithelial clusters (red arrow) (Giemsa, ×200). (b) Smears reveal neoplastic epithelial cells with signet ring morphology containing intracellular mucin (Giemsa, ×200); inset (Giemsa, ×400). (c) Biopsy from lung mass showing neoplastic cells with signet ring morphology (H and E, ×200). (d) Tumor cells expressing strong nuclear positivity for Thyroid transcription factor -1 (DAB, ×200)

Discussion

Metastatic involvement of the thyroid gland is infrequent even though the gland has a rich vascular supply. The incidence of clinically significant (palpable mass) metastasis is much lower than the incidence found at autopsy since metastasis of autopsy cases includes nonclinical subjects comprising of occult cancer and widespread cancer at the time of death.[15] According to literature, most of the series have documented conventional renal cell carcinoma to be the commonest primary site of origin, followed by breast and lung.[1-46] Majority of the thyroid metastasis are detected after the diagnosis of the primary or simultaneously during the work up. The metastatic involvement of the thyroid as the first presenting symptom is an extremely rare finding and only a handful of cases are known till date, majority of which comprised of conventional renal cell carcinoma as primary and lung being the primary is still rare.[3578]

The diagnosis of metastasis in our case was based on FNAC, which was further substantiated by the biopsy and IHC. FNAC has low morbidity, low cost and high negative predictive value. Several reports have described the good accuracy of FNAC for confirming the clinical suspicion of metastasis to thyroid gland and in some patients it can even detect an unanticipated malignancy.[68] Since there is nothing clinically to differentiate a thyroid metastasis from primary thyroid cancer, metastatic disease involving the thyroid with no known primary presents as a diagnostic problem as many of them are poorly or moderately differentiated adenocarcinoma, squamous cell carcinoma, or undifferentiated carcinoma.[5] In our case, it was a poorly differentiated mucinous adenocarcinoma of lung origin.

Metastatic involvement of thyroid gland often indicates advanced disease stage with dismal prognosis. There is no specific consensus regarding the treatment modality of thyroid metastasis and management should depend on individual case. Although many authors recommend a thyroid lobectomy and or isthmectomy in case of a solitary thyroid metastasis or for palliation of airway obstruction.[24]