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Thyroid Cancer

NICE guideline [NG230] Thyroid cancer: assessment and management. Published: Dec 2022.

NICE guideline [NG145] Thyroid disease: assessment and management. Last updated: Oct 2023.

Overview of Thyroid Cancer

Shared Clinical Features

  • Painless lump in the neck – often the first and only symptom
    • Slow progressive enlargement
    • Lump moves on swallowing but NOT on tongue protrusion
  • Mass effect (if the lump is large)
    • On oesophagus → dysphagia
    • On trachea → dyspnoea
    • Non-specific neck fullness / discomfort
  • Dysphonia (if the tumour invades / compresses the recurrent laryngeal nerve)

Importantly, most thyroid cancers do NOT cause hyper- or hypothyroid symptoms; TFTs are often normal. This key feature differentiates thyroid cancer from other causes of thyroid mass (e.g. Graves’ disease, toxic adenoma, toxic multinodular goitre)

Type-Specific Features

[Ref]

Type Histology Characteristics Distribution
Papillary thyroid carcinoma Tissue of origin: thyrocytes

Well differentiated – ground-glass nuclei with psammoma bodies

  • Lymphatic spread +++ (often detectable before the primary tumour)
  • Very good prognosis
Most common type of thyroid cancer (~80% cases)
Follicular thyroid carcinoma Tissue of origin: thyrocytes

Well differentiated – many colloid-filled follicles, resembling normal thyroid tissue

  • Haematogenous spread +++ (esp. to the lungs and bone – lytic lesions)
  • Good prognosis
  • ~10% cases
Medullary thyroid carcinoma Tissue of origin: C cells (parafollicular cells)

Poorly differentiated –polygonalspindle-shaped cells associated with amyloid deposits

~30% associated with MEN2 syndrome, the rest is sporadic

Secretes calcitonin, which can cause a carcinoid syndrome-like presentation:

  • Diarrhoea
  • Cutaneous flushing
  • ~5% cases
Anaplastic thyroid carcinoma Tissue of origin: thyrocytes

Poorly differentiated – pleomorphic giant cells

  • Rapid local growth
  • Compression of neck structures +++ (e.g. dyspnoea, dysphagia)
  • Very poor prognosis
  • ~1-2%
Thyroid lymphoma Most common: large atypical B cells (diffuse large B-cell lymphoma)

2nd most common: lymphoepithelial lesions (MALT lymphoma)

  • Strong association with Hashimoto’s thyroiditis
  • Rapidly enlarging thyroid mass (often mistaken for anaplastic thyroid carcinoma)
  • Rare

Investigation and Diagnosis

1st line: ultrasound neck – malignancy-suggesting features

  • If ultrasound is abnormal → perform ultrasound-guided final needle aspiration for cytology
  • Further testing (if needed) → core needle biopsy

Tumour markers (NICE does not recommend routine measuring for diagnosis, but it’s important to learn for exams):

  • Medullary thyroid carcinoma: calcitonin
  • Other types of cancer (papillary, follicular, etc): thyroglobulin

Management

Definitive Management

Key management principles:

  • Surgical management (total thyroidectomy or hemithyroidectomy) is the standard of care for most patients with thyroid cancer
  • Radioactive iodine is primarily used as an adjunctive treatment following surgical intervention in, rather than as an isolated therapy (unlike in Graves disease where radioactive iodine is a well-established primary treatment)
  • Active surveillance is only reserved for those with solitary microcarcinoma

There are 3 main scenarios:

Recommended management Indications
Surgery is optional:
  • Active surveillance, or
  • Hemithyroidectomy
  • Solitary microcarcinoma (≤1cm) (T1a) with no node disease and no metastasis
Surgery needed:
  • Hemithyroidectomy, or
  • Total thyroidectomy
  • Multifocal disease, or
  • Thyroid tumour >1cm with no node disease and no metastasis (T2N0M0)
Total thyroidectomy
  • T3 tumour (>4cm limited to the thyroid +/ strap muscles invasion)
  • T4 tumour (invasion beyond the strap muscles – e.g. subcutaneous soft tissue, larynx, prevertebral fascia, mediastinal vessels)
  • Regional lymph node involvement
  • Distant metastatic disease
  • Adverse pathological features
Compartment-oriented central / lateral neck dissection
  • Structural nodal disease in the lateral and/or central neck

Post-Operative Supplementation

Levothyroxine (life-long) is standardly offered after total thyroidectomy for thyroid cancer to maintain euthyroid status

  • If the patient underwent hemithyroidectomy, levothyroxine is only offered if the patient develops hypothyroidism

Calcium and vitamin D supplementation is recommended post-thyroidectomy to prevent transient hypocalcaemia due to parathyroid manipulation / injury

  • Long-term supplementation is only offered if there are persistent hypoparathyroidism

Adjunct Management

As a blunt rule, the following is generally offered to those needing a total thyroidectomy (refer to 3rd row in the table above):

Thyrotropin alfa (recombinant human TSH) To be given before radioactive iodine to maximise radioactive iodine uptake
Radioactive iodine To be given after thyroidectomy to ablate residual thyroid tissue
TSH suppression with levothyroxine To be given to reduce risk of recurrence (to limit TSH-driven stimulation of residual or metastatic differentiated thyroid cancer cells)
  • Not routinely indicated, only in high-risk differentiated thyroid cancer
  • Supraphysiological doses of levothyroxine is given to achieve TSH <0.1 mIU/L

Consider external beam radiotherapy if there is macroscopic disease after surgery or local disease that is unlikely to be controlled with radioactive iodine

Post-Thyroidectomy Monitoring

NICE recommends measuring:

  • Thyroglobulin (detectable thyroglobulin levels suggest residual thyroid tissue or residual or recurrent cancer), and
  • Thyroglobulin antibodies (the presence of thyroglobulin antibodies would affect the measurement of thyroglobulin levels)
  • Neck ultrasound

Other commonly measured parameters in practice:

  • TFTs are also routinely monitored in practice to detect the development of hypothyroidism and to titrate levothyroxine dose (for those who are on it)
  • Calcium level to detect hypoparathyroidism.

References

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