Definition/General
Introduction:
Papillary thyroid carcinoma (PTC) represents the most common malignant thyroid neoplasm
It constitutes 80-85% of all thyroid cancers
It arises from follicular epithelial cells
It demonstrates papillary architecture with characteristic nuclear features.
Origin:
Originates from thyroid follicular epithelial cells
Associated with RET/PTC rearrangements
Associated with BRAF mutations
Radiation exposure is a risk factor
Iodine deficiency and excess both predispose to PTC.
Classification:
Classified into classical variant (most common)
Follicular variant (15-20%)
Tall cell variant (aggressive)
Columnar cell variant (rare, aggressive)
Solid variant
Warthin-like variant
Oncocytic variant.
Epidemiology:
Peak incidence in 3rd-5th decades
Female predominance (3:1 ratio)
Risk factors include radiation exposure
Family history
Iodine intake variations
Previous thyroid disease
Indian population shows increasing incidence in urban areas.
Clinical Features
Presentation:
Thyroid nodule (most common)
Cervical lymphadenopathy (30-40%)
Hoarseness (recurrent laryngeal nerve involvement)
Dysphagia
Dyspnea
Asymptomatic nodule detected on imaging
Incidental finding at autopsy.
Symptoms:
Neck mass or swelling
Difficulty swallowing
Voice changes
Cough
Neck pain (uncommon)
Hyperthyroidism (rare, in functioning nodules)
Weight loss
Palpitations.
Risk Factors:
Radiation exposure (especially childhood)
Family history of thyroid cancer
Previous thyroid disease
Hashimoto thyroiditis
Iodine deficiency
Excessive iodine intake
Female gender
Age 30-50 years.
Screening:
Thyroid ultrasound
Fine needle aspiration (FNAC)
Thyroid function tests
High-risk patients: Regular surveillance
Family screening for hereditary syndromes.
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Gross Description
Appearance:
Well-defined to infiltrative mass
Gray-white cut surface
Firm consistency
Size varies from microscopic to several centimeters
Calcifications may be present
Cut surface may show fibrosis.
Characteristics:
Solid, firm mass with irregular borders
Gray-white appearance on cut surface
May show areas of cystic degeneration
Psammoma bodies may be grossly visible as gritty areas
Capsule may be present or absent.
Size Location:
Size ranges from microcarcinoma (<1 cm) to large masses (>4 cm)
Can occur in any lobe
Multifocal in 20-30% cases
Bilateral in 10-20% cases
May extend beyond thyroid capsule.
Multifocality:
Multifocal disease common (20-30%)
Bilateral involvement in 10-20%
Lymph node metastases in 30-40%
Microcarcinomas may be incidental findings.
Microscopic Description
Histological Features:
Papillary architecture with fibrovascular cores
Cells lining papillae show characteristic nuclear features
Ground glass nuclei
Nuclear grooves
Intranuclear inclusions
Psammoma bodies (pathognomonic).
Cellular Characteristics:
Cells with enlarged, oval nuclei
Ground glass chromatin pattern
Nuclear grooves and pseudo-inclusions
Overlapping nuclei
Eosinophilic cytoplasm
Nuclear membrane irregularities.
Architectural Patterns:
Papillary (classical)
Follicular (follicular variant)
Solid patterns
Mixed patterns common
Stromal sclerosis
Lymphocytic infiltration
Calcifications and psammoma bodies.
Grading Criteria:
No standard grading system
Variants classified by architectural pattern
Tall cell variant: cells twice as tall as wide
Columnar cell variant: pseudostratified columnar cells
Aggressive variants show increased mitoses.
Immunohistochemistry
Positive Markers:
TTF-1 (positive)
Thyroglobulin (positive)
PAX-8 (positive)
CK7 (positive)
CK19 (strongly positive)
HBME-1 (positive)
Galectin-3 (positive)
RET (in RET/PTC rearrangements).
Negative Markers:
Calcitonin (negative, helps exclude medullary carcinoma)
CEA (negative)
Chromogranin (negative)
Synaptophysin (negative)
These markers distinguish from medullary thyroid carcinoma.
Diagnostic Utility:
Essential for diagnosis confirmation
Essential for distinguishing from other thyroid neoplasms
TTF-1 and thyroglobulin confirm thyroid origin
CK19 and HBME-1 suggest malignancy
BRAF mutation testing guides prognosis and therapy.
Molecular Subtypes:
BRAF-mutated (50-60% classical PTC)
RET/PTC rearranged (10-20%, radiation-associated)
RAS-mutated (follicular variant)
Wild-type (no major driver mutation)
TERT promoter mutations (aggressive behavior).
Molecular/Genetic
Genetic Mutations:
BRAF V600E mutations (50-60% classical PTC)
RET/PTC rearrangements (10-20%)
RAS mutations (follicular variant)
TERT promoter mutations (aggressive cases)
PIK3CA mutations
TP53 mutations (poorly differentiated areas).
Molecular Markers:
BRAF V600E most common mutation
RET/PTC1 and RET/PTC3 rearrangements
RAS mutations (NRAS, HRAS, KRAS)
TERT promoter mutations indicate poor prognosis
Microsatellite instability (rare).
Prognostic Significance:
BRAF mutation associated with aggressive behavior
TERT promoter mutations predict poor prognosis
RET/PTC rearrangements better prognosis in young patients
RAS mutations intermediate prognosis
Tall cell variant more aggressive.
Therapeutic Targets:
BRAF inhibitors: dabrafenib, vemurafenib
MEK inhibitors: trametinib
RET inhibitors: selpercatinib, pralsetinib
Lenvatinib: multi-kinase inhibitor
Sorafenib: radioiodine-refractory disease
Immunotherapy: pembrolizumab (MSI-high tumors).
Differential Diagnosis
Similar Entities:
Follicular carcinoma (lacks nuclear features of PTC)
Medullary carcinoma (calcitonin positive, neuroendocrine markers)
Anaplastic carcinoma (poorly differentiated, aggressive)
Metastatic carcinoma (lung, breast, kidney)
Follicular adenoma (benign).
Distinguishing Features:
PTC: Characteristic nuclear features
PTC: Ground glass nuclei
PTC: Nuclear grooves
PTC: Psammoma bodies
Follicular: Lacks nuclear features
Follicular: Capsular/vascular invasion defines malignancy
Medullary: Calcitonin positive
Medullary: Neuroendocrine morphology
Anaplastic: Highly pleomorphic
Anaplastic: High mitotic rate.
Diagnostic Challenges:
Follicular variant of PTC vs follicular carcinoma
Nuclear features key for PTC diagnosis
Hyalinizing trabecular tumor vs PTC
Immunohistochemistry essential
Microcarcinoma vs atypical nodule
Size criteria important for clinical significance.
Rare Variants:
Warthin-like variant (oncocytic cells, lymphoid stroma)
Clear cell variant (clear cytoplasm)
Hobnail variant (micropapillary pattern)
Solid variant (solid growth pattern)
Diffuse sclerosing variant (extensive fibrosis).
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
[specimen type], measuring [size] cm in greatest dimension
Diagnosis
Papillary thyroid carcinoma, [variant]
Classification
WHO Classification: Papillary carcinoma, [variant type]
Histological Features
Shows [architectural pattern] with characteristic nuclear features including [nuclear features]
Size and Extent
Size: [X] cm ([microcarcinoma if <1cm]), extent: [intrathyroidal/extrathyroidal]
Capsular Invasion
Capsular invasion: [present/absent]
Vascular Invasion
Vascular invasion: [present/absent]
Lymph Node Status
Lymph nodes: [X] positive out of [X] examined
Special Studies
IHC: [TTF-1, thyroglobulin, CK19]: [results]
Molecular: [BRAF, RET/PTC]: [results]
[other studies]: [results]
TNM Staging
pT[X]N[X]M[X], Stage [I-IV]
Final Diagnosis
Final diagnosis: Papillary thyroid carcinoma, [variant], [size] cm