High-Risk Thyroid Cancer Histological Subtypes
The high-risk histological subtypes of thyroid cancer include the tall cell, columnar, hobnail, and solid variants of papillary thyroid carcinoma, poorly differentiated carcinomas, widely invasive follicular thyroid carcinoma, and Hürthle cell carcinoma with extensive vascular/capsular invasion. 1
Aggressive Papillary Thyroid Carcinoma Variants
The following PTC variants are particularly aggressive and consistently associated with higher tumor stages and lymph node metastases at diagnosis:
Tall cell variant: This is the most common aggressive variant of PTC, though controversy exists regarding whether the aggressive behavior stems from the histologic subtype itself or associated clinicopathologic features 1, 2
Columnar variant: Particularly aggressive in older patients with larger tumors showing diffusely infiltrative growth patterns and extrathyroidal extension 2
Hobnail variant: A moderately differentiated PTC variant with aggressive clinical behavior, significant mortality, and strong propensity for disease progression 1, 3, 2. This variant shows loss of cellular polarity and cohesiveness, suggesting epithelial-mesenchymal transition as a mechanism of metastasis 3
Solid variant: Designated when all or nearly all of the tumor has a solid, trabecular, or nested appearance while maintaining nuclear features of PTC 1, 2
Poorly Differentiated Carcinomas
These tumors behave aggressively while maintaining some degree of functional differentiation (e.g., thyroglobulin production) and are defined by the Turin proposal criteria as invasive tumors with solid/trabecular/insular growth pattern plus at least one of the following 1:
- Mitotic index ≥3 per 10 high-power fields
- Necrosis
- Convoluted nuclei (smaller and darker than typical PTC nuclei with irregular contours)
Follicular Thyroid Carcinoma Subtypes
Widely invasive FTC: Reserved for follicular cancers with neoplastic emboli involving ≥4 blood vessels, conferring high-risk status 1
Angioinvasive FTC: Involves <4 blood vessels but still represents higher risk than minimally invasive disease 1
Hürthle Cell Carcinoma
Hürthle cell carcinoma with extensive vascular and/or capsular invasion should be managed as high-risk carcinoma, with recurrence risk of 30-55% 1, 4, 5. Pure Hürthle cell carcinomas (>75% Hürthle cell component) have distinct molecular abnormalities from conventional follicular carcinomas 1
Critical Pitfalls to Avoid
Do not confuse minimally invasive FTC with widely invasive disease: Only widely invasive FTC (≥4 vessels involved) qualifies as high-risk histology 1
Do not overlook the hobnail variant: This recently recognized variant in the WHO classification has significant mortality and requires aggressive management 3, 2, 6
Do not assume all oncocytic variants are aggressive: Oncocytic PTCs and oncocytic variants of poorly differentiated carcinomas are no more aggressive than their conventional counterparts 1
Distinguish from NIFTP: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features has <1% recurrence risk and should not be managed as high-risk disease 1