Papillary thyroid carcinoma

Papillary thyroid carcinoma, abbreviated PTC, is the most common thyroid gland malignancy. It usually has an indolent course.

General

Medical school memory device P's:

• Palpable nodes.
• Popular (most common malignant neoplasm of the thyroid).
• Prognosis is good.
• Pre-Tx iodine scan.
• Post-Sx iodine scan.
• Psammoma bodies.

Notes:

• PTC is associated with radiation exposure.
• Papillary thyroid microcarcinoma is defined as a tumour with a maximal dimension of 1.0 cm or less.

Prognosis

Prognosis can be predicted by MAICS score. It which includes:

• Metastases.
• Age.
• Invasion of surround tissues.
• Ccompleteness of excision.
• Size of tumour.

Microscopic

Features:

• Nuclear changes - key feature.
  1. "Shrivelled nuclei"/"raisin" like nuclei, nuclei with a wavy ("textured", convoluted) nuclear membrane -- usu. easy to find.
  2. Nuclear pseudoinclusions -- usu. harder to find; have high specificity (nuclear pseudoinclusions appear as a result of the very convoluted nuclear membrane wrapping around parts of the cytoplasm; true nuclear inclusions in contrast are seen only in viral infections).
  3. Nuclear grooves, seen as a result of the highly "textured" nuclear membrane.
  4. Nuclear clearing (only on permanent section) - also known as "Orphan Annie eyes".
• Overlap of nuclei - "cells do not respect each other's borders" (easy to see at key feature at low power).
• Classically has papillae (nipple-like shape); papilla (definition): epithelium on fibrovascular core.
  • Absence of papillae does not exclude diagnosis.
• Psammoma bodies.
  • Circular, acellular, eosinophilic whorled bodies.
  • Not necessary to make diagnosis - but very specific in the context of a specimen labeled "thyroid".
  • Arise from infarction & calcification of papilla tips.

Notes:

• Psammoma bodies are awesome if you see 'em, i.e. useful for arriving at the diagnosis.
  • If there are no papillae structures -- you're unlikely to see psammoma bodies.
• At low power look for cellular areas/loss of follicles.
• Nuclear clearing seen in:
  • Hashimoto's and papillary thyroid carcinoma.
  • May be an artifact of fixation/processing.
• Nuclear overlapping is easy to see at lower power-- should be the tip-off to look at high power for nuclear features.
• Nuclear inclusions are quite rare and not required to make the diagnosis -- but a very convincing feature if seen.
• Papillae may be seen in Graves disease.

DDx:

• Lymphocytic thyroiditis:
  • Graves disease.
  • Hashimoto thyroiditis.
• Solid cell nest of thyroid.

Subtypes of papillary thyroid carcinoma

There are many.

Poor prognosis variants:

• Tall cell variant.
• Columnar cell variant.
• Solid variant.
• Diffuse sclerosing variant.

Papillary thyroid carcinoma tall cell variant

General

• ~10% of PTC.
• Often large > 6 cm.

Microscopic

Features:

• 50% of cells with height 2x the width.
  • There is some disagreement on these criteria; Raphael believes the height ought to be ~3x width, for 50% of the cells.
• Eosinophilic cytoplasm.
• Well-defined cell borders.
• Nucleus stratified; basal location, i.e. closer to the basement membrane.

Negative:

• Nuclei not pseudostratified, if pseudostratified consider columnar cell variant.

Images:

• PTC tall cell variant - intermed. mag. (WC).
• PTC tall cell variant - high mag. (WC).

Papillary thyroid carcinoma columnar cell variant

General

Epidemiology:

• Poor prognosis.
• Very rare.

Microscopic

Features:

• Elongated nuclei (similar to colorectal adenocarcinoma) - key feature.
• +/-Pseudostratification of the nuclei (like in colorectal adenocarcinoma), differentiates from tall cell variant.
• Nuclear stratification - key feature.
• "Minimal" papillary features.
• "Tall cells".
• Clear-eosinophilic cytoplasm.
• Mitoses common.

Image: Columnar variant PTC (wiley.com).

Papillary thyroid carcinoma follicular variant

General

• May be confused with follicular carcinoma or follicular adenoma.
• Pathologists often disagree about this diagnosis.

Microscopic

Features:

• Small tightly packed follicles - key feature.
• Hypereosinophilic colloid.
• Nuclear features of PTC.
  • Large nuclei.
  • Typically have less nuclear pseudoinclusions than the conventional type.
• +/-Fibrous capsule (common).

DDx:

• Follicular thyroid carcinoma - has a fibrous capsule and invasion though it.
• Follicular thyroid adenoma - surrounded by a fibrous capsule.
• Adenomatoid nodule - round nuclei, no nuclear features of PTC.

Images:

• PTC follicular variant (surgicalpathologyatlas.com).
• PTC follicular variant (surgicalpathologyatlas.com).
• PTC follicular variant (thyroidcancercanada.org).

Papillary thyroid carcinoma cribriform-morular variant

General

• Associated with familial adenomatous polyposis (FAP).

Microscopic

Features:

• Cribriform architectural pattern.
• Morules - balls of tissue.

Papillary thyroid carcinoma diffuse sclerosing variant

General

• Usually young adults, children.

Microscopic

Features:

• Papillae - usu. prominent.
• Squamous morules - key features.
• Lymphocytes - abundant.
• Fibrosis.

DDx:

• Lymphocytic thyroiditis (esp. Hashimoto's thyroiditis).

Papillary thyroid carcinoma warthin-like variant

• Resemble Warthin tumour.

Microscopic

Features:

• Eosinophilic cytoplasm.
• Lymphocytic thyroiditis.
• Papillae.

Papillary thyroid carcinoma solid variant

Features:

• Some studies suggest this has a poor prognosis.
• More common in children.
• Associated with Chernobyl nuclear accident.

Microscopic

Features:

• Solid sheets >50% of tumour mass.

Papillary thyroid carcinoma oncocytic variant

Features:

• Possible association with autoimmune thyroiditis.

Microscopic

Features:

• Abundant oncocytic tumour cells with apical nuclei.
• Classic features of PTC:
  • Grooves and and abundant pseudoinclusions.
• >70% papillary architecture.
• +/-Degenerative changes.

Note:

• CK19 +ve -- though not specific or sensitive.

IHC

Thyroid versus something else:

• Thyroglobulin +ve.
• TTF-1 (thyroid transcription factor-1) +ve.
• CD15 +ve.^{[citation needed]}

PTC versus benign:

• HBME-1 +ve (strong, diffuse).
• CK19 +ve (strong, diffuse).
• Galectin-3 +ve (strong, diffuse).

Molecular

• Currently not widely used in a diagnostic context.

Tabular summary

Molecular changes in papillary thyroid carcinoma as per Adeniran et al:

Molecular change	Frequency	Histology	Notes
BRAF point mutations	~ 40%	tall cell variant	poorer prognosis, older individuals
RET/PTC rearrangments	~ 20%	papillary architecture, psammoma bodies	younger individuals
RAS point mutations	~ 15%	exclusively follicular variant	-

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HEMITHYROID, RIGHT, COMPLETION OF TOTAL THYROIDECTOMY:
- PAPILLARY THYROID CARCINOMA, FOLLICULAR VARIANT.
-- TUMOUR SIZE: 4 MM (MAXIMAL).
-- ARCHITECTURE: FOLLICULAR.
-- CYTOMORPHOLOGY: CLASSICAL.
-- HISTOLOGIC GRADE: G1 (WELL DIFFERENTIATED).
-- NO TUMOUR CAPSULE IDENTIFIED.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
-- NEGATIVE FOR EXTRATHYROIDAL EXTENSION.
-- SURGICAL MARGINS NEGATIVE FOR MALIGNANCY.

Note:

• If it is a completion thyroidectomy and the staging changes one should do a full synoptic report.

Microcarcinoma

A. LEFT HEMITHYROID, THYROIDECTOMY COMPLETION:
- PAPILLARY THYROID MICROCARCINOMA.
-- MARGINS NEGATIVE FOR MALIGNANCY.
-- TUMOUR SIZE ~ 1 MM.
-- NEGATIVE FOR LYMPHOVASCULAR INVASION.
-- NEGATIVE FOR PERINEURAL INVASION.
- PALPATION THYROIDITIS, FOCAL.
- NODULAR HYPERPLASIA.

B. LYMPH NODES, LEVEL 6 AND 7, LYMPH NODE DISSECTION:
- TWO LYMPH NODES, NEGATIVE FOR MALIGNANCY ( 0 POSITIVE / 2 ).

See also

• Thyroid gland.