L14~15 – Pathology of Endocrine Disorders Flashcards
List the eosinophilic cells in the pituitary gland + their secretion?
1) Somatotrophs =Growth hormone (GH)
2) Lactotrophs = Prolactin
List the basophilic cells in pituitary and their secretion?
1) Corticotrophs =Adrenocorticotropic hormone (ACTH)
2) Thyrotrophs = Thyroid-stimulating hormone (TSH)
2) Gonadotrophs = Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
How to define pituitary adenoma based on size?
macroadenoma (>1cm) vs. microadenoma (<1cm)
Which cell types are most commonly affected in Pituitary adenoma?
Lactotrophs
Somatotrophs
Corticotrophs
Describe the histological organization of pituitary adenoma?
- POLYGONAL cells with round nucleus, arranged in sheets / cords
- GRANULAR cytoplasm with rich vasculature
- rare mitotic figures, little pleomorphism
Name the immunostain used for pituitary adenoma?
Synaptophysin = endocrine marker
Can use antibody for prolactin, growth hormone etc.
List some causes of hypopituitarism?
Tumor / mass lesion (compresses on pituitary fossa)
Surgery / radiation
Trauma
Ischemic necrosis, Sheehan syndrome (associated with pregnancy)
Infection/inflammation
Cell types in the endocrine component of pancreas?
◦ Islets of Langerhans
> > β, α, δ (somatostatin), and PP (pancreatic polypeptide)cells
Disease caused by hypofunctional pancreas?
Diabetes mellitus
How does DM affect glucose, protein and lipid metabolism?
Increase lipolysis
Decreased protein synthesis, increase proteolysis
Overproduction of glucose, failure of glycogenesis
3 histological features of pancreatic cells in DM?
◦ Low number, smaller islets**
◦ Leukocytic infiltrates** in the islets (insulitis): T lymphocytes and eosinophils
◦ Amyloid deposition** within islets, around capillaries and between cells (type 2 diabetes )
Name 4 hyperfunctional pancreatic disease and list one complication each?
islet cell tumors:
Insulinoma > hypoglycaemia
Gastrinoma > Severe peptic ulcer (Zollinger-Ellison Syndrome)
Glucagonoma > Secondary diabetes
VIP-oma >Watery diarrhea
Histological appearance of islet cell tumours of pancreas?
Arranged in ribbons, anastomosing trabeculae
Richly vascularized background (capillaries)
Monotonous: round nuclei, fine chromatin, granular eosinophilic cytoplasm
Define the 3 layers and respective secretions in the adrenal cortex?
Superficial to deep:
◦ Zona glomerulosa (mineralocorticoids)
◦ Zona fasciculata (glucocorticoids)
◦ Zona reticularis (sex steroids)
Compare the embryonic origin between adrenal medulla and cortex?
Cortex = mesoderm
Medulla = neural crest»_space; part of sympathetic nervous system
Cell types and function of adrenal medulla?
chromaffin cells and sympathetic nerve endings
synthesize and secrete catecholamines, mainly epinephrine, some NE
Difference between primary and secondary adrenal gland hypofunction?
Primary (etiology resides in adrenal gland itself) vs.
secondary (etiology resides higher up in the axis, e.g. hypothalamus, pituitary)
List 2 adrenal gland hypofunctional diseases?
Waterhouse-Friderichsen Syndrome = acute primary insufficiency
Addison Disease = primary chronic adrenocortical insufficiency
Pathogenesis of Waterhouse-Friderichsen Syndrome?
Acute primary insufficiency:
Overwhelming / fulminant bacterial infection
> > hypotension, shock, DIC
> > massive adrenal hemorrhage, necrosis
> > adrenocortical insufficiency
List causes of Addison disease/ primary chronic adrenocortical insufficiency?
◦ Autoimmune adrenalitis**
◦ Tuberculosis & infections
◦ Amyloidosis
◦ Metastatic cancers
How does AMyloidosis lead to Addison disease?
abnormal systemic/nonspecific extracellular matrix deposition (e.g. renal, adrenal)
> > replaces normal tissue, removes normal function of adrenal gland
List 4 hyperfunctional adrenal gland diseases?
◦ Hyperplasia
◦ Cortical adenomas
◦ Pheochromocytoma
Secondary aldosteronism
Which layer of the adrenal cortex is affected in Cushing’s syndrome?
Zona fasciculata: glucocorticoids
Clinical presentation and causes (3) of Cushing’s syndrome?
central obesity, hirsutism, hypertension, diabetes, osteoporosis
- Cortical adenoma
- Secondary to pituitary hypersecretion of ACTH
- Iatrogenic by ACTH or steroid admin.
Which layer of the adrenal gland is affected in Conn’s syndrome? Effect?
Cortical adenoma in Zona glomerulosa: mineralocorticoids
Autonomous secretion of excess aldosterone» primary hyperaldosteronism:
Renal retention of Na+ Loss of K+
» Electrolyte disturbance
Histological appearance of cortical adenoma in adrenal cortex?
Very typical endocrine histology
Arranged in packets in a vascularized background
Central regular nuclei
Pale to clear, granular cytoplasm
Clinical presentation of pheochromocytoma? Give one fatal complication?
hypertension, tachycardia, palpitations, headache, sweating, tremor, sense of apprehension
Malignant hypertension + vasoconstriction» myocardial infarct
Explain why pheochromocytoma is called a “10% tumour”?
10% extra-adrenal (along aorta)
10% sporadic tumors are bilateral
10% biologically malignant (defined by presence of metastasis)
10% not associated with hypertension
What is the key Dx test for pheochromocytoma?
Increased urine catecholamines, vanillylmandelic acid
Gross morphology of pheochromocytoma?
◦ Pale gray or brown,
◦ Hemorrhage, necrosis, cystic change
Histological feature of Pheochromocytoma?
◦ Zellballen, trabecular or solid pattern
◦ POLYGONAL or spindle cells + RICHLY VASCULARIZED BACKGROUND
◦ Finely basophilic or amphophilic GRANULAR cytoplasm “Dirty Blue”
Mechanism of aldosterone?
glomerular perfusion (e.g. low BP)
> > stimulates renin-angiotensin system
> > secrete aldosterone (retains Na+, water)
> > brings BP back to normal
List 2 neoplasms from adrenal cortex, 2 from medulla?
Cortex: Adenoma and carcinoma
Medulla: Pheochromocytoma and Neuroblastoma
Adrenal adenoma affect children more, whereas adrenal carcinoma affect adults more. T or F?
False
In adults: adenomas, carcinomas
In children: carcinoma predominates
Etiology, gross and histological appearance of adrenal medulla neuroblastoma?
infants, children (most before the age of 3)
Grossly: soft, lobulated
Histologically: small blue round cell tumor, undifferentiated
How to ddx lymphoma at adrenal gland vs neuroblastoma?
need immunophenotyping to distinguish
Normal histology of thyroid gland?
Lobules divided by thin fibrous septa
Each lobule consists of 20-40 follicles lined by cuboidal to low columnar epithelium: follicular and parafollicular cells
Causes of thyroid hyperplasia?
1) Iodine deficiency**
2) GOITROGEN
3) Hereditary defect in enzyme synthesis
> > Compensatory increase in TSH, growth of follicular cells and increase T3,T4
2 stages of thyroid hyperplasia?
- Hyperplastic stage (enlarged follicles filled with colloid)
- Colloid involution
Clinical presentation of multinodular goiter?
1) EUTHYROID / subclinical hyperthyroidism
2) Toxic or non-toxic
3) Compression on trachea, larynx
4) ASYMMETRICAL LOBES on neck
Histological appearance of multinodular goitre?
VARIABLE- SIZED FOLLICLES with FIBROSIS
HEMORRHAGE into colloid
cystic change, calcification
Glassy appearance
Outline 1 benign and 4 malignant thyroid neoplasms?
Follicular adenoma (benign)
Malignant: ◦ Papillary carcinoma***common*** ◦ Follicular carcinoma ◦ Anaplastic carcinoma ◦ Medullary carcinoma (parafollicular cell origin)
Follicular adenoma leads to hyperthyroidism. T or F?
Most are non-functional = no hyperthyroidism
Histological appearance of thyroid follicular adenoma?
- ENCAPSULATED nodule, well-circumcised mass
- Follicles + MICROFOLLICLES with colloid
- Mild cytological atypia
- No capsular or vascular invasion**
- No papillary carcinoma features
Risk factor, peak age of incidence, prognostic factors of Papillary adenoma of thyroid?
Age of presentation: 25-50 years
Risk factor: ionizing radiation exposure
Excellent prognosis:
10-year survival rate >95%
Prognostic factors: age, stage/metastasis, extrathyroidal extension
CLinical symptoms of papillary carcinoma of thyroid?
ASYMPTOMATIC thyroid nodules (appear as multifocal tumors)
Lymphatic spread to CERVICAL LYMPH NODES
Late: hoarseness, dysphagia, cough, dyspnea
Histological features of thyroid papillary carcinoma?
PSEUDONUCLEAR INCLUSIONS (pink globule in nucleus)
NUCLEAR GROOVES
PAPILLARY STRUCTURE
PSAMOMMA bodies (= calcified bodies)
Overlapping ground-glass nuclei
Multinucleated giant cells
2 differences between the behavior of follicular carcinoma and papillary carcinoma of thyroid?
papillary carinoma = lymphatic spread, no capsule or vascular invasion
Follicular carcinoma = hematogenous metastasis (to bone, liver, lungs), invasion into capsule
Histological features of follicular carcinoma?
(Same as Follicular Adenoma:)
◦ Encapsulated
◦ Colloid-containing follicles and microfollicles
◦ Cytological atypia
Ddx from Follicular adenoma:
◦ CAPSULAR/ VASCULAR INVASION
Age of onset, preceding condition, prognosis of anaplastic/ undifferentiated carcinoma of thyroid?
Mean age: 65 years (elderly)
Preceding / concurrent well-differentiated thyroid carcinoma (e.g. papillary, follicular carcinoma)
Bad prognosis: mortality rate approaches 100%
Histological appearacne of anaplastic carcinoma of thyroid?
markedly pleormorphic cells / spindle cells / squamoid cells
Histology of medullary carcinoma of thyroid?
No follicles, no colloid, no carcinoma features
Loss of architecture
Cell of origin and 2 types of medullary carcinoma?
parafollicular (C) cells
70% = sporadic
30% = multiple endocrine neoplasia (MEN) syndrome
Define MEN syndrome?
Multiple Endocrine Neoplasia(MEN) syndromes
group of genetically inherited diseases
> > proliferative lesions (hyperplasia, adenomas, and carcinomas) of multiple endocrine organs
MULTIFOCAL, MULTIPLE ORGANS, AGGRESSIVE
Define the defective gene in MEN1 and neoplasia caused?
MEN 1 (Wermer Syndrome)
MEN1 encoding MENIN
Pituitary tumor (frequently prolactinoma)
Parathyroid hyperplasia / adenoma
Pancreas endocrine tumour: islet cell tumours
Define the defective gene in MEN2A and 2B and compare the neoplasms caused?
Defective gene: RET
Both MEN2A and 2B:
- Medullary thyroid carcinoma
- Pheochromocytoma
MEN2A:
- Parathyroid hyperplasia
MEN2B:
- Neuromas/ ganglioneuromas of skin, oral musosa, GIT, Resp. tract, eyes
Treatment and dx for MEN syndromes?
surgical intervention
diagnose with molecular technologies (genetic test + genetic counselling)
General treatment of endocrine carcinoma?
- Surgical removal
- Radiation ablation
- Hormone replacement
- Monitoring for recurrence
