Thyroid Fine Needle Aspiration Biopsy (FNAB):

Inside the Eye of a Cytopathologist

Ian Jaffee, MD FCAP

Director of Cytopathology

California Pacific Medical Center

Outline of Discussion• Utility of FNAB

• Applications to thyroid nodules

• Cytology…

• Understanding the cytopathology report

FNA of the Thyroid Gland

• Safe, widely accepted, and cost-effective

• Accurate “triage” of the thyroid nodule

• Current estimates of ~30,000,000 people in U.S. with thyroid nodules > 1 cm

• ~30,000 with malignant thyroid nodules

• Goal: Identify patients who require surgical intervention

Good practice in cytopathology

• Direct communication

• Collaboration with endocrinologist, surgeon (general vs ENT), radiologist, and PCP

• Follow-up correlation with final surgical pathology

Good practice in cytopathology

• Benign• Malignant• The in betweens…• Suboptimal samples (quality/quantity)• Diagnostic guidelines

– Papanicolaou Society of Cytopathology Task Force– American Thyroid Association– None have been necessarily universally accepted

Diagnostic approach

• Non-diagnostic

• Benign

• Atypical follicular lesion of undetermined significance (AFL-US)

• Suspicious for follicular neoplasm/follicular lesion

• Suspicious for malignancy

• Malignant

Non-diagnostic

• Findings– Blood only– Absence of colloid– Insufficient cellularity (“6/10 rule”)– Colloid only (cyst contents)

• Management: Follow-up U/S and repeat FNA• Repeated non-diagnostics and risk of malignancy

– “quite low” (<5%)

» McHenry CR, Walfish PG, Rosen IB. Non-diagnostic fine-needle aspiration biopsy: a dilemma in management of nodular thyroid disease. Am Surg. 1993;59:415-419.

» Renshaw A, Significance of repeatedly non-diagnostic thyroid FNAs. Am J Clin Pathol 2011;135:750-752

Benign

• “Most things in the thyroid are benign”

• Risk of malignancy (~3%)

Benign Thyroid Nodules (BTN)

• Management: Clinical follow-up

Atypical follicular lesion of undetermined significance (AFL-US)• I don’t use it

• Poorly defined category

• Theoretical risk of malignancy is 5-15%

• Management: Repeat FNA or molecular triage (more later)

Follicular lesions

• Suspicious for follicular neoplasm

• Follicular neoplasm

• Follicular lesion

• Hürthle cell lesion

• Risk of malignancy: ~15-20%

Cytology of follicular lesions

Follicular adenoma

• Capsule; no vascular invasion

Follicular carcinoma

• Capsular invasion

• Vascular invasion

Follicular lesions

• Management Options:– Lobectomy– Lobectomy with frozen section– Total thyroidectomy– Molecular testing (more later…)

Malignant

• Suspicious for malignancy (risk of malignancy 60-75%)– Management: Lobectomy vs total thyroidectomy

• Malignant (risk of malignancy 99%)– Management: Thyroidectomy

Malignant

• Papillary thyroid carcinoma

• Follicular carcinoma

• Medullary carcinoma

• Anaplastic carcinoma

• Poorly differentiated carcinoma

• Lymphoma

• Metastatic carcinoma

Papillary thyroid carcinoma

PTC: Surgical pathology

Molecular triage of FNA samples

• 60-70% of thyroid malignancies harbor at least one genetic mutation– BRAF– RAS– RET/PTC– PAX8-PPARγ

Molecular triage of FNA samples

• Indeterminate by cytology– AFL-US– Follicular category

Available tests

• VeraCyte (Afirma)– mRNA gene expression classifier– High NPV (>90%) but modest specificity (50+%)

• Asuragen– Reportedly specific (rule-in/confirmatory)– RNA-based assay (RAS, BRAF, RET/PTC, and

PAX8-PPARγ)

• Quest

Bonus

Final comments

• FNAB is highly accurate with high sensitivity and specificity• Accuracy in diagnosing thyroid abnormalities

– dependant on the expertise of the cytopathologist interpreting the biopsy specimen

– physician performing the biopsy• Categorization of samples

– Non-diagnostic– Benign– AFL-US– Follicular (Suspicious for) lesion/neoplasm– Suspicious for malignancy– Malignant

• FNA cannot reliably distinguish benign from malignant follicular neoplasm

• New molecular triage testing (lukewarm)

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