Transcript Slackers Advanced Topics Pathology Fact Stack

Slackers Advanced Topics
Pathology Fact Stack
Mike Ori
Disclaimer
• These represent my understanding of the subject
and have not been vetted or reviewed by faculty.
Use at your own peril.
• I can’t type so below are common missing letters
you may need to supply
• erl
• I didn’t use greek letters because they are a pain
to cut and paste in.
• What are the three most important properties
of a tumor that affect its prognosis
• Tumor type
• Tumor grade
• Tumor stage
• Define grade
• A quantification of the degree of
differentiation of the tumor. Higher grades
are less differentiated.
• What is the relationship of grading between
tumor types
• Tumors are graded based on features that are
prognostic to each tumor type. Often these
prognostic features are the similar from one
tumor to another but this is not always the
case.
• What are three common histologic features
that are used in grading
• Nuclear atypia
• Growth pattern
• Mitotic activity
• Are grading systems objective or subjective
• Somewhat subjective especially in the middle.
• Define prognostic markers as they pertain to
grading
• These are substances that help determine the
prognosis and sometimes possible effective
treatments of a tumor but that are not used
for diagnosis.
• List several common prognostic markers
• Measure area of highest intensity
• Nuclear
– ER
• Percent showing any stain
– PR
• Percent showing any stain
– KI-67
• Percent showing any stain
• Plasma Membrane
– HER2/Neu
• Stain intensity (0-3)
• Define stage
• The measure of how far advanced (far afield)
a tumor is
• What is the primary descriptive system used
for staging
• TNM system
• Explain the relationships of the TNM system
between cancers
• Each cancer uses its own rules for staging.
• What does an X mean in the TNM system
• X indicates that that aspect has not been
evaluated.
• T1N0MX
• MX = Metastasis was not looked for so the
status is unknown
• M0 = Metastasis was looked for and not found
• Describe the staging of colon cancer
• Defined by anatomical boundary crossed
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T1 = Muscularis mucosa
T2 = Inner edge of muscularis propria
T3 = Outer edge of MP
T4 = Serosa surface (into adjacent structures)
• List common environmental causes of
esophageal cancer
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Alcohol
Tobacco
Fungi and nitrosamine (common in Asia)
Acid reflux/Barretts esophagus
• List a common cause of stomach cancer
• H. pylori
• How does the environment contribute to
colon cancer
• Diet is a major factor in sporadic colon
cancers.
• What are the gene defects associated with
FAP and HNPCC
• FAP
– Chromosomal instability
– APC gene
• HNPCC
– Microsatellite instability
– MSH2, MLH1, PMS2 genes
• Why is pancreatic cancer a “nightmare”
• Because the learning objective is poorly
defined?
• Because it tends to present with at least
locally advanced disease that typically involves
the aorta or other important structures.
• What element is typically elevated with
cholestatic disease
• Copper
• List two autoimmune related diseases of the
biliary tree.
• Primary biliary cirrhosis
• Primary sclerosing cholangitis
• What portion of the biliary tree is attacked by
PBC and PSC
• PBC = intrahepatic small ducts
• PSC = intra and extrahepatic mediumish ducts
• What is the typical patient for PBC and PSC
• PBC = female
• PSC = inflammatory bowel diseases like
ulcerative cholitis
• List 5 common causes of steatohepatitis
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Alcohol related
Non-alcoholic fatty liver disease
Reye syndrome
Acute fatty liver of pregnancy
Drug toxicity
• Distinguish between alcoholic and nonalcoholic steatohepatitis
• Alcoholic
– Hx of alcohol
• M>F
– Neutrophil infiltration
– Mallory hyaline
• Non-alcoholic
– M=F
– Obesity, HLD, DMII
• Describe Reyes syndrome
• An underlying metabolic disorder is unmasked
by a combination of viral illness and
salicylates.
• Mitochondrial swelling.
• Massive microvesicular steatohepatitis
• Describe fatty liver of pregnancy
• Very similar in concept to reyes disease except
that the fetus is the source of the toxic insult.
• Maternal hydroxylacyl CoA dehydrogenase
deficiency cannot metabolize fetal
hydroxylacyl metabolite.
• Massive microvesicular steatohepatitis
• Describe the pattern of hepatocyte damage
that occurs with toxic drug exposure
• Damage can be periportal to centrilobular
depending on the agent and the enzymes
expressed within the region
• Acetaminophen is classically centrilobular
necrosis
• Describe the pattern of hepatocyte damage
from common substances
• peripheral/periportal
– Phosphorus
• Centrilobular
– Tetracycline
– Alcohol
– Acetaminophen
• Microvesicular
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Tetracycline
Aflotoxin
Reye
Fatty liver of pregnancy
• Necrosis
– CCl4
– Acetaminophen
– Tannic acid
• Do microvesicular represent acute or chronic
processes
• Acute
• What are the three broad categories of
thyroid neoplasm?
• Differentiated carcinoma
– Papillary (80%)
– Follicular (10%)
• Anaplastic carcinoma (2%)
• Medullary carcinoma (5%)
• List the risk factors for each category of
thyroid cancer
Differentiated
anaplastic
Medullary
•Ionizing radiation
•Familial non-medullary
thyroid cancer
•Familial adenomatous
polyposis
•Cowden disease
•Gardners syndroms
•Previous or concurrent
thyroid disease
•Differentiated thyroid
cancer
•Familial – RET oncogene
•MEN 2A
•MEN 2B
• List common workup steps for suspected
thyroid disease
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TSH levels
Ultrasound
Fine-needle biopsy
Surgical resection
• When should a total thyroidectomy be
performed
• Proven malignancy
• Bilateral disease
• Suspicious nodules
– Fhx of thyoid disease
– Hx of radiation exposure
• Distinguish MEN 2a from MEN 2b
MEN 2a
MEN 2b
Parathyroid hyperplasia
X
Pheochromocytoma
X
X
Thyroid C-cell hyperplasia
X
X
Thyroid medullary carcinoma
X
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Mucocutaneous ganglioneuroma
X
Marfanoid habitus
X
RET oncogene
X
X
• Define adrenal incidentaloma
• A mass in the adrenal gland found incidentally
during workup for a non-adrenal disease. Up
to 8% of autopsies show adrenal
incidentalomas.
• What are the broad categories of
incidentalomas
• Adrenal origin
– Non malignant
• Non-secreting (80%)
• Secreting
– Cushings (9%)
– Pheo (5%)
– Malignant
• Adrenal adenocarcinoma (5%)
• Non-adrenal
– Metastatic (2.5%)
– Lymphoma
• What compounds might an adrenal tumor
secrete and what are the primary symptoms
• Glucorticoids
– Cushings
• Aldosterone
– Hypertension
– Hypo K
• Sex steroids
– Masculinizing
– Feminizing
• Catecholamines
– Sympathetic outflow states
• What are signs of subclinical cushings
• DMII
– Especiall poorly controlled diabetes despite
multiple agents and adherence
• Weight gain
• Hypertension
• What tests can be used to determine cortisol
levels
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24h urine free cortisol
Late night salivary cortisol levels
Low dose dexamethasone suppression test
48h low dose DST
• What is the sx triad in pheochromocytoma
pt’s
• Headache
• Sweating
• Tachycardia
• When is adrenalectomy required
• Functional tumors (that fails medical
management?)
• Tumors > 4cm
• Tumor features suggestive of malignancy
• Growing tumors
• What factors are suggestive of adrenal
malignancy
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Feminization
Masculinization
Rapid onset cushing
Multiple/mixed hormone secretion
• What is the typical patient profile of a lung
carcinoma patient
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Age: 35 +
Gender M > F
Probably no significant physical exam findings
Masses on MRI/CT/CXR
– Adenocarcinoma
– Squamous
– Small cell
• Describe the typical patient with colon cancer
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Age 45+
M=F
Complaining of a mass or obstruction
Can be visualized with barium or CT, MRI
Typical finding of an adenocarcinoma
• Describe the typical breast cancer pt
• Age 35+
• F>M
• Mass in breast is discoverable on
mammography, sonogram, or MRI
• Typically an adenocarcinoma
• Describe the typical skin cancer patient
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Age 45+
M>F
Nodule with or without ulceration
Usually no imaging is performed
Cancers are basal cell or squamous cell types
• Which cancer is cytokeratin positive for
• Carcinomas – epithelial origin cancers
• Which markers are positive in melanoma
• S-100 and HMB-45
• What marker is used to identify ewing
sarcoma
• CD99
• What marker is used to detect thyroid cancer
• Thyroid transcription factor.
• List the sarcomas of the bone and soft tissue
• Bone
– Osteogenic
– Chondrosarcoma
– Ewing sarcoma
• Soft tissue
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Liposarcoma
Rhabdosarcoma
Synovial sarcoma
Fibrosarcoma
Malignant fibrous histiocytoma
Angiosarcoma
• What is the characteristic age range for
osteogenic sarcoma, chondrosarcoma, and
ewing sarcoma
• Osteogenic
– Teens and young adults
– Adults over 60 in association with pagets
• Chondrosarcoma
– Adults > 40
• Ewing
– Childhood
– Young adulthood
• What are the radiographic findings for
osteogenic sarcoma
• Spiculated mass about the knee
• What are the radiographic findings of
chondrosarcoma
• Irregularly destructive lesion within bone
• Lytic areas
• Soft tissue extension with speckled
calcifications
• What are the radiographic findings of Ewing
Sarcoma
• Irregularly destructive, lytic lesions often with
disproportionately large soft tissue mass
relative to the bone involvement
• Differentiate Osteogenic sarcoma,
chondrosarcoma, and ewing sarcoma
histologically
• Osteogenic
– Bone
– Malignant osteoblasts
• Chondro
– Cartilage
• Ewing
– Small round blue cell tumor
• What genetic change is characteristic of Ewing
sarcoma
• T(11:22)
• What are the common locations and age of
presentation of the soft tissue sarcomas
Age
Liposarcoma
40+
Retroperitoneum
Deep tissues of the thigh
Rhabdomyosarcoma Children
Head and neck
Urogenital
Deep soft tissues (adults)
Synovial sarcoma
Adults <
50
Lower extremity typically the knee
Malignant fibrous
histiocytoma
40+
Lower extremity
Angiosarcoma
Fibrosarcoma
Deep soft tissues of extremities
• Identify the histology of the soft tissue
sarcomas
Liposarcoma
Fat in cells
Myxoid variant = gelatinous
Round cell variant similar to lymphoma and ewing
Rhabdomyosarcoma
Embryonal – round to oval cells suggestive of muscle
Botryoid – small dark cells (usually in urogenital tract)
Alveolar – dark cells arranged around fibrous trabeculae
Pleomorphic – large, bizarre cells with abundant eosinophilic
cytoplasm
Synovial sarcoma
Glandular epithelial cells mixed with spindle cells that may
express cytokeratin
Malignant fibrous
histiocytoma
Mixed spindle cells and polygonal cells
Angiosarcoma
Fibrosarcoma
Cells arranged with nuclei parallel to each other in
herringbone pattern
• What are the gene transformations in Ewing,
liposarcoma, and synovial sarcoma?
• Ewing = t(11;22) FLI1-EWS
• Liposarcoma = t(12,16) CHOP/TLS
• Synovial = t(X:18) SYT-SSX
• What are the important features for grading
sarcomas
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Degree of differentiation
Cellularity
Mitotic activity
Pleomorphism
Extent of necrosis
• Differentiate wegener, goodpastures, and
microscopic poly arteritis
• All are vasculidities that can affect small
vessels
Wegener
Goodpasture
Microscopic
Granuloma
Yes
No
No
Antibodies
c-ANCA
Anti-GBM
p-ANCA
Affected area
Kidney
Lungs
Upper
respiratory
tract
Kidney
lower
respiratory
tract
Skin
Others?
• If vasculitis is suspected, why must a relatively
long segment of affected vessel be biopsied?
• Vasculitis often skips segments within an
affected vessels so a short biopsy may not
contain diagnostic information.
• What is acute necrotizing vasculitis?
• A rapidly destructive vasculitis that results
from rejection in transplant patients
• What is the target in temporal arteritis?
• Giant cell destruction of the elastic lamina.
• List several common markers used to localize
liver injury
• Hepatocyte damage
– AST
– ALT
• Bile duct damage
– Alkaline phosphatase
• Bilirubin
– Direct
– Indirect
• Not yet conjugated by hepatocytes
• What diseases cause microvesicular steatosis
• Reye syndrome
• Fatty liver of pregnancy
• Also
– Tetracycline
– Aflotoxin
• What antibody is associated with primary
biliary cirrhosis?
• Anti-mitochondrial antibody
• What are he principle mechanisms by which
hepatitis B is spread
• Vertical
• Sexual contact
• IVDA/needle sharing
• Why can disruption of hypothalamus function
cause a rise in prolactin
• Prolactin secretion is inhibited by dopamine
(prolactin inhibitory factor) released from the
hypothalamus. Removing this negative
modulator allows prolactin secretion.
• List several common causes of hypercalcemia
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CHIMPS
Cancer
Hyperparathyroidism
Intoxication with vitamin D
Milk alkalai syndrome
Pagets disease
Sarcoidosis
• Distinguish parathyroid hormone from
parathyroid hormone related peptide
• PTH is secreted by the parathyroid glands
• PTH-rp is secreted by cancers.
• List several common cancers that may secrete
PTH-rp
• Squamous cell carcinoma – most common
• Adult T-cell leukemia
• Adenocarcinoma
– Breast
– Esophagus
– Colon
• Decreased renal blood flow will cause
increases in what hormones
• Renin
• Angiotensin I/II
• Aldosterone
• Distinguish the gross pathology of a
pheochromocytoma from a adrenal adenoma
• Pheo – beefy red
• Adenoma – golden yellow due to steroids
• What are the two types of malignant gliomas
and what are their common ages of
presentation
• anaplastic astrocytoma (grade III), 45 year olds
• glioblastoma (grade IV), 64 year olds,
• What is the only proven risk factor for
malignant gliomas
• Ionizing radiation
• What are symptoms of malignant glioma
• increased intra-cranial pressure and mass effect
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Headache
Mental status changes/behavior changes
Papilledema
Vomiting
Diploplia
• Focal
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Motor deficits
Sensory deficits
Agnosia
Aphsia
Apraxia
Ataxia