Endocrine Pathology

January 26, 2009 lecture trans Page 1 of 15

Pituitary Gland
A. Functional Anatomy
Found in a depression in the sphenoid bone (Sella turcica) Wt: 0.5g and <15mm in diameter Influenced by the hypothalamus (releasing and inhibiting factors) via the portal system (80-90%: Anterior part and 10-20% for the posterior) Two Tissue types: Pars distalis / Adenohypophysis / Anterior pituitary gland Made up of secretory cells w/c are derivative of the Rathkes pouch (primitive oral cavity) Pars nervosa / Neurohypophysis / Posterior pituitary gland Made up of neuroglial cells (unmyelinated) from the direct extension of the stalk or the pars tuberalis Rare neoplastic lesions, more on secondary effects like head trauma, surgery, extension of local tumors or radiation Cause of diabetes insipidus Notice the densely staining property of the anterior lobe vs. the posterior lobe. This is because the anterior lobe is made up of secretory cells which take up mostly of the stain.

Anterior

Posterior

Stalk

Histology of a normal anterior pituitary gland (image on the right) composed of round to polygonal epithelial cells arranged in cords and nests, with rich fibrovascular network (seen as capillaries, C) cells release their granules in response to releasing factors elaborated in the hypothalamus H&E stain classification (past diagnostic exam) acidophils(A) basophils(B) and chromophobes (D, neither take up the acidophilic or basophilic stain) Immunoperoxidase test (present diagnostic) Classify the cells into the hormones that they produce Histology of the Adenohypophysis 1. Somatotrophs (GH cells) 2. Lactotrophs (Prl cells) 3. Mammosomatotrophs (GH and Prl) 4. Gonadotrophs (FSH- LH cells) 5. Tyrotrophs (TSH cells) 6. Corticotrophs (ACTH- MSH, Blipoprotein and B- endorphin) Histology of the Neurohypophysis nerve fibers with specialized glial cells called Pituicytes that secrete octapeptides: 1. ADH (vasopressin) 2. Oxytocin Corticotrophs Thyrotrophs

Immunohistochemistry of the Adenohypophysis Somatotrophs Gonadotrophs

**all are brown staining

Neurohypophysis contains a looser texture compared to the adenohypophysis that contains the Pituicytes (C), some capillary (B) and Herring Bodies (A), which are accumulation of the neurosecretory granules.

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 2 of 15

B. Pathology of the Pituitary Glands

1. Hyperpituitarism
hypersecretion of one or more of the trophic hormones of the anterior lobe due to: 1. defect in the feedback mechanism by the hypothalamus low level of hypothalamic stimulation makes the pituitary more active 2. by functioning neoplasms Adenoma of the adenohyphysis: 70% elaborate a single tropic hormone: prolactin, GH, ACTH. Secretion of TSH, LH and FSH are very rare more common in men between 20-50 Signs and Symptoms 1. Gigantism (excess of GH before the closure of the epiphyseal bone) 2. Acromegaly (excess of GH after closure of the epiphyseal plate) 3. Hyperprolactinemia - excess of prolactin - amennorhea-galactorrhea syndrome - impotence and loss of libido in males

Gigantism: Seen on the middle female **Difference between acromegaly is the time of fusion of the epiphyseal plate (not fused during childhood)

Spade like appearance of hands (left) + the prominent jaw = acromegaly

2.

Hypopituitarism
Complete loss of the pituitary function 1. Sheehans syndrome Postpartum, after a very difficult obstetric event E.g. Excessive bleeding hypovolemic shock

hypoperfusion of the pituitary

liquefactive necrosis

Area of
liquefaction

necrosis

2. 3.

Simmonds syndrome Empty sella syndrome the arachnoid (meninges) herniated into the sella turcica compressing the pituitary gland pressure atrophy which will eventually lead to hypopituitarism

loss of the gland due to

4. 5.

Dwarfism Diabetes insipidus (interruption of the ADH production)

Differential Diagnosis a. Craniopharyngioma A neoplasm characterized by the proliferation of the Rathkes pouch expanding mass of secretory cells which are derivatives of the primitive oral cavity that are dental cell components producing enamel Cystic lesions with oily fluid -Columnar cells arranged in gland like formation supported by reticulin type of fibrous tissue stroma - called Ameloblastoma if found in oral cavity

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 3 of 15 b. Rathkes cyst Remnant of pars intermedia1 may produce colloid filled cyst and may cause compression atrophy of the pituitary gland
1

pars intermedia region between the anterior and the posterior lobe

Cystic lesion

Colloid like cyst similar to a thyroid follicle in the region of pars intermedia

Whether it is an adenoma or a carcinoma the only effects are 1. Pressure or mass effect (compression of the nearby structures can be attributed to the enlarging mass)

3.

Pituitary Tumors

Diffuse, sinusoidal and papillary pattern 1. Pituitary Adenoma (mostly are functioning adenoma) a. Microadenoma (<10mm in diameter) Present as incidental findings in 25% of autopsies (due to its small size) 2. Hormonal effect Most are nonfunctioning and with little mass effect b. Macroadenoma (>10mm in diameter) Notorious for causing pressure or mass effects Press on the CN III, IV and VI, Hypothalamus, cavernous sinus and the Optic chiasm 2. Pituitary Carcinoma (very rare)

Distinct circumscribed mass

Primary macroadenoma resting on sella turcica (in many instances, the sella may be eroded by the expanding mass of the adenoma)

Stalk

** take note that all adenomas are grossly similar in appearance, hence we need tissue staining
Pituitary microadenoma: Autonomous proliferating secretory cells that is sharply demarcated (yellow lines) from the surrounding normal pituitary cells H&E

Functioning adenoma
Cells in lobules without the glandular appearance

Immunoperoxide (refer to page 1)

Acidophilic staining adenoma (GH and Prolactin producing adenoma)

Basophilic staining adenoma (ACTH producing adenoma)

Chromophobic adenoma (25% Prolactin producing adenoma)

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 4 of 15

Parathyroid Gland
A. Functional Anatomy
Normally four in number (2 at the left lobe and 2 on the right) small glands embedded in the posterior aspect of the thyroid substance, however, anatomic variation in numbers may occur (3 to 8) and also variation in location (thymus and mediastinum) Derived from the 3rd and 4th brachial pouches (endoderm) yellowish-brown, flattened nodules each weighing approximately 35-45mg made up of both parenchymal cells(secretory) and stromal cells (supporting tissue with fat deposits) Histology: Effects of PTH 1. chief cells spheroidal cells that produce much of the parathyroid hormone (PTH) -mobilization of Ca2+ 2. oxyphil cells homogenous, granular, eosinophilic cytoplasm 3. clear cells a. induces osteoclast activity b. renal tubular absorption of Ca2+ c. urinary phosphate Intimate association of the fat secretion that blends with the very d. GI Ca2+ absorption cellular structure of the gland Grossly: can be mistaken as a small lump of fat

B.

Pathology of the Parathyroid Gland

1.

Hyperparathyroidism

Rule: malignancies usually Excessive amount of PTH involve one (1) gland only Classification: while in hyperplastic a. Primary changes, it involves all of Problem is in the parathyroid gland itself (neoplasm #1 and #2) the parathyroid glands 1. Parathyroid Adenoma (80%) 2. Parathyroid Carcinoma (2-3%) rare! 3. Primary parathyroid (chief cell) hyperplasia (15%) adaptive changes 4. Component of MEN syndrome i. Multiple tumors or Hyperplastic lesion involving multiple endocrine organs PTH, hypercalcemia, hypophosphatemia and hypercalciuria Effects: a. Nephrolithiasis/ Nephrocalcinosis (stones in the kidney) b. Metastatic calcification (in the case of neoplasm of the parathyroid) c. Generalized osteitis fibrosa cystica (punctuation of the bone due to immobilization of Ca2+) d. Depression, anxiety, coma, psychosis and hypertension* (due to hypercalcemia) Fatty stroma Hyperplasia of the clear cells Hyperplasia of the oxyphilic and some of the chief cells

Normal tissue Capsule

Differential of Adenoma to Carcinoma 1. Capsular invasion 2. Metastasis Malignant neoplasm: Overwhelming metastasis or breakage of the capsule or invasion of the nearby blood vessel

Adenoma

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 5 of 15 b. Secondary Problem do not lie in the parathyroid itself but from a condition in which it stimulates the gland Ca2+ levels stimulate the compensatory hyperplasia = PTH production a. Chronic renal insufficiency ( Ca2+ excretion) b. Vitamin D deficiency (dietary) c. Intestinal malabsorption syndrome (anatomic defect) d. Hyperphosphatemia Tertiary Complication of the secondary hyperparathyroidism Persistent hyperplastic change despite the correction of the hypocalcemic state An autonomous nodule may have formed that continue to secrete PTH

c.

2.

Hypoparathyroidism
Loss of PTH function hypocalcemic states Mostly by iatrogenic causes: a. Surgically induced (No re-implantation of the parathyroid gland after thyroidectomy) b. Congenital absence of the glands c. Familial hypoparathyroidism (autoimmune polyendocrine syndrome type 1) d. Idiopathic hypoparathyroidism Effects: a. Tetany characterized by neuromuscular irritability (+ Chvostek sign and Trousseau sign) -earliest manifestation b. Mental status change c. Ocular disease (cataract) d. Intracranial manifestation Long standing effects e. Cardiovascular manifestation f. Dental abnormalities

3.

Tumors of the Parathyroid glands Parathyroid Adenoma - common Parathyroid Carcinoma - rare

Thyroid Gland
A. Functional Anatomy
Starts as a primitive anlage foramen caecum Descends thyroglossal duct in the midline (up to the C4-C6 level) expand laterally into left and right lobes and some vestige of pyramidal lobe lobes: 2 lateral, 1 isthmus & pyramidal weight: 15-20 grams blood supply: superior and inferior thyroid arteries/ veins Histology o 20-40 dispersed rounded follicles lined by simple cuboidal (follicular) epithelium w/ central colloid (thyroglobulin)

Follicle with rich colloid content Single layer of cuboidal cells Gross Thryoid: Similar to a shield, Thyreos (gk)

Tryrotrophs are stimulated by the hypothalamus via the TRH TSH stimulates the thyroid follicular cells to liberate T3 and T4 from thyroglobin T3 and T4 binds to a plasma protein TBG Parafollicular C cells produces calcitonin that lowers the plasma Ca2+ levels

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 6 of 15

Cyst lined by stratified squamous epithelium with remnants of the thyroid anlage

*Ask the Px to swallow and take note of the movement of the cyst **Px adviced for surgical removal due to high probability of harboring malignancy

Gross: Thyroid covered in colloid (yellow appearance) Prominent mound along the anterior neck region that goes up upon swallowing

B. Pathology of the Thyroid Gland

1. Hyperthyroidism
Excess release of the thyroid hormones ( leakage in plasma = thyrotoxicosis) T3, T4 by hyperfunctioning gland o e.g. Graves disease may be caused by Primary or secondary hyperthyroidism Laboratory TSH a measure of pituitary function T3 with T4 are for the circulating thyroid hormones T4 commonly measured because of its less protein binding capacity TSH- binding inhibitor immunoglobulin Abnormal auto-antibodies Thyroid growth stimulating immunoglobulin (TSI) Clinical manifestation Tachycardia, palpitations, nervousness, rapid pulse easy fatigability, muscular weakness wt loss despite of the appetite, heat intolerance warm skin, hyperhydrosis, amotional lability, menstrual changes, tremors eye changes (exophthalmos), goiter Causes: Diffuse hyperplasia associated w/ Graves (approx. 85% of ALL cases) Exogenous thyroid hormones (synthetic drug intake) Functioning goiter Functioning neoplasm Thyroiditis (early phase)

Graves Disease

Exophthalmos due to the overactivity of the SNS and also the accumulation of loose CT behind the eyeballs

Most common cause of hyperthyroidism Autoimmune disorder: defect in the T lymphocytes (sensitized to antigens within the thyroid) T cells signals the B cells to produce antibodies attack the TSH receptors in the thyroid cells Binding of the autoantibody mimics TSH and causes hyperplasia and hypertrophy Triad of manifestation: 1. thyrotoxicosis due to hyperfunctioning gland 2. exopthalmos 3. pretibial myxedema localized, infiltrative dermopathy Irregular stellate luminal border of the follicle due to the cell # infolding towards the center (take note of the punctuated colloid, which is due to the increased formation of the thyroid hormones) Genetic predisposition incited by: 1. pregnancy 2. iodine excess 3. lithium therapy 4. infections 5. steroid withdrawal Papillary infoldings

Meaty enlargement of the thyroid gland

Colloid with scalloped margin

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 7 of 15

2.

Hypothyroidism
Deficiency of the thyroid hormones Common causes of Structural or functional derangement that interferes with the production of hypothyroidism: adequate levels of thyroid hormones 1. Hashimotos thyroiditis Defect anywhere the hypothalamic- pituitary-thyroid axis 2. radiation injury Primary (most common) or secondary 3. surgical ablation Clinical Manifestation 4. drugs (PTU, lithium) 1. Cretinism 5. Infiltrative diseases Hypothyroidism developing in infants and children (Sarcoidosis, TB) Caused by inborn errors of metabolism and/or Iodine deficiency 6. Primary idiopathic Impaired development of CNS and etc. hypothyroidism 2. Myxedema (Gulls disease) Hypothyroidism developing in older children and adults cretinoid state in adults Mental sluggishness and generalized apathy Accumulation of mucopolysaccharide-rich edema in skin, visceral sites and others

3.

Thyroiditis
Inflammatory lesions Infections are very rare in the thyroid due to its high vascularity a. b. Acute thyroiditis Infectious Subacute thyroiditis Granulomatous (Type IV hypersensitivity) Associated with viral infection (post viral URTI) **De Quervains thyroiditis Can also occur in Parasitic, Fungal infection of the thyroid or foreign body reaction Ssx: Pain, fever and thyroid mass Usually localized, rarely are the diffused pattern of inflammation Histology: Granuloma formation! (giant cells and histiocytes) with atrophic follicles and no colloid Giant cells

Focal involvement of the thyroid (compare to the other side) c.

Granuloma Formation

Fibrous tyroiditis Riedel struma or ligneous thyroiditis (woody hardness) Rare condition (elderly female) Thyroid is normal, there is a fibrosis reaction in the neck area that will enclose the thyroid gland and eventually destroy it. confused with a malignancy Marked atrophy of the follicles replaced by extensive collagenous fibrosis Hashimotos thyroiditis (struma lymphomatosa) Wood-like appearance Most common cause of hypothyroidism Autoimmune inflammatory disorder (HLA-DR3 and HLA-DR5) destruction of the gland T cell defect stimulates B cells to produce anti-thyroglobulin, thyroid peroxidase Ab and anti TSH Anti-TSH receptor Ab blocks the action of TSH hypothyroidism Thyroid becomes heavily infiltrated by WBC that it mimics the appearance of a lymph node (histologically similar to a lymphoid follicle) Painless fibrosis diffuse enlargement, symmetrical (not hyperplasia!) TSH in response to T4 and T3 hashitoxicosis: intial surge of T hormones due to release via destruction of the gland

d.

Marked stunted growth, obese due to the hypothyroid state

Normal

Cretin

Inactive thyroid - does not take in the radioactive iodine

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 8 of 15

Diffuse enlargement of the gland, it can be nodular. It has a fleshy lymph node like appearance

Hurtle cells -enlarged eosinophilic granular cytoplasm containing cells

Dense lymphocytic infiltrates

Deposition of the autoantibodies in immunofluorescence (Type III hypersensitivity)

Lymphocytic infiltrates

Hurtle cells

Lack of thyroglobulin

4.

Tumors of the Thyroid Gland

Benign o Follicular Adenoma Malignant o Papillary Carcinoma o Follicular Carcinoma o Medullary Carcinoma o Anaplastic Carcinoma a. All follicular neoplasms (adenoma or carcinoma) are nonfunctioning tumors

75-85% 10-20% 5% rare

Follicular Adenoma Discrete solitary mass of <2.5cm in size Completely encapsulated (defines an adenoma from a carcinoma) Difficult to differentiate from solitary adenomatous goiter (Goiter has a cystic hemorrhagic degeneration) Functioning or non functioning Negligible risk to malignancy

Radioactive iodine scan showing a hypofunctional follicular adenoma (shadow outline of cold nodule) Discrete and encapsulated mass Follicular adenoma may have the propensity to have hemorrhagic degeneration and cystic change similar to an adenomatous goiter making it hard to differentiate them with each other

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 9 of 15 Microfollicular adenoma Intact capsule with no vascular invasion

Microfollicles devoid of colloid Adenoma Normal thyroid

Follicular adenoma--Hurtle cell variant: propensity to invade and high recurrence rate

Hurtle cells: Large granular acidophilic cells Intact stroma Adenoma b. Normal thyroid

Follicular Carcinoma Slowly enlarging painless nodule (occur in elderly) Mostly cold nodules (nonfunctioning) with some warm nodules (hyperdunctioning) If the pathology is seen microscopically follicular CA w/ minimal invasion; If Gross follicular CA with wide invasion Gross: **thickly encapsulated Histology: transcapsular invasion and vascular invasion Vascular spread bone, lung, liver and brain Papillary Carcinoma Most common (all ages, females>males, risk in exposure to radiation, gardners syndrome) Solitary and multicentric neoplasm (many foci) Papillary cauliflower like granular lesions Margins are infiltrative and irregular (not regular) Psoamomma bodies area of fibrosis and calcifications Cystic degeneration both in primary and metastatic foci (same as with goiter = not all cyst are benign) Histology: o Orphan annie (empty appearing nucleus/ ground glass appearance) o Psoammoma bodies o Multinucleated giant cells

c.

Solitary foci but can be multicentric

Capsulated variant

Intrathyroid metastasis

Cystic degeneration

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 10 of 15

Capillary

Papillae with a fibrovascular core

Orphan annie nuclei

Complex papillary fronds

Papillary Carcinoma variants 1. Encapsulated 2. Tall cell 3. Hurtle cell 4. Diffuse sclerosing marked lymphatic invasion 5. Papillary microcarcinoma (Occult sclerosing papillaty carcinoma) **Manifestation of the Px with metastasis large cervical nodes 6. Mixed papillary follicular carcinoma Follicular neoplasm with papillary architecture

Papillary Microcarcinoma variant (<10mm) **same with microadenoma in the pituitary but notice the surrounding (made up of follicles = in the thyroid) Clinical Course: Palpable mass with and cervical lymph node hypertrophy Hoarseness, dysphagia, cough and dyspnea advanced disease Most are cold lesion (non functional) Pre-op Dx: FNAB FNAB Papillary CA 10 year survival rate with stage 1

According to Dr. Yolo Papillary CA is a good CA due to a good prognosis as long as it is detected in its early stage. (Remember: if you go face to face with the Creator and He asked what cancer do you want? Answer Him: can I have papillary thyroid carcinoma, stage 1 please)

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 11 of 15 d. Medullary Carcinoma (poorly differentiate CA) Neuroendocrine neoplasm derived from Parafollicular (C) cells Secretes calcitonin Sporadic or associated in MEN syndrome Gross: somewhat the same with papillary CA Histology: Amyloid deposits pathognomonic for medullary CA Congo red

Amyloid deposits

H&E

e.

Anaplastic Carcinoma Worst cancer of the thyroid (<3-6 months of prognosis) Undifferentiated carcinoma May occur in: o Hx of multinodular goiter (50%) o Differentiate CA (20%) o Concurrent papillary/follicular CA (20-30%) Gross o Large bulky mass deformed and unrecognized thyroid o Extensive hemorrhage + rapidly enlarging mass (compresses other structures) Histology o Marked necrosis and hemorrhage o Undifferentiated (Differentiated: Papillary and Follicular) o Different from medullary (undifferentiated) NO amyloid deposits

Adrenal cortex
A. Functional Anatomy
Zona glomerulosa Zona fasciculate Zona reticularis (G)- mineralocorticoids (aldosterone) (F)- glucocorticoids (cortisol) (R) sex steroids (estrogen and androgens)

B. Pathology of the Adrenal Cortex

1. Hyperadrenalism
a. Hypercortisolism (Cushing syndrome) Different causes of hypercortisolism Most common cause is exogenous intake of steroids followed by endogenous hypercortisolism 2 to pituitary adenoma (Cushing disease)

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 12 of 15

Morphology Exogenous glucocorticoids causes bilateral atrophy of the adrenal cortices due to the suppression of the endogenous ACTH. (no stimulation = atrophy) **only the fasciculata and the reticularis are the ones affected and not the glomerulosa (independent of ACTH) Endogenous glucocorticoids causes bilateral hyperplastic states Primary adrenocortical neoplasms o Adenoma encapsulated, expansile, yellow tumors(lipid rich cells) o Carcinoma larger than the adenoma **take note of the bilateral enlargement of the hyperplastic states that differentiates it from the neoplastic counterpart Clinical Feature Early: Hypertension and weight gain Late: Truncal obesity, moon fascies, buffalo hump Causes selective atrophy of the fast twitch (type II) muscle fibers = muscle mass Hyperglycemia, glucosuria and polydipsia (gluconeogenesis and glucose uptake by the cell) Osteoporosis Hirsutism and menstrual abnormalities Mental disturbances

b.

Hyperaldosteronism levels of aldosterone = Na retention and K excretion = hypertension (surgically correctable) and hypokalemia due not suppress ACTH secretion = cortex is not atrophic 1. Primary Hyperaldosteronism Decreased plasma rennin activity due to overproduction of aldosterone 2. Secondary Hypersldosteronism Increase aldosterone release due to activation of the renin-angiotensin system = levels of plasma renin Morphology: Aldosterone secreting adenoma (80%) Conns syndrome o Solitary or multiple Primary adrenocortical hyperplasia (15%) idiopathic o Diffusely or irregularly hyperplastic

c.

Adrenogenital syndrome Virilization Primary gonadal disorders and several primary adrenal disorders Congenital adrenal hyperplasia o Autosomal recessive disorders o cortisol production ACTH secretion = adrenal hyperplasia o 21 hyroxylase deficiency mutation in the 21-hyroxylase gene on chromosome 6

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 13 of 15 Morphology: bilateral adrenal hyperplasia + corticotroph (ACTH producing) cells hyperplasia in anterior pituitary gland Bilateral atrophy

Bilateral hyperplasia

Clinical Features: 21-hydroxylase deficiency excess androgen activity o masculinization in females, clitoral hypertrophy and pseudohermaphrodism in infants o enlargement of the genitalia in males and oligospermia

Masculinization of the female external genitalia

17-hydroxylase deficiency Androgen deficiency o absence of secondary sexual characteristics in females and pseudohermaphrodism in male - sodium wasting

2.

Hypoadrenalism or adrenal insufficiency

Primary adrenal disease Secondary stimulation due to ACTH deficiency a. Acute Adrenocortical insufficiency Due to a rapid withdrawal of steroids or failure to increase steroid doses in response to stress from chronic AI Massive adrenal hemorrhage may also destroy cortex to cause acute ardrenocortocal insufficiency May also be caused by overwhelming sepsis (Waterhouse-Friderichsen syndrome) Endotoxin-induced vascular injury with DIC Chronic Adrenocortical insufficiency (Addisons disease) progressive destruction of the adrenal cortex clinical sign do not appear if <90% Autoimmune adrenalitis (60-70%) Polyglandular syndromes Infection tuberculous adrenilitis Metastatic neoplasms (from lungs or breast)

b.

Waterhouse-Fridrichsen syndrome

Massive hemorrhage

Shrunken and bilateral adrenal hemorrhage

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 14 of 15

3.

Tumors of the Adrenal Cortex

a. Adrenocortical Adenoma most do not cause hypofunction Normally seen in autopsy Yellow to yellow brown in color (lipid)

Yellow appearance of the tumor

Vacuolated neoplasmic cells due to the presence of intracytoplasmic lipid (lipid rich)

b.

Adrenocortical Carcinoma Rare High variations and with poorly demarcated lesions containing areas of necrosis, hemorrhage and cystic changes

Adrenal Medulla
A. Functional Anatomy
Made up of chromaffin cells o Derived from neural crest o Synthesizes catecholamines

B. Pathology of the Adrenal Medulla

1. Phaeochromocytoma
Rare tumor involving the chromaffin cells Occurs at any age Surgically correctable form of hypertension Rule of 10s 10% associated with several familial syndromes (MEN-2A and MEN-2B) 10% are extra-adrenal (organ of Zuckerkandl and carotid body) 10% bilateral (can go to 50% if associated with familial syndromes) 10% are biologically malignant 10% occurs in children Clinical Manifestation: production and secretion of catecholamines (e.g. NE) hypertensive with severe headache, palpitations, diaphoresis (classic triad), anxiety, and nervousness. Gross Small to large well circumscribed lesion Small tumors are yellow in appearance while large tumors usually shows hemorrhage, necrosis and cystic degeneration If given with potassium dichromate turn into dark brown in color Small tumor Large tumor

Hemorrhage and necrosis Cystic degeneration

Marvined
UST-FMS BMD2011

Endocrine Pathology
January 26, 2009 lecture trans Page 15 of 15 Microscopic Composed chromaffin cells and their supporting cells compartmentalized into small nest or Zellbalen by a rich vascularized network Granular cytoplasm (highlighted by silver stains presence of catecholamines)

Zellbalen with granular chromaffin cells surrounded by capillaries

Presence of nuclear pleomorphism

2.

Neuronal neoplasms (neuroblastoma and mature ganglion cell tumors)

Most common extra-cranial solid tumor of childhood May arise anywhere in the sympathetic nervous system (mostly in adrenal medulla)

Multiple Endocrine Neoplasia (MEN syndromes) A group of inherited diseases resulting into proliferative lesions of multiple endrocine organs MEN Type 1 Autosomal dominant pattern MEN1 tumor suppressor gene MEN Type 2 Mutations of the RET oncogene at chromosome 10q11.2 Autosomal dominant pattern Different mutation pattern = different type

Endocrine Organ Pituitary Parathyroid Pacreatic islets Adrenal Thyroid Extraendocrine changes Mutant gene locus

MEN I (Wermers syndrome) Adenomas Hyperplasia Adenomas Hyperplasia Adenomas Carcinoma Cortical Hyperplasia C-cell hyperplasia

MEN II or IIa (Sipples syndrome Hyperplasia

MEN IIb or III

Phaeochromocytoma Medullary carcinoma

11q13

10q11.2 (RET)

Phaeochromocytoma Medullary carcinoma Mucocutaneous ganglioneuromas Marfanoid habitus 10q11.2 (RET)

Reference: Kumar et. al. Robbins Basic Pathology 8th ed. 2000. Elsevier Saunders. Pages 637-665. Kumar et al. Robbins and Cotran Pathologic Basis of Disease. 7th ed. 2005. Elsevier Saunders. Pages 1155-1224.

Acknowledgement I would like to thank Dr. Yolo for letting me record his lecture and also Joyce Ignacio for taking pictures of the presentation to complete this trans, which are not seen in the powerpoint presentation of the previous batches. Good luck in the exams! God bless!

Marvined
UST-FMS BMD2011