Sarcoidosis presenting as thyromegaly

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A 41-year-old female patient presented with a painless swelling in front of the neck for 5 months. There was no history suggestive of hypothyroidism or hyperthyroidism. The patient did not give any history of preceding fever or upper respiratory tract infection. On examination, the swelling was smooth, firm, nontender, and moved with deglutition. Multiple level III and IV cervical lymph nodes were palpable on both sides, having a discrete firm consistency. On investigation, her thyroid profile was normal, with T3 being 125.1 ng/dL (84–202 ng/dL), T4 being 14.67 (5.1–14.1 ng/dL), and thyroid-stimulating hormone being 1.52 μIU/mL (0.27–4.2 μIU/mL). Ultrasonography of the neck showed an ill-defined hypoechoic lesion measuring 2.2 × 2.2 × 1.5 cm in the right lobe of thyroid associated with calcifications, corresponding to a Thyroid Imaging Reporting and Data System (TIRADS) score of 5. In addition, there were multiple enlarged lymph nodes at levels III and IV on both sides, with the largest measuring 1.5 cm. A fine needle aspiration cytology (FNAC) performed under ultrasonographic guidance showed moderately cellular smears composed of monolayered follicular epithelial cells associated with presence of few well-formed epithelioid cell granulomas (Fig. 1A) against a background of thin colloid. An opinion of granulomatous thyroiditis (Bethesda system category II) was offered. In view of the high TIRADS score and presence of bilateral cervical lymphadenopathy, the patient was taken up for right hemithyroidectomy. An intraoperative frozen section consultation for the right level III cervical lymph node was taken, which showed near total replacement of the nodal architecture by compact noncaseating granulomas. No metastatic tumor was identified. On gross, the right hemithyroidectomy specimen weighed 11 g and measured 3 × 2.5 × 1.2 cm. Serial sections of the specimen revealed an irregular yellowish-white firm homogenous lesion measuring 2.4 × 2.3 × 1.3 cm (Fig. 1B). Microscopy showed the right thyroid parenchyma to be overrun by multiple compact noncaseating epithelioid cell granulomas associated with sparse lymphocytes and frequent Langhans and Foreign body giant cells (Fig. 2A and B). Few of the multinucleated giant cells showed the presence of cytoplasmic Schaumann (Fig. 2C) and Asteroid bodies. A reticulin stain highlighted the reticulin fiber–rich granulomas (Fig. 2D). Ziehl-Neilson and Periodic acid Schiff's stains did not reveal any organisms. Based on the histomorphology, the patient was further evaluated. Computed tomography of the chest revealed prominent hilar and mediastinal lymphadenopathy along with irregular thickening of the bronchovascular bundles. An endoscopic bronchoscopic ultrasonographic-assisted fine needle aspiration of the mediastinal lymph node and endobronchial biopsy showed the presence of compact epithelioid cell granulomas. GeneXpert of the bronchoalveolar lavage fluid and lymph node aspirate were negative. Her serum calcium level was normal at 8.9 mg/dL (8.5–10.1 mg/dL). The serum angiotensin-converting enzyme levels were elevated at 151 units/L (14–82 units/L). Based on the results of the abovementioned investigations, the patient was diagnosed to have sarcoidosis presenting as a solitary nodule thyroid. She was initially started on oral glucocorticoids and later methotrexate therapy and is presently on regular follow-up and symptom free. Patient consent was obtained for use of data and images for publication purpose.

Fig. 1.

(A) Romanowsky-stained aspirate smear from right lobe of thyroid with well-formed epithelioid cell granuloma. (B) Serial sections of right lobe of thyroid with an ill-defined yellowish-white homogeneous lesion.

Fig. 2.

(A) Hematoxylin and eosin (40× magnification). Thyroid parenchyma being destroyed by multiple granulomas. (B) Hematoxylin and eosin (100× magnification). The granulomas are compact, noncaseating and have sparse accompanying lymphocytes. (C) Hematoxylin and eosin (400× magnification). The multinucleated giant cells show intracytoplasmic calcifications. (D) Reticulin stain (100× magnification) highlights the reticulin fiber–rich granulomas.

Sarcoidosis is a multisystem aliment, which does not have any known etiology.¹ The disease is characterized by the presence of compact noncaseating epithelioid cell granulomas in the involved tissue.¹ The most common organ to be affected is the lung, with the patient usually presenting with cough and dyspnea. Common extrapulmonary manifestations of sarcoidosis include uveitis and cutaneous papulonodular lesions.² Sarcoidosis affecting the thyroid gland is a rarity, with an autopsy series of systemic sarcoidosis reporting a prevalence of 1%–4%.² Diagnosis of thyroid sarcoidosis is challenging, given that the disease is usually accompanied by cervical lymphadenopathy and ultrasonographic evaluation reporting a TIRADS score of ≥4, indicating a neoplastic pathology.³ Granulomas on thyroid FNAC warrant consideration of the following differential diagnosis: de Quervain thyroiditis, tuberculosis, and fungal infections.³ However, the most important differential diagnosis to be considered is the presence of a concomitant neoplastic pathology in the thyroid gland accompanying the granulomatous inflammation, as shown in studies by Spikerman et al and Wenter et al.^4,5 Extensive sampling of the thyroid gland and careful examination of the histology are usually required to exclude the differential diagnosis. The definitive diagnosis of sarcoidosis requires co-relation with other systemic manifestations along with supportive investigations, such as estimating serum calcium and serum angiotensin-converting enzyme levels. Hypercalcemia in sarcoidosis has been reported in approximately 6% of patients.⁶ The cause of hypercalcemia has been attributed to the in vivo synthesis of 1,23-dihydroxyvitamin D–like metabolite by activated macrophages.⁶ The factors influencing hypercalcemia have been associated with ultraviolet rays exposure, HLA DRB1∗1101 allele, and exposure to insecticides.⁶ Twenty to thirty percent positivity rate has been reported for antithyroid peroxidase antibodies in patients having sarcoidosis.⁷ It is hypothesized that 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (¹⁸F-FDG-PET/CT) will be useful, as it has shown a 90% sensitivity in detecting extrapulmonary sarcoidosis.⁸ The role of Iodine 131 scan in a case of sarcoidosis of thyroid gland is restricted to the assessment of the functional status: hyperthyroid, normothyroid, or hypothyroid status of thyroid gland.⁹ Knowledge of this rare presentation is vital to differentiate it from more sinister causes.

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