A focal nodular Hürthle cell hyperplasia in Hashimoto's thyroiditis: A diagnostic dilemma on fine needle aspiration

Abstract

Hürthle cells are seen in a variety of nonneoplastic and neoplastic thyroid gland lesions. Number and morphology of Hürthle cell vary in thyroid aspirate. Occasionally, thyroid aspirate in focal nodular Hürthle cell hyperplasia in Hashimoto's thyroiditis exclusively comprise of Hürthle cells and mimics Hürthle cell neoplasm. Fine needle aspiration (FNA) diagnosis in such cases is challenging. A 60-year-old female presented with goiter and clinical features of hyperthyroidism. FNA smears showed Hürthle cells arranged in flat sheets and lying singly with occasional lymphocytes in Hürthle cell sheets. Repeat aspiration from other site showed lymphocytes, infiltrating the thyroid follicular cells. We conclude that a careful search of lymphocytes in Hürthle cell sheets in cytology smears, multiple aspirates, associated clinical findings and ancillary techniques reduce the diagnostic pitfall and avoid unnecessary surgery.

Introduction

Variable number of Hürthle (Oxyphilic) cells in thyroid aspirates is seen in various non-neoplastic and neoplastic lesions of the thyroid. Hyperplastic nodules in the setting of multinodular goiter and Hashimoto's thyroiditis varies in the extent of Hürthle cell metaplasia.[1] Occasionally thyroid aspirates in these conditions consist exclusively of Hürthle cells. In such aspirates, cytologic distinction from Hürthle cell neoplasm can be a diagnostic challenge.[1,2,3,4,5] We report one such case of an elderly woman who had clinical features of hyperthyroidism and presented with goiter.

Case Report

A 60-year-old female came to the surgical outpatient unit with complaint of painless midline neck swelling of 3 months duration. She gave history of weight loss, heat intolerance, tremors and palpitation since 15 days. There was no history of difficulty in swallowing or change in voice. Thyroid hormone evaluation revealed hyperthyroid function viz: T3 – 280 mg/dL, T4 – 16 μg/dL and thyroid-stimulating hormone – 0.21μm/mL.

Ultrasonography of the neck showed uneven enlargement of both the lobes of thyroid gland and showed isoechoic to hypoechoic texture. Left lobe showed well-defined nodule (2.8 cm × 1.7 cm) with mixed echogenicity and without any cavitations or calcification. There were no enlarged lymph nodes. Parotid and submandibular salivary glands appeared normal.

Fine needle aspiration (FNA) smears from the left thyroid lobe were cellular, hemorrhagic and comprised of Hürthle cells arranged in flat sheets and lying singly. Hürthle cells showed moderate nuclear pleomorphism, abundant granular cytoplasm and well defined cytoplasmic borders. Few cells showed prominent nucleoli. Occasional cluster showed nuclear crowding [Figure 1a]. Scanty colloid was seen. Thyroid follicular cells were not seen. Occasional lymphocyte was seen in Hürthle cell sheets [Figure 1a and b, arrows]. Repeat aspiration from right thyroid lobe had low cellular yield and showed small cluster of thyroid follicular cells infiltrated by lymphocytes. The diagnosis of Hashimoto's thyroiditis was made. Elevated anti-thyroid peroxidase antibody titer (21 IU/mL) supported the diagnosis.

Figure 1.

(a) Hürthle cells showed moderate nuclear pleomorphism, and few cells showed prominent nucleoli, (b) occasional lymphocyte in Hürthle cell sheets (arrow), (Leishman stain ×400)

Discussion

Hürthle cell in thyroid aspirates is seen in variety of lesions such as Hashimoto's thyroiditis, multinodular goitre, Hürthle cell neoplasms (adenoma/carcinoma), head and neck irradiation, systemic chemotherapy, oncocytic variant of medullary, papillary carcinoma and long-standing Graves disease.[5] Several studies have reached contradictory conclusions regarding the value of specific cytologic findings in these lesions.[1,4,5,6,7]

A mixture of Hürthle cells and normal follicular epithelial cells is more consistent with a hyperplastic nodule. Hürthle cells may show nuclear pleomorphism. Nuclei tend to be more uniform in size in Hürthle cell tumors than Hashimoto's thyroiditis.[7,8] In our case, Hürthle cells showed moderate nuclear pleomorphism but normal thyroid follicular cells were not seen in the aspirate.

Elliott et al.[4] correlated cytology features of thyroid nodules showing predominant Hürthle cell component with corresponding histological features in 139 cases. The following 14 cytological features were studied: Overall cellularity, cytoarchitecture, percentage of Hürthle cells, percentage of single Hürthle cells, percentage of follicular cells observed as naked Hürthle cell nuclei, background colloid, chronic inflammation, cystic change, transgressing blood vessels, intracytoplasmic lumina, multinucleated Hürthle cells, nuclear to cytoplasmic ratio, nuclear pleomorphism/atypia and nucleolar prominence. Out of the 14 features, non-macrofollicular architecture, absence of background colloid, absence of chronic inflammation and presence of transgressing blood vessels were statistically significant in predicting Hürthle cell neoplasm in 86% of Hürthle cell lesions. They found >90% Hürthle cells and >10% single Hürthle cells in cytology smears of Hürthle cell neoplasms. In our case, thyroid aspirates exclusively comprised of Hürthle cells and up to 30% were single cells. After careful search, occasional lymphocyte was seen lying in Hürthle cell sheets which made us to think of Hashimoto's thyroiditis. Hyperthyroid function in our case can be explained by the fact that the patient had hashitoxicosis which is a transient hyperthyroid phase of Hashimoto's thyroiditis. Most patients recover from hyperthyroidism.

Roh et al.[1] observed that some cases of non-neoplastic Hürthle cell proliferations in Hashimoto's thyroiditis mimic suspicious/follicular neoplasm of Hürthle cell type on cytology. They found the discordance between the predicted and actual risk of malignancy, associated with suspicious or follicular neoplasm of Hürthle cell type pattern in patients with Hashimoto's thyroiditis.

Failure to demonstrate lymphocytes and to appreciate non-neoplastic nature of Hürthle cells in cytology smears, often results in misdiagnosis of Hürthle cell neoplasm.[9] Disorganised and poorly cohesive masses of oxyphilic cells with prominent nucleoli are more indicative of a neoplastic lesion. Sheets of Hürthle cells, infiltrated by lymphocytes are seen in hyperplastic lesion.[10] Although prominent nucleoli are commonly seen in Hürthle cell neoplasms, they may be seen in non-neoplastic Hürthle cell lesions.[7] Similar findings were seen in our case.

In spite of all these criteria, in many instances, making a clear distinction between neoplastic and nonneoplastic Hürthle cell lesions may be difficult.[6] In our case, occasional lymphocyte in Hürthle cell sheets and repeat aspiration from the other lobe of the thyroid established the correct diagnosis of Hashimoto's thyroiditis.

Conclusion

Focal nodular hyperplasia of the Hürthle cells in Hashimoto's thyroiditis varies in the extent of Hürthle cell metaplasia. Occasionally FNA smears show only Hürthle cells. Distinction from Hürthle cell neoplasm is a diagnostic challenge. Careful search of lymphocytes in Hüürthle cell sheets on FNA smears, multiple aspirates, associated clinical findings and ancillary techniques, reduce the diagnostic pitfall and avoides unnecessary surgery.