Flashcards in Sweep 2 Deck (46):
o small nests of ------- scattered between the follicles; not visible without special stains
o Most common cause of hypothyroidism where ------- is sufficient
o Autoimmune; progressive destruction of ======== with inflammatory infiltrates
o Involves CD4+, CD8+, and NK cells
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
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
Medullary Thyroid Carcinoma
I. Normal Parathyroid Glands
o composed mostly of
chief cells (principal cells, clear cells), secrete PTH
o oxyphil cells; unknown function
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
o Brown tumor of hyperparathyroidism can develop in the ====
o ---------- appearance
o Metastatic ---------
• Deposition of -------- in throughout body, including blood vessels
• Pancreatic islet cell tumor, hypersecretion of gastric acid, severe peptic ulcers
• Most are malignant (60%), surgical resection
III. Islet Cell Tumors
• Zollinger-Ellison Syndrome
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
Hypercortisolism (Cushing Syndrome)
• Characterized by chronic excess aldosterone secretion – causes:
o Sodium retention, Potassium excretion
o Hypertension and hypokalemia
o Very rare
o Hyperplasia, neoplasm, idiopathic
o Decreased levels of plasma renin
o Aldosterone release in response to activation of renin-angiotensin system
o Increased levels of plasma renin
• Primary or
• Decreased stimulation of --------- from deficiency of ACTH
• Don’t appear until at least 90% of ----------- gland has been destroyed
• GI disturbances (anorexia, nausea, vomiting, weight loss, diarrhea)
• 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
o Autoimmune destruction of steroid-producing cells
• Most common, 60-70% of cases
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
Primary Chronic Adrenocortical Insufficiency (Addison’s Disease)
• Any disorder of hypothalamus of pituitary that reduces output of ACTH
• Symptoms similar to Addison’s disease
o But no skin/mucosa pigmentation
Secondary Adrenocortical Insufficiency
• Types I, 2A, and 2B
• Tumors of multiple endocrine organs
o Medullary Thyroid Carcinoma
• 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
• Multiple Endocrine Neoplasia (MEN) Syndromes
: 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)
Astrocytes and injury
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.
-blood brain barrier disruption and increased vascular permeability-note fluid shift from vascular component to the brain.
-increased intracellular fluid secondary to neuronal glial or endothelial cell membrane injury e.g. hypoxic or metabolic damage.
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
2. Hypertensive cerebrovascular disease and intraparenchymal hemorrhage.
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
g. Subarachnoid hemorrhage i.e. blood in CSF may be seen together with
3. Subarachnoid hemorrhage
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.
e. : Less aggressive, often in pediatric patients, usually located in the cerebellum.
Pilocytic astrocytoma (gliomas)
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.
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%.
= pain on swallowing.
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.
a. Esophageal adenocarcinoma
• Linitis plastica “leather bottle appearance” markedly thickened stomach wall, reactive to diffusely-infiltrative, aggressive form of stomach cancer.
B. Stomach neoplasia
3. Gastric adenocarcinoma:
-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.
1. Secondary biliary cirrhosis
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.
Primary biliary cirrhosis (PBS)
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
Primary sclerosing cholangitis (PSC)
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
2. Benign liver neoplasms.
• 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
a. Cholangiocarcinoma (CCA)
Met spread to liver
• Often only sign is
hepatomegaly-liver has tremendous functional reserve
• 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.
a. Acute Pancreatitis
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.
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.
serum alkaline phosphatase
Hematogenous osteomyelitis is caused most frequently by ----------------; while mixed infections, often with anaerobes, are seen in those secondary to trauma or dental problems.
: 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.
1. Monostotic fibrous dysplasia (single bone)
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.
2. Polyostotic fibrous dysplasia without endocrine involvement (Jaffe-Lichtenstein Syndrome):
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.
3. Polyostotic fibrous dysplasia in association with endocrinopathies (McCune-Albright syndrome):
• ------- is responsible for majority of female reproductive tract diseases
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.
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.
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.
------------ 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.