Thyroid Pathology Flashcards
Normal embryological development
Develops from evagination of pharyngeal epithelium
Descent from foramen caecum to normal location in anterior neck below larynx along thyroglossal duct
Embryological Abnormalities
Failure of descent
–> lingual thyroid
Excessive descent
–> retrosternal location in mediastinum
Thyroglossal duct cyst
Thyroid composition
Composed of lobules defined by thin fibrous septa each containing follicles
Each follicle surrounded by flat to cuboidal follicular epithelial cells
Within centre each each follicle is dense amorphous pink material containing thyroglobulin
Occasionally scattered C cells
C cells
parafollicular cells
Slightly larger cells with clearer cytoplasm
Secrete calcitonin
Results in lower serum Ca levels (little clinical significance)
Thyroid Function: BMR
Increases basal metabolic rate
Hypothalamus produces TRH
TRH stimulates anterior pituitary to release TSH
TSH binds to TSH receptor on surface of thyroid epithelial cells.
G-proteins activated with conversion of GTP to GDP and production of cAMP
cAMP increases production and release of T3 and T4
T3 and T4 circulate in free and bound forms
On release T3 and T4 bind to receptor in target cells
- complex translocates to nucleus
- binds to thyroid response elements on target genes
- stimulates transcription of genes
- -> increases BMR
Thyroiditis
Inflammation of the thyroid gland
Acute: bacterial infection
Subacute (de Quervain’s): Viral infection
Chronic: abnormal immune response
Thyroiditis Autoimmune Disease
Hypofunction: Hashimotos Thyroiditis
Hyperfunction: Graves Disease
Susceptibility associated with HLA calotype
Polymorphisms in immune regulation associated genes
- CTLA-4
- PTPN-22
Thyrotoxicosis
Syndrome occurs as a result of excess T3 and T4
hyperthyroidism aetiology
Graves disease hyper functioning nodules and tumours TSH secreting pituitary adenoma Thyroiditis Ectopic production
Graves Disease
Autoimmune Disorder
- hyperthyroidism
Autoantibodies to TSH receptor, thyroid peroxisomes and thyroglobulin
Anti-TSH receptor autoantibodies (seen in Graves)
Thyroid stimulating immunoglobulin
Thyroid growth stimulating Immunoglobulin
TSH binding inhibitor immunoglobulin
Graves Disease features
Hyperthyroidism with diffuse enlargement of the thyroid
Eye changes (exophthalmos) - results from fibroblasts expressive TSH receptor
Pretibial Myxoedemaa
Follicles contain little or no thyroglobulin
Abundance of lymphoid follicles
Hypothyroidism
Symptoms and signs due to low levels of T3 and t4
hypothyroidism aetiology
hashimotos thyroiditis (most common cause) iodine deficiency drugs (lithium) post therapy congenital abnormalities
Rare
- Secondary (pituitary) pathology
- tertiary (hypothalamic) pathology
Hashimoto Thyroiditis
Gradual failure of thyroid function
Autoimmune destruction of thyroid tissue
Hashimotos Thyroiditis Epidemiology
Affects middle aged women
Associated with other autoimmune disease
HLA-DR3 and DR5
Anti-thyroid antibodies (hashimotos thyroiditis)
Anti-thyroglobulin and anti-peroxidase
When bound cause antibody dependent cell mediated cytotoxicity
Hashimotos Thyroiditis Pathophysiology
Antibody dependent cell cytoxicity due to anti-thyroglobulin and anti-peroxidase
CD8+ve cells mediate destruction of thyroid epithelium
Cytokin mediated cell death
- gama interferon from T cell activation recruits macrophages that may damage thyroid follicles
Thyroid may be diffusely enlarged
Hashimotos Thyroiditis: Histology and Follicles
Prominent lymphoid infiltrate
- lymphocytes
- plasma cells
- reactive follicles with germinal centres
Thyroid follicles atrophy
- follicular cells have abundant eosinophilic cytoplasm
- -> Hurthle cells
may see progressive fibrosis within gland
hashitoxicosis
Transient hyper function of gland
can precede progressive fibrosis within gland
Hashimotos Thyroiditis risks
Increased risk of other autoimmune disease
Increased risk of developing B cell NHL in affected glands
Goitre
Enlargement of thyroid gland
Reduced t3/T4 production causes rise in TSH, stimulating gland enlargement
Diffuse goitre
T3/T4 normal
TSH elevated
usually euthyroid- present with mass effects
Sporadic
- F>M
- Puberty and young adults
multi-nodular goitre
Evolution from long-standing simple goitre
- recurrent hyperplasia and involution
Variation of response of follicular cells to external stimuli
-mutations of TSH signalling pathway
Ruptures of follicles, haemorrhage, scaring and calcification
Mass Effects: Cosmetics, airway obstruction, dysphagia, compress vessels
May develop autonomous nodule
-hyperthyroid (low risk of malignancy <5%)
neoplasms
Adenomas
- follicular adenoma
carcinoma
- papillary
- follicular
- medullary
- anaplastic
Adenomas
Discrete solitary mass
Encapsulated by a surrounding collagen cuff
Composed of neoplastic thyroid follicles
–> follicular adenoma
Can be difficult to distinguish from
- dominant nodule in MNG
- follicular carcinoma
Adenomas- function
Usually non-functional
Can secreted thyroid hormone
- thyrotoxicosis
- -> TSH independent
Functional
-Thyroid adenoma
Thyroid Adenomas
Mutations of TSHR signalling pathway in functional adenomas
Activating
- TSHR
- G-proteins
Increase cAMP levels
Carcinomas epidemiology
Can affect any age group
- female predominance
Thyroid malignancy
Most are well differentiated and derived from follicular epithelium
(Medullary from C cells)
Carcinomas
- Papillary
- Follicular
- Medullary
- Anaplastic
Carcinoma Aetiology (Environment Associations)
Ionising Radiation
- Papillary carcinoma
Iodine Deficiency
- follicular carcinoma
Carcinoma Aetiology (genetic Features)
Papillary: Activate MAP kinase pathway
- Rearrangements of RET or NTKR1
- Activating point mutation in BRAF
- Mutation of RAS
Follicular
- Mutations in P13k/ AKT pathway
- Mutation in ras family
- translocation involving Pax8 and PPAR-gamma-1
Anaplastic
- features of. above types
- p53 and B-catenin
medullary
-MEN2
Papillary carcinomas
Most common type of thyroid cancer
Usually solitary nodule
- can be multifocal
- often cystic
- may be calcified: psammoma bodies
Sometimes present with lymph node metastasis
Papillary carcinoma presentation
Lesion in thyroid gland or cervical lymph node mass
Local effects
- hoarseness
- dysphagia
- cough
- dysponoea
haematogenous spread is uncommon
- usually to lungs
Overall good survival rates
Follicular carcinoma epidemiology
Females> Males
Older than with papillary (40s and 50s0)
Follicular Carcinoma Presentation
Usually single nodule
- slowly enlarging, painless and non-functional
Rare lymphatic spread
Propensity from haematogenous spread
-bones, lungs, liver
invasive growth pattern
Follicular Carcinoma Prognosis
Depends on extent of invasion and stage of presentation
High stage at presentation
-50% mortality art 10 years
Minimally invasive lesions
- >90% survival at 10 years
Medullary Thyroid Carcinoma
Relatively rare
Derived from C-cells (neuroendocrine)
- secrete calcitonin
Medullary thyroid carcinoma aetiology
Sporadic: solitary nodule
Associated with Men IIA or IIB
Familial medullary carcinoma
Familial cases: bilateral or multi centric
- C-cell hyperplasia
Medullary thyroid carcinoma composition
Composed of spindle or polygonal cells arranged in nests, trabecular or follicles
Medullary Thyroid Carcinoma Associations
Associated amyloid deposition
Amyloid represents deposition of abnormally folded protein: calcitonin
Medullary Thyroid Carcinoma presentation
neck mass with local effects
- dysphagia
- hoarseness
- airway compromise
paraneoplastic Syndrome
- diarrhoea (VIP production)
- Cushings (ACTH production0
medullary thyroid carcinoma mangement
Total thyroidectomy
Local recurrence in 35%
Good prognostic factors
- young age, female
- tumour size, confined to thyroid, no. mets
MENIIB has more aggressive potential
Anaplastic Carcinoma
Undifferentiated and aggressive tumours
Anaplastic Carcinoma Presentation
Usually older patients
may occur in people with a history of differentiated thyroid cancer
Rapid growth and involvement of neck structures and death
