Papillary and Follicular Carcinomas (DCTs)

Differentiated thyroid cancer (DTC) refers to papillary and follicular variants

Aetiology

• Can affect any age group - childhood to elderly

• In females, rates increase from 15-40 then plateaus

• In males rates steadily increase with age

• Not associated with diet, other proven malignancies, family history, smoking or other lifestyle factors

• Other than clusters associated with nuclear incidence, the overall incidence is constant at present

Papillary carcinoma

• Derived from follicular epithelium

• Associated with Hashimotos

• Associated with ionising radiation

• Activation of MAP kinase pathway

• Rearrangements of RET or NTKR1

• Activating point mutation in BRAF

• Mutation of ras

Follicular carcinoma

• Derived from follicular epithelium

• Higher incidence in females

• Higher incidence at 40-50 years

• Incidence slightly higher in regions of iodine deficiency

• Mutations in PI3K/AKT pathway

• Mutations in ras family

• Translocation involving Pax8 and PPAR𝛾1

Pathophysiology

• 'Differentiated' refers to histological appearance but also to physiological characteristics
• Means good prognosis compared to other solid tumours

• Most take up iodine and secrete thyroglobulin

• DTC are TSH driven

Histology

• Can be multifocal

• Often cystic

• May be calcified - psammoma bodies

• Diagnosis depends on invasion of the capsule or vascular invasion

• Classed as minimally invasive or widely invasive
• Widely invasive: more solid architecture, less follicular architecture, more mitotic activity
• Minimally invasive: (most common) follicular architecture (well differentiated), may have part surrounding capsule, difficult to distinguish from adenoma

Spread of disease

• Papillary carcinomas tend to spread via lymphatics e.g. cervical lymph node metastases

• Haematogenous spread is uncommon but if occurs spread is usually to the lung, bone, liver and brain

• Rarely lymphatic spread, propensity for haematogenous spread (bones, lungs, liver)

• Uncommon to have multicentric disease

Clinical presentation

• Majority present with palpable nodules

• Small percentage are chance findings on histological section of thyroidectomy tissue

• Approx. 5% present with local or disseminated metastases
• Local effects e.g. hoarseness, dysphagia, cough suggest advanced disease

Investigations

• TSH, US

• Confirmation: usually US-FNA, can involve excisional biopsy of lymph node

• No role for isotope thyroid scan (in diagnosis), CT or MRI

• Pre-operative laryngyoscopy if vocal cord palsy suspected clinically

Management

Surgery

• Age <50 years, tumour <4 cm

• Thyroid lobectomy + biopsy, thyroidectomy following biopsy results if needed

• Stage Thy3 or higher on FNA (atypical)

• Subtotal/total thyroidectomy

• Consider radioactive iodine

Whole body iodine scanning (I-131)

• Used in patients who have undergone sub-total or total thyroidectomy

• Usually performed 3-6 months post-op

• Used to determine incomplete incision or present of occult metastases, and therefore inform need for further investigation/treatment

RAI ablation

• Ablate residual thyroid tissue in order to destroy occult microfoci

• Remove residual thyroid tissue which may be a source of Tg and therefore confound the levels during follow-up

• Permit predictively useful scanning in whole body scans and subsequent high dose therapy if required

• Small but significant incidence of acute myeloid leukaemia, no convincing evidence of increase in incidence of other solid tumours

Followup

• In both the low and high risk groups, measure TSH and Tg every 6 months for first 5 years, then annually for next 5 years
• Consider discharge after 5 years if low risk

• To minimise risk of recurrence patients are treated with suppressive doses of levothroxane (sufficient to suppress TSH below the normal range)

• For low risk group, TSH should be kept in lower range of normal (0.4-4 mU/L), whereas in the high risk group TSH should be kept <0.1 mU/L and fT4 below 25

• Thyroglobulin (Tg) is the protein precursor of T4/T3, made by thyroid follicular epithelial cell - can be used as 'tumour marker'

Management of recurrent disease

• Can be detected clinically, by rising Tg, or by imaging

• Recurrence in cervical lymph nodes is more common in papillary cancer

• Haematogenous spread to lungs, bone or brain more common in follicular lesions

• Usually patients undergo whole body scan to determine ability to take up iodine with a view to RAI

• Difficult group are those with rising Tg but negative whole body iodine scan - management options include PET scan to allow targeted treatment, and systemic anti-cancer therapy e.g. sorafenib and levatinib