Thyroid Pathology
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Direct answer
Graves disease is autoimmune hyperthyroidism driven by stimulating antibody against the thyrotropin receptor — diffuse hyperplasia with scalloped colloid and papillary infoldings, plus orbitopathy and pretibial myxoedema — while Hashimoto thyroiditis is destructive autoimmune hypothyroidism with anti-thyroid peroxidase antibody, Hürthle cell change and lymphoid follicles with germinal centres. De Quervain subacute thyroiditis is the painful, post-viral, self-limiting granulomatous form, and endemic iodine-deficiency goitre remains the world's commonest thyroid disease. The four carcinomas behave in fixed, examinable ways: papillary, the most common, with orphan Annie nuclei and psammoma bodies, spreads lymphatically and carries the best prognosis; follicular spreads by blood; medullary arises from C cells with calcitonin and amyloid; anaplastic kills rapidly in the elderly.
What you must remember
- Goitre: iodine deficiency drives colloid goitre — the sub-Himalayan Indian goitre belt being the classic endemic zone — progressing to multinodular goitre, which may become toxic; iodised salt under the National Iodine Deficiency Disorders Control Programme is the countermeasure.
- Graves disease: thyroid-stimulating immunoglobulins; histology of tall hyperplastic epithelium, papillary infoldings and scalloped colloid; extrathyroidal features — orbitopathy, pretibial myxoedema, thyroid acropachy — which do not resolve with thyroid control.
- Hashimoto: anti-TPO and anti-thyroglobulin; dense lymphoplasmacytic infiltrate with germinal centres, oxyphilic Hürthle cell change; the commonest cause of hypothyroidism in iodine-replete regions; small increased risk of lymphoma.
- De Quervain (subacute granulomatous) thyroiditis: painful tender goitre after viral illness, giant-cell granulomas, high erythrocyte sedimentation rate, self-limiting course through a transient thyrotoxic then hypothyroid phase.
- Riedel thyroiditis: woody, fibrous gland fixed to surrounding structures, now grouped with IgG4-related disease; mimics carcinoma on examination.
- Papillary carcinoma: orphan Annie (clear) nuclei with grooves and pseudoinclusions, psammoma bodies in about half, lymphatic spread to cervical nodes common yet survival excellent; radioactive iodine avid.
- Follicular carcinoma and medullary carcinoma: follicular — diagnosis rests on capsular or vascular invasion, so fine-needle aspiration cannot distinguish it from follicular adenoma; medullary — C-cell origin, calcitonin and carcinoembryonic antigen secretion, amyloid stroma, and germline RET mutation in MEN2 families.
- Anaplastic carcinoma: elderly patients, rapidly enlarging fixed mass with tracheal invasion, p53-driven, essentially incurable with any modality.
Reading the four carcinomas against each other
The four thyroid carcinomas reward comparison more than memorisation. Papillary carcinoma, the most common at roughly 80 per cent of thyroid cancers in iodine-replete areas, is a nuclear diagnosis: the cells look washed-out, with nuclear grooves and cytoplasmic pseudoinclusions, and half of tumours carry concentric calcified psammoma bodies. It spreads first to regional lymph nodes — a young woman presenting with a neck node rather than a thyroid lump is the classic vignette — yet ten-year survival exceeds 95 per cent, which is why limited surgery with radioactive iodine suffices.
Follicular carcinoma is the haematogenous twin: it metastasises to lung and bone, and its defining criterion is invasion of the capsule or vessels, a finding that requires the whole tumour in histology — hence the surgical dictum that a follicular lesion on cytology ("follicular neoplasm") cannot be resolved by fine-needle aspiration and proceeds to lobectomy. Medullary carcinoma shifts the cell of origin: parafollicular C cells, neuroendocrine markers, calcitonin staining, stromal amyloid;RET germline mutation families (MEN2A and 2B) demand prophylactic thyroidectomy in childhood, sometimes in the first years of life. Anaplastic carcinoma closes the comparison: an elderly patient, a fixed rapidly growing mass, dysphagia and stridor, and a median survival measured in months — the tumour that turns a longstanding goitre into an emergency.
Where students slip
Orphan Annie nuclei and psammoma bodies are quoted for the wrong tumours — psammoma bodies also occur in serous ovarian tumours and meningiomas, but within the thyroid they belong to papillary carcinoma alone. The follicular fine-needle aspiration trap catches even postgraduates: cytology reports "follicular neoplasm" precisely because adenoma and carcinoma look identical on aspiration; only capsular or vascular invasion on histology separates them. And the painful-versus-painless split is reversed under pressure — De Quervain and suppurative thyroiditis hurt, while Hashimoto, Riedel (though symptomatic from compression), and the carcinomas are typically painless.
Frequently asked questions
Which antibody causes Graves disease and which defines Hashimoto?
Thyrotropin-receptor stimulating antibody in Graves disease; anti-thyroid peroxidase (with anti-thyroglobulin) in Hashimoto thyroiditis.
Which nuclear features define papillary thyroid carcinoma?
Orphan Annie eye nuclei — clear nuclei with grooves and pseudoinclusions — accompanied by psammoma bodies in about half of cases; lymphatic spread with excellent prognosis.
Why can fine-needle aspiration not diagnose follicular carcinoma?
Because follicular adenoma and carcinoma are cytologically identical; the diagnosis requires histological demonstration of capsular or vascular invasion.
From which cell does medullary carcinoma arise and what does it secrete?
Parafollicular C cells, secreting calcitonin (and carcinoembryonic antigen), with amyloid stroma and association with RET-mutated MEN2 syndromes.
Which thyroiditis is painful and self-limiting?
De Quervain subacute granulomatous thyroiditis — post-viral, tender goitre with giant-cell granulomas and a high erythrocyte sedimentation rate.
Which thyroid carcinoma occurs in the elderly with rapid enlargement?
Anaplastic carcinoma — a fixed invasive mass with dismal prognosis, often arising in a long-standing goitre.