thyroid pathology Flashcards
causes of diffuse goiter
Graves disease, Hashimoto Thyroiditis, DeQuervain thyroiditis, simple goitre
causes of localized swelling/nodular goitre
nodular goitre, neoplasms, thyroiditis
causes of hyperthyroidism/thyrotoxicosis
Graves disease, hyperplasia, nodular goitre, neoplasms
causes of hypothyroidism
Hashimoto Thyroiditis, congenital abnormalities
causes of euthyroid derangement
nodular goitre, neoplasms
hyperthyroid symptoms
weight loss, heat intolerance, oligomenorrhea, diarrhoea, irritable mental state, increased appetite
symptoms of hypothyroidism
weight gain, cold intolerance, menorrhagia, constipation, mental slowness, poor appetite
hyperthyroidism signs
loss of weight, staring gaze, lid lag, *exophthalmos, warm and sweaty skin, tachycardia, atrial fibrillation, *pretibial myxedema, proximal myopathy
*: only in Graves
hypothyroidism signs
weight gain, peaches and cream skin, dry cool skin, bradycardia, pericardial effusion, proximal myopathy
congenital thyroid diseases
- thyroglossal duct cyst
- abnormal development of thyroid gland
- ectopic thyroid tissue
- thyroid dyshormonogenesis
causes of diffuse and multinodular goitre
due to iodine deficiency or dyshormonogenetic goitre causing a compensatory increase in TSH –> hypertrophy and hyperplasia of follicular cells
progression of disease of diffuse non-toxic non-hyperfunctioning goitre
- hyperplastic stage: diffuse mild enlargement, crowded columnar cells, pseudopapillae
- colloid involution stage: flattened cuboidal epithelium, abundant colloid
- multinodular goitre stage: extreme irregular enlargement, cystic change, haemorrhage, compression on trachea and recurrent laryngeal nerve
Hashimoto Thyroiditis risk factors
female, 45-60yo, HLA-DR3/DR5 genes, other autoimmune diseases
Hashimoto Thyroiditis pathogenesis
- sensitisation of CD4+ Th cells to thyroid antigens
- cytotoxic CD8+ T cell mediated cell death
- cytokine (IFN-γ) mediated cell death - ADCC via autoantibodies against thyroglobulin, TSH receptor and thyroid peroxidase
morphology of Hashimoto Thyroiditis
grossly: pale diffusely enlarged gland, pale yellow firm cut surface ± nodules
microscopically: infiltrates including reactive lymphoid follicles, lymphocytes, plasma cells, thyroid follicles that are atrophic, Hurthle cell change, larger eosinophilic granular cytoplasm, fibrosis
Graves disease risk factors
female, 20-40yo, family history of HLA-B8/DR3 genes, other autoimmune conditions
clinical triad for Graves disease
- hyperthyroidism
- infiltrative ophthalmopathy
- infiltrative dermopathy (pretibial myxedema)
pathogenesis of Graves disease
- breakdown in Th cell tolerance
- autoantibodies to TSH receptors (thyroid stimulating immunoglobulin, TSH-binding inhibitor immunoglobulin)
- overstimulation of thyroid gland, leading to thyrotoxicosis, diffuse goitre ±bruit, ophthalmopathy and dermopathy due to Th cells cytokines attacking retro orbital tissue
morphology of thyroid with Graves disease
grossly: symmetrical diffuse enlargement, soft reddish meaty cut surface
microscopically: tall columnar crowded follicular cells with pseudopapillae, pale scalloped colloid, lymphoid infiltrates and reactive lymphoid follicles
risk factors for DeQuervain thyroiditis
female, 30-50yo, short history (weeks), self limiting, recent URTI
pathogenesis of DeQuervain thyroiditis
virus-induced cytotoxic T-cell response to thyroid antigens leading to follicular cell damage, neck pain, and goitre
DeQuervain thyroiditis morphology
grossly: enlarged firm gland, patchy (firm yellow pale areas with intervening normal parenchyma)
microscopically: destruction of follicles, neutrophilic invasion, microabscesses, lymphocytes, plasma cells, histiocytes around damaged follicles, multinucleated giant cells engulfing pools of colloid
IgG4 related thyroiditis pathogenesis
assoc with IgG4-related fibroscleretic disease, increase with serum IgG4 increase, mimics malignancy with progressive fibrosis, enlargement and adherence to neck structures
morphology of thyroid with IgG4-related thyroiditis
microscopically: lymphoplasmacytic infiltration, fibrosis, obliterative thrombophlebitis
types of benign follicular neoplasms
follicular adenoma and oncocytic (Hurthle cell) adenoma
morphology of benign follicular cells adenomas (follicular adenoma and oncocytic Hurthle cell adenoma)
grossly: rounded, encapsulated and well demarcated nodule with an intact capsule, bulges from the cut surface
microscopically: completely surrounded by an intact capsule with no capsular or vascular invasion (follicular adenoma: no oncocytic change, Hurthle cell adenoma: oncocytic change)
follicular carcinoma risk factors
female, RAS family mutations, PPARγ/PAX8 rearrangements
clinical presentation (and subtypes) of follicular carcinoma
slow growing painless cold nodule, metastasis through bloodstream to lungs and bone
WHO subtypes:
1. minimally invasive (capsular invasion only)
2. encapsulated angioinvasive
3. widely invasive with gross extension into extrathyroidal tissues
oncocytic carcinoma presentation and cells
(similar to follicular carcinoma)
slow growing painless cold nodule, metastasises through bloodstream to lungs and bone
oncocytic cells present in capsular and vascular invasion
papillary carcinoma risk factors
20-40yo or children, exposure to ionising radiation, RET/PTC gene rearrangements, BRAF mutations
papillary carcinoma presentation
cold painless nodule, enlarged cervical lymph nodes, metastasis via lymph nodes: hoarseness, cough, dysphagia
classic papillary carcinoma vs follicular variant papillary carcinoma
branching well formed papillae with fibrovascular core vs non-encapsulated infiltrative follicular growth pattern
cells have psammoma bodies, fibrosis, calcifications, lymphatic invasion vs finely dispersed chromatin with ground glass / orphan annie eye nuclei, nuclear grooves, pseudoinclusions
morphology of papillary carcinoma
grossly: solitary or multifocal masses, encapsulated or infiltrative whitish nodules, cystic change, calcifications, fibrosis
microscopically: differs based on classic vs follicular papillary carcinoma
poorly differentiated thyroid carcinoma gene mutations
TP53, TERT promoter mutations + low grade mutations
morphology of poorly differentiated thyroid carcinoma
grossly: usually invasive
microscopically: trabecular/insular growth in large islands, high mitotic count and tumour necrosis
risk factors for anaplastic thyroid carcinoma
65yo, underlying multinodular goitre/well differentiated thyroid adenocarcinoma, TP53 / TERT promoter mutations
clinical presentation of anaplastic thyroid carcinoma
rapidly enlarging bulky thyroid mass, compressive symptoms of dyspnoea, dysphagia, hoarseness, metastasis to lungs
morphology of anaplastic thyroid carcinoma
grossly: bulky mass
microscopically: highly pleomorphic and barely recognisable cells, giant tumour cells, spindle cells, small anaplastic cells
medullary carcinoma risk factors
40-50yo, RET proto-oncogene mutation, MEN 2A/2B hereditary genes
RET mutant tumours more likely to respond to RET-inhibitor treatment, MEN 2B tumours more aggressive
medullary carcinoma clinical presentation
grey white infiltrative mass, paraneoplastic syndromes, raised serum calcitonin, MEN syndrome related tumours
medullary carcinoma morphology
microscopically: epithelioid or spindled cells, salt and pepper chromatin, nests, trabeculae, follicles, stain of Congo Red and C cell hyperplasia
thyroid lymphoma types
B cell non-Hodgkin lymphoma, MALT lymphomas, large B cell lymphomas
