thyroid pathology

Question 1

causes of diffuse goiter

Answer 1

Graves disease, Hashimoto Thyroiditis, DeQuervain thyroiditis, simple goitre

Question 2

causes of localized swelling/nodular goitre

Answer 2

nodular goitre, neoplasms, thyroiditis

Question 3

causes of hyperthyroidism/thyrotoxicosis

Answer 3

Graves disease, hyperplasia, nodular goitre, neoplasms

Question 4

causes of hypothyroidism

Answer 4

Hashimoto Thyroiditis, congenital abnormalities

Question 5

causes of euthyroid derangement

Answer 5

nodular goitre, neoplasms

Question 6

hyperthyroid symptoms

Answer 6

weight loss, heat intolerance, oligomenorrhea, diarrhoea, irritable mental state, increased appetite

Question 7

symptoms of hypothyroidism

Answer 7

weight gain, cold intolerance, menorrhagia, constipation, mental slowness, poor appetite

Question 8

hyperthyroidism signs

Answer 8

loss of weight, staring gaze, lid lag, *exophthalmos, warm and sweaty skin, tachycardia, atrial fibrillation, *pretibial myxedema, proximal myopathy

*: only in Graves

Question 9

hypothyroidism signs

Answer 9

weight gain, peaches and cream skin, dry cool skin, bradycardia, pericardial effusion, proximal myopathy

Question 10

congenital thyroid diseases

Answer 10

1. thyroglossal duct cyst
2. abnormal development of thyroid gland
3. ectopic thyroid tissue
4. thyroid dyshormonogenesis

Question 11

causes of diffuse and multinodular goitre

Answer 11

due to iodine deficiency or dyshormonogenetic goitre causing a compensatory increase in TSH –> hypertrophy and hyperplasia of follicular cells

Question 12

progression of disease of diffuse non-toxic non-hyperfunctioning goitre

Answer 12

1. hyperplastic stage: diffuse mild enlargement, crowded columnar cells, pseudopapillae
2. colloid involution stage: flattened cuboidal epithelium, abundant colloid
3. multinodular goitre stage: extreme irregular enlargement, cystic change, haemorrhage, compression on trachea and recurrent laryngeal nerve

Question 13

Hashimoto Thyroiditis risk factors

Answer 13

female, 45-60yo, HLA-DR3/DR5 genes, other autoimmune diseases

Question 14

Hashimoto Thyroiditis pathogenesis

Answer 14

1. sensitisation of CD4+ Th cells to thyroid antigens
2. cytotoxic CD8+ T cell mediated cell death
3. cytokine (IFN-γ) mediated cell death - ADCC via autoantibodies against thyroglobulin, TSH receptor and thyroid peroxidase

Question 15

morphology of Hashimoto Thyroiditis

Answer 15

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

Question 16

Graves disease risk factors

Answer 16

female, 20-40yo, family history of HLA-B8/DR3 genes, other autoimmune conditions

Question 17

clinical triad for Graves disease

Answer 17

1. hyperthyroidism
2. infiltrative ophthalmopathy
3. infiltrative dermopathy (pretibial myxedema)

Question 18

pathogenesis of Graves disease

Answer 18

1. breakdown in Th cell tolerance
2. autoantibodies to TSH receptors (thyroid stimulating immunoglobulin, TSH-binding inhibitor immunoglobulin)
3. overstimulation of thyroid gland, leading to thyrotoxicosis, diffuse goitre ±bruit, ophthalmopathy and dermopathy due to Th cells cytokines attacking retro orbital tissue

Question 19

morphology of thyroid with Graves disease

Answer 19

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

Question 20

risk factors for DeQuervain thyroiditis

Answer 20

female, 30-50yo, short history (weeks), self limiting, recent URTI

Question 21

pathogenesis of DeQuervain thyroiditis

Answer 21

virus-induced cytotoxic T-cell response to thyroid antigens leading to follicular cell damage, neck pain, and goitre

Question 22

DeQuervain thyroiditis morphology

Answer 22

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

Question 23

IgG4 related thyroiditis pathogenesis

Answer 23

assoc with IgG4-related fibroscleretic disease, increase with serum IgG4 increase, mimics malignancy with progressive fibrosis, enlargement and adherence to neck structures

Question 24

morphology of thyroid with IgG4-related thyroiditis

Answer 24

microscopically: lymphoplasmacytic infiltration, fibrosis, obliterative thrombophlebitis

Question 25

types of benign follicular neoplasms

Answer 25

follicular adenoma and oncocytic (Hurthle cell) adenoma

Question 26

morphology of benign follicular cells adenomas (follicular adenoma and oncocytic Hurthle cell adenoma)

Answer 26

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)

Question 27

follicular carcinoma risk factors

Answer 27

female, RAS family mutations, PPARγ/PAX8 rearrangements

Question 28

clinical presentation (and subtypes) of thyroid follicular carcinoma

Answer 28

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

Question 29

oncocytic thyroid carcinoma presentation and cells

Answer 29

(similar to follicular carcinoma) slow growing painless cold nodule, metastasises through bloodstream to lungs and bone oncocytic cells present in capsular and vascular invasion

Question 30

papillary carcinoma risk factors

Answer 30

20-40yo or children, exposure to ionising radiation, RET/PTC gene rearrangements, BRAF mutations

Question 31

papillary thyroid carcinoma presentation

Answer 31

cold painless nodule, enlarged cervical lymph nodes, metastasis via lymph nodes: hoarseness, cough, dysphagia

Question 32

classic papillary carcinoma vs follicular variant papillary carcinoma

Answer 32

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

Question 33

morphology of papillary carcinoma

Answer 33

grossly: solitary or multifocal masses, encapsulated or infiltrative whitish nodules, cystic change, calcifications, fibrosis microscopically: differs based on classic vs follicular papillary carcinoma

Question 34

poorly differentiated thyroid carcinoma gene mutations

Answer 34

TP53, TERT promoter mutations + low grade mutations

Question 35

morphology of poorly differentiated thyroid carcinoma

Answer 35

grossly: usually invasive microscopically: trabecular/insular growth in large islands, high mitotic count and tumour necrosis

Question 36

risk factors for anaplastic thyroid carcinoma

Answer 36

65yo, underlying multinodular goitre/well differentiated thyroid adenocarcinoma, TP53 / TERT promoter mutations

Question 37

clinical presentation of anaplastic thyroid carcinoma

Answer 37

rapidly enlarging bulky thyroid mass, compressive symptoms of dyspnoea, dysphagia, hoarseness, metastasis to lungs

Question 38

morphology of anaplastic thyroid carcinoma

Answer 38

grossly: bulky mass microscopically: highly pleomorphic and barely recognisable cells, giant tumour cells, spindle cells, small anaplastic cells

Question 39

medullary thyroid carcinoma risk factors

Answer 39

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

Question 40

medullary thyroid carcinoma clinical presentation

Answer 40

grey white infiltrative mass, paraneoplastic syndromes, raised serum calcitonin, MEN syndrome related tumours

Question 41

medullary thyroid carcinoma morphology

Answer 41

microscopically: epithelioid or spindled cells, salt and pepper chromatin, nests, trabeculae, follicles, stain of Congo Red and C cell hyperplasia

Question 42

thyroid lymphoma types

Answer 42

B cell non-Hodgkin lymphoma, MALT lymphomas, large B cell lymphomas