Definition/General
Introduction:
Thyroid papillary carcinoma is the most common thyroid malignancy, representing 80-85% of thyroid cancers
FNAC is the primary diagnostic modality for thyroid nodules, with characteristic cytologic features enabling accurate diagnosis.
Origin:
Arises from thyroid follicular epithelial cells
Develops through accumulation of genetic alterations including RET/PTC rearrangements and BRAF mutations
Often associated with radiation exposure.
Classification:
Bethesda System for Reporting Thyroid Cytopathology classifies as Category VI (Malignant)
WHO histologic variants include classical, follicular variant, tall cell, and others.
Epidemiology:
Female predominance (3:1)
Can occur at any age but peaks in 30-50 years
Excellent prognosis with appropriate treatment
Associated with prior radiation exposure.
Clinical Features
Presentation:
Palpable thyroid nodule (most common)
Cervical lymphadenopathy
Hoarseness (recurrent laryngeal nerve involvement)
Dysphagia (large masses)
Usually euthyroid state.
Symptoms:
Neck mass or swelling
Sensation of fullness in neck
Change in voice quality
Difficulty swallowing
Usually asymptomatic thyroid function.
Risk Factors:
Previous radiation exposure (especially in childhood)
Family history of thyroid cancer
Female gender
Iodine deficiency or excess
Genetic syndromes (Cowden, Carney complex).
Screening:
Clinical examination
Ultrasound-guided FNAC for suspicious nodules
TSH measurement
Thyroglobulin levels post-operatively
Genetic testing in familial cases.
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Gross Description
Appearance:
FNAC specimen appears as cellular smears with variable cellularity
May contain blood and colloid
Papillary fragments may be visible grossly.
Characteristics:
Air-dried and alcohol-fixed smears prepared
Cellular yield usually adequate
Background may show colloid, blood, or inflammatory cells.
Size Location:
Needle tracks through thyroid parenchyma
Sampling depends on nodule size and location
Multiple passes may be needed for adequate cellularity.
Multifocality:
May sample multiple nodules if present
Bilateral disease possible
Lymph node sampling if clinically enlarged.
Microscopic Description
Histological Features:
Papillary architecture with fibrovascular cores
Characteristic nuclear features: enlarged, overlapping, grooved nuclei
Nuclear pseudoinclusions
Psammoma bodies.
Cellular Characteristics:
Enlarged cells with increased nuclear-cytoplasmic ratio
Nuclei are oval, enlarged, with irregular nuclear membranes
Ground-glass chromatin
Prominent nuclear grooves and pseudoinclusions.
Architectural Patterns:
Papillary structures with fibrovascular cores
Follicular architecture possible (follicular variant)
Sheets and clusters of cells
Single cells may be present.
Grading Criteria:
Cytologic grading not routinely performed for papillary carcinoma
Diagnosis based on nuclear morphology rather than architectural features.
Immunohistochemistry
Positive Markers:
Thyroglobulin positive (confirms thyroid origin)
TTF-1 positive
PAX8 positive
CK19 positive
HBME-1 positive (in tissue sections).
Negative Markers:
Calcitonin negative (excludes medullary carcinoma)
Parathyroid hormone negative
CK20 negative
CDX2 negative.
Diagnostic Utility:
Immunocytochemistry rarely needed for FNAC diagnosis
Nuclear morphology sufficient for diagnosis
Molecular testing may be performed on FNAC material.
Molecular Subtypes:
BRAF V600E mutations (40-45%)
RET/PTC rearrangements (20%)
RAS mutations (follicular variant)
TERT promoter mutations (advanced cancers).
Molecular/Genetic
Genetic Mutations:
BRAF V600E mutations most common (40-45%)
RET/PTC rearrangements (especially RET/PTC1 and RET/PTC3)
RAS mutations in follicular variant
PIK3CA mutations.
Molecular Markers:
Molecular testing can be performed on FNAC material
ThyroSeq, Afirma gene expression classifier
BRAF mutation testing widely available.
Prognostic Significance:
BRAF mutations associated with more aggressive behavior
TERT promoter mutations indicate worse prognosis
Overall excellent prognosis for most cases.
Therapeutic Targets:
BRAF inhibitors (vemurafenib, dabrafenib) for advanced BRAF-mutated cancers
Multikinase inhibitors (sorafenib, lenvatinib) for radioiodine-refractory disease.
Differential Diagnosis
Similar Entities:
Follicular neoplasm
Hurthle cell neoplasm
Medullary thyroid carcinoma
Anaplastic thyroid carcinoma
Metastatic carcinoma
Lymphoma.
Distinguishing Features:
Papillary carcinoma: Nuclear grooves, pseudoinclusions, papillary architecture
Follicular neoplasm: Microfollicular pattern, lacks nuclear features
Medullary: Neuroendocrine morphology, calcitonin+.
Diagnostic Challenges:
Follicular variant of papillary carcinoma may lack papillary architecture
Cystic papillary carcinoma may be paucicellular
Distinction from benign follicular nodule.
Rare Variants:
Tall cell variant (aggressive)
Columnar cell variant
Solid variant
Warthin-like variant
Hobnail variant (aggressive).
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
Thyroid fine needle aspiration, [location] nodule
Adequacy
Satisfactory for evaluation (at least 6 groups of 10 cells each)
Bethesda Category
Category VI - Malignant
Cytologic Features
Cellular smears showing papillary architecture with characteristic nuclear features
Nuclear Features
Enlarged, overlapping nuclei with grooves and pseudoinclusions
Architectural Pattern
[Papillary/Follicular/Mixed] architecture
Background
Background shows [colloid/blood/inflammatory cells]
Special Features
Psammoma bodies: [Present/Absent]
Molecular Testing
Molecular analysis: [performed/recommended/not indicated]
Risk Stratification
Risk of malignancy: >95-99% (Category VI)
Recommended Management
Surgical consultation recommended
Final Diagnosis
Final diagnosis: Papillary thyroid carcinoma (Bethesda Category VI)