- Clinical science
The majority of thyroid cancers are well-differentiated carcinomas. The principal risk factors are exposure to ionizing radiation and genetic predisposition; thyroid cancers also disproportionately affect women. A distinction is made between well-differentiated thyroid carcinomas (papillary or follicular carcinoma) and poorly differentiated carcinomas (medullary or anaplastic carcinoma); the two groups vary considerably with regard to treatment options, metastatic pathways, and prognosis. Papillary thyroid carcinomas are the most common type of thyroid cancer. Early detection is crucial for improving the prognosis but challenging because symptoms often appear late in the course of the disease. Imaging plays a central role in detection: nodules that appear hypoechoic on ultrasound and cold on scintigraphy should raise suspicion of malignancy. Additional testing is needed to determine the type of thyroid cancer, including measuring hormone levels, tumor markers, and/or biopsy via fine-needle aspiration. Most thyroid cancers are treated surgically (hemithyroidectomy or thyroidectomy), followed by thyroid hormone therapy to replace physiological hormone production and to limit the growth stimulus for any remaining metastases. Further therapeutic measures depend on the type of thyroid cancer involved and include radioiodine therapy and possibly chemotherapy.
- 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
|Tissue of origin||Carcinoma||Differentiation||Characteristics||Distribution||Peak incidence|
|Thyrocytes||Papillary thyroid carcinoma|| |
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|Parafollicular cells (C cells)|| || |
Remember that Papillary carcinoma is the most Prevalent type of thyroid cancer, that it features Palpable lymph nodes, and that it has the best Prognosis compared to all other types of thyroid cancer.
Hurthle cell carcinoma
- 3–10% of all well-differentiated thyroid cancers
- Often classified as subtype of follicular carcinoma
- Thyroid histopathology: hypercellularity with a predominance of Hurthle cells (large, polygonal epithelial cell with eosinophilic granular cytoplasm as a result of numerous altered mitochondria)
- B-cell lymphoma: usually develops from Hashimoto thyroiditis
- Sarcoma: rare
- Metastatic (e.g., breast, renal, melanoma): rare
- Often asymptomatic
- Firm, painless thyroid nodules may be palpated.
- Late stages: 
Thyroid function tests:
- Basal TSH
- fT3 and fT4
- Thyroglobulin (Tg): should be measured as a follow‑up to thyroidectomy in follicular or papillary thyroid carcinoma
- For supporting diagnosis of medullary thyroid carcinoma and follow‑up
- Patients with medullary thyroid carcinoma often also have elevated levels of carcinoembryonic antigen (CEA) and chromogranin A (which serve to support diagnosis in unclear cases).
- Hypoechoic thyroid lesions with irregular margins > 1 cm are potentially malignant although normal echogenicity does not rule out carcinoma!
- Malignancies often show microcalcifications; (typical for papillary thyroid carcinomas)
- Findings: decreased tracer uptake suggests a malignant non-functioning (cold) nodule.
Nodules that appear hypoechoic on ultrasound and cold in scintigraphy are highly suspicious for malignancy!
Indicated if malignancy is suspected based on ultrasound or scintigraphy
- If biopsy results are unclear or in any way suspicious, surgery is usually recommended.
- Chest x-ray
- Abdominal ultrasound
- Neck CT/MRT
- Bone scintigraphy or PET for detecting metastases
- Family screening
Psammoma bodies 
- Morphology: concentric lamellar calcifications
- Occurrence: seen in diseases associated with calcific degeneration
“Orphan Annie” eyes nuclei
- Morphology: empty-appearing large oval nuclei with central clearing
Nuclear grooves 
- Morphology: longitudinal invaginations of nuclear bilayer
- Occurrence: papillary thyroid carcinomas
- Uniform follicles
- Vascular and/or capsular invasion
- Ovoid cells of C cell origin and therefore without follicle development
- Amyloid in the stroma (stains with Congo red)
- Surgical management: primary treatment of choice (see )
- : often conducted 4–6 weeks after surgery to destroy remaining thyroid tissue or metastases
- Thyroid hormone therapy with L-thyroxine after thyroidectomy
- Total thyroidectomy with adjuvant radiochemotherapy if operable
- Radiochemotherapy if locally advanced, inoperable
- Accidental removal of parathyroid glands → hypocalcemia 
Transection of superior and recurrent laryngeal nerve → dysphonia (hoarseness), dysphagia
- May occur during ligation of the superior laryngeal artery and inferior thyroid artery due to the proximity of the nerves to the arteries.
- If only the external branch of the superior laryngeal nerve is damaged, complete loss of voice is unlikely, but a loss of vocal range may occur (with potentially career-damaging consequences for occupational voice users, e.g., singers).
- Physical examination
- Biochemical tests
- Neck ultrasound
- Further imaging, if a relapse is suspected