Hurthle Cell Adenoma: Key Signs, Diagnosis, and Treatment

Hurthle cell adenoma is a rare, benign thyroid tumor arising from Hurthle cells, a type of follicular thyroid cell. Though noncancerous, it requires careful evaluation due to its resemblance to more aggressive thyroid conditions.

Early detection and accurate diagnosis are essential for proper management. Understanding its key signs, diagnostic approaches, and treatment options ensures optimal patient outcomes.

Pathological Characteristics

Hurthle cell adenoma consists predominantly of Hurthle cells, or oncocytic cells, which have abundant eosinophilic cytoplasm and densely packed mitochondria. These cells originate from follicular epithelial cells of the thyroid and undergo metaplastic transformation, giving them a distinct granular appearance under a microscope. Their high mitochondrial content sets them apart from other thyroid neoplasms.

Histologically, the tumor is encapsulated by a well-defined fibrous capsule, distinguishing it from its malignant counterpart, Hurthle cell carcinoma. It exhibits a solid, trabecular, or microfollicular growth pattern. While Hurthle cells often have enlarged, hyperchromatic nuclei, they lack the nuclear atypia and mitotic activity seen in malignancies. Unlike Hurthle cell carcinoma, which can invade blood vessels or the tumor capsule, adenomas remain confined within their fibrous boundary, preventing metastatic spread. Immunohistochemical staining typically shows strong positivity for thyroid transcription factor-1 (TTF-1) and thyroglobulin, confirming the tumor’s thyroid origin. Additionally, mitochondrial markers such as cytochrome c oxidase subunit 1 (COX1) are frequently overexpressed, reflecting the high mitochondrial density.

Molecular studies indicate that while Hurthle cell adenomas share genetic features with follicular thyroid adenomas, they also exhibit unique mitochondrial DNA mutations contributing to their oncocytic phenotype. Mutations in mitochondrial respiratory chain complexes I and IV may drive their metabolic reprogramming. Unlike Hurthle cell carcinomas, which frequently harbor TP53, NRAS, or TERT promoter mutations, adenomas generally lack these high-risk alterations, reinforcing their benign nature. However, some show chromosomal instability, raising concerns about potential malignant transformation in rare cases.

Clinical Presentation

Hurthle cell adenomas often present as a solitary thyroid nodule, typically discovered incidentally during routine physical exams or imaging. These nodules are usually slow-growing and asymptomatic, though their size and location can lead to clinical symptoms. Some patients may notice a visible swelling in the neck or a sensation of fullness, particularly if the lesion enlarges significantly. Unlike aggressive thyroid neoplasms, Hurthle cell adenomas rarely cause systemic symptoms like unexplained weight loss or night sweats.

Larger tumors may exert pressure on adjacent structures, leading to difficulty swallowing (dysphagia) if they impinge on the esophagus or persistent hoarseness if they affect the recurrent laryngeal nerve. While these symptoms are more commonly associated with malignancies, large benign nodules can also produce similar effects. Some patients may experience mild discomfort or a dull ache in the anterior neck, though pain is uncommon.

Most Hurthle cell adenomas are non-secretory and do not significantly alter thyroid hormone levels. However, in rare cases, they become autonomously functioning, leading to hyperthyroidism. Symptoms of hyperthyroidism include palpitations, increased sweating, heat intolerance, and unintentional weight loss. In such cases, laboratory tests reveal suppressed thyroid-stimulating hormone (TSH) levels with elevated free thyroxine (T4) or triiodothyronine (T3). Radionuclide thyroid scintigraphy is used to assess autonomous activity when hyperfunctioning adenomas are suspected.

Diagnostic Methods

Evaluation begins with a clinical assessment and imaging studies to characterize the thyroid nodule’s size, composition, and vascularity. High-resolution ultrasound is the primary imaging tool, providing details on echogenicity, margins, and vascular patterns. Hurthle cell adenomas appear as well-defined, hypoechoic or isoechoic solid lesions. While ultrasound cannot reliably distinguish benign from malignant Hurthle cell tumors, irregular borders, microcalcifications, or increased vascularity may raise suspicion for malignancy. Doppler ultrasound helps assess blood flow patterns, as highly vascular nodules warrant further scrutiny.

Fine-needle aspiration (FNA) biopsy follows, offering cytological evaluation. However, distinguishing Hurthle cell adenoma from carcinoma using FNA alone is difficult due to overlapping cytologic features. Both lesions contain large, eosinophilic oncocytic cells with abundant granular cytoplasm, making malignancy determination based solely on cellular morphology unreliable. The presence of nuclear atypia, prominent nucleoli, and increased cellularity may suggest a more aggressive process, but definitive diagnosis requires histopathologic examination after surgical excision. The Bethesda System for Reporting Thyroid Cytopathology classifies Hurthle cell lesions as indeterminate (Bethesda III or IV), often necessitating further molecular or histological testing.

Molecular testing aids in evaluating indeterminate thyroid nodules. Genetic panels analyzing NRAS, HRAS, and KRAS mutations, as well as mitochondrial DNA alterations, help assess tumor behavior. TERT promoter mutations or TP53 alterations strongly suggest malignancy, but their absence does not confirm benignity. Gene expression classifiers and next-generation sequencing (NGS) are being explored for risk stratification, though their role in Hurthle cell lesions remains under study.

Differentiating From Other Thyroid Tumors

Hurthle cell adenomas share histological and cytological features with various thyroid neoplasms, complicating their distinction from other tumors. A key differentiator is the presence of oncocytic cells, which also appear in Hurthle cell carcinoma and certain follicular neoplasms. While both Hurthle cell adenomas and carcinomas contain large, granular eosinophilic cells rich in mitochondria, adenomas remain confined within an intact fibrous capsule, whereas carcinomas exhibit capsular or vascular invasion. This distinction is confirmed only through histopathologic examination after surgical excision, as FNA alone cannot reliably differentiate them.

Follicular adenomas also present similarly, as both originate from thyroid follicular cells and form encapsulated nodules. However, Hurthle cell adenomas have a higher mitochondrial content and more prominent eosinophilic cytoplasm. Papillary thyroid carcinoma (PTC) may exhibit oncocytic changes, but its hallmark nuclear features—such as intranuclear grooves and pseudoinclusions—aid in differentiation. Additionally, PTC frequently harbors BRAF V600E mutations, absent in benign Hurthle cell tumors.

Management Options

Surgical intervention is the primary treatment, as observation alone is often inadequate due to the difficulty in preoperative differentiation from malignancy. The decision to proceed with surgery depends on factors such as nodule size, growth rate, compressive symptoms, and cytological findings. While small, asymptomatic adenomas with benign cytology may be monitored with serial ultrasounds, surgical removal is typically recommended for nodules larger than 4 cm or those with suspicious features.

Lobectomy, or hemithyroidectomy, is the preferred surgical approach for confirmed Hurthle cell adenomas. This procedure removes the affected thyroid lobe while preserving the contralateral lobe, maintaining some thyroid function and reducing the likelihood of lifelong hormone replacement therapy. Postoperative histopathological examination is essential for ruling out malignancy, as Hurthle cell carcinoma is diagnosed only upon identifying capsular or vascular invasion. If malignancy is unexpectedly discovered, a completion thyroidectomy may be necessary. In patients with autonomous functioning Hurthle cell adenomas causing hyperthyroidism, surgery is often favored over radioactive iodine therapy, as oncocytic cells exhibit reduced iodine uptake, making radioiodine treatment less effective.