What is Hurthle cell carcinoma?

What is Hürthle Cell Carcinoma?

Hürthle cell carcinoma (HCC) is a distinct type of differentiated thyroid cancer, now classified separately from follicular thyroid carcinoma by the World Health Organization, representing approximately 3% of all thyroid malignancies and characterized by cells with abundant eosinophilic cytoplasm and more aggressive behavior than conventional differentiated thyroid cancers. 1, 2

Classification and Pathological Definition

• HCC is defined as a tumor where Hürthle cells (also called oncocytic cells) comprise more than 75% of the tumor composition, distinguishing it as a "pure" Hürthle cell carcinoma 1
• The WHO now recognizes HCC as a distinct entity rather than a variant of follicular carcinoma, reflecting its unique molecular abnormalities and clinical behavior 2
• Definitive diagnosis requires histological evidence of capsular and/or vascular invasion, which can only be determined after surgical excision—fine-needle aspiration alone cannot reliably distinguish benign from malignant Hürthle cell neoplasms 1, 2

Clinical Presentation and Demographics

• HCC typically presents as a solitary thyroid nodule, with bilateral involvement being rare 1, 2
• The disease affects women more commonly (approximately 67.5% of cases) with a mean age at diagnosis of 57-58 years 3, 4
• Tumors are generally larger at diagnosis compared to other differentiated thyroid cancers, with mean size around 30-36 mm 3, 4
• Unlike some thyroid cancers, there is no established association between HCC and previous neck radiation exposure 1

Aggressive Features and Metastatic Pattern

• HCC demonstrates more aggressive behavior than papillary or follicular thyroid carcinoma, with extrathyroidal extension occurring in approximately 24% of cases 3
• Interestingly, lymph node metastases are relatively uncommon (approximately 9%), which is less frequent than other high-risk thyroid carcinomas 1, 3
• When extensive vascular invasion is present (>4 foci), the risk of recurrence is classified as high (30-55%) 1, 2
• Distant metastases, when they occur, most commonly involve the lungs, followed by bone and liver 5

Prognosis and Survival

• The 10-year relative survival rate for HCC is approximately 76%, which is notably lower than papillary thyroid carcinoma (93%) and follicular carcinoma (85%) 1
• Five-year overall survival is approximately 91%, declining to 76% at 10 years 3
• Age ≥45 years, distant disease stage, and advanced T-stage are independent risk factors for mortality 6, 4
• Male gender, multifocal tumors, and extensive tumors are associated with increased risk of late-stage disease 6

Diagnostic Challenges

• A critical pitfall: molecular diagnostics may not perform well for Hürthle cell neoplasms, with historically high false-positive rates for malignancy 7, 1
• The NCCN specifically notes that older molecular tests like the Afirma Gene Expression Classifier resulted in 86% of patients with suspicious findings undergoing unnecessary surgery 7
• Newer tests (Afirma Genomic Sequencing Classifier and ThyroSeq v3) show improved performance with sensitivities of 88.9% and 92.9% respectively, but data remain insufficient for routine recommendation 7
• Surgical excision remains necessary for definitive diagnosis and treatment 1, 2

Treatment Implications

• Total thyroidectomy is the standard treatment for HCC, not lobectomy, due to its more aggressive behavior 1
• Treating HCC with lobectomy alone represents inadequate management and should be avoided 1
• All patients should receive TSH suppression therapy with levothyroxine following surgery 1
• Radioactive iodine (RAI) ablation should be considered for residual thyroid tissue, though HCC is often less RAI-avid than other differentiated thyroid cancers 1, 8
• For advanced, progressive disease not amenable to surgery, kinase inhibitors such as lenvatinib may be considered 7, 8