L2 Pathology of Thyroid Flashcards
What are some effects of thyroid hormones ?
- Stimulate the contraction of heart
- Increase oxygen consumption and heat production in all tissue
- Stimulate gut motility
- Important of CNS development
- Stimulate production of structural proteins
What are the disorders of thyroid ?
- Hyper
- Hypo
- Diffuse/nodular/multi-nodular goiter
- Thyroid cancer (adenoma/ carcinoma )
- Thyroiditis
- Congenital > thyroglossal duct cyst
What is thyroglossal duct cyst ?
It is a fluid-filled cyst occurs anywhere along the thyroglossal duct in the midline
Most commonly near hyoid bone or attached to soft tissue
What is the structure of the cyst ?
- Made of squamous or respiratory type epithelium
2. Variable amount of thyroid tissue
What type of tumor can develop in these cyst ?
Papillary carcinoma
What are the main causes of hyper?
- Abnormal stimulator of the thyroid ( grave disease )
- Intrinsic disease of thyroid ( toxic multi-nodular goiter / functional thyroid adenoma )
- Abnormal secretion of TSH ( pituitary adenoma)
What are the triad for people with grave disease ?
- Hyperthyroidism
- Exophthalmus
- Peri-tibial myxedema / clubbing
What are the gross and microscopic features of thyroid in grave disease ?
GROSS :
- moderately enlarged
- firm and beefy red ( due to increased vascularity )
MICROSCOPIC :
- lymphoid infiltrate
- glands show hyperplasia of :
- acinar epithelium
- tall columnar cells
- papillary folds
What is the cause of exophthalmus and peri-tibial myxedema ?
- Lymphocytic infiltrate
2. Glycosaminoglycans ( hyaluronic acid ) deposition
What are the causes of hypothyroidism (myxedema ) ?
- Iodine deficiency
- Hashimoto disease
- Drugs
- Radiation / surgery
What are the types of thyroiditis ?
- Acute thyroiditis ( bacterial or fungal infection )
- Chronic autoimmune thyroiditis ( Hashimoto disease )
- Granulomatous thyroiditis ( viral infection ):
- de queen
- giant cell thyroiditis - Subacute lymphocytic thyroiditis ( post-partum )
- Riedel thyroiditis ( IgG-4 related - thyroid fibrosis )
What is the underlying cause of Hashimoto disease ?
It is an autoimmune disease caused by ab against :
- ER
- Thyroglobulin
- Thyroperoxidase
Due to HLA B8 / DR5
What are the gross and microscopic features of Hashimoto disease?
Gross :
- firm diffuse goiter
Microscopic:
- follicle atrophy with lymphocyte
- hurthle cells ( eosinophilic epithelial cells )
What is the pathological mechanisms in Hashimoto disease ?
- CD8+ cytotoxic T cell mediated killing
- Cytokine mediated cell death ( interferon will activate more cells / Macrophages )
- Binding of antithyroid antibodies then ADCC
What is the genetic cause of granulomatous thyroiditis?
HLA B35
What is the microscopic features of granulomatous thyroiditis ?
- Patchy Micro abscess
2. Granulomas with giant cells
What is happening in the iodine deficiency goiter ?
Hyperplasia of the epithelium of the gland and appearance of less active areas that will be compressed by the hyper-plastic areas
What will lead to multi-modular goiter in iodine deficiency goiter ?
The tracts of fibrosis that will separate areas
What are the features of thyroid neoplasms ?
- Most are solitary and benign
- Low mortality rate
- May be functional ( hot )
What are the main types of thyroid cancer ?
- Papillary carcinoma ( most common )
- Follicular adenoma
- Follicular carcinoma
- Anaplastic carcinoma
- Medullary carcinoma ( least )
What is the gross and microscopic features of follicular adenoma ?
GROSS:
- solid mass with fibrous capsule that is not breached
- centre may contain areas of hemorrhage and cystic changes
MICROSCOPIC :
- compacted follicles
- lined with epithelial cells that show hyperchromtism
- little collied
- rarely, it can produce T3 and T4 so considered as hot
Which age is usually affected by each type of thyroid cancer ? What is the prognosis ?
- Papillary carcinoma ( young adults >45 ) ( only 5% is familial )
- Follicular ( young middle < 45 )
- Anaplastic ( elderly / very poor prognosis )
- Medullary ( elderly / can be familial which will be more aggressive )
What are the possible risk factors of papillary carcinoma ?
- High iodine intake
- Radiation
- Genetic factors
- Somatic mutations
What are the different somatic mutations that increase the risk of papillary carcinoma?
- Familial granulomatous polyposis
- Somatic rearrangement of RET proto-oncogenes on chromosome 10
- Chromosomal rearrangement of RET or NTRK1
- Mutations in BRAF
What is the gross and microscopic features of papillary carcinoma ?
GROSS :
- Non-encapsulated infiltrative mass
- Firm and whitish due to fibrosis
MICROSCOPIC:
- Epithelial papillary projections
- Psammoma bodies
- Characteristic nuclei with central clear mass ( orphan Annie nuclei )
Through what does the papillary and follicular carcinoma metastasize ?
- Papillary > lymphatics to cervical lymph node
1. Follicular > blood vessels to bones and lungs
Why follicular carcinoma has god prognosis ?
As many tumors retain their ability to uptake the I311 ( radiotherapy )
What are the possible genetic causes underlying follicular carcinoma?
Either
- RAS mutations
Or
- PAX8-PPAR gamma 1 rearrangement
What are anaplastic carcinoma ? and what is the microscopic features ?
- It is poorly differentiated adenocarcinoma from thyroid epithelium
- It has many histological appearances but the commonest is :
- giant cell
- spindle cell
Why anaplastic carcinoma has very poor prognosis ?
Due to rapid local invasion
What is medullary carcinoma ?
Derived from C cells
What does medullary carcinoma secrete ?
- Calcitonin
- Serotonin
- ACTH
- somatostatin
What are the features of the tumor in medullary carcinoma?
- Solid mass
- Sheets of neoplastic cells
- Hyaline stroma
- Amyloid reactions
