Thyroid pathology Flashcards
Macro appearance of Papillary thyroid cancer
solid, grey white tumour, firm, invasive with ill-defined margins (<10% surrounded by complete capsule)
Micro appearance of papillary thyroid cancer
Nuclear features are defining
- Nuclear enlargement and elongation
- Nuclear overlapping
- Irregular nuclear contours
- Intranuclear pseudo inclusions
- Longitudinal nuclear grooves
- Nuclear chromatin clearing
After formalin fixation nuclei may appear pale and clear, “Orphan Annie eyes”
List subtype variants of papillary thyroid carcinoma
- Classic
- Follicular variant
- Cribriform-morular variant
- Diffuse sclerosing variant
- Encapsulated variant
- Encapsulated follicular variant with invasion
- Infiltrative follicular variant
- Micro-carcinoma
- Tall cell variant
*Oncocytic - Hobnail
IHC papillary carcinoma
o TTF1+, thyroglobulin+, PAX8+, cytokeratin AE1/ AE3 +
o Tg +
o Cytokeratin: CK7+ and CK20-
o Calcitonin negative
o Variant specific:
▪ CDX2+ (columnar cell variant)
▪ Beta-catenin+ (cribriform morular variant)
Molecular genetics seen in Papillary thyroid carcinoma
o BRAF mutation (30-90%) (=poor prognosis) – most frequent mutation esp. tall cell and classic variants
o BRAF mutation is the most common type in PTC
o often V600E
o TERT promoter mutation (5-25%) (=poor prognosis)
o RET
o RAS
These lead to MAPK activation
Describe the difference between PTC and FTC in terms of what is needed for diagnosis.
What type of tissue sample is required because of this?
Papillary- cytology is sufficient for diagnosis so FNA suffices
Follicular- diagnosis of malignancy requires:
1. evidence of invasion through the tumour capsule (not thyroid capsule)
2. evidence of vascular invasion
so diagnosis usually requires at least a lobectomy
Why is multicentric disease often present with papillary thyroid cancer?
PTC is strongly lymphotrophic
multi centric disease can occur due to early lymphatic spread within thyroid
What is the hypothesis for where anaplastic cancers come from?
that they originated as less aggressive follicular neoplasms which have dedifferentiated
Which types of thyroid cancer arise from follicular cells?
PTC, FC, ATC
Features of diffuse sclerosing variant of papillary thyroid cancer
- locoregionally aggressive,
- high rate of nodal mets, locoregional recurrence, extra-thryoidal extension
- usually in younger patients,
- require aggressive surgical management including more
extensive node dissection - Diffuse involvement with sclerosis and solid nests of tumour cells
- background lymphocytic inflammation and psammoma bodies
Features of Cribiform-Morular variant of papillary thyroid cancer
- mixture of cribiform, follicular, papillary, trabecular and solid growth with round squamoid structures (morules)
- frequent vascular invasion
- characterised by APC/ beta-catenin mutations, a/w familial adenomatous
polyposis (FAP) - IHC: LEF-1 positive
Features of Tall cell variant
- abundant eosinophilic cytoplasm
- cells 2-3x as tall as they are wide;
- must account for greater than 30% of tumour
- aggressive, poor prognosis; - - higher prevalence of BRAF mutation; RAI refractory
Micro features of classic type papillary thryoid cancer
- Papillary architecture
- may have mixed in other architectures like follicles
- frequent PSAMMOMA bodies
- Occasional squamous metaplasia
- Often cystic degeneration
- Densely eosinophilic colloid
Features of Papillary microcarcinoma
- Tumour variant less than or equal to 1cm
- often missed macroscopically or incidental finding
- malignant but excellent prognosis
Features of encapsulated variant of papillary thyroid cancer
Totally surrounded by fibrous capsule (intact or focally infiltrated)
excellent prognosis
