Thyroid Cancer: Assessment and Management

Introduction

Thyroid cancer is the most common endocrine malignancy, and its clinical behaviour varies enormously depending on histological subtype - from indolent papillary carcinoma with an excellent long-term prognosis, to anaplastic carcinoma, one of the most aggressive solid tumours in oncology.¹ Most cases present as an otherwise asymptomatic thyroid nodule, so a structured approach to nodule assessment is central to this topic.

Understanding the four main histological subtypes - papillary, follicular, medullary and anaplastic - explains why investigation, treatment and prognosis differ so markedly between patients who may present with an apparently similar lump in the neck.

Classification and pathophysiology

Papillary and follicular carcinoma are together termed differentiated thyroid cancer, since the tumour cells retain enough normal thyroid function to take up iodine and produce thyroglobulin - properties directly exploited in treatment and follow-up. Medullary carcinoma arises from the parafollicular (C) cells, which are not derived from the same cell line and do not take up iodine, instead secreting calcitonin, a useful tumour marker.^1,2

Anaplastic carcinoma is thought to arise, in some cases, from dedifferentiation of a pre-existing papillary or follicular cancer, explaining its tendency to occur in older patients with a long-standing goitre. Thyroid lymphoma is a rare, distinct entity strongly associated with pre-existing Hashimoto's thyroiditis.

Risk factors

• Female sex (thyroid cancer is roughly 3 times more common in women)
• History of head/neck radiation exposure, particularly in childhood
• Family history of thyroid cancer, or a known MEN2 mutation (for medullary cancer)
• Hashimoto's thyroiditis (associated with thyroid lymphoma)
• Iodine deficiency (associated with follicular cancer)
• Pre-existing longstanding multinodular goitre (a recognised, though uncommon, precursor to anaplastic transformation)

Clinical features

Most thyroid cancers present as a painless thyroid nodule or neck lump, often noticed incidentally by the patient or found on examination or imaging performed for another reason.¹ The majority of thyroid nodules overall are benign, which is precisely why a structured risk-stratification approach to assessment matters.

Features that increase concern for malignancy include rapid growth, a hard, irregular or fixed nodule, hoarseness (suggesting recurrent laryngeal nerve invasion), dysphagia, associated cervical lymphadenopathy, and stridor in advanced disease. Age under 20 or over 60, male sex, and a history of neck irradiation also raise suspicion.^1,2

Examination

Palpate the thyroid for size, consistency, mobility and any discrete nodule, and assess whether the mass moves on swallowing (a thyroid mass characteristically does) and whether it moves on tongue protrusion (a thyroglossal cyst does, a thyroid nodule does not). Examine the neck systematically for cervical lymphadenopathy and assess the voice, since hoarseness raises specific concern.¹

Investigations

Thyroid function tests are checked first; the great majority of thyroid cancers are found in euthyroid patients, since a hyperfunctioning ("hot") nodule is very rarely malignant.¹ Ultrasound of the neck is the primary imaging investigation, characterising nodule features (the British Thyroid Association U1-U5 classification) to estimate malignancy risk and to identify nodules warranting biopsy.

Ultrasound-guided fine needle aspiration cytology (FNAC) is the key diagnostic test, reported using the Thy classification:

Laryngoscopy to assess vocal cord function is performed before surgery, particularly if hoarseness is present, to document baseline recurrent laryngeal nerve function. Serum calcitonin and genetic testing for RET mutations are checked when medullary thyroid cancer is suspected or confirmed, given the strong association with MEN2 and the implications for family screening. CT or further staging imaging is reserved for locally advanced or suspected metastatic disease.

Management

Surgery is the primary treatment for essentially all thyroid cancers where feasible. A hemithyroidectomy is sufficient for small, low-risk, unifocal papillary or follicular cancer, while total thyroidectomy is used for larger tumours, bilateral or multifocal disease, higher-risk histology, or where nodal or distant metastases are present. Central and/or lateral neck dissection is added when there is nodal involvement.^1,2

For differentiated (papillary/follicular) thyroid cancer, radioactive iodine ablation is often given after total thyroidectomy to destroy any remaining normal thyroid tissue and microscopic residual disease, exploiting the fact that these cells still take up iodine. Patients are then maintained on TSH-suppressive doses of levothyroxine, since TSH can stimulate growth of any residual differentiated cancer cells, and serum thyroglobulin is monitored as a sensitive tumour marker - a rising level after apparently complete treatment suggests recurrence.

Medullary thyroid cancer does not take up iodine, so radioactive iodine has no role; management is surgical, with calcitonin used as the tumour marker for follow-up, and genetic counselling and family screening for RET mutations where a hereditary (MEN2) cause is identified or suspected. Anaplastic thyroid cancer is often unresectable at presentation because of rapid local invasion; management is largely palliative, focused on airway protection (sometimes requiring tracheostomy), external beam radiotherapy for local control, and best supportive care.

Complications

Complications relate mainly to thyroid surgery itself, given its proximity to the recurrent laryngeal nerves and parathyroid glands:¹

• Recurrent laryngeal nerve injury: causing voice change (unilateral) or, rarely, airway compromise (bilateral)
• Hypoparathyroidism: from inadvertent removal or devascularisation of the parathyroid glands, causing hypocalcaemia that may be transient or permanent
• Hypothyroidism: an expected consequence of total thyroidectomy, requiring lifelong levothyroxine replacement
• Post-operative neck haematoma: an early and potentially catastrophic complication (see red flags below)
• Local recurrence or nodal/distant metastasis, particularly with higher-risk histology or incomplete initial treatment

Red flags

Prognosis

Papillary and follicular (differentiated) thyroid cancer has an excellent prognosis overall, with 10-year survival exceeding 90% even in the presence of nodal metastases, particularly in younger patients. Medullary thyroid cancer has a more variable prognosis, dependent on stage at diagnosis and whether it is sporadic or hereditary.^1,2

Anaplastic thyroid cancer carries a very poor prognosis, with median survival typically measured in months from diagnosis, reflecting its rapid growth and tendency to present with locally advanced, unresectable disease. This stark contrast in outcomes across subtypes is the reason histological diagnosis, rather than the presence of a lump alone, drives every subsequent management decision.