Description
Thyroid carcinoma is a malignant neoplasm originating from the follicular or parafollicular cells of the thyroid gland. It encompasses a spectrum of tumours, from well-differentiated types (Papillary and Follicular Thyroid Carcinoma) to poorly differentiated (Anaplastic Thyroid Carcinoma) and medullary types. The clinical behaviour and management significantly vary between these types, making correct classification crucial.
Pathogenesis
Thyroid carcinomas arise due to a variety of genetic and environmental factors. For instance, radiation exposure, particularly during childhood, is a significant risk factor for Papillary Thyroid Carcinoma (PTC), which is characterised by the presence of BRAF and RET/PTC gene mutations. Follicular Thyroid Carcinoma (FTC) typically occurs in iodine-deficient areas and is associated with RAS and PAX8-PPARG gene mutations. Medullary Thyroid Carcinoma (MTC) is linked to RET proto-oncogene mutations, and Anaplastic Thyroid Carcinoma (ATC) often arises from a pre-existing well-differentiated tumour.
Subtypes
Thyroid carcinomas are categorised into four main types:
- Papillary Thyroid Carcinoma (PTC): It’s the most common subtype, accounting for ~80% of all thyroid cancers. It usually has an excellent prognosis.
- Follicular Thyroid Carcinoma (FTC): FTC makes up ~10-15% of all thyroid cancers and is more aggressive than PTC.
- Medullary Thyroid Carcinoma (MTC): MTC arises from the parafollicular C cells of the thyroid and constitutes ~3% of all thyroid cancers. It can be sporadic or familial.
- Anaplastic Thyroid Carcinoma (ATC): It’s the rarest (~1-2% of cases) and the most aggressive form of thyroid cancer with a very poor prognosis.
Epidemiology, Risk Factors & Associations
Thyroid carcinoma is the most common endocrine malignancy, accounting for over 90% of endocrine cancers. Its incidence has been increasing globally (0.5-10% per year).
- Predominantly affects women (female to male ratio: 3:1)
- Most commonly diagnosed between ages 25 and 65.
The different subtypes of thyroid carcinoma have varied risk factors and associations:
Papillary Thyroid Carcinoma
- Exposure to ionising radiation, especially head and neck radiation in childhood (Hodgkin lymphoma, brain tumours), is a significant risk factor.
- Certain genetic syndromes, such as Familial Adenomatous Polyposis (FAP) and PTEN Hamartoma Tumor Syndrome, increase the risk of PTC.
- Hashimoto’s thyroiditis is associated with a slightly increased risk of PTC.
- PTC can occur sporadically or in a familial setting, with a familial tendency seen in around 5-10% of cases.
Follicular Thyroid Carcinoma
- Iodine deficiency is a prominent risk factor, hence the higher incidence of FTC in areas where iodine deficiency is prevalent (Central and South America, Central and Eastern Europe, and Asia).
- There’s an association with Cowden syndrome, an autosomal dominant disorder characterised by multiple hamartomas.
Medullary Thyroid Carcinoma
- Approximately 25% of MTC cases are hereditary and occur as part of the Multiple Endocrine Neoplasia type 2 (MEN2) syndrome, which also includes pheochromocytoma and hyperparathyroidism.
- Sporadic MTC is typically unilateral and is associated with somatic RET mutations, whereas familial MTC (part of MEN2) is usually bilateral and associated with germline RET mutations.
Anaplastic Thyroid Carcinoma
- ATC is often associated with a history of goiter or well-differentiated thyroid carcinoma (either PTC or FTC), suggesting it might arise from these pre-existing conditions.
- Risk factors include older age and a history of radiation exposure.
Clinical Features
Thyroid carcinomas usually present as asymptomatic neck nodules discovered on physical examination or incidentally on imaging. Some patients may have neck pain, hoarseness, dysphagia, or lymphadenopathy. MTC is associated with elevated calcitonin levels, which can cause diarrhoea and flushing.
Complications
Metastasis is a severe complication, with FTC commonly metastasising hematogenously and PTC via lymphatics. ATC often invades local structures (trachea, oesophagus, and recurrent laryngeal nerves), causing compressive symptoms and frequently metastasises to the lungs and bones.
Pathological Features
Histopathology
- PTC: Characterised by papillary structures lined by tumour cells. Nuclei feature nuclear grooves and inclusions with cleared out appearance, characteristically termed “Orphan Annie Eyes”. Psammoma bodies are commonly seen (50% of cases).
- FTC: Shows follicular growth pattern without the nuclear features of PTC.
- MTC: Composed of sheets of cells that secrete calcitonin, amyloid deposits often seen.
- ATC: Highly anaplastic cells with necrosis and high mitotic activity.
Serology
- MTC: High serum calcitonin levels.
- Well-differentiated thyroid cancers: Usually normal thyroid function tests unless the tumour causes thyroiditis.
Genetics
- PTC: BRAF and RET/PTC gene mutations.
- FTC: RAS and PAX8-PPARG gene mutations.
- MTC: RET proto-oncogene mutations.
Radiological Features
General Features
- Usually present as a nodule within the thyroid gland.
- May be associated cervical lymphadenopathy or local invasion into surrounding structures, particularly in the case of ATC.
US
- PTC: Hypoechoic nodule with microcalcifications, irregular margins, taller-than-wide shape, and central vascularity.
- FTC: Isoechoic or hypoechoic nodule, often with a thick, irregular halo.
- MTC: Hypoechoic with a pseudocapsule and punctate calcifications.
- ATC: Large, necrotic, poorly-defined mass often with invasion into surrounding structures.
CT
- PTC: Marked nodal enhancement.
NM
Radioactive iodine scanning is useful for identifying functional (“hot”) and non-functional (“cold”) nodules, the latter being more likely to be malignant. MTC and ATC do not concentrate iodine.
XR
Chest X-ray can identify lung metastases or a tracheal deviation due to mass effect.
MRI
MRI provides superior soft tissue contrast and can be used for evaluating local invasion or distant metastases.
Grading and Staging
The tumour staging for thyroid carcinoma is determined by the TNM classification (Tumour, Node, Metastasis). The grading of thyroid cancer isn’t routinely performed, except for poorly differentiated or anaplastic types.
Diagnosis
The diagnosis of thyroid carcinoma relies on the integration of clinical, radiological, and pathological data. Fine-needle aspiration biopsy (FNAB) of thyroid nodules is the primary diagnostic modality, allowing for cytological examination and genetic testing when indicated.
Differential Diagnosis
- Benign thyroid nodules: Most thyroid nodules are benign and include colloid nodules and follicular adenomas.
- Thyroiditis: Inflammatory conditions of the thyroid, such as Hashimoto’s thyroiditis or De Quervain’s thyroiditis, can mimic thyroid carcinoma.
- Lymphoma: Primary thyroid lymphoma is a rare malignancy that can present as a rapidly enlarging thyroid mass.
- Parathyroid tumours: Overlying or adjacent parathyroid tumours can mimic thyroid nodules on imaging.
Management
Management of thyroid carcinoma depends on the subtype and stage. It typically involves surgery (total or subtotal thyroidectomy) followed by radioactive iodine therapy in differentiated tumours. TSH suppression therapy with levothyroxine is commonly used. Targeted therapies (tyrosine kinase inhibitors) and chemotherapy are reserved for advanced or refractory cases. Patients should be referred to an endocrinologist for further management. In the case of suspected MTC, genetic counselling and testing for RET mutations should be considered.