Papillary thyroid cancer

Sub-section: Thyroid Section: Endocrine

Definition

• Malignant epithelial tumour of thyroid follicular cells
• Differentiated thyroid cancer
• Identified by distinctive nuclear features

Incidence and Risk Factors

• Most common thyroid malignancy
  • 80% of Thyroid Ca
  • 14.9 per 100,000 incidence
  • Autopsy studies showed small PTCs in 30% of all
• 2.5 x female: male
• Peak incidence ages 30-50yrs
• Excellent prognosis
  • Particularly in young female patients

Pathogenesis

• Usually due to mutations in the mitogen-activated protein kinase pathway (MAPK) - this includes RET proto-oncogene (which encodes receptor tyrosine kinase), as well as RAS and BRAF.
• 60% BRAF mutations, 15% RAS mutations.

Risk factors

• Most important risk factor
  • Childhood radiation exposure
• Family history
  • Thyroid Ca in 1st degree relative
  • Familial syndromes that include Thyroid Ca
    • Cowden’s syndrome
    • Carney complex
    • Familial adenomatous polyposis

Clinical Presentation

• Most commonly
  • Palpable nodule or
  • Incidental nodule on imaging/exam
  • Occasionally get palpable lateral neck mass as first sign of Metastatic PTC
• Features concerning for malignancy are:
  • Rapid growth
  • Fixation to surrounding tissues
  • New onset hoarse voice/vocal cord paralysis
  • Ipsilateral cervical lymphadenopathy
  • Non-palpable nodules have the same risk of malignancy as palpable nodules of the same size
• Typically spreads via lymphatics
• Distant mets can occur (3-5%, most to lungs and bone)

Cytology

• Diagnosis of PTC can be made on individual cell morphology (can see this on FNA)
• FNA diagnosis of PTC has almost 100% correlation with diagnosis of PTC on final pathology

Histology

Overview

• Characteristic findings
  • Papillary architecture
    • Papillae consisting of one or two layers of tumor cells surrounding a well-defined fibrovascular core
  • Orphan-Annie nuclei
  • Nuclear grooves
  • Psammoma bodies
  • Stain positive for thyroglobulin

Orphan Annie Eye Nuclei

• Nuclei with uniform staining - appear empty due to inclusions (powdery chromatin) and marginal micronucleoli

Nuclear Grooves

• Present in other thyroid pathologies, but more seen in PTC

Psammoma Bodies

• Calcified clumps of cells caused by sloughed papillary projections
• Concentric circle (laminar) appearance

Immunohistochemistry

• Positive:
  • Cytokeratins
  • Thyroglobulin (Tg)
  • Thyroid Transcription Factor-1 (TTF-1)
• Negative:
  • Synaptophysin
  • Chromogranin

Other sites of Papillary Ca

• Lung
• Kidney
• Bladder

	Tg	TTF-1
Thyroid	+	+
Lung	-	+
Other sites	-	-

Subtypes of PTC

• Good prognosis
  • Classic PTC
    • Typically unencapsulated
  • Follicular variant (10%)
    • Follicular architecture but cytologically look papillary
    • Infiltrative
      • Biological behavior and molecular profile that is more similar to classic papillary thyroid cancer than follicular cancers
    • Encapsulated with invasion
      • Encapsulated with invasion have a worst prognosis - behave more like a follicular cancer with higher likelihood of distant metastasis and less likely to spread to nodes.
    • Encapsulated without invasion
      • Because of the very low malignant potential, this type was renamed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), emphasizing that this tumor can be managed as a neoplasm rather than a malignancy
• Prognosis not quite as good
  • Solid/Trabecular variant
    • Associated with RET-PTC3 Rearrangement mutation
    • High rates of extrathyroidal extension
  • Sclerosing variant
    • Prominent lymphocyte infiltrate
    • Can often me mistaken for Hashimoto’s Thyroiditis
• More aggressive forms (occur in older pts, <1% of PTCs)
  • Columnar variant
  • Insular hobnail variant
  • Tall cell variant

Prognosis

• Excellent
  • 10yr survival > 95% for favourable stages
• Poor prognostic factors
  • Age > 40 male or > 50 female
  • Male
  • Extrathyroidal extension/Capsular invasion/
  • Size > 4cm
  • Poorly differentiated
  • Regional or distant Mets
• Even pts with lung mets have 50% 10yr survival
  • Although brain mets median survival 1yr
• Impact of positive LNs depends on age
  • < 45yrs, presence of positive LNs has no effect on survival

  • 45yrs, presence of positive LNs increases the risk of death by 46%

Treatment

• See Differentiated thyroid cancer