Neoplasms of the thyroid: classification, pathomorphology
The thyroid can have various benign or malignant neoplasia, as well as non-neoplastic nodules. Here we will consider the most important neoplasia of the thyroid.
Adenomas
Benign neoplasms derived from follicular epithelium, these are generally solitary. The vast majority are non-functioning (don’t produce hormones) but some can cause thyrotoxicosis.
Most functioning adenomas are caused by an activating mutation in the TSH receptor signalling pathway, which causes an overactivation of the thyroid follicles.
Typically, adenomas are solitary, spherical and compress the adjacent non-neoplastic thyroid. They sit in a well-defined capsule, which helps differentiate it from multinodular goiters. On microscopic examination the cells are in uniform structure.
Clinical features of functioning adenomas are that of thyrotoxicosis (see above) and hyperthyroidism.
Carcinomas
Carcinomas are relatively uncommon. Most thyroid carcinomas are derived from thyroid follicular epithelium, there are four major subtypes:
- Papillary carcinoma (85% of cases)
- Follicular carcinoma
- Anaplastic (undifferentiated) carcinoma
- Medullary carcinoma
Genetic and environmental factors are implicated in the pathogenesis of these carcinomas:
- Papillary thyroid carcinomas - activation of MAP kinase pathway is a major feature
- Follicular thyroid carcinoma - mutations in PI-3K/AKT signalling pathway
- Anaplastic carcinoma - dedifferentiation of well-differentiated papillary/follicular carcinoma
- Medullary thyroid carcinoma - arise from parafollicular C cells, associated with RET proto-oncogene mutation
Some brief details about each major carcinoma type:
- Papillary carcinoma
- Manifest as solitary or multifocal lesions in thyroid
- May be well circumscribed and encapsulated
- Diagnosis based on observation of nuclear features with finely dispersed chromatin (known as ground glass or ‘Orphan Annie eye’ nuclei)
- Follicular carcinoma
- Mostly uniform cells forming small follicles, similar to normal tissue
- May be widely invasive or minimally invasive
- Anaplastic carcinoma
- Almost 100% mortality
- Fast growing bulky masses that are highly invasive
- Contain large pleomorphic giant cells and/or spindle cells
- Medullary carcinoma
- Derived from neuroendocrine parafollicular cells
- Multicentricity is common
- Larger lesions often with hemorrhage and or necrosis
- Amyloid deposits may also be observed
H&E, papillary carcinoma: crowded, overlapping, enlarged nuclei with pale, finely dispersed chromatin ('Orphan Annie eye') and nuclear grooves; the diagnosis rests on these nuclei.
Image: “Thyroid papillary carcinoma histopathology (2)” by unknown author, CC BY-SA 3.0, via Wikimedia Commons.
Remember: how each carcinoma is recognised and spreads:
- Papillary: diagnosed by the nuclei (Orphan Annie, grooves, pseudo-inclusions), often psammoma bodies; spreads by lymphatics to neck nodes
- Follicular: diagnosed only by capsular or vascular invasion; spreads by blood to bone and lungs