Pathology Exam 4

Question 1

2 Main categories of hormones

Answer 1

1. Hormones that bind to cell surface receptors

2. Hormones that bind to intracellular receptors

Question 2

Hormones to cell surface receptors

Answer 2

peptide hormone and small molecules, which when bound to surface receptors leads to an increase in intracellular second messengers (cAMP)

Question 3

Hormones that bind to intracellular receptors

Answer 3

lipid soluble hormones that pass through plasma membrane and interact with receptors in the cytosol. These complexes then bind to regulatory elements in DNA (steroids, retinoids, thyroxine)

Question 4

3 main causes of endocrine diseases

Answer 4

1. Underproduction or overproduction of hormones with associated biochemical and clinical consequences
2. End-organ resistance to hormone effect
3. Neoplasms (nonfunctional, hormone overproduction, hormone underproduction)

Question 5

Pituitary Gland

Answer 5

is a small bean shaped structure that lies at the base of the brain within the sella turcica. It is connected to the hypothalamus via a stalk composed of axons and portal circulation.

Question 6

Anterior pituitary gland

Answer 6

Hormones released by anterior pituitary gland are produced in response to the release of hypothalamic factors carried to the anterior pituitary gland via portal circulation.

Question 7

Posterior pituitary gland

Answer 7

Posterior pituitary (neurohypophysis) is made of modified glial cells and axons that extend from the hypothalamus. Hormones synthesized by hypothalamus are stored in these axon terminals and will be released by posterior pituitary gland.

Question 8

Anterior pituitary gland hormones

Answer 8

• Thyroid stimulating hormone (TSH)
• Adrenocorticotropic hormone (ACTH)
• Prolactin (PRL)
• Growth hormone (GH)
• Follicle stimulating hormone (FSH)
• Luteinizing hormone (LH)

Question 9

Posterior pituitary gland hormones

Answer 9

Oxytocin

Vasopressin (ADH)

Question 10

Hypothalamus Hormones

Answer 10

1. Thyroid releasing hormone (TRH)
2. Corticotropin-releasing hormone (CRH)
3. Growth hormone releasing hormone (GHRH)
4. Gonadotropin releasing hormone (GnRH)
5. Somatostatin (GIH)
6. Dopamine (PIF)

Question 11

The most common cause of hyperpituitarism

Answer 11

is an adenoma arising in the anterior lobe

Question 12

Pituitary adenomas are classified on the basis of…

Answer 12

hormone(s) produced by the neoplastic cells.

Question 13

Silent Pituitary Adenoma

Answer 13

produces hormones only at the tissue level → no clinical manifestations

Question 14

Functional Pituitary Adenoma

Answer 14

pituitary adenoma that produces hormones

Usually: composed of a single cell-type, produce a single predominant hormone

Question 15

Non-functional Pituitary Adenoma

Answer 15

1. Does not produce hormones and is often found late
2. Destroys adjacent pituitary parenchyma → hypopituitarism
3. Can also compress the optic chiasm → visual changes, loss of vision

Question 16

Microadenoma Size

Answer 16

< 1 cm

Question 17

Macroadenoma Size

Answer 17

> 1 cm

Question 18

3 most common types of functioning pituitary adenomas

Answer 18

1. Lactotroph (most common)
2. Somatotroph (2nd most common)
3. Corticotroph

Question 19

Lactotroph

Answer 19

Most common, accounts for 30%. Prolactin-secreting adenomas = hyperprolactinemia which causes amenorrhea, galactorrhea, loss of libido, and infertility.
Clinical Presentation: Tumors size ranges from microadenomas to large. They are diagnosed earlier in premenopausal women because of amenorrhea and small in size. The effects of the tumor are much more subtle in older women and men and the tumor may reach a large size before detection.

Question 20

Somatotroph

Answer 20

Tumor that secretes growth hormone (GH).
Clinical Presentation: Causes gigantism in children and acromegaly in adults. GH stimulates hepatic insulin-like growth factor 1 (IGF1) which works with GH to start overgrowth of muscles and bones.
Persistent GH excess can lead to metabolic abnormalities, most importantly diabetes mellitus

Question 21

Corticotroph

Answer 21

Excess production of ACTH which leads to adrenal hypersecretion of cortisol and eventually the development of hypercortisolism (a.k.a Cushing Syndrome)
Clinical Presentation: Usually small sized tumors. Nelson Syndrome: May develop after surgical removal of adrenal glands for treatment of Cushing Syndrome.

Question 22

Definition of hypothyroidism

Answer 22

loss or absence of +75% of anterior pituitary

Question 23

Sheehan Syndrome

Answer 23

(postpartum necrosis) ischemic necrosis of anterior pituitary

hyperplasia of anterior pituitary w/o blood supply

Question 24

Antidiuretic Hormone (ADH)

Answer 24

Acts on collecting tubules of kidney to promote resorption of water.

Question 25

Oxytocin

Answer 25

Stimulates contraction of smooth muscle in the pregnant uterus and the lactiferous ducts of mammary glands.

Question 26

2 subtypes of Diabetes Insipidus

Answer 26

1. Central | 2. Nephrogenic

Question 27

Central DI

Answer 27

Central = ADH deficiency Etiology: head trauma, neoplasms, inflammation disorders of hypothalamus/pituitary, surgical procedures of hypothalamus/pituitary

Question 28

Nephrogenic DI

Answer 28

Nephrogenic = Renal tubular unresponsiveness to circulating ADH Etiology: Due to underlying kidney pathology

Question 29

Syndrome of inappropriate ADH (SIADH)

Answer 29

secretion is associated with: | excess ADH → resorption of excessive amounts of free water → hyponatremia

Question 30

Causes of SIADH

Answer 30

1) malignant neoplasms (especially small-cell carcinoma of lung) that secretes ectopic ADH, 2) non-neoplastic disease of the lung, & 3) local injury to the hypothalamus or neurohypophysis (posterior pituitary)

Question 31

Breast Objective #2: Most common symptoms of women with breast complaints

Answer 31

1. Pain (5% cancer) 2. Inflammation (<1% cancer) 3. Nipple discharge (7& cancer) 4. Lumpiness (1% cancers) 5. Palpable masses (5% cancer)

Question 32

Breast Objective #3: 2 principal mammographic signs of breast carcinomas

Answer 32

1. Densities: Normal breast tissue is replaced with radio-plaque breast lesions 2. Calcification: Formed on secretions, necrotic debris, and hyalinized stroma

Question 33

Breast Objective #4: 3 groups of benign epithelial lesions of the breast each associated with different degree of cancer risk

Answer 33

1. Non-proliferative disease: Not associated with increased CA risk 2. Proliferative disease w/out atypia: encompasses polyclonal hyperplasias that are associated with a slight increase for breast CA risk 3. Proliferative disease w/ atypia: Includes monoclonal "precancers" that are associated with a modest increase in breast CA (13-17% develop breast CA)

Question 34

Breast Objective #5: Define gynecomastia, underlying hormone imbalance, examples of predisposing factors, and risk of CA.

Answer 34

Definition: Increased breast tissue in males. Only common symptom in males. An increase in both stroma and epithelia cells. Hormones: Imbalance between estrogens, which stimulate breast tissue, and androgens, which counteract these effects Predisposing factors: Risk of CA:

Question 35

Breast Objective #6: List risk factors that convey highest relative risk for invasive breast carcinomas & indicate life time risk in US

Answer 35

Most important: 1. Age and gender 2. Family Hx of breast CA 3. Geographic factors 4. Race/Ethnicity 5. Reproductive Hx 6. Ionizing radiation 7. Other risk factors Lifetime risk: 1 in 8 women living to age 90

Question 36

Breast Objective #7: 3 groups of hormone receptor breast cancers

Answer 36

1. Estrogen receptor 2. Progesterone receptor 3. HER2

Question 37

Breast Objective #7: Incidence by expression of hormone receptor

Answer 37

1. ER + (HER2-): 50-65% 2. HER2 + (ER +/-): 10-20% 3. Triple Neg (ER, PR, HER2 -): 10-20%

Question 38

Breast Objective #7: Mutations responsible for most single gene familial breast cancer

Answer 38

1. BRCA 1 2. BRCA 2 These account for half of the cases associated with single gene mutations

Question 39

Breast Objective #8: The 2 most common locations of tumors

Answer 39

1. Upper outer quadrant 50% | 2. Central portion 20%

Question 40

Breast Objective #9: ER positive / HER2 Negative frequency, typical patient groups, common metastatic patterns, and relapse pattern

Answer 40

Frequency: 50-65% Patient Groups: older women, men. cancers detected by screening; germline BRCA2 mutation carriers Metastatic: Bone (70%), viscera (25%), brain (<10%) Relapse: May be late (>10 years after diagnosis)

Question 41

Breast Objective #9: HER2 + / ER + or - : frequency, typical patient groups, common metastatic patterns, and relapse pattern

Answer 41

Frequency: 20% Patient group: Young women, germline TP53 mutation carriers Metastatic: Bone (70%), viscera (45%), brain (30%) Relapse: short (10 years; survival with mets is rate)

Question 42

Breast Objective #9: Triple Negative: frequency, typical patient groups, common metastatic patterns, and relapse pattern

Answer 42

Frequency: 15% Patient group: young women; germline BRCA1 mutation carriers Metastatic: Bone (40%), viscera (35%), brain (25%) Relapse: Short (<5 years; survival with mets rare

Question 43

Breast Objective #10: Distingush between LCIS and DCIS on basis of calcification and risk for invasive carcinoma

Answer 43

DCIS: Ductal carcinoma in situ Calcification: frequently associated Invasive Risk: 1/3rd if not treated , but 97% long-term survival LCIS: Lobular carcinoma in situ Calcification: Rarely associated Invasive Risk: Approx 1/3rd of women will develop invasive

Question 44

Breast Objective #11: List prognostic factors for invasive breast cancer, and know which is the most important

Answer 44

Need lecture first***

Question 45

Breast Objective #12: Describe the epidemiology of, the typical clinical presentation of, and any associated risk of malignancy with fibroadenoma.

Answer 45

Fibroadenoma: benign tumor contains a mixture of proliferating ductal elements (adenoma) embedded in loose fibrous tissue (fibroma) Epidemiology: Most common benign tumor of the female breast; most occur in women in their 20s and 30s, and they are frequently multiple and bilateral. 10% of women will develop a fibroadenoma during their lifetime Clinical presentation: Vary in size from <1 cm to large tumors that replace most of the breast; well-circumscribed, rubbery, grayish white nodules that bulge above the surrounding tissue and often contain slitlike spaces (feels like a moveable marble in the breast) Associated risk of malignancy: Benign, but a mildly increased risk of subsequent cancer