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Glossary of Endocrine, Repro, and Perinatal Peds

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How does insulin function to bring glucose into cells?
Binds receptors on fat and skeletal muscle. Intracellular signal transduction --> translocation of GLUT4 to plasma membrane. Brings glucose into the cell.
What causes the Dawn Phenomenon?
Increased cortisol levels early in the morning. Counterregulatory --> raises blood glucose.
What are the onset, peak, and duration of Lispro insulin?
Onset: 5-10 min.
Peak: 1 hr
Duration 2-3 hr
What are the onset, peak, and duration of regular insulin?
Onset: 35-40 min
Peak: 1-2 hr
Duration: 3-4 hr
What are the onset, peak, and duration of NPH?
Onset: 2 hr
Peak: 4-6 hr
Duration: 8-10 hr
What are the onset, peak, and duration of Lente insulin?
Onset: 2 hr
Peak: 4-6 hr
Duration: 8-10 hr
What are the onset, peak, and duration of Ultralente insulin?
No peak, lasts 24-36 hr
What are the onset, peak, and duration of Glargine?
No peak.
24-36 hr duration
When should regular insulin be taken?
1 hr before eating
What is the regimen with short and intermediate insulins?
Take S and I before breakfast. I will also cover lunchtime.
Take S before dinner.
Take I before bed to cover dawn phenom.
What are examples of the sulfonylureas?
1st gen: tolbutamide, chlorpropamide
2nd gen: Glyburide, glipizide, glymeprimide
How do the sulfonylureas work?
Increase insulin release by inhibiting K+ efflux, depolarizing and allowing influx of calcium, leading to insulin release
Also inhibit glucagon
May potentiate insulin's actions
Which sulfonylurea is safest in kidney failure?
Glymeprimide
What is an ADR of chlorpropamide?
SIADH --> water retention and hyponatremia
What is the mechanism of action of meglitinde (repaglinidine)? How is that different from sulfonylureas?
Trigger insulin release by regulating ATP-sensitive K+ channels on beta cells. Binds different proteins on the surface, has different duration --> pulsatile increase in secretion
Don't have direct exocytosis effect on insulin
What is a barrier to compliance for meglitinide?
Brief duration, multiple daily doses
Which oral hypoglycemic is not associated with hypoglycemia?
Metformin
What drug is especially indicated in obese patients?
Metformin (a biguanide) - helps insulin work in liver (insulin resistance is high in obese)
What are ADRs of metformin?
Lactic acidosis (don't give in hepatic failure, CHF, renal failure, or vascular disease)
GI disturbances
What are examples of thiazolidinediones?
Pioglitizone, rosiglitizone, ciglitizone
How do thiazolidinediones work?
Decrease insulin resistance
Agonizes PPAR gamma receptor, which is downstream in the insulin signal pathway
Lowered insulin levels --> prevent secondary complications
What are ADRs of thiazolidinediones?
P450 interactions
Peripheral edema
Weight gain
What is an example of an alpha-glucosidase inhibitor?
acarbose
How do alpha-glucosidase inhibitors work?
Oligosaccharide that binds avidly to dissacharidases - absorption of carbs is delayed, decreaseing post-prandial rise in glucose
What are the ADRs of acarbose?
Flatulence (increased carbs in lg intestine)
Diarrhea rare
Don't use with metformin (interferes with absorption)
What are the characteristics of pineocytomas?
Origin
Growth
Pineal parenchymal cells, advanced differentiation
Indolent, but may be unpredictable and disseminate in CSF

What pineal tumor is this?
Pineocytoma
Note small cells (like lymphocytes), lack of pleomorphism (regular nuclei), lack of mitosis
What are the characteristics of a pineal PNET (pineoblastoma)?
Who?
Size
Dissemination
Cell differentiation
Occurs mostly in kids
Bulky --> obstructive hydrocephalus
High degree of dissemination via CSF
Cells may have neural or glial features, or even other types (e.g. muscle)
What are the characteristics of pineal germ cell tumors?
Cure rate w/radiation/chemo
What are they positive for?
90%
Placental alkaline phosphatase

What pineal tumor is this?
Germinoma - note large tumor cells surrounded by reactive lymphocytes
What substance do yolk-sac tumors secrete?
Alpha fetoprotein

What tumor of the pineal is this?
Endodermal sinus tumor (a.k.a. yolk sac tumor)
Top: Note hyaline deposits in cytoplasm - this is AFP
Bottom: Schiller-Duval body, papillary projection into cyst with central vessel
What does a choriocarcinoma secrete?
beta-HCG - suggestive of choriocarcinoma is HCG levels rise, but no sign of pregnancy
They often spontaneously hemorrhage

What tumor of the pineal is this?
Choriocarcinoma - see syncytiotrophoblast in lower left corner, as well as single nucleate cytotrophoblasts

What pineal tumor is this?
Immature teratoma
See all kinds of tissues, plus necrosis and calcification
These are ALWAYS malignant
What is the effect of severing the pituitary stalk?
Decreased levels of most pituitary hormones. Elevated prolactin (normally inhibited by dopamine).
What results from excessive ACTH?
Cushing's disease (excessive adrenal steroid production)
What results from excessive growth hormone?
Gigantism (if growth plates have not fused yet)
Acromegaly (if growth plates have fused)
What results from excessive prolactin release?
Amenorrhea, galactorrhea, infertility (both men and women)
What results from insufficient growth hormone?
Pituitary dwarfism
What results from deficient ACTH release?
secondary adrenal insufficiency
What results from insufficient LH/FSH secretion?
Hypogonadism, delayed/absent puberty
If it is alpha chain deficiency (shared by LH/FSH/TSH), you have deficiency of all three

What is this?
Normal adenohypophysis (anterior pituitary)
Cells are heterogenous, arranged into packets separated by capillaries
What type of craniopharyngiomas develop in kids? Adults?
Are they benign or malignant?
Kids - adamantinomatous type
Adults - papillary squamous type
Benign - 0-20% recurrence after gross total resection

What kind of tumor is this?
Craniopharyngioma - note large multicystic nature, pushing into 3rd ventricle

What kind of tumor is this?
Adamantinomatous craniopharyngioma - see keratin, with giant cell reaction to it in cyst lumen
What are the signs of a prolactinoma?
Galactorrhea, amenorrhea, decreased libido and erectile dysfunction, osteoporosis (decreased testosterone and estrogen)
What is the medical treatment of prolactinoma?
Dopaminergic agonists (bromocriptine, cabergoline, pergolide mesylate, quinagolide)
What are the symptoms of a gonadotropin tumor?
Generally asymptomatic, but may have neurologic sx, pituitary deficiency, rarely hyperfunction (irreg menses, ovarian hyperstimulation, boys - acne, oily skin, premature puberty)
What stimulates and inhibits GH release?
GHRH stimulates
Somatostain inhibits
Why is octreotide used instead of regular somatostatin?
Does not bind well to SSTR5, which is the receptor in pancreas, so it doesn't suppress insulin and glucagon release
What is pegvisomant, and how does it work?
Binds one GH receptor, doesn't allow dimerization, preventing signal transduction.
What lab tests can help differentiate primary hyperthyroidism from pituitary hyperthyroidism?
Low TSH - primary
High TSH - pituitary

What is this?
Normal thyroid. See colloid.

What disease of the thyroid is this?
Graves' disease - see "fire flares" of actively secreted colloid

What disease of the thyroid is this?
Hashimoto's.
See lymphocytic infiltration, plus oncocytic follicular epithelial cells (Hurthle cells) with abundant eosinophilic granular cytoplasm.
What is the origin and pathophysiology of subacute thyroiditis?
Viral infection stimulates cytotoxic T-cells, disrupt follicles, releasing thyroid hormone --> transient hyperthyroidism. TSH is low. Low RAI uptake.
Followed by longer period of hypothyroidism.
When is silent (subacute lymphocytic) thyroiditis most often seen?
Postpartum and middle aged women
What are the lab findings of silent thyroiditis?
Elevated T4, decreased TSH. RAI uptake decreased (contrasted with Graves, which has high RAI uptake)
What is Riedel's thyroiditis?
Rare fibrosing process --> gets stuck to surrounding structures

What is this?
Goiter - some big, some small follicles

What is this FNA of?
Papillary carcinoma of thyroid.
Optically clear or empty nuclei. Pseudoinclusions (eosinophilic invaginations of cytoplasm into nucleus)
There would also be psammoma bodies (concentric calcifications from slow-growth)
How can you tell a thyroid medullary carcinoma on histo slide?
Stains for calcitonin.
Polygonal to spindle-shaped cells, forming nests, trabeculae and solid patterns

If this is necrotic and hemorrhagic, with a rapidly advancing course, what is this?
Anaplastic (undifferentiated) carcinoma

Giant cells, spindle cells, small cells.
May have arisen from previous, better differentiated tumor.

What is this?
Malignant lymphoma.
Often arises in background of lymphocytic or Hashimoto's thyroiditis
If a person has high thyroid hormone levels, but a low RAI uptake, what do they have?
Silent thyroiditis with thyrotoxicosis
In hypothyroidism, what patterns of RAI uptake can you have?
-Very low intake
-Abundant uptake that is quickly discharged (maybe an abnormality in organification)
-Elevated uptake that is discharged more slowly (maybe making some precursor of thyroxine)
What are the three main classes of thyrotoxicosis with hyperthyroidism?
Abnormal stimulator (Graves')
Normal stimulator (e.g. high TSH from pituitary tumor or central insensitivity to T4/T3, cross-reacting HCG)
Toxic autonomous nodule (extracellular domain of TSH receptor is mutated --> clonal expansion)
(Can also be caused by struma ovarii, metastatic carcinoma)
What are the physiological effects of thyroxine?
Regulation of protein synthesis, effects on normal growth and development, regulates lipid, protein, carbohydrate, and vitamin metabolism.
What are the adverse effects of thyroxine?
Tachycardia, CHF, angina, exophthalmos, heat intolerance, sweating, nervousness, muscular weakness and fatigue, menstrual irregularities, increased metabolic rate (hyperglycemia, hypoTG, hypocholesterolemia)
What drugs increase the metabolism of triiodothyronine and thyroxine by inducing microsomal enzyme metabolism?
Rifampin, rifabutin, phenobarbital, phenytoin, carbamazepine
What drugs decrease the concentration of triiodthyronine by inhibition of 5'-deiodinase?
Ipodate, propylthiouracil, corticosteroids, amiodarone, beta-blockers
Wht drugs decrease intestinal absorption of thyroxine?
Cholestyramine, colestipol, aluminum hydroxide, sucralfate
What is the mechanism of thioamides, methimazole, and propylthiouracil?
Prevent synthesis of thyroid hormone via inhibition of thyroid peroxidase --> decreased iodine organification
Blocks coupling of iodotyrosines
PTU inhibits conversion of thyroxine to triiodothyronine
What are the ADRs of thioamides, methimazole, and PTU?
maculopapular rash, agranulocytosis, vascultitis, polyserositis, jaundice
What are thioamides, methimazole, and PTU used for?
Thyrotoxicosis and uncomplicated hyperthyroidism
What is ipodate used for?
Adjunctive therapy in thyroid storm, and when iodide salts and thioamides are contraindicated
What is the mechanism of ipodate?
Inhibition of conversion of thyroxine to triiodothyronine by inhibiting 5'-deiodinase
What is the mechanism of iodide salts?
Inhibition of organification, inhibition of T3/T4 release, decrease size and vascularity of thyroid
What are ADRs of iodide salts?
Acneiform rash, swollen salivary glands, metallic taste
What are iodide salts used for?
Thyroid storm, thyrotoxicosis, prior to removal of thyroid
What are radioactive iodides used for?
Thyrotoxicosis (permanent cure)
What is the mechanism of radioactive iodide?
Rapidly absorbed and concentrated by thyroid, incorporated into storage follicles, beta-ray emission leads to permanent destruction of thyroid tissue
What is Conn syndrome?
An aldosterone-producing adenoma, leading to Na retention, hypokalemia, and hypertension

Same symptoms can also come from idiopathic hyperplasia of glomerulosa cells
What is Cushing's Disease?
Hypothalamic-pituitary disease causing hypersecretion of ACTH
Often a small ACTH-producing pituitary adenoma
What is adrenal Cushing syndrome?
ACTH-independent hypersecretion of cortisol by adrenals. Due to adrenal adenoma, carcinoma, or hyperplasia.
What is Crooke hyaline degeneration?
Pituitary basophilic hyaline degeneration of ACTH-producing cells due to elevated glucocorticoids. Seen regardless of cause of Cushing syndrome.
What hormone is most often deficient in congential adrenal hyperplasia, leading to adrenal virilism?
21-hydroxylase
No synthesis of cortisol or aldo --> channeled to androgens
What is Addison's disease?
chronic adrenocortical insufficiency - progressive destruction of most of the adrenal cortex with deficiency in glucocorticoids and mineralocorticoids, elevated ACTH
What are the symptoms of Addison's disease?
weakness, anorexia, nausea, weight loss, diarrhea, skin hyperpigmentation, hypotension
What is Waterhouse-Friderichsen syndrome?
Overwhelming bacterial infection (typically Neisseria meningitides) with fever, rapid hypotension.
DIC with purpura and massive adrenal hemorrhage, adrenocortical insufficiency.
Need to replace cortical hormones immediately.
With what familial syndrome are neuroblastomas associated?
Beckwidth-Wiedemann syndrome

What is this?
Homer-Wright pseudorosettes in neuroblastoma
What do the presence of a del 1p and high expression of Trk A gene indicate in a neuroblastoma?
dep 1p --> worse prognosis
Trk A --> good prognosis
What is Nelson's syndrome?
Residual pituitary tumor may grow after bilateral adrenalectomy for Cushing's syndrome. Associated with hyperpigmentation of skin and mucosa due to beta-lipotropin/ACTH molecule.
What is Schmidt's syndrome?
Concurrent hypothyroidism and hypoadrenalism from Addison's (due to antibodies that affect both thyroid and adrenals)
What problems in other systems are associated with idiopathic adrenocortical insufficiency?
Thyroid (hypothyroid)
Stomach (pernicious anemia)
Parathyroid (hyper)
Gonads (premature ovarian or testicular dysfunction --> early menopause, low testosterone)
Vitiligo
What drugs can cause adrenal insufficiency?
Prior corticosteroids, opiates, diphenylhydantoin, rifampin, ketoconazole, suramin
What is Sheehan's syndrome?
Hypopituitarism resulting from an infarct of the pituitary following postpartum shock or haemorrhage. Damage to the anterior pituitary gland causes partial or complete loss of thyroid, adrenocortical, and gonadal function.
What are the signs of adrenal crisis?
Fever, postural hypotension, tachycardia, nausea, vomiting, abdominal pain, hyponatremia, hypoglycemia, hyperkalemia
How do you treat chronic primary adrenal insufficiency?
Replace glucocorticoids and mineralocorticoids (with fludrocortisone - brand Florinaf - which is like aldo)
What endocrine effect does DiGeorge's syndrome have?
Congenital absence of parathyroid glands, associated with thymic dysplasia.
What are some causes of hypoparathyroidism?
How is it treated?
DiGeorge's syndrome (congenital absence)
Primary (idiopathic) atrophy - Ab to Ca-sensing receptor
Familial - associated with mucocutaneous candidiasis and primary insufficiency

Tx: long term Ca++/Vitamin D, monitor Ca levels
What are the signs of hypoparathyroidism?
Tetany, neuromuscular irritability (Chvosteck-tap facial nerve and Trousseau-induce carpal spasm with bp cuff)
Mental status changes
Parkinsonism, papilledema
Cataract
Increased QT, T changes
Dental hypoplasia
What is pseudohypoparathyroidism?
An abnormal interaction of PTH with its receptor leads to low Ca and high PO4. PTH is actually HIGH.
What are some causes of pseudohypoparathyroidism?
Albright's hereditary osteodystrophy (Type I - decreased cAMP response to PTH)
Type II - blunted response to second messenger
Does parathyroiditis lead to hyper or hypoparathyroidism?
Hypo
What is the most common cause of secondary hyperparathyroidism?
Chronic renal failure
(also osteomalacia (vit D deficiency) and pseudohypoparathyroidism)
What is the treatment of secondary hyperplasia of parathyroid?
Medical: restriction of phosphorus, phosphate binders, Vit D, 1-alpha-hydroxycholecalciferol (suppresses PTH secretion)
Surgical: subtotal parathyroidectomy
What is tertiary hyperplasia of the parathyroid?
Autonomous overactivity of parathyroid in setting of secondary hyperplasia
When should you suspect tertiary hyperplasia of parathyroid?
When there is normal or increased Ca++ levels while there is renal disease, continued hypercalcemia despite dialysis or transplantation
Associated w/chr 11.

What tissue is this?
Normal parathyroid.

What is this?
Nodular hyperplasia of parathyroid
How do you calculate ionized Ca given the total Ca and albumin?
For every gram of albumin below normal (4), multiply the measured calcium by 0.8. (4/5)
What are the effects of PTH in general, on bone, and on kidney?
General: stimulates adenylate cyclase on cell surface to maintain extracellular calcium levels
Bone: resorption, calcium release, remodeling
Kidney: stimulates formation of 1,25-vitD, decreases tubular reabsorption of phosphate, increases reabsorption of Ca, decreases reabsorption of bicarb --> acidosis
No direct effect on GI tract. Works through vitamin D
What is a good serum indicator of bone formation?
Alkaline phosphatase (released by osteoblasts)
What does calcitonin do?
Blocks osteoclast activity, but probably has little role in human physiology.
What is the effect of Ca on the kidney?
Poisons tubules --> can't respond to ADH --> polyuria and polydipsia
How do tumors cause hypercalcemia?
Eat through bone - direct reabsorption via cytokines
Humoral/endocrine - many produce PTHRP, or prostaglandins. some hematological malignancies break down bone by producing osteoclast activating factors, TNF, IL-6, calcitriol (active vitD)
What is the effect of lithium on the parathyroid gland?
Makes it produce more PTH --> hypercalcemia
What is Familial Hypocalciuric Hypercalcemia?
Ca receptor in PT doesn't recognize Ca--> more PTH --> hypercalcemia
Also, kidneys reabsorb calcium, so you get low Uca. Removing PTs is ineffective.
If PTH is high and calcium is high, what is the disorder?
Hyperparathyroidism
If PTH is low and Ca is high, what disorder is it?
Anything but hyperparathyroidism - may be malignancy, VitD intox, sarcoid, TB, hyperthyroid, immobilization, thiazides, milk alkali syndrome (too much milk and antacids), acute adrenal insufficiency (steroids break down vitD), Paget's disease of bone
If PTH and Ca are low, what is the disorder?
Hypoparathyroidism
If PTH is high and Ca is low, what is the disorder?
Renal disease (secondary hyperparathyroidism)
Ca is low b/c there's not enough VitD b/c phosphate is being retained
Elevated serum phosphate and Ca indicate what?
Hyperthyroidism secondary to malignancy
(Both are released from bone, PTH goes down to zero, then there's nothing to block phosphate resorption --> hyperphosphatemia)
How does Mg affect Ca levels?
Low Mg --> low Ca beause parathyroid can't produce enough PTH because the calcium sensing is affected.
What are vitamin D-related causes of hypocalcemia?
Chronic renal failure (Vit D is not converted to active form), VitD deficiency, anticonvulsant therapy (P450), Ricketts, Malabsorption
What are the hyperphosphatemia-related causes of hypocalcemia?
Renal failure, tumor lysis, rhabdomyolysis, pancreatitis
What are symptoms of ACUTE hypocalcemia?
Trousseau's sign and Chvostek's sign (hyperirritability of nerves and muscles)
Hyperreflexia
Laryngeal spasm
Convulsions
Papilledema
Prolonged QT interval
What are symptoms of CHRONIC hypocalcemia?
Cataracts, mental retardation, low cell-mediated immunity (Candida), hypoplastic teeth, basal ganglia calcification
What are causes of secondary osteoporosis?
HyperPTH, excess corticosteroids, hyperthyroid, immobilization, Turner's syndrome, anticonvolsants, multiple myeloma
What is defined as the first day of the menstrual cycle?
First day of bleeding
What structures are being stimulated to secrete what hormones during the proliferative phase?
LH and FSH stimulate granulosa cells surrounding follicles to produce estrogen. (Estrogen causes proliferation)
What structures are being stimulated to secrete what hormones during the secretory phase?
LH induces corpus luteum to produce mainly progesterone (and some estrogen). (Pg decreases number of estrogen receptors)
What day does progesterone peak?
22 - this is when implantation would occur if there has been fertilization
This is also when the second estrogen peak occurs to prepare the endometrium for implantation
What endometrial appearance proves that ovulation has occurred?
Subnuclear vacuoles ("piano-key" appearance)

What day of the menstrual cycle does this represent?
Day 17 - note subnuclear vacuoles in all glands.

What day of the menstrual cycle is this?
Day 18 - the subnuclear vacuoles are now supranuclear vacuoles

What day of the menstrual cycle does this represent?
Day 19 - presence of intraepithelial secretions and frayed luminal epithelium. After Day 19, mitoses disappear.

What day of the cycle is this?
Day 21 - focal edema and thick-walled blood vessels
(Edema is due to activation of COX by estrogen --> PGs --> vessel permeability)

What day is this?
Day 22 - peak of stromal edema - this coincides with implantation

What day is this?
Day 23 - predecidual change in perivascular areas (stromal cells acquire more cytoplasm, nuclei become round, and they look more epithelioid)

What day is this?
Day 25 - extensive decidual change throughout stroma

What day?
Day 26 - exhausted glands with saw-toothed appearance

What day is this?
Day 27 - endometrial granulocytes (T cell that prepares endometrium for sloughing)

What day is this?
Day 28 - stromal condensation and focal breakdown of functionalis layer (sloughing) occurs when corpus luteum becomes unresponsive to LH and stops releasing progesterone (needed to maintain lysosomal integrity in endometrial cells)
What is metorrhagia?
Bleeding between periods

What condition is this?
Chronic/subacute endometritis (plasma cells and lymphocytes, plus you can see glands and stroma, unlike in acute)
What is Asherman's syndrome?
Atrophic endometrium in reproductive age women.
Cause: extensive curettage followed by infxn
Adhesions develop
Tx: cure adhesions, give exogenous hormones
What are the three main causes of anovulatory cycles?
Endocrine disorders (e.g. thyroid), primary ovarian disorders (e.g. PCOS), generalized metabolic disturbance (severe malnutrition)
What happens to the endometrium during an anovulatory phase?
Since corpus luteum doesn't form, granulosa cells continue to secrete estrogen, causing endometrium to continue to proliferate due to prolonged estrogen stimulation and lack of progesterone
Glands proliferate and breadown without secretory phase (unscheduled breakdown)

What stage of the menstrual cycle is this?
Anovulatory cycle - fibrin deposition, inflammatory cells, and endometrial breakdown characteristic of sloughing,
but the small, tubular glands show that it is in the proliferative phase.
What are the symptoms and signs of an inadequate luteal phase?
Abnormal uterine bleeding, infertility
Rise in basal temp < 10 days
What is irregular shedding?
What is the treatment?
Irregular uterine bleeding due to a persistent corpus luteum.
Menses begin at appropriate time, but last longer, are heavier

Tx: estrogen to stabilize and promote growth of endometrium
What is endometrial hyperplasia?
When is it seen most?
What is it related to?
What can it lead to?
Excessive proliferation of endometrial glands compared to stroma
Peri-menopausal
Abnormally high and prolonged estrogenic stimulation w/o sufficient progesterone
Endometrial carcinoma

What is this?
Simple endometrial hyperplasia - notice crowding of glands with little intervening stroma

What is this?
Complex endometrial hyperplasia - reduced stroma and outpouchings and infoldings of glands

What type of endometrial hyperplasia is this?
Atypical simple - note cytological atypia - clumped nuclear chromatin, causing empty spots in nuclei, and prominent nucleoli
What is the most common malignant neoplasm of the female reproductive tract?
Endometrial adenocarcinoma - 55-65 years old

Remember - there are two types (endometrioid and serous)
endometrioid is more common, associated with estrogen, obesity, diabetes, infertility, low parity, HTN, PCOS in young
How are endometrial carcinomas graded? What are 5-year surivival rates?
1 - 1/3 of myometrium - 80%
2 - 1/2 - 70%
3 - 2/3 - 60%
4 - invades all the way to serosa - 40%
How is endometrial carcinoma staged? What are 5-yr survival rates?
I - confined to uterus - 85%
II - extends to endocervix - 40%
III - Pelvic disease - 30%
IV - Abdominal disease - 3%

What neoplasm is this?
Endometrioid adenocarcinoma - copious amt of glandular formation w/o intervening stroma - glands invade underlying myometrium - may see squamous differentiation
What are the characteristics of endometrioid carcinomas?
Background of hyperplasia
Tumors have numerous est and progest receptors
Gland forming w/low nuclear grade
Good survival at stage I (which is when most present)
What are characteristics of papillary serous endometrial carcinoma?
Background of atrophy
No hyperestrogenism
Fewer estrogen and progesterone receptors
More poorly differentiated
High nuclear grade (HOBNAIL nuclei)
Present later - stage III
Poor survival

What neoplasia is this?
Type II adenocarcinoma of endometrium (papillary serous carcinoma) - papillary structures w/fibroblast cores
Hobnail nuclei
What is a malignant mixed mullerian tumor (carcinosarcoma) comprised of?
Malignant epithelial and stromal elements

What neoplasm is this?
Carcinosarcoma - see epithelial cpt (papillary serous ca) and mesenchymal cpt (rhabdomyoblastic)
What is the most common tumor of the uterus?
Leiomyoma ("fibroids")
What are the symptoms of leiomyoma?
Submucosal - bleeding, decreased fertility, recurrent pregnancy loss
Intramural - bleeding, mass
Subserosal - compression of adjacent organs, obstipation, frequency of urination, pain

What is this?
Leiomyoma - smooth muscles separated by CT
What is adenomyosis?
Presence of endometrial glands and stroma in myometrium, causing smooth muscle hyperplasia in myometrium, uterine wall thickening

What is this?
Adenomyosis - presence of endometrial glands and stroma in myometrium
What is endometriosis?
Presence of endometrial glands and stroma outside the uterus corpus.

What is this?
Leiomyosarcoma - see smooth muscle cells, bizarre nuclei
This cancer sucks - median survival 43 months, 78% develop distant metastases
What are the characteristics of an endometrial stromal sarcoma?
less than 10% of all uterine sarcomas
40-50 years
Looks like secretory phase
Expresses progesterone receptors (treat w/ high dose progesterone)
40% local recurrence, rarely metastasizes

What does this Pap smear tell you?
Normal. Cells have abundant cytoplasm and small nuclei.

What does this Pap tell you?
Changes associated with condyloma (HPV infection) - perinuclear clearing, nuclear enlargement

What does this Pap tell you?
High grade dysplasia - large nuclei and scant cytoplasm

What do you see here?
Right - koilocytosis (clearing and enlargement) - associated with HPV infection
Left - Dysplasia causing loss of maturation
They are geographically related, and koilocytosis can lead to dysplasia
What is the epithelium of the different parts of the cervix?
Exocervix - squamous
Endocervix - columnar
How does HPV lead to dysplasia?
E6 binds to p53 --> apoptosis blocked
E7 binds to Rb --> increased proliferation

E1 and E2 are lost when integrated, and they normally inhibit production of E6 and E7.

Allows accumulation of other genetic changes

What level of cervical dysplasia is this?
High grade

What is this?
Invasive squamous carcinoma
Notice the keratin whorls
What is the staging schemata for cervical carcinoma?
Also 5-yr survival
I - cervix only -85%
a - stromal invasion < 5mm 98%
b - > 5mm 80%
II - upper 2/3 of vagina involved 70%
III - involves lower 1/3 of vagina, or extends to pelvic sidewall - 35%
IV - mucosa of bladder or rectum has metastases - 10%

What is this? It's endocervix, p.s.
Microglandular hyperplasia - see cribriform architecture of glands
What is adenosis?
An increase in the number of acinar units per breast lobule.
This is a marker for increased risk of cancer.
Which lymph nodes do cervical carcinomas spread to? Vulvar?
Cervical --> pelvic
Vulvar --> inguinal
Do estrogenic therapy and OCs increase the risk of fibrocystic changes in the breast?
No - OCs may DECREASE risk.

What is this (in the breast)
Apocrine cyst, with microcalcifications

What is this?
Sclerosing adenosis -
Number of acini is increased, acini are compressed by stromal fibrosis, myoepithelial cells are prominent (they are absent in carcinoma)

What is this?
Radial scar, sclerosing lesion
What is the most common benign tumor of the breast? What plays a role in its development?
Fibroadenoma - estrogen increase
They peak in 3rd decade

What breast pathology is this?
Fibroadenoma - proliferation of stroma and glands, well-circumscribed
What substances can be measured to monitor patients with surface epithelial malignancies of the ovary?
CA125 and inhibin
How is ovarian carcinoma staged?
What are the 5-yr survival rates of each?
Stage I - one or both ovaries - 90%
Stage II - involvement of pelvic tissue - 80%
Stage III - involvement of lymph nodes or extrapelvic peritoneum - 20%
Stage IV - abdominal or distant organs - 5%
What are the 5 year survival rates of:
Papillary serous adenocarcinoma
Endometrioid adenocarcinoma
Mucinoid adenocarcinoma
20-30%
60%
40%

What tumor of the ovary is this?
Mucinoid - tall cells with basal nuclei, mucinous content, cribriform arrangement

What tumor of the ovary is this? With what is is associated?
Survival?
Clear cell carcinoma, associated with endometriosis (50%)
Survival is 50%

What tumor of the ovary is this? Is it malignant?
Brenner tumor - very rarely malignant
Note the biphasic pattern of transitional-type epithelium with fibroblast-like stroma
Almost always has a nuclear groove up close
What is the main epidemiological difference between endothelial and germ cell tumors of the ovary?
Epithelial tumors occur in older patients.
What chromosome region has been associated with ovarian germ cell tumors?
isochromosome 12p

What kind of tumor is this?
Immature teratoma - note the neural rosettes (neuroblastoma-like)
What is the survival rate with chemotherapy of immature teratomas?
80-90%
What are some things to look for microscopically in a dysgerminoma?
Clear cytoplasm, round and uniform nuclei, lots of lymphocytes, granulomatous reaction
What enzyme can be elevated in dysgerminomas?
Placental alkaline phosphatase
What enzyme can be elevated in endodermal sinus tumor?
alpha fetoprotein

What is this and what does it indicate?
Schiller-Duval body.
Endodermal sinus tumor
These produce alpha-fetoprotein
What enzymes are elevated in embryonal carcinoma?
beta-HCG and alpha-fetoprotein

What ovarian tumor is this?
Embryonal carcinoma - least differentiated of germ cell tumors.
Cyst-like spaces, poorly formed glandular structures
What ovarian tumor may cause a pseudoprecocious puberty?
Granulosa cell tumor that produces estrogen (it's pseudo because it's not also producing progesterone or ovulating)

What kind of ovarian tumor is this?
Granulosa cell - notice the Call-Exner body (microfollicular pattern)

What kind of ovarian tumor is this?
Leydig cell - follicular cells with uniform nuclei, some have crystalloid material - (Reinke cells)
What serum markers are used for these ovarian tumors?
Carcinoma
Endodermal sinus tumor
Choriocarcinoma
Granulosa cell tumor
CA125
AFP
HCG
Inhibin, estrogen
What characterizes a Krukenberg tumor?
Signet ring cells with cellular reactive stroma
Usually come from stomach primary

What kind of ovarian tumor is this?
Krukenberg - signet ring with reactive stroma and spindle cells around it.
What is Stein-Leventhal syndrome?
Amenorrhea, infertility, polycystic ovaries, hirsutism, glucose intolerance, obesity
What are two possible etiologies of Stein-Leventhal syndrome?
1) Hypothalamic mediated increase in LH
2) Persistant anovulation --> loss of cyclic variations in hormones, higher steady state of androstenedione, estradiol, LH, and testosterone. FSH is decreased.

high LH --> high androgens --> high estrogen from androgen aromatization --> high FSH
What is the therapy of Stein-Leventhal syndrome?
Clomiphene - induces ovulation
or partial bilateral oophorectomy

What does this cytopathological sample indicate?
Herpes - with multinucleation, nuclear molding

What are these and what do they indicate?
Koilocytes - HPV infection
(enlarged, hyperchromative nuclei with cavitation around them)

What is this?
High grade squamous carcinoma
Spindle cells - when a squamous cell becomes malignant
Orange cytoplasm - keratin

What type of cells are these? What could they indicate?
Endometrial cells.
Endometrial polyp, abnormality, or endometrial carcinoma (and rarely ovarian endometrioid carcinoma)
What are the 1st and 2nd most prognostic markers for breast cancer?
1) number of lymph nodes involved
2) tumor size
How is invasive lobular cancer different from invasive ductal cancer?
ILC has greater predilection for bilaterality, likes serosal surfaces
How does lumpectomy plus radiation compare to mastectomy in terms of recurrence rate and survival?
Equivalent
What is the treatment for cancers that are secondary to previous radiation exposure?
Mastectomy.
What is a rule of thumb for estimating recurrence of breast cancer after resection?
6% per 1 cm
10% per lymph node
What is trastuzumab?
antibody to her-2 protein.
No side effects of chemo.
What is cyclophosphamide?
alkalating agent - works in DNA synthesis
What is doxorubicin?
Topoisomerase inhibitor
What is taxotere?
Microtubulin inhibitor - stabilizes microtubules

What breast pathology is this?
Epithelial hyperplasia - proliferating epithelium extends into duct lumen and obliterates it, leaves irregular lumen.

What breast pathology is this?
Proliferative fibrocystic change with atypia -

What breast tumor is this?
Phyllodes - increased stromal cellularity, mitosis and nuclear pleomorphism, stromal overgrowth, infiltrating borders, hyperchromatic cells with large nuclei and cellular stroma

What breast tumor is this?
Large duct papilloma - papillary structure, lined with ductal and myoepithelial cells
How much do the proliferative breast diseases increase risk for breast carcinoma?
Moderate or florid ductal hyperplasia without atypia and sclerosing adenosis - 1.5-2x
Atypical ductal hyperplasia - 4-5x
What role does obesity play in risk for breast carcinoma?
If <40 - decreased risk due to anovulatory cycles and lower progesterone levels
If post-menopausal - increased due to synthesis of estrogen in fat deposits

What kind of breast tumor is this?
Comedocarcinoma DCIS - high grade malignant cells with central necrosis.
Necrosis calcifies and is seen on mammogram as clustered linear or branching.
What is Paget's disease of the nipple?
Form of DCIS that extends from ducts into contiguous skin of nipple and areola.
How do you distinguish Paget's of the nipple from melanoma?
Large, clear cells secreting mucin.
What is treatment of DCIS?
Segmental excision with radiation. If extensive --> mastectomy
Most are thought to progress to invasive carcinoma if not treated.

What breast carcinoma is this?
LCIS - round nuclei, small nucleoli, expands into lobules.
What does LCIS indicate?
Increased risk of developing invasive carcinoma bilaterally, but no increased risk locally. Surgery is not reccommended, therefore.

What breast tumor is this?
Invasive Ductal Carcinoma - malignant cells in cords, solid cell nests, tubules, or masses invading stroma. Lobular configuration is lost. Cytology ranges from low to high grade.

What breast tumor is this?
Invasive lobular carcinoma - see single file pattern of cords (Indian File) of infiltrating tumor cells that are small with little pleomorphism, without formation of tubules.
Lacks e-cadherin

What breast tumor is this?
Medullary carcinoma - solid syncytial sheets of large cells, vesicular, pleomorphic nuclei w/prominent nucleoli, frequent mitoses. Non-infiltrative border --> well-circumscribed. Lymphoplasmacytic infiltrate surrounding and within

What breast tumor is this?
Colloid carcinoma - excellent prognosis.
Epithelial clusters embedded in light purple mucinous material. Well-circumscribed, slow-growing.

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