Systemic Pathology - Endocrine System - Mirani

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  1. Endocrine System
    • System of ductless glands.
    • Hormones secreted into the bloodstream.
    • Orchestrate a state of metabolic equilibrium or homeostasis.
    • Endocrine organs dedicated to production of hormones e.g. pituitary, thyroid….etc
    • Endocrine components in clusters in organs having mixed functions e.g. pancreas, ovary, testes…..
    • Diffuse endocrine system comprising scattered cells within organs acting locally on adjacent cells without entry into blood stream, paracrine or autocrine.
  2. Endocrine glands
    • Exocrine - ducted; carry secretion to outside surface, eg. sweat (eccrine), sebaceous, mammary, digestive (pancreas, liver, gall bladder), etc.
    • Endocrine - ductless; secrete into interstitial fluid, diffuse into blood.
  3. Endocrine glands
    • Pituitary, thyroid, parathyroid, adrenal, pineal glands.
    • Hypothalamus, thymus, pancreas, ovaries, testes, kidneys, stomach, liver, small intestine, skin, heart, adipose tissue, placenta - NOT exclusively endocrine glands.
  4. Transportation of Hormones
    • Bounded to plasma proteins such as thyroid and steroid (they serve as a reserve for acute changes).
    • Some are transported free in the blood.
    • Only free hormones are biological active
  5. General characteristic of hormones
    • Specific rates and patterns of secretion: diurnal, pulsatile, cyclic patterns, depending on the level of circulating substrates.
    • Feedback systems: positive (rare) or negative, to maintain an optimal internal environment.
    • Affect only cells with appropriate receptors -> specific cell function(s) is initiated
    • Excreted by the kidney, deactivated by the liver or by other mechanisms
  6. Functions of endocrine system
    • Response to stress and injury
    • Growth and development
    • Reproduction
    • Homeostasis
    • Energy metabolism
  7. Diseases divided into
    • Hyperfunction - overproduction
    • Hypofunction - underproduction
    • Mass effects (Tumors) - nonfunctioning
    • Correlation of hormonal assays, clinical, biochemical, and pathological findings, are of extreme importance in most conditions.
  8. Pancreas
    Exocrine (digestive enzymes) as well endocrine (hormones such as insulin).
  9. Pancreatic Anatomy
    • Location - retro-peritoneum, 2nd lumbar vertebral level.
    • Extends in an oblique, transverse position.
    • Parts of pancreas: head, neck, body and tail. Most Islet of Langerhans cells are located in the body and tail; the part to look at when there is a tumor.
  10. Islet of Langerhans
    • One million islets of Langerhans
    • Different types of cells can be identified immunohistologically.
    • α cells - glucagon; stimulates Glucose synthesis & glycogen breakdown in liver; raise blood glucose concentration (normal level ~ 0.9 gram per Liter).
    • β cells - insulin; Stimulation of lipids & glycogen storage & formation; Lower blood glucose concentration.
    • δ cells - somatostatin; Inhibits secretion of insulin & glucagon. Pancreatic polypeptide (PP) becomes VIP (vasoactive interstitial polypeptide
  11. Islet cell diseases
    • Diabetes
    • Islet Cell Tumors
  12. Diabetes Mellitus
    • Metabolic disorders
    • Hyperglycemia
    • Defects in insulin secretion, or insulin action, or most commonly, both.
    • Accelerates atherosclerosis, hypertension and Affects multiple organ systems - kidneys, eyes, nerves and blood vessels
    • Affects over 20 million in adults and children.
    • Leading cause of end stage liver disease, adult-onset blindness and non-traumatic lower extremity amputation in US.
  13. Diabetes Classification
    • Causes could be Primary in the pancreas or secondary to other disease conditions
    • Primary diabetes is classified into :
    • A- Type 1 (approximately 10%)
    • B- Type 2 (approximately 90%)
    • C- Genetic & Miscellaneous causes
    • Whatever the type, complications are the same.
  14. Type 1
    • Develops in childhood.
    • Autoimmune destruction of islet cells
    • Insulitis - Heavy lymphocytic (CD4, CD8) infiltrates appear in and around islets.
    • The islets of Langerhans are destroyed (90% of cells lost before metabolic changes appear)
    • Polyuria , Polydipsia, Polyphagia (3P’s)
    • Metabolic acidosis, weight loss, dehydration, & electrolyte imbalance.
    • Ketoacidosis is common.
  15. Type 2
    • Age > 30yrs, often present incidentally
    • Sedentary life style and overweight
    • Insulin resistance & β cells dysfunction , resulting in relative insulin deficiency
    • Fibrosis and deposition of amylin polypeptide within islets: amyloid deposition; very few islet cells left
    • 3 P’s and symptoms of complications
    • Rare ketoacidosis
  16. Secondary Miscellaneous Causes
    • Diseases of exocrine pancreas e.g. chronic pancreatitis
    • Endocrinopathies e.g. Cushing’s Syndrome, Acromegaly
    • Infections e.g. CMV
    • Drugs e.g. glucocorticoids
    • Gestational diabetes
  17. Common differences between type 1 and type 2 diabetes
    • Age of diagnosis: childhood vs. 30 plus
    • Associated with obesity: no vs. yes
    • Blood pressure and/or cholesterol level: normal vs. high
    • Ketone level: high vs. normal
    • Insulin dependent: yes vs. no
    • Treatment: insulin injection/pump vs. no medication or insulin tablets.
  18. Laboratory Diagnosis
    • Random glucose over 2gram per Liter + symptoms.
    • Fasting glucose over 1.26gram per Liter on more
    • than one occasion.
    • Abnormal oral glucose tolerance test when glucose level is more than 2 gram per Liter 2hrs after standard glucose load of 75 gram.
  19. Diagnosis Glycosylated Hemoglobin - H b A 1 c
    • Measures the amount of glucose that has been incorporated into the hemoglobin protein of the red blood cell (RBC).
    • More stable than sugar levels.
    • Not affected by short-term fluctuations in sugar.
    • Normal is 4-6%.
    • Evaluated periodically (1-2 per year).
  20. Blood test levels for diagnosis of Diabetes and Prediabetes
    • A1C %
    • - Normal ~5
    • - Prediabetes 5.7-6.4
    • - Diabetes 6.5 or above
    • Fasting plasma glucose mg/dl
    • - Normal no more than 99
    • - Prediabetes 100-125
    • - Diabetes 126 or above
    • Oral glucose Tolerance test mg/dl
    • - Normal no more than 139
    • - Prediabetes 140-199
    • - Diabetes 200 or above
  21. Complications of diabetes
    • Microangiopathy - cerebral vascular infarcts; hemorrhage
    • Retinophathy - cataracts; glaucoma
    • Nephrosclerosis - glomerulosclerosis
    • Peripheral vascular atherosclerosis - gangrene, infections
  22. Renal Complications
    • Both nodular (Kimmelstiel - Wilson lesion) and diffuse glomerulosclerosis
    • Chronic renal failure eventually
    • Infections – pyelonephritis (bacterial and fungal infections)
  23. Ocular Complications - Diabetic retinopathy
    • One of the leading causes for irreversible blindness in the United States
    • Cataract - developed at very early age
    • Glaucoma
    • Blindness
  24. Atherosclerosis
    • Early and accelerated atherosclerosis
    • Hypertension
    • Heart disease, cerebrovascular disease, and renal disease
    • The most common cause of death - myocardial infarction
    • Peripheral vascular disease - gangrene leg and amputation
    • Diabetic neuropathy, leading to propensity for injury
  25. Diabetes Mellitus Treatment
    • Type 1: insulin administration
    • Type 2: diet & exercise
    • - Oral hypoglycemics
    • - Insulin
  26. Pancreatic Neuroendocrine Tumors (PanNETs)
    • a.k.a. Islet cell tumors
    • 2% of all pancreatic neoplasms
    • Common in adults, in body or tail
    • Single or multifocal
    • Functional (excessive hormone production) and nonfunctional (without hormone production; larger and metastasize)
    • Slow growing, metastases to nodes, liver, bone.
    • 80% occur in MEN1 patients.
    • Insulinoma: most common; followed by gastrinoma
  27. Types of Islet cell tumors
    • Insulinoma – Beta cells; insulin-secreting tumor
    • Gastrinoma – Delta cells
    • Somasostatinoma – Delta cells
    • Glucagonoma – Alpha cells
    • VIPoma – Delta cells
    • Nonfunctional
  28. Islet cell tumor Histology
    • Solid, gyriform, trabecular and glandular patterns.
    • Nests of polygonal cells with moderate to abundant eosinophilic cytoplasm.
    • Amyloid is produced by insulin-secreting tumors (from amylin or somatostatin).
    • Immunostains not necessary for diagnosis.
    • - Synaptophysin
    • - Chromogranin
    • - Insulin
    • - EM – dense core granules
  29. W.H.O. grading system
    • Low grade (G1): <2 mitoses per 10 hpf (high power field) and <3% Ki67 (immunostain, discriminate cells according to cell cycle phases) index
    • Intermediate grade (G2): 2-20 mitoses per 10 HPF or 3%-20% Ki67 index
    • High grade (G3): >20 mitoses per 10 hpf or >20% Ki67 index
  30. Insulinoma
    • Commonest type.
    • Hypoglycemia ≤ 0.5 gram per liter.
    • Attack induced by fasting or exercise, relieved by eating or glucose administration
    • Lab - low serum glucose, high serum insulin.
    • Most tumors solitary (< 2 cm), can be multiple.
    • Majority are benign, 10% malignant.
    • 90% cured by resection.
  31. Gastrinoma
    • 2/3 of cases malignant.
    • Present with Zollinger-Ellison Syndrome (triad - hypersecretion of gastric acid, severe peptic ulceration, and non-beta cell tumor of the pancreas or duodenum).
    • Marked elevation of serum gastrin (>1000 pg/ml).
    • Medical therapy for control of the acid hypersecretion.
    • Histologically bland.
    • May be associated with MEN1.
  32. Nonfunctional islet cell tumors
    • 25% of islet cell tumors
    • 90% malignant
    • Age 50 year, female predominance
    • Compression related symptoms
    • Treatment - surgery
  33. Parathyroid
    • Normally on the posterior thyroid surface
    • Most persons have four; may vary between 1 to 12.
    • Well capsulated.
    • Derivatives of third and fourth branchial pouches.
    • Ectopic locations:
    • - intrathyroid
    • - intrathymic
    • - anterior mediastinum
  34. Histology of Parathyroid
    • Chief cells – polygonal cells with clear cytoplasm (glycogen) and central uniform nuclei; secrete PTH.
    • Oxyphil cells – larger than chief cells, acidophilic cytoplasm (pink), packed with mitochondria.
    • Stromal fat – approximately 30% of the gland; increases when older.
  35. Activity of parathyroid gland in regulating systemic calcium homeostasis is controlled by free (ionized) calcium rather than trophic hormones.
  36. Normal calcium level
    • Serum Calcium: 8 to 10 mg per dl
    • Ionized (free) Calcium: 4 to 5.6 mg per dl
  37. PTH function
    • increase plasma calcium level via
    • - increase bone resorption.
    • - lower renal phosphate reabsorption and increase calcium reabsorption.
    • - increase intestinal calcium absorption (by stimulating renal secretion of 1,25-DH-viatmin D3).
  38. Causes of hypercalcemia
    • Raised PTH - Hyperparathyroidism (primary, secondary and tertiary); Parathyroid tumor. Normal level - 10-65 nmol per Liter.
    • Decreased PTH (non-PTH)
    • - Hypercalcemia of malignancy (most common, esp lung)
    • - Vitamin D toxicity
    • - Immobilization
    • - Thiazide diuretics
    • - Granulomatous disease (sarcoidosis)
  39. Hyperparathyroidism
    • Normal PTH - 10 to 65 nanomoles per Liter.
    • Increased parathyroid hormone.
    • Serum calcium may be decreased, increased or normal, depending upon renal function.
    • Primary hyperparathyroidism – excess of parathyroid hormone from adenoma (85 to 95%), hyperplasia (5 to 10%) or carcinoma (1%).
    • Secondary hyperparathyroidism – adaptive increase in parathyroid hormone secondary to hypocalcemia and hyperphosphatemia of chronic renal failure.
    • Tertiary hyperparathyroidism – autonomous parathyroid hyperfunction in patients with secondary hyperparathyroidism.
  40. Parathyroid hormone and calcium in hyperparathyroidism
    • Primary - normal or high PTH; high calcium.
    • Secondary - high PTH; high or normal calcium.
    • Tertiary - very high PTH; high calcium.
  41. Hyperparathyroidism Signs / Symptoms
    • Hypercalcemia, hypophosphatemia
    • Asymptomatic mostly or present with nonspecfic symptoms such as fatigue, lethargy and muscle weakness.
    • “Bones, stones, abdominal groans, psychic moans”
    • Bones - pain, arthralgia - osteoporosis, osteitis fibrosa cystica (brown tumor, similar to the ones in jaw bones), fracture.
    • Renal - Stones, polyuria, nephrocalcinosis.
    • G.I. - Pain, duodenal ulcer, pancreatitis, gallstones.
    • Neuro - Depression, apathy
    • Cardiac - Hypertension, heart block
  42. Parathyroid adenoma
    • Benign neoplasm.
    • Involve a single gland, rarely two or more (<1%).
    • Major cause of primary hyperparathyroidism.
    • Any age, F:M 3:1.
    • Excellent prognosis after excision.
    • Sharply demarcated from the adjacent rim of normal parathyroid.
    • Predominantly chief cells in sheets or tubules.
    • Adipose tissue inconspicuous.
  43. Parathyroid hyperplasia
    • Classically all four parathyroid involved (frequently asymmetrical).
    • Sporadic or as a component of MEN syndrome.
    • 75% sporadic
    • 15% part of MEN 2A (not MEN 2B)
    • 15% of hyperparathyroidism cases
    • Diagnosis of adenoma versus hyperplasia may depend on the size of the other glands (one is adenoma, two or more is hyperplasia).
    • Enlarged parathyroids.
    • Usually chief cell hyperplasia, diffuse or nodular
    • Variable oncocytes.
    • Cystic change in markedly enlarged glands.
    • Stromal fat inconspicuous.
  44. Parathyroid carcinoma
    • Palpable neck mass (75%)
    • Excessive PTH secretion, high serum calcium > 14 mg/dl.
    • Non-functioning tumors are rare.
    • Diagnosis based on local invasion and metastases (clinical criteria, NOT microscopic criteria).
    • 1/3 recur locally; 1/3 have distant metastases.
    • Densely adherent to surrounding soft tissue.
    • Thick fibrous bands.
    • Predominantly chief cells arranged in solid or trabecular pattern.
    • Macronucleoli, more than five mitoses per 50 hpf, necrosis associated with aggressive behavior.
    • Cytological detail, unreliable for the diagnosis of carcinoma.
  45. Hypoparathyroidism
    • Insufficient parathyroid hormone is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood.
    • Hypoparathyroidism is far less common.
    • Causes
    • – Damage to the gland or its vessels during thyroid surgery
    • - Idiopathic, autoimmune disease, congenital
    • Clinical features:
    • - Tetany, convulsion, neuromuscular irritability, cardiac arrhythmias, increased intracranial pressure, seizures, ...
  46. Multiple Endocrine Neoplasia
    • MEN I (Wermer syndrome)
    • - Neoplasia of Pituitary, Parathyroids, Pancreas and Carcinoids;
    • - Parathyroid hyperplasia.
    • MEN IIA (Sipple's syndrome)
    • - Parathyroid hyperplasia
    • - Medullary thyroid (c-cell) carcinoma
    • - Pheochromocytomas.
    • MEN IIB
    • - Medullary thyroid (c-cell) carcinoma
    • - Pheochromocytomas
    • - Neuromas of eye, buccal mucosa and GI mucosa.
  47. Thyroid gland anatomy
    • Pyramidal lobe (present in 40% population)
    • Isthmus
    • Left and right lobes
  48. Thyroid gland Histology
    • Follicles made of Colloid surrounded by follicular epithelial cells (squamous, cuboid, or columnar; secreting thyroid hormones - T3 and T4).
    • Parafollicular cell (C cell; fewer and scattered) secretes calcitonin, can be picked up by calcitonin stain.
    • Capillary in the connective tissue.
  49. Thyroid
    • Largest endocrine organ
    • Thyroid hormones (TH)
    • - Thyroxine (T4)
    • - Triiodothyronine (T3)
    • - Calcitonin
  50. Thyroid physiology
    • Hypothalamus stimulates pituitory to release T.S.H. via T.R.H.
    • Serum free hormone level inhibits pituitary to release T.S.H.
    • T.S.H. stimulates thyroid to release T3 and T4
    • liver releases thyroid binding proteins to bind T3/T4.
  51. Heterotopic thyroid
    • Duct from Foramen cecum to suprasternal notch.
    • Lingual thyroid - Most frequent; more in children; base of tongue with total migration failure; 75% have no other thyroid tissue.
    • Other sites – anterior tongue, larynx, trachea, mediastinum, heart.
  52. Thyroglossal duct cyst
    • Persistence and dilatation of thyroglossal duct in midline of neck.
    • Asymptomatic unless infected.
    • Moves with swallowing.
    • Squamous or respiratory epithelium lining cyst.
  53. Hypothyroidism
    • Primary:
    • - Loss of thyroid tissue due to surgery or radiation therapy
    • - Hashimoto’s thyroiditis (most common cause in USA)
    • - Iodine deficiency (in endemic areas; most common cause worldwide)
    • - Drugs e.g. iodides, lithium…..
    • Secondary:
    • - Pituitary or Hypothalamic failure
  54. Hypothyroidism (underactive thyroid)
    • High TSH, low T3, T4
    • Hypothyroidism in infants – cretinism (poor growth, resulting in short stature, delayed development of permanent teeth, Delayed puberty, poor mental development).
    • Hypothyroidism in adults - myxedema
    • Treatment - Synthetic thyroid hormone
  55. Classification of Thyroiditis
    • Chronic lymphocytic
    • - Chronic lymphocytic thyroiditis
    • - Hashimoto's thyroiditis
    • Granulomatous
    • - Subacute granulomatous thyroiditis
    • - de Quervain's thyroiditis
    • Invasive fibrous
    • - Riedel's struma
    • - Riedel's thyroiditis
  56. Hashimoto thyroiditis (Stuma Lymphomatosa)
    • Most common cause of goiter in the United States.
    • Autoimmune origin.
    • Painless enlargement, no tenderness when palpated.
    • Diffuse nontender rubbery thyroid enlargement.
    • Variable functional status: euthyroid (normal serum level), hyperthyroid (Hashitoxicosis; when follicle ruptures and T3/4 released) or hypothyroid.
    • Flashy cut surface.
    • Histologic diagnostic triad:
    • - lymphocytic infiltrate
    • - lymphoid follicles with germinal centers
    • - Hurthle cell metaplasia of follicular epithelium
    • High risk for B-cell lymphoma, papillary carcinoma and Hurthle cell neoplasm
  57. Subacute thyroiditis (granulomatous thyroiditis or De Quervain thyroiditis)
    • Caused by viral infection.
    • Most common cause of painful thyroid.
    • Onset often acute, fever and malaise.
    • Triphasic clinical course - hyperthyroidism, hypothyroidism, and return to normal thyroid function (within 6-8 weeks).
    • Disruption of follicles with inflammation.
    • Granulomatous reaction to colloid.
    • Multinucleated giant cells.
  58. Riedel’s thyroiditis (Riedel’s struma, fibrous thyroiditis)
    • Rare.
    • Autoimmune etiology.
    • Stony hard painless thyroid gland.
    • Extensive fibrosis.
    • Clinically resembles carcinoma, compress trachea.
    • Broad bands of fibrosis with keloid like fibers.
    • Patchy lymphocytes, plasma cells and eosinophils.
    • Follicles are obliterated.
    • Obliterating phlebitis.
  59. Thyrotoxicosis
    • Hypermetabolic state caused by T4, T3
    • Primary: Graves Disease
    • Secondary: TSH-secreting pituitary adenoma
  60. Clinical Picture of Thyrotoxicosis
    • Heat intolerance, sweating, warm skin, malabsorption
    • Cardiac - palpitation, tachycardia, CHF
    • Menstrual disturbances
    • Neuromuscular - Tremor, muscle weakness
    • Ocular - thyroid ophthalmopathy
  61. Diffuse goiter (Graves’ Disease)
    • Autoimmune disease.
    • Thyrotoxicosis with smooth symmetrical enlargement of thyroid.
    • Infiltrative ophthalmopathy with exophthalmus in 40%
    • of patients.
    • Lab findings - increased T4 & T3, decreased TSH.
    • Radioactive study- Diffuse uptake of radioactive Iodine.
    • Most common cause of endogenous hyperthyroidism.
    • Triad of clinical findings:
    • - diffuse enlargement of thyroid
    • - infiltrative ophthalmopathy (exophthalmos)
    • - Infiltrative dermatopathy (periorbital myxedema)
  62. Histology of Diffuse goiter (Graves’ Disease)
    • Diffuse hyperplasia of thyroid follicular cells.
    • Papillary hyperplasia.
    • Scalloped appearance of the edges of the colloid.
    • Lymphoid follicles.
  63. Risk factors of malignant/neoplastic thyroid nodules
    • Solitary nodule.
    • Cold nodules - Up to 10% of cold nodules prove to be malignant.
    • Younger patients.
    • Males.
    • History of previous radiation to the neck.
  64. Multinodular goiter
    • Incidence 3-5%, and 50% in autopsy cases.
    • Sometime extends in the mediastinum.
    • Pressure effect on trachea.
    • Endemic (iodine deficiency) and sporadic.
    • Can have gelatinous colloid, cysts.
    • Distended follicles of various sizes, filled with colloid, flat follicular epithelium.
    • Fibrosis.
    • Focal hyperplasia, scalloping
    • Hemorrhage
    • Calcification
  65. Thyroid neoplasm
    • Most common endocrine malignancy.
    • Less than 2% of all human cancers.
    • Generally more common in women.
    • Associated with radiation exposure and endemic goiters.
    • Benign to malignant ratio is 10:1.
    • Low mortality rate - 0.4% of cancer deaths.
  66. Clinical manifestations of thyroid neoplasm
    • Euthyroid and present with thyroid nodule.
    • Symptoms such as dysphagia, dyspnea, and hoarseness usually indicate advanced disease.
    • Ipsilateral cervical lymph nodes may be present.
  67. Thyroid neoplasm Diagnosis
    • Ultrasound examination of neck and thyroid.
    • Blood tests of thyroid function.
    • A radioactive thyroid scan.
    • A fine needle aspiration biopsy.
    • A chest X-ray.
    • A CT or MRI scan.
  68. Thyroid Neoplasms
    • Follicle derived give rises to well differentiated and anaplastic,
    • - Well differentiated give rises to papillary carcinoma and follicular tumors.
    • - - Follicular tumors give rises to follicular adenoma and follicular carcinoma.
    • C(hief)-cell derived give rise to Medullary carcinoma.
  69. Classification and Incidence of thyroid cancer
    • Tumors of follicular cell origin, differentiated
    • - Papillary 75%
    • - Follicular 10%
    • - Hurthle cell 5%
    • Tumors of follicular cell origin, undifferentiated
    • - Anaplastic 5%
    • Tumors of parafollicular cell origin
    • - Medullary 5%
    • Others
    • - Lymphoma <1%
  70. Follicular adenoma
    • Most common thyroid neoplasm.
    • Benign.
    • Almost always solitary.
    • Well capsulated.
    • Uniform follicles within the lesion.
    • Compress adjacent normal thyroid tissue.
    • No vascular or capsular invasion.
  71. Follicular carcinoma
    • 10 -15% of thyroid cancer.
    • Usually “cold” on radionuclide scan.
    • More aggressive.
    • Hematologic spread.
    • 60% 10 year surviva.l
    • Architectural patterns, follicular or solid.
    • Capsular invasion.
    • Vascular invasion beyond the capsule.
    • Integrity of capsule is important in differentiating adenoma from well differentiated follicular carcinoma.
  72. Papillary carcinoma
    • The most common malignant thyroid tumor (75%).
    • Any age.
    • Associated with prior radiation.
    • Spread via lymphatics – propensity for lymph node
    • metastasis.
    • Excellent prognosis.
    • 10 yr survival >95%.
  73. Branching papillae with fibrovascular core, lined by cuboidal to columnar epithelial cells and psammoma bodies.
    • Optically clear nuclei (Orphan Annie).
    • Intranuclear inclusion and groove.
  74. Papillary carcinoma PROGNOSTIC FACTORS: SAGES
    • SEX: WOMEN - good
    • AGE: CHIDREN - good
    • GRADE: DEDIFFERENTIATION - POOR
    • EXTENT: EXTRATHYROID EXTension - POOR
    • SIZE: LARGE - POOR
  75. Medullary carcinoma
    • Neuroendocrine neoplasm originate from calcitonin-producing parafollicular chief cells.
    • Solitary or multiple lesions.
    • 5-10% of all thyroid cancers.
    • 80% Sporadic.
    • 20% occurs in the setting of MEN 2A or 2B or as familial tumors.
    • Form nests, trabeculae or follicles.
    • Polygonal to spindle-shaped cells.
    • Acellular amyloid deposits (congo red positive; polarize).
    • Positive to Calcitonin immunostain.
  76. Anaplastic carcinoma
    • Originates from follicular cells.
    • Constitute 5-10% of all thyroid carcinomas.
    • Peak incidence – 7th decade.
    • Highly fatal, most die within one year.
    • Grows rapidly (needs to be treated immediately), spreads locally, invades trachea, esophagus, mediastinum by local invasion.
    • Gross - large solid tumor with necrosis and hemorrhage.
    • Pathology
    • - Multinucleated osteoclast-type giant cells
    • - Spindle cell sarcoma-like morphology
    • - Squamoid morphology
  77. Thyroid Carcinoma comparison
    • Type - %
    • - Papillary 75
    • - Follicular 15
    • - Anaplastic 5
    • - Medullary 5
    • Age
    • - Young <45y
    • - Middle age
    • - elderly
    • - Elderly, familial
    • Spread
    • - Lymph
    • - B.V.
    • - Local
    • - All
    • Prognosis
    • - Excellent
    • - Good
    • - Poor
    • - variable
  78. Anatomy of Pituitary gland
    • In sella turcica of sphenoid bone.
    • Weighs about 0.5gm.
    • Connected to the Hypothalamus with stalk.
    • Composed of:
    • - Anterior lobe - Adenohypophysis (80% volume)
    • - Posterior lobe - Neurohypophysis (20%); close to third ventricle, optic chiasm, cranial nerves, tumor can affect them.
    • Embryology - Roof of the oral cavity and diencephalon come together.
  79. Neurohypophysis
    • Pinker in color compared to adenohypophysis.
    • Stores and releases hormones secreted by hypothalamus: Oxytocin and Anti Diuretic hormone (ADH).
  80. Adenohypophysis
    • Releases hormones:
    • Growth hormone (GH)
    • Thyroid Stimulating hormone (TSH)
    • Adenocorticotropic hormone (ACTH)
    • Lutenizing hormone (LH) - target ovary
    • Follicle stimulating hormone (FSH) - target ovary
    • Prolactin (PRL) - tumor most common
    • Melanocyte stimulating hormone (MSH) - pigmentation
  81. Pituitary Diseases
    • TSH
    • –hypersecretion = hyperthyroidism
    • –hyposecretion = hypothyroisism
    • ACTH
    • –hyposecretion = secondary adrenal insufficiency, Addison’s disease
    • –hypersecretion = Cushing’s disease
    • FSH
    • –hyposecretion
    • •M = poor sperm production
    • •F = low estrogen, amenorrhea
    • –hypersecretion
    • •F = menopause
    • LH
    • –hyposecretion
    • •F = no ovulation
    • •M = low testosterone
    • MSH
    • –hypersecretion = excess pigment
    • GH
    • –hypersecretion = gigantism if during growth or acromegaly after growth
    • –hyposecretion = dwarfism
    • PRL
    • –hypersecretion = galactorrhea, infertility
    • –hyposecretion = poor milk production
    • ADH
    • –Hypersecretion = SIADH, Syndrome of Inappropriate ADH Secretion
    • –hyposecretion = diabetes insipidus
  82. Histology of Anterior Pituitary
    • The pink acidophils (acidophilic cytoplasm) secrete growth hormone (GH) and prolactin.
    • The dark purple basophils secrete corticotrophin (ACTH), thyroid stimulating hormone (TSH), and gonadotrophins, i.e. follicle stimulating hormone and luteinizing hormone.
    • The pale staining chromophobes have few cytoplasmic granules, but may have secretory activity, secretion is not much affected if tumor is developed from them.
  83. Pituitary Diseases
    • Hyperpituitarism-related effects:
    • - Excessive secretion of tropic hormones.
    • - Anterior pituitary adenoma (benign).
    • Hypopituitary-related effects:
    • - Deficiency of tropic hormones.
    • - Destructive processes (injury, inflammation, surgery, radiation).
    • Local mass effect:
    • - Compressive effect of optic chiasm or third ventricle (Headache, loss of vision, hydrocephalus).
  84. Hyperpituitarism
    In most cases due to ADENOMA of the anterior lobe.
  85. Benign pituitary adenomas
    • Pressure symptoms from glandular enlargement - Headache, seizures, drowsiness, visual defects.
    • Hormonal effects
    • - Usually stimulatory if functional tumor.
    • - May be inhibitory (non-functional with pressure necrosis).
    • Most common hormonally active adenomas - prolactinoma, followed by growth hormone related adenoma.
  86. Features common to all pituitary adenomas
    • 10% of all intracranial neoplasms & 25% incidental.
    • Most sporadic.
    • 3% occur with MEN I syndrome (3 P's).
    • Usually benign.
    • May or may not be functional.
    • If Functional, the clinical effects are secondary to the hormone produced, most commonly Prolactin and GH.
    • If Non-functional – large size, hypopituitarism (destroy adjacent anterior Pituitary), visual field abnormalities.
    • Microadenomas <1 cm, may cause focal bulging.
    • Macroadenoma >1 cm, mass effect.
  87. Diagnosis of Pituitary adenoma
    • Imaging:
    • - MRI brain with and without I.V. contrast (include thin cuts through pituitary); Tumor enhances less than gland, more lucent appearance.
    • Labs - Prolactin, FSH, LH, GH, ACTH, testosterone, GH, cortisol, IGF-1
    • Visual Fields - Performed by an ophthalmologist, temporal fields lost, central field remains.
  88. Morphology of Pituitary adenoma
    • Well circumscribed, invasive in up to 30%.
    • Size 1cm or more, specially in nonfunctioning tumor.
    • Hemorrhage & necrosis seen in large tumors.
    • Uniform cells - one cell type (monomorphism), less granular and hard to tell what hormones are secreted.
    • No reticulin network, no surrounding nest.
    • Rare or absent mitosis.
  89. Pituitary adenoma types
    • PRL secreting adenoma (prolactinoma) – Most common, 30% of pituitary adenoma, prolactin level is similar or higher than that during pregnancy.
    • ACTH secreting adenoma
    • Null cell adenoma
    • Gonadotropin-secreting adenoma
    • GH-secreting adenoma
    • GH and PRL-secreting adenoma
    • TSH-secreting adenoma
    • Can test by immunohisto stain.
  90. Growth hormone-producing adenoma - Gigantism
    • High linear growth due to excessive action of insulin-like growth factor I (IGF-I) while the epiphyseal growth plates are open during childhood.
    • Very tall, very long legs and arms.
    • Other symptoms - diabetes, arthritis, large jaw & hands, osteoporosis, hypertension, heart failure …..
  91. Growth hormone-producing adenoma - Acromegaly in adults
    • After the epiphyseal growth plates are closed.
    • Enlarged hands and feet.
    • Coarsened, enlarged facial features.
    • Impaired vision.
    • Headaches.
    • Enlarged tongue.
    • Menstrual cycle irregularities in women.
    • Erectile dysfunction in men.
    • Enlarged liver, heart, kidneys, spleen and other organs.
    • Increased chest size (barrel chest).
  92. Non-functioning adenomas - Null cell adenoma
    • 25-30% of patients do not have classical hypersecretory syndromes.
    • May grow to a large size before they are detected (mass effect).
    • Visual deficits - double vision; Bitemporal hemianopsia.
  93. Hypopituitarism
    • Congenital or acquired.
    • Loss of 75% of anterior Pituitary to show Symptoms.
    • Symptoms include dwarfism, effect of individual hormone deficiencies.
    • Acquired causes include:
    • 1- Nonsecretory pituitary adenoma.
    • 2- Ischemic necrosis e.g. postpartum.
    • 3- Iatrogenic by radiation or surgery.
    • 4- Autoimmune (lymphocytic) hypophysitis.
    • 5- Inflammatory e.g. sarcoidosis or TB …..
  94. Pituitary dwarfism
    • Pituitary gland does not produce enough growth hormones.
    • Height lies between 2' 8'' to 4' 8''.
  95. Posterior pituitary
    Hypothalamic neurons produce two peptides – ADH and oxytocin. They are stored in axon terminals in neurohypophysis and released with appropriate stimuli.
  96. Posterior Pituitary Syndromes - Abnormal oxytocin secretion
    Not associated with any significant abnormality.
  97. Posterior Pituitary Syndromes - associated with ADH
    • ADH deficiency - causes Diabetes Insipidus, Excessive urination, dilute urine , due to inability to reabsorb water from the collecting tubules.
    • Secretion of inappropriately high level of ADH (SIADH – syndrome of inappropriate ADH) - Causes excessive resorption of water, hyponatremia (low serum level of Sodium).
  98. Metastatic tumors in pituitary
    • From Breast, lung ,GI tract.
    • Posterior lobe mostly affected.
    • Anterior lobe rarely involved.
  99. Craniopharyngioma
    • 1-5 % of intracranial neoplasms.
    • Derived from remnants of Rathke’s Pouch.
    • Suprasellar or intrasellar, often cystic with calcification.
    • Children or adolescents most affected.
    • Symptoms of hypofunction or hyperfunction of pituitary and /or visual disturbances, diabetes insipidus.
    • Benign & slow growing.
    • Low grade circumscribed epithelial tumors.
    • Partly cystic and calcified mass.
    • Squamoid and columnar epithelium lining cystic spaces filled with oily fluid (keratin debris).
    • "Stellate reticulum" and "wet keratin" are prominent features.
  100. Summary of pituitary adenoma
    • The most common cause of hyperpituitarism is an anterior lobe pituitary adenoma.
    • Pituitary adenomas can be macroadenomas (>1 cm) or microadenomas (<1 cm).
    • Macroadenoma – mass effects including visual disturbances.
    • Clinically, can be functional or silent.
    • Functioning adenomas – associated with distinct endocrine signs and symptoms.
    • The two distinctive morphologic features of most adenomas are their cellular monomorphism and absence of a reticulin network.
  101. Adrenal gland
    • A pair of endocrine glands just above the kidney.
    • Secretion:
    • - steroids from cortex.
    • - catecholamines from medulla.
  102. Adrenal Cortex
    • Zona glomerulosa - outer most; mineralocorticoids (aldosterone), associated with SALT.
    • Zona fasciculata - glucocorticoids (cortisol), associated with SUGAR.
    • Zona reticularis - inner most; estrogens & androgens, SEX.
    • Diseases are those of hyperfunction & hypofunction & tumors.
  103. Adrenal cortical Hyperfunction associated syndromes:
    • Cushing’s Syndrome (excess of cortisol)
    • Hyperaldosteronism
    • Adrenogenital or virilizing syndrome (excess of androgen)
  104. Cushing’ Syndrome
    • Elevation of cortisol level
    • Endogenous causes: all have adrenal hyperplasia
    • - Pituitary Cushing syndrome: hypersecretion of ACTH (70% of endogenous hypercortisolism).
    • - Ectopic secretion of ACTH by non-pituitary neoplasm (10%) - paraneoplastic Cushing Syndrome, small cell lung cancer.
    • - Primary adrenocortical neoplasm and rarely nodular hyperplasia (15-20%)
    • Exogenous cause:
    • - Steroid Therapy: most common cause of hypercortisolism; iatrogenic; can also cause adrenal atrophy.
  105. Cushing Syndrome Clinical features
    • Central obesity 85-90%
    • Moon face 85%
    • Weakness and fatigability 85%
    • Hirsutism 75%
    • Hypertension 75%
    • Glucose intolerance/diabetes 75%
    • Osteoporosis 75%
    • Menstrual abnormalities 70%
    • Cutaneous striae 50%
  106. Hyperaldosteronism
    • High aldosterone causes Na retention & K excretion, increase blood pressure, Hypokalemia.
    • Primary – adrenal (decreases plasma renin)
    • - Potential causes – Nodular hyperplasia (60%), Neoplasm (35%), Rarely familial.
    • Secondary – extra adrenal (increases plasma renin)
    • - Potential causes – Decreased renal perfusion, Arterial hypovolemia and edema, Pregnancy.
  107. Virilizing Syndromes
    • Causes
    • - Primary gonadal disorders
    • - Adrenocortical Neoplasms
    • - Congenital adrenal hyperplasia
    • Neoplasms can occur at any age, frequently malignant.
    • Virilization, precocious puberty, ambiguous genitalia.
    • Patients have risk for acute adrenocortical insufficiency.
  108. Adrenal cortical tumors
    • Encapsulated, solitary, usually yellow.
    • Benign or malignant.
    • Nonfunctioning or functioning.
    • Malignant tumors with necrosis, hemorrhage (≥ 300gms)
    • Hypercorticolism is usually more marked with carcinomas than with adenomas or hyperplasia.
    • Size variable.
    • Local invasion, & the presence of metastases differentiate benign from malignant tumors.
  109. Adrenal cortical adenoma
    • Capsulated tumor with uniform or slightly pleomorphic cells, may be eosinophilic or clear cell type
    • Spironolactone bodies in hyperaldosteronism
  110. Adrenal cortical carcinoma
    Lager than adenoma, non-capsulated with nuclear pleomorphism, mitoses and necrosis.
  111. Adrenocortical insufficiency
    • Acute :
    • 1- Massive adrenal hemorrhage as in anticoagulant
    • therapy, DIC, sepsis by N.meningitidis, pseudomonas
    • (Waterhouse- Frederickson syndrome).
    • 2- Sudden withdrawal of steroid therapy.
    • 3- Stress in patient with underlying chronic insufficiency.
    • Chronic (Addison’s disease): Progressive destruction of the adrenal by:
    • 1- Autoimmune Disorder: 75-90%, may be sporadic.
    • 2- Infections e.g. Tuberculosis , fungi ( AIDS).
    • 3- Metastatic tumors destroying adrenal e.g. lung, breast , …others.
  112. Addison’s disease - JFK
    • Symptoms
    • - fatigue, lassitude, malaise, weakness, anorexia.
    • - postural dizziness, syncope.
    • - GI - nausea, vomitting, abdominal pain, diarrhea, constipation.
    • - myalgias, arthralgias, rarely flexion contractures.
    • - decreased libido, amenorrhea.
    • Signs
    • - Weight loss
    • - Hyperpigmentation
    • - Hypotension
    • - Thinning of axillary and pubic hair
    • - Vitiligo
  113. Adrenal medulla
    • Derived from neural crest.
    • Part of sympathetic system.
    • Composed of Chromaffin cells secreting catecholamines.
    • Diseases are mainly tumors: Pheochromocytoma and Neuroblastoma.
  114. Pheochromocytoma
    • Neuroendocrine tumor of adrenal medulla.
    • Originates from the chromaffin cells along the paravertebral sympathetic chain extending from pelvis to base of skull.
    • >95% are abdominal.
    • >90% in adrenal medulla.
    • Secretes excessive amounts of adrenaline and noradrenaline.
    • Diagnosis – increased urinary excretion of free catecholamine and their metabolites (VMA and metanephrins).
    • A familial syndrome that predisposes to catecholamine-secreting tumors (MEN2, NF1, VHL).
  115. Pheochromocytom - ‘Rule of 10’
    • 10% extra-adrenal (closer to 15%)
    • 10% occur in children
    • 10% familial (closer to 20%)
    • 10% bilateral or multiple (more if familial)
    • 10% recur (more if extra-adrenal)
    • 10% malignant
    • 10% discovered incidentally
  116. Signs & Symptoms of Pheochromocytoma
    • The five P’s:
    • - Pain (Headache) 80%
    • - Perspiration (sweaty) 71%
    • - Palpitation 64%
    • - Pallor 42%
    • - Pressure (HTN) 9% - Surgically correctable
    • - - Paroxysms (the sixth P!)
    • The Classical Triad:
    • - Pain (Headache)
    • - Perspiration
    • - Palpitations
    • - Lack of all 3 virtually excluded diagnosis of pheo in a series of > 21,0000 patients
  117. Morphology of Pheochromocytoma
    • Zellballen (small nests or alveolar pattern), trabecular or solid patterns of polygonal / spindle shaped cells in rich vascular network.
    • May have mitoses and marked pleomorphism.
    • Capsular and vascular invasion common in benign behaving tumors.
    • Definitive diagnosis of malignancy – presence of metastasis
  118. Neuroblastoma
    • Second most common solid childhood neoplasm, after CNS tumors.
    • Usually adrenal but maybe extra-adrenal (sympathetic nervous system).
    • Familial or sporadic.
    • Associated with deletion of short arm of chromosome 1.
    • 90% associated with catecholamine secretion.
    • 24hr urinal VMA excretion is helpful in diagnosis.
    • Some differentiate (ganglioneuroblastoma) and spontaneously regress.
    • Rapid growth & widespread metastasis.
    • Treatment complex - surgery, RT, chemotherapy.
  119. Morphology of Neuroblastoma
    • Large mass with necrosis.
    • Small round blue cell tumor with rosettes.
    • Areas of necrosis and calcification.
    • May differentiate to ganglion cells.
  120. MEN Syndrome
    • Inherited diseases resulting in hyperplasia, adenomas and carcinomas.
    • Younger age.
    • Multiple endocrine organ Involvement (synchronous or metachronous).
    • Asymptomatic stage of endocrine hyperplasia.
    • More aggressive and recur.

Card Set Information

Author:
neopho
ID:
326022
Filename:
Systemic Pathology - Endocrine System - Mirani
Updated:
2016-11-26 03:12:53
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SystemicPathology
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SystemicPathology
Description:
Systemic Pathology - Endocrine System - Mirani
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