Sweep 2

Question 1

Normal Thyroid
• histology
o small nests of ——- scattered between the follicles; not visible without special stains

Answer 1

C-cells

Question 2

Hashimoto Thyroiditis
o Most common cause of hypothyroidism where ——- is sufficient
o Autoimmune; progressive destruction of ======== with inflammatory infiltrates
o Involves CD4+, CD8+, and NK cells

Answer 2

dietary iodine

parenchyma

Question 3

o accounts for 5-15% of thyroid cancers
o Older age than papillary; areas with dietary iodine deficiency
o grossly may resemble an adenoma with a discrete capsule
o Must see invasion through the capsule or into the blood vessels

Answer 3

Follicular Carcinoma

Question 4

o uncommon, accounts for 5% of thyroid cancer
o derived from the parafollicular (C) cells
o may be sporadic or familial (component of MEN syndromes)
o All have mutation in the RET proto-oncogene
o Increased serum calcitonin

Answer 4

Medullary Thyroid Carcinoma

Question 5

I. Normal Parathyroid Glands

o histology
o composed mostly of

Answer 5

chief cells (principal cells, clear cells), secrete PTH
o	oxyphil cells; unknown function

Question 6

o Clinical features
o Classic constellation of symptoms
• Painful bones: Fractures associated with osteoporosis
• Renal stones
• Abdominal groans: Constipation, peptic ulcers, and gallstones
• Psychic moans: Refers to depression, lethargy and seizures

Answer 6

Primary hyperparathyroidism

Question 7

o Brown tumor of hyperparathyroidism can develop in the ====
o ———- appearance
o Metastatic ———
• Deposition of ——– in throughout body, including blood vessels

Answer 7

jaws

Ground glass

calcifications

calcium

Question 8

• Pancreatic islet cell tumor, hypersecretion of gastric acid, severe peptic ulcers
• Most are malignant (60%), surgical resection

Answer 8

III. Islet Cell Tumors
• Gastrinoma
• Zollinger-Ellison Syndrome

Question 9

• Causes
o Most commonly by excess administration of exogenous glucocorticoids
o Primary adrenal hyperplasia or neoplasm (e.g. adrenal adenoma)
o Primary pituitary source
• ACTH oversecretion by pituitary microadenoma
o Ectopic ACTH secretion by neoplasm, e.g. lung

Answer 9

Hypercortisolism (Cushing Syndrome)

Question 10

•	Characterized by chronic excess aldosterone secretion – causes:
o	Sodium retention, Potassium excretion
o	Hypertension and hypokalemia
•	Primary
o	Very rare
o	Hyperplasia, neoplasm, idiopathic
o	Decreased levels of plasma renin
•	Secondary
o	Aldosterone release in response to activation of renin-angiotensin system
o	Increased levels of plasma renin

Answer 10

Hyperaldosteronism

Question 11

• Primary or
• Secondary
• Decreased stimulation of ——— from deficiency of ACTH
• Don’t appear until at least 90% of ———– gland has been destroyed
• Manifestations
• Weakness
• Fatigue
• GI disturbances (anorexia, nausea, vomiting, weight loss, diarrhea)

Answer 11

III. Hypoadrenalism

Question 12

• Progressive destruction of adrenal cortex
• Serum ACTH may be elevated → skin and mucosal pigmentation
• Destruction of cortex prevents response to ACTH
• Potassium retention, sodium loss, hyperkalemia, hyponatremia, volume depletion, and hypotension
• Causes
o Autoimmune destruction of steroid-producing cells
• Most common, 60-70% of cases
o TB
o AIDS
o Metastatic disease
• Clinical features
• Progressive weakness—easily fatigued
• GI disturbances: nausea, vomiting, anorexia, weight loss, diarrhea
• Hyperpigmentation—often involves the oral mucosa
• A craving for salt
• Treatment: Corticosteroid replacement therapy
• Prognosis: Guarded. Can result in death if not recognized and treated properly

Answer 12

Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)

Question 13

• Any disorder of hypothalamus of pituitary that reduces output of ACTH
• Symptoms similar to Addison’s disease
o But no skin/mucosa pigmentation

Answer 13

Secondary Adrenocortical Insufficiency

Question 14

•	Types I, 2A, and 2B
•	Tumors of multiple endocrine organs
o	Medullary Thyroid Carcinoma
o	Pheochromocytoma
o	Parathyroid 
o	Pituitary
o	Pancreas
•	RET proto-oncogene
•	MEN 2B notable for early orofacial manifestations
o	Mucosal neuromas (tongue, labial commisure)
o	Large, blubbery lips
o	Marfanoid body habitus
o	Early onset medullary carcinoma of thyroid

Answer 14

• Multiple Endocrine Neoplasia (MEN) Syndromes

Question 15

: Often show astrogliosis (repair and/or scar formation). Increased bright pink cytoplasm, cytoplasmic swelling, formation Rosenthal fibers (thick eosinophilic protein aggregates seen in chronic gliosis)

Answer 15

Astrocytes and injury

Question 16

Fixed macrophages in CNS are CD68 and CR3 positive. Can also note blood borne macrophages with inflammation. Proliferation, elongated nuclei (rod cells), foci microglial nodules, neuronophagia.

Answer 16

a. Microglia:

Question 17

-blood brain barrier disruption and increased vascular permeability-note fluid shift from vascular component to the brain.

Answer 17

Vasogenic edema

Question 18

-increased intracellular fluid secondary to neuronal glial or endothelial cell membrane injury e.g. hypoxic or metabolic damage.

Answer 18

Cytotoxic edema

Question 19

a. Hypertension is the most common underlying cause of primary parenchymal hemorrhage.
b. Accelerated atherosclerosis in larger vessels and hyaline arteriolosclerosis in smaller vessels weakens the vessel walls.
c. Subsequently note wall rupture and hemorrhage, which is most common in the regions of the basal ganglia, followed by pons, thalamus and cerebellum.
d. Can be clinically devastating if it affects large portions of brain and extends into ventricular system.
e. Severe headache, hemiparesis, hemisensory loss

Answer 19

2. Hypertensive cerebrovascular disease and intraparenchymal hemorrhage.

Question 20

a. Defined as abrupt onset extravasation of blood in space between arachnoid and pia (arterial bifurcations of the circle of Willis) matter due to rupture of vessels in arachnoid space.
b. Often are spontaneous, but could also be precipitated by traumatic injury.
c. Chief complaint of patient “Worst headache of my life”.
d. Ruptured berry (saccular) aneurysm (of major brain arteries) is the most common cause of non-traumatic hemorrhage.
e. Most aneurysms arise from branches of the middle cerebral, internal carotid and the junction between the anterior cerebral and anterior communicating arteries.
f. Probably represents an acquired, degenerative process, aggravated by
hypertension.
g. Subarachnoid hemorrhage i.e. blood in CSF may be seen together with
intraparenchymal hemorrhage.

Answer 20

3. Subarachnoid hemorrhage

Question 21

a. Astrocytomas (infiltrating) comprise 80% of adult tumors. Symptoms include seizures, headaches and focal neurologic deficits.
b. In adults, mostly affects the cerebral hemisphere
c. Pilocytic astrocytoma (Grade I) → Astrocytoma (Grade II) → Anaplastic astrocytoma (Highly cellular with mitotic figures, Grade III) → Glioblastoma (Necrosis and microvascular proliferation, Grade IV). Glioblastoma → note endothelial cell proliferation.
d. Clinical features-may remain “silent” until increase in growth. Treatment consists of surgical resection, then radiation and chemotherapy. ~ 15 month survival.

Answer 21

Gliomas

Question 22

e. : Less aggressive, often in pediatric patients, usually located in the cerebellum.

Answer 22

Pilocytic astrocytoma (gliomas)

Question 23

.

a. Patients often have several years of neurologic symptoms including seizures.
b. Mostly cerebral hemisphere.
c. Well circumscribed, often calcified. Cells with uniform, round nuclei and perinuclear halo (fried egg look)
d. Generally better prognosis than astrocytoma.

Answer 23

Oligodendroglioma

Question 24

a. Primarily seen in pediatric patients in cerebellum (by definition).
b. Rapid growth with cells disseminating through CSF. May block CSF flow-note hydrocephalus.
c. Cells form Homer-Wright rosettes
d. Very aggressive (Grade IV tumor) but radiosensitive. Surgical excision and radiation. Five year survival as high as 75%.

Answer 24

Medulloblastoma.

Question 25

= pain on swallowing.

Answer 25

Odynophagia

Question 26

Esophagus-benign and malignant tumors

• Worldwide rate < SCCa or esophagus
• Usually affect the distal third of the esophagus
• Associated with long-standing GERD or Barrett change
• Increased in Caucasians
• Increased in males over females (7:1)
• Dysphagia, “Chest Pain”, weight loss
• Often detected at late stage: 25% 5yr survival.

Answer 26

a. Esophageal adenocarcinoma

Question 27

• Linitis plastica “leather bottle appearance” markedly thickened stomach wall, reactive to diffusely-infiltrative, aggressive form of stomach cancer.

Answer 27

B. Stomach neoplasia

3. Gastric adenocarcinoma:

Question 28

• results from obstruction extrahepatic duct
  a. Biliary tree obstruction-the primary cause is cholelithiasis (gall stones), then malignancies of biliary tree or head of pancreas.
  b. Develop secondary inflammation-then fibrosis, hepatic scarring.

Answer 28

1. Secondary biliary cirrhosis

Question 29

a. Inflammatory autoimmune disease-affects intrahepatic bile ducts.
b. Primary feature-nonsuppurative inflammatory destruction of medium sized intrahepatic ducts-also get portal inflammation, scarring and eventually cirrhosis.
c. Thought to be an autoimmune etiology.

Answer 29

Primary biliary cirrhosis (PBS)

Question 30

a. Fibrosing cholangitis of bile ducts-develop luminal obliteration
b. Liver eventually develops biliary cirrhosis
c. NOTE: same common endpoint i.e. biliary cirrhosis as primary and secondary biliary cirrhosis
d. Note an increase in chronic pancreatitis and hepatocellular carcinoma (HCC) in PSC patients

Answer 30

Primary sclerosing cholangitis (PSC)

Question 31

b. Cavernous hemangioma
c. Hepatic adenoma-increase in young women using oral contraceptives
d. Concerns with these: 1) mimic HCC, 2) subcapsular hemorrhage-from a rupture and bleed, 3) may transform to HCC.
e. Are associated with hormonal stimulation

Answer 31

2. Benign liver neoplasms.

Question 32

• Cancer of biliary tree-most are adenoCAs
• Very desmoplastic tumor-tumors are firm and gritty
• Can get collision tumor with HCC
• Asymptomatic until late stage
• Generally fatal within 6 months

Answer 32

a. Cholangiocarcinoma (CCA)

Question 33

Met spread to liver

• Often only sign is

Answer 33

hepatomegaly-liver has tremendous functional reserve

Question 34

• Reversible parenchymal injury associated with inflammation,
• 80% of cases related to biliary tract disease or alcoholism; infections e.g. mumps, trauma, metabolic diseases (e.g. hypercalcemic states), medications (e.g. estrogens, chemotherapy), idiopathic.

Answer 34

a. Acute Pancreatitis

Question 35

1. • e.g. serous cystadenomas, females over males, 2:1, usually seventh decade
     • Close to 95% of mucinous cystic neoplasms arise in women. Can be associated with invasive cancer.
     • Intraductal papillary mucinous neoplasms increased males over females.

Answer 35

Cystic

Question 36

Paget disease (osteitis deformans)
The diagnosis is made secondary to the radiographic and microscopic appearances combined with demonstration of elevated levels of --------- (⇑bone resorption) and ---------------- (⇑bone apposition). Most patients have mild symptoms which can be controlled by --------- or bisphosphonates and analgesics.

Answer 36

urinary hydroxyproline

serum alkaline phosphatase

calcitonin

Question 37

Hematogenous osteomyelitis is caused most frequently by —————-; while mixed infections, often with anaerobes, are seen in those secondary to trauma or dental problems.

Answer 37

Staphylococcus aureus

Question 38

: 70% of all cases. It usually manifests in childhood and often becomes stationary at puberty. The most common sites of involvement in descending order of frequency are the ribs, femur, tibia, jaws, calvarium, and humerus.

Answer 38

1. Monostotic fibrous dysplasia (single bone)

Question 39

Multiple bones are affected, and the involvement often tends to be unilateral. This pattern accounts for about 25% of the cases, often arises at an earlier age, and can continue to cause problems during adulthood. Frequently affected bones are craniofacial bones (including jaws), femur, tibia, humerus, and pelvis. Café-au-lait pigmentations are variable but not rare; related endocrine abnormalities are absent.

Answer 39

2. Polyostotic fibrous dysplasia without endocrine involvement (Jaffe-Lichtenstein Syndrome):

Question 40

This pattern is the least common, represents around 3% of all cases, and typically is accompanied by melanin pigmentation of the skin (café-au-lait spots) and endocrine abnormalities. Although precocious sexual development is the most common endocrine abnormality, other disorders such as hyperthyroidism, excess growth hormone, and primary adrenal hyperplasia may be seen. Females are affected much more than males. The process often is unilateral and affects the majority of the bones on the altered side.

Answer 40

3. Polyostotic fibrous dysplasia in association with endocrinopathies (McCune-Albright syndrome):

Question 41

• ——- is responsible for majority of female reproductive tract diseases

Answer 41

Uterine corpus

Question 42

Any bone can be affected, however the metaphyseal region of long bones in the extremities is the most frequent site (60% occurring in the knee vs 8 % in the jaws). The radiographic appearance is generally that of a large, destructive, mixed radiolucent-radiopaque lesion that may present with a “sunburst” appearance. A characteristic feature is the formation of an acute angle between the neoplastic bone and the cortex (Codman’s triangle). Diagnosis requires histologic evidence of direct production of osteoid by malignant mesenchymal cells.

Answer 42

Osteosarcoma

Question 43

refers to hyperplasia of the epithelial lining of the uterus that is thought secondary to an excess of estrogen. The process often arises in perimenopausal women from obesity (estrogen synthesis in fat deposits), failure of ovulation, administration of estrogen or from estrogen-secreting tumors.

Answer 43

Endometrial hyperplasia

Question 44

Leiomyomas are benign tumors of ——— smooth muscle origin. When arising in the uterus, these neoplasms historically have been called ——–. These arise from the myometrium in 30-50% of women during active reproductive life; this makes leiomyoma the most common benign tumor in females. Although the cause is unknown, they seem to be estrogen dependent, as evidenced by their rapid growth during pregnancy and the tendency to regress after menopause.

Answer 44

myometrial

fibroids

Question 45

Breast cancer
———— apply to breast alterations which arise as an exaggeration and distortion of the cyclic breast changes that occur normally in the menstrual cycle. ————- consist of overgrowths of the fibrous stroma, the epithelial elements or a proliferation of both. All tend to arise during reproductive life but may persist after menopause. The lesions frequently are bilateral and/or multiple. They sometimes produce masses requiring differentiation from cancer. The great majority of these lesions do not predispose to cancer. However, there is a slightly increased risk with florid ductal hyperplasia; and if the hyperplasia is atypical, there is a significant increased risk.

Answer 45

Fibrocystic changes

Question 46

————— is a common hormonal disorder affecting 5-10% of females of reproductive age. It is generally diagnosed after menarche in teenage girls or young adults. The condition was named due to the presence of multiple cystic follicles in ovaries, resulting in increased size of ovaries and excess production of androgens and estrogens. While there seems to be a genetic influence, the cause of this disorder is incompletely understood. Patients may present with delayed or absent menstruation, oligomenorrhea, hirsutism (increased body hair), acne, fertility problems, and obesity. These women are also at increased risk for type II diabetes and cardiovascular disease.

Answer 46

Polycystic ovarian disease