Thyroid Pathology Flashcards
is thyroid bigger in men or women
slightly larger in women
what level is the thyroid
C5/6-T1
describe the embryological development of the thyroid gland
develops from evagination of pharyngeal epithelium
descends from foramen caecum to normal location along the thryoglossal duct
what are the three common embryological abnormalities of the thryoid
failure of descent (lingual thyroid)
excessive descent (retrosternal location in mediastinum)
thyroglossal duct cyst
what makes up the thyroid
composed of follicles that are surrounded by flat cuboidal follicular epithelial cells
what is in the centre of each follicle
dense amorphic pink material containing thryoglobulin
what cells are scattered throughout the thyroid gland
C cells (parafollicular)- have slightly larger with clearer cytoplasms
what do C cells produce
calcitonin- lowers serum Ca
what cells produce thyroid hormones
thyroid follicular epithelium cells
describe how TSH works
binds to TSH surface receptor on surface of thyroid epithelial cells. G proteins activated with conversion of GTP to GDP and production of cAMP which stimulates production and release of T3 and 4, circulate in bound and free forms
what happens when T3 binds to receptors in target cells
complex translocates to the nucleus, binds to thyroid response elements on target genes, stimulates transcription of these genes- increase BMR
what can cause a thyroid gland to shrink in size
atrophy- presentation of reduced function a
what can a mass effect if an enlarged thyroid gland be
airway obstruction
polymorphisms in what genes are associated with autoimmune thyroid problems
CTLA-4 (negative regulator of T cell responses)
PTPN-22 (inhibits T cell function)
what are causes of inflammation in the thyroid
autoimmune disordersm infection, palpation, subacute lymphocytic, de Quervains, riedels
what does riedels do to the thyroid
makes it hard, claggy
what autoimmune disease causes hypothyroidism
hashimotos thyroiditis
what autoimmune disease causes 8% of hyperthyroidism cases
graves disease
what is thyrotoxoicosis
hyperthyroidism
what else can cause hyperthyroidism
hyperfunctioning nodules, tumours (adenomas, carcinomas)
TSH secreting pituitary adenomas (rare),
thyroditis, ectopic production (struma ovarii)
is graves more common in men or women
women 10:1
what age to people gets graves
20-40 years old
what is the triad of symptoms seen in graves
hyperthyroidism with diffuse enlargement of the thryoid
eye changes (exophthalamos),
partial myxoedema
what autoantibodies are seen in graves
Antibodies to TSH receptor, thyroid peroxisomes and thyroglobulin.
Anti TSH receptor antibodies: thyroid stimulating immunoglobulin, thyroid growth stimulating immunilogbulin,
TSH binding inhibitor immunoglobulins
what do the antibodies in graves do
stimulate thyroid hormone to function- except TSH binding inhibitor which causes episodes of hypofunction seen in graves
what is seen histologically in graves
thyroid follicles lack the ‘pink collar’ of follicular cells aka scalloping due to uptake of colloid
what causes symptoms in hypothyroidism
lack of thyroid hormones
who gets hashimotos
middle aged women
what genes is hashimotos associated
HLA- DR3 and DR5
what else can cause hypothyroidism
iodine deficiency, drugs (lithium), post therapy (surgery, irradiation), congenital abnormalities
what is hashimotos thyroiditis
autoimmune disease which causes gradual failure of thyroid function
what antibodies are in hashimotos thyroiditis
anti thyroid antibodies
(anti thyroglobulin and anti peroxidase)
when bound cause anti body dependent cell mediated cytotoxicity
what cells mediate hashimotos thyroiditis
CD8 +ve cells (destroy cell epithelium)
cytokine mediated cell death (gamma interferon from T cell activation recruits macrophages that may damage thyroid follicles)
what is the histology of hashimotos
follicles that remain dont have scalloping as retention of thyroid hormone
inflammatory infiltrate
what might hashimotos thyroiditis be preceded by
transient hyperfunction (hashitoxicosis)
what cancer is at increased risk in hashimotos thyroiditis
B cell non hogkins lymphoma
what is a goitre
any enlargement of the thyroid gland
what commonly causes goitres
lack of dietary, reduced T3/4 production causing rise in TSH which stimulates gland enlargement
who gets diffuse goitres
females more than men, puberty and young adults
what causes a diffuse goire
ingestion of substances limiting T3/4 production, dyshormogenesis, idiopathic (most)
what are the usual symptoms of a goitre
usually euthyroid
presents with mass effects- cosmesis, airway obstruction, dysphagia, compresses vessels
what can dyshormogenesis cause in children
cretinism
what is seen in blood test in diffuse goitres
normal thyroid hormones but increase or upper side of normal TSH
what causes a multinodular goitre
recurrent hyperplasia and involution, mutations in TSH, rupture of follicles, haemorrhage, scarring, calcification
what do many multi nodular goitres develop
autonomous nodule- hyperthyroid
describe the structure of a thyroid adenoma
discrete solitary mass, encapsulated by a surrounding collagen cuff, composed of neoplastic thyroid follicles (follicular adenoma)
are thyroid adenomas benign
yes
what is it hard to differentiate a thyroid adenoma from
dominant nodule in multinodular goitre, follicular carcinoma
what are the effects of an adenoma
mass effects
usually non functional- can secrete thyroid hormones (thyrotoxicosis)- are TSH independent
what mutations are seen in thyroid adenomas
<20% have mutant ras or PIK3CA
mutations of TSHR signalling pathway in functional adenomas
-activating TSHR, G proteins which increases cAMP levels
what cells do thryoid malignancies come from
follicular epithelium (medullary from C cells)
list the thyroid malignancies from most to least common
papillary (75-85%), follicular, medullary, anaplastic
what is the aetiology of each of the thryoid cancers
environment-radiation (papillary), iodine deficiency (follicular)
genetics-
papillary- activate MAP kinase pathway, activation of BRAF, mutation in ras
follicular- mutations in ras family
anaplastic- above + p53 and beta-catenin mutations
medullary- MEN2
what is the most common thyroid malignancy
papillary
what is the usual structure of papillary carcinomas
usually solitary, can be mutlifocal, often cystic, may be calcified (psammoma bodies)
do papillary carcinomas spread via the lymph
yes
if find thyroid tissue or psammoma body in a lymph node look for occult papillary carcinoma
how do papillary carcinomas present
lesion in thyroid gland or cervical lymph node mass (metastasis)
local effects: -hoarseness -dysphagia -cough -dyspnoea (all suggest locally advanced disease)
do papillary carcinomas spread via the lung
not usually- if they do its commonly to the lung
what is the second most common thyroid carcinoma
follicular
who gets follicular carcinomas
F>M, older than papillary (40s and 50s)
when is there not a female predominance in thyroid carcinomad
childhood and old age
what are the survival rates for papillary carcinoma
95% at 10 years
follicular carcinomas: onset, character and spread
slowly enlarging, painless, non functional, invasive growth pattern
dont spread via the lymph (unlike papillary) but spread haematogenous spread to the bones lungs and liver
describe the structure of widely invasive follicular carcinomas
more solid architecture, less follicular architecture, more mitotic activity
describe the structure of minimally invasive follicular carcinomas
follicular architecture (well differentiated), may have surrounding capsule, hard to distinguish from adenoma
what is the difference between follicular adenoma and carcinoma
carcinoma need vascular or capsular invasion
what is the prognosis for follicular carcinoma
depends on extent of invasion and stage of presentation
if high stage at presentation 50% mortality at 10 years
less invasive 90% at 10 years
what is autoimmune thyroiditis
hashimotos
what type of tumour is a medullary thyroid carcinoma
neuoendocrine (derived from C cells)
what can medullary thyroid carcinoma secrete
calcitonin
what are the forms of medullary thyroid carcinoma
can be specific, associated with multiple endocrine neoplasm, familial
what type of medullary thyroid carcinoma can arise in very young patients
MEN cases
who gets sporadic and familial medullary thyroid carcinoma
40s-50s
what form do sporadic medullary carcinomas take
solitary nodules
what form do familial medullary carcinomas take
bilateral/ multicentric (c cell hyperplasia)
what is the histology of medullary carcinomas
spindle or polygonal cells arranged in nests, trabeculae or follicles
associated amyloid deposition
what paraneoplastic syndromes are seen in medullary carcinomas
diarrhoea (VIP production)
cushings (ACTH production)
what is the treatment for medullary carcinoma
total thyroidectomy
what is the survival rates for medullary carcinoma
70-80% in 5 years
what are the good prognostic factors for medullary carcinoma
young, female, familial setting, tumour size, confined to the gland
what histological features suggest a tumour with more aggressive behavior
necrosis, many mitosis, small cell morphology
describe anaplastic carcinomas
undifferentiated and aggressive tumours
rapid growth an involvement of neck structure and death
who gets anaplastic carcinomas
older patients
people with a history of differentiated thyroid cancer
