What is correct regarding Hurthle cell thyroid carcinoma, specifically that 75% of the tumor consists of Hurthle cells, in relation to diagnosis with fine-needle aspiration (FNA) and association with previous neck radiation?

Hürthle Cell Thyroid Carcinoma: Diagnostic Challenges and Radiation Association

Fine-needle aspiration (FNA) cannot reliably distinguish between Hürthle cell adenoma and carcinoma, requiring surgical excision for definitive diagnosis. There is no strong association between Hürthle cell carcinoma and previous neck radiation exposure. 1, 2

Diagnostic Challenges with FNA

• Hürthle cell carcinoma (HCC) cannot be definitively diagnosed by FNA alone, as cytology cannot reliably distinguish between benign and malignant Hürthle cell neoplasms 1
• Definitive diagnosis requires histological evidence of capsular and/or vascular invasion, which can only be determined after surgical excision 2
• Historically, molecular diagnostic testing has performed poorly for Hürthle cell neoplasms, with high false-positive rates for malignancy 3
• Recent advances with newer molecular tests (Afirma Genomic Sequencing Classifier and ThyroSeq v3) show promise but are not yet considered standard practice for Hürthle cell lesions 3
• The NCCN panel has noted that "molecular diagnostics may not perform well for Hürthle cell neoplasms" 3

Risk Factors and Radiation Association

• Unlike some other thyroid cancers, there is no established association between Hürthle cell carcinoma and previous neck radiation exposure 2
• Risk factors for malignancy in Hürthle cell neoplasms include:
  • Nodules measuring ≥2 cm 4
  • Patient age ≥40 years 4
  • Male gender (though this association is not statistically significant) 4

Pathological Characteristics

• "Pure" Hürthle cell carcinomas are defined as those with a Hürthle cell component exceeding 75% of the tumor 3
• HCC is now classified as a distinct type of differentiated thyroid cancer by the WHO, rather than a variant of follicular thyroid carcinoma 2
• HCC presents with molecular abnormalities that distinguish it from conventional follicular carcinomas 3
• HCC is generally less aggressive and less likely to present with lymph node metastases compared to other high-risk thyroid carcinomas 3

Diagnostic Pitfalls

• The presence of Hürthle cells in FNA samples can be misleading, as they can occur in both benign and malignant conditions 5
• When Hürthle cells are predominant (>75% of cellular population), the risk of malignancy is significantly elevated even in FNAs initially interpreted as benign/Bethesda II 6
• Careful observation of nuclear features, predominant cell population, and background elements (colloid, lymphocytes) is essential for accurate interpretation 5

Management Implications

• HCC with extensive vascular and/or capsular invasion should be managed like other high-risk carcinomas 3
• The risk of recurrence is classified as high (30-55%) when HCC is associated with extensive vascular invasion (>4 foci) 2
• Surgical excision is necessary for definitive diagnosis and treatment 2

Understanding these diagnostic limitations and clinical characteristics is crucial for appropriate management of patients with suspected Hürthle cell neoplasms, as misdiagnosis can lead to either unnecessary surgery or delayed treatment of malignancy.