Etiology
- Genetic factors
- Medullary carcinoma: associated with MEN2 (RET gene mutations) or familial medullary carcinoma
- Papillary carcinoma: associated with RET/PTC rearrangements and BRAF mutations
- Follicular carcinoma: associated with PAX8-PPAR-γ rearrangement and RAS mutation
- Undifferentiated/anaplastic carcinoma: associated with TP53 mutation
- Ionizing radiation (particularly during childhood): mostly associated with papillary carcinoma
Overview
Papillary thyroid carcinoma
- Tissue of origin: Thyrocytes
- Well differentiated
- Characteristics
- Most common type of thyroid cancer
- Palpable lymph nodes due to metastatic spread (often detected before primary tumor)
- May be multifocal
- Very good prognosis
- Pathology
- Psammoma bodies
- Morphology: concentric lamellar calcifications
- Occurrence: seen in diseases associated with calcific degeneration
- Papillary thyroid carcinomas (evidence of psammoma bodies in thyroid tissue should always raise suspicion of malignancy)
- Serous papillary cystadenocarcinoma of ovary and endometrium
- Meningiomas
- Mesotheliomas
- “Orphan Annie” eyes nuclei
- Morphology: empty-appearing large oval nuclei with central clearing
- Occurrence
- Papillary thyroid carcinomas
- Autoimmune thyroiditis (e.g., Hashimoto disease, Grave disease)
- Morphology: empty-appearing large oval nuclei with central clearing
- Psammoma bodies
Mnemonic
Papi and Moma adopted Orphan Annie.
Follicular thyroid carcinoma
- Well differentiated
- Characteristics
- Hematogenous metastasis especially to
- Lungs
- Bone (lytic lesions)
- Rarely multifocal
- Vascular and capsular invasion
- Good prognosis
- Hematogenous metastasis especially to
Medullary carcinoma
- Tissue of origin: Parafollicular cells (C cells)
- The parafollicular cells are located in the connective tissue between the thyroid follicles, which can be considered a “medullary” (central) part of the thyroid gland, although not in the same sense as the medulla in other organs like the adrenal glands.
- Poorly differentiated
- Characteristics
- Sometimes a genetic predisposition → multiple endocrine neoplasia type 2 (MEN2) (25% of medullary carcinomas)
- Sporadic (75% of medullary carcinomas)
- Produces calcitonin
- Pathology
- Ovoid cells of C cell origin and therefore without follicle development
- Amyloid in the stroma (stains with Congo red)
- These amyloid deposits are derived from calcitonin secreted by the neoplastic C cells