Pathology Flashcards
Hyper pituitary
Adenoma in ant lobe
Hyperplasia
Carcinoma
Ectopic
Hypothalamus
Classification of pituitary adenoma
On the basis of hormones produced by neoplastic cells
Somatostatin
Inhibits GH and TSH
Analogs are used to treat acromegaly
Pathogenesis of pituitary adenoma
1- mutation in GNAS abrogates the activity of Gsa of GTPase leading to constitutive activation of Gsa , cAMP is produced continuously and unchecked cellular proliferation
2- MEN1, CDKN1B, PRKAR1A & AIP gene
3- cell cycle : CD1 overexpression, mutations TP 53, epigenetic silencing of RB gene, RAS oncogene.
Somatotroph adenomas
GH +++IGF1~ overgrowth of bones n muscle
In child before epiphysis close: increase in body size, disproportionately long arms and legs.
After closure of epiphysis: growth of soft tissue, skin, viscera, bones of face.
Prognathism: lower jaw grows
Teeth separate
Sausage like fingers, ACROMEGALY
Diabetes mellitus: GH induced peripheral insulin resistance.
Test for acromegaly
GH is not suppressed in response to oral load of glucose.
Morphology of pituitary adenoma
May compress ,erode and extend in optic chiasm nd adjacent structure
Uniform polygonal cells arranged in sheets,cords and papillae
* cellular monomorphism and absence of reticulin in neoplastic adenomas
Atypical adenoma: TP53 mutations, high mitotic activity, aggressive,
Genes in Marfan syndrome
Fibrillin 1
TGFBR in MFS Type II
ACTA2
MYTH11
How to see if thyroid nodule is neoplastic?
Solitary nodules
In ver young or very old
Males
Radiation exposure history
Cold nodules that do not take up radioactive iodine
Thyroid adenomas (painless) (cold)
Derived from follicular epithelium
Less common toxic adenomas that cause thyrotoxicosis
Pathogenesis =
Gain of function mutations in TSHR and GNAS
Thyroid autonomy
Over abundance of thyroid hormone = hyperthyroidism (HOT NODULE)
Morphology of thyroid adenomas
Solitary
INTACT CAPSULE, well defined
Oxyphil change: bright eosinophilic granular cytoplasm
Nuclear pleomorphism,atypia and prominent nuclei
Thyroid carcinoma pathogenesis
Female predominance
ionizing radiation in first 2 decades of life.
PAPILLARY: +MAP kinase pathway > rearranged tyrosine kinase RET and NTRK1 , point mutation in BRAF
FOLLICULAR: driver mutations in RAS or PI3K/AKT (GOF) , LOF mutations in PTEN, PAX8 , PPARG
ANAPLASTIC: RAS, TP53
These are derived from follicular epithelium.
MEDULLARY: arise from parafollicular C cells. In MEN 2
RET mutations in tyrosine kinase receptor
Papillary carcinoma thyroid
Presents as painless mass in thyroid or neck when metastases to lymph nodes.
Poor prognosis in elderly.
Encapsulated,Papillae with multiple layers of cuboidal epithelial cells, orphan annie eye nuclei due to dispersed chromatin, pseudo inclusions, psamomoma bodies present. What is it?
Papillary carcinoma of thyroid
Presents as solitary cold nodule , no nodal metastases but to lungs,bone,liver, in a female above 40-60, resembling the follicles of normal thyroid, infiltrates thyroid parenchyma,hurthle cells are seen. No capsule, What is it?
Exclude capsule✅
Vascular invasion ✅
This is follicular carcinoma (not adenoma)
Widely invasive
A follicular variant of papillary carcinoma may progress to follicular carcinoma.
Presents as bulky mass in neck age 65 with history + .
Highly anaplastic undifferentiated pleomorphic / spindle shaped cells
What is it.
Anaplastic carcinoma
Poor prognosis due to extensive growth and compromising neck structures.
Neuroendocrine tumor that secretes calcitonin and other pp hormones. Patient has MEN 2. Patient is young child. He has dysphagiA / hoarseness,
Symptoms like diarrhoea due to VIP.
Elevated calcitoninlevels.
Medullary carcinoma
Morphology = both lobes, amyloid deposits, multicentricity , polygonal or spindle cells,calcitonin in cytoplasms,
Familial: multicentric C cell hyperplasia
Arise from focal hyperplasia
3 causes of thyrotoxicosis
Graves’ disease: hyperplasia, autoimmune
Hyper functioning: multi nodular goiter
And adenoma of thyroid.
Radioactive iodine determines etiology
Graves’ disease and toxic adenoma: increased uptake
Thyroditis: decreased uptake
Causes of hypothyroidism
Thyroid dysgenesis
Deficiency of iodine (enlarged thyroid)
Hashimoto thyroiditis (enlarged thyroid)
Iatrogenic
Baby presents after 18 day with impaired development of skeleton nd CNS , mental retardation, short stature, coarse facial features, protruding tongue, umbilical hernia. Diagnosis.
Cretinism
Pathogenesis of myxedema
Decreased cardiac output: thyroid regulates Ca ATPase leades to SOB and less exercise capacity
Decreased blood flow: cool and pale skin
Decreased sympathetic activity: constipation and decreased sweating
Increase cholesterol and LDL
Accumulation of GAGs, hyaluronic acid in skin, SC nd viscera resulting in non pitting edema , broade and coarse facial features, large tongue and deep voice
Symmetrical , diffuse painless enlargement in neck
Decreased TSH, Radioactive iodine uptake is low, initially raised T3 and T4.
Then levels fall with increase in TSH.
mononuclear inflammatory infiltrate, germinal centres
Hashitoxicosid: initially a hyper state due to disruption of thyroid follicles with release of thyroid hormones
#hurthle cells: abundant eosinophilic granular cytoplasm (metaplasia), many mitochondrion
#may be atrophic dur to fibrosis
Neck pain wd swallowing
Fever,malaise, enlargement
ESR raised also leukocyte cpunt
History of respiratory infection
Subacute granulomatous thyroiditis , de quervain
Pathogenesis of graves disease
Thyroid stimulating immunoglobulin mimics TSH : stimulates adenylyl cyclase.
Same by thyroid growth stimulating immunoglobulins.
TSH binding inhibitor immunoglobulins.
Infiltrative opthalmopathy: T cell mediated
Volume of retro orbit CT and extraocular muscles increase (fats, mononuclear cells, edema,matrix)
Morphology of Graves’ disease
Diffuse hypertrophy and hyperplasia
Capsule intact
Small papillae but LACK FIBROVASCULAR CORE
Lymphoid hyperplasia
Large neck mass, dysphagia, breathing problem, SVCsyndrome,
No dermopathy or eye changes
Graves disease
Thyrotoxicosis may develop due to autonomous nodules (TOXIC MULTINODULAR GOITRE)
