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Slackers Advanced Topics Pathology Fact Stack Mike Ori.

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Presentation on theme: "Slackers Advanced Topics Pathology Fact Stack Mike Ori."— Presentation transcript:

1 Slackers Advanced Topics Pathology Fact Stack Mike Ori

2 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 e r l I didn’t use greek letters because they are a pain to cut and paste in.

3 What are the three most important properties of a tumor that affect its prognosis

4 Tumor type Tumor grade Tumor stage

5 Define grade

6 A quantification of the degree of differentiation of the tumor. Higher grades are less differentiated.

7 What is the relationship of grading between tumor types

8 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.

9 What are three common histologic features that are used in grading

10 Nuclear atypia Growth pattern Mitotic activity

11 Are grading systems objective or subjective

12 Somewhat subjective especially in the middle.

13 Define prognostic markers as they pertain to grading

14 These are substances that help determine the prognosis and sometimes possible effective treatments of a tumor but that are not used for diagnosis.

15 List several common prognostic markers

16 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)

17 Define stage

18 The measure of how far advanced (far afield) a tumor is

19 What is the primary descriptive system used for staging

20 TNM system

21 Explain the relationships of the TNM system between cancers

22 Each cancer uses its own rules for staging.

23 What does an X mean in the TNM system

24 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

25 Describe the staging of colon cancer

26 Defined by anatomical boundary crossed T1 = Muscularis mucosa T2 = Inner edge of muscularis propria T3 = Outer edge of MP T4 = Serosa surface (into adjacent structures)

27 List common environmental causes of esophageal cancer

28 Alcohol Tobacco Fungi and nitrosamine (common in Asia) Acid reflux/Barretts esophagus

29 List a common cause of stomach cancer

30 H. pylori

31 How does the environment contribute to colon cancer

32 Diet is a major factor in sporadic colon cancers.

33 What are the gene defects associated with FAP and HNPCC

34 FAP – Chromosomal instability – APC gene HNPCC – Microsatellite instability – MSH2, MLH1, PMS2 genes

35 Why is pancreatic cancer a “nightmare”

36 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.

37 What element is typically elevated with cholestatic disease

38 Copper

39 List two autoimmune related diseases of the biliary tree.

40 Primary biliary cirrhosis Primary sclerosing cholangitis

41 What portion of the biliary tree is attacked by PBC and PSC

42 PBC = intrahepatic small ducts PSC = intra and extrahepatic mediumish ducts

43 What is the typical patient for PBC and PSC

44 PBC = female PSC = inflammatory bowel diseases like ulcerative cholitis

45 List 5 common causes of steatohepatitis

46 Alcohol related Non-alcoholic fatty liver disease Reye syndrome Acute fatty liver of pregnancy Drug toxicity

47 Distinguish between alcoholic and non- alcoholic steatohepatitis

48 Alcoholic – Hx of alcohol M > F – Neutrophil infiltration – Mallory hyaline Non-alcoholic – M=F – Obesity, HLD, DMII

49 Describe Reyes syndrome

50 An underlying metabolic disorder is unmasked by a combination of viral illness and salicylates. Mitochondrial swelling. Massive microvesicular steatohepatitis

51 Describe fatty liver of pregnancy

52 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

53 Describe the pattern of hepatocyte damage that occurs with toxic drug exposure

54 Damage can be periportal to centrilobular depending on the agent and the enzymes expressed within the region Acetaminophen is classically centrilobular necrosis

55 Describe the pattern of hepatocyte damage from common substances

56 peripheral/periportal – Phosphorus Centrilobular – Tetracycline – Alcohol – Acetaminophen Microvesicular – Tetracycline – Aflotoxin – Reye – Fatty liver of pregnancy Necrosis – CCl4 – Acetaminophen – Tannic acid

57 Do microvesicular represent acute or chronic processes

58 Acute

59 What are the three broad categories of thyroid neoplasm?

60 Differentiated carcinoma – Papillary (80%) – Follicular (10%) Anaplastic carcinoma (2%) Medullary carcinoma (5%)

61 List the risk factors for each category of thyroid cancer

62 DifferentiatedanaplasticMedullary 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

63 List common workup steps for suspected thyroid disease

64 TSH levels Ultrasound Fine-needle biopsy Surgical resection

65 When should a total thyroidectomy be performed

66 Proven malignancy Bilateral disease Suspicious nodules – Fhx of thyoid disease – Hx of radiation exposure

67 Distinguish MEN 2a from MEN 2b

68 MEN 2aMEN 2b Parathyroid hyperplasiaX PheochromocytomaXX Thyroid C-cell hyperplasiaXX Thyroid medullary carcinomaXX Mucocutaneous ganglioneuromaX Marfanoid habitusX RET oncogeneXX

69 Define adrenal incidentaloma

70 A mass in the adrenal gland found incidentally during workup for a non-adrenal disease. Up to 8% of autopsies show adrenal incidentalomas.

71 What are the broad categories of incidentalomas

72 Adrenal origin – Non malignant Non-secreting (80%) Secreting – Cushings (9%) – Pheo (5%) – Malignant Adrenal adenocarcinoma (5%) Non-adrenal – Metastatic (2.5%) – Lymphoma

73 What compounds might an adrenal tumor secrete and what are the primary symptoms

74 Glucorticoids – Cushings Aldosterone – Hypertension – Hypo K Sex steroids – Masculinizing – Feminizing Catecholamines – Sympathetic outflow states

75 What are signs of subclinical cushings

76 DMII – Especiall poorly controlled diabetes despite multiple agents and adherence Weight gain Hypertension

77 What tests can be used to determine cortisol levels

78 24h urine free cortisol Late night salivary cortisol levels Low dose dexamethasone suppression test 48h low dose DST

79 What is the sx triad in pheochromocytoma pt’s

80 Headache Sweating Tachycardia

81 When is adrenalectomy required

82 Functional tumors (that fails medical management?) Tumors > 4cm Tumor features suggestive of malignancy Growing tumors

83 What factors are suggestive of adrenal malignancy

84 Feminization Masculinization Rapid onset cushing Multiple/mixed hormone secretion

85 What is the typical patient profile of a lung carcinoma patient

86 Age: 35 + Gender M > F Probably no significant physical exam findings Masses on MRI/CT/CXR – Adenocarcinoma – Squamous – Small cell

87 Describe the typical patient with colon cancer

88 Age 45+ M=F Complaining of a mass or obstruction Can be visualized with barium or CT, MRI Typical finding of an adenocarcinoma

89 Describe the typical breast cancer pt

90 Age 35+ F > M Mass in breast is discoverable on mammography, sonogram, or MRI Typically an adenocarcinoma

91 Describe the typical skin cancer patient

92 Age 45+ M>F Nodule with or without ulceration Usually no imaging is performed Cancers are basal cell or squamous cell types

93 Which cancer is cytokeratin positive for

94 Carcinomas – epithelial origin cancers

95 Which markers are positive in melanoma

96 S-100 and HMB-45

97 What marker is used to identify ewing sarcoma

98 CD99

99 What marker is used to detect thyroid cancer

100 Thyroid transcription factor.

101 List the sarcomas of the bone and soft tissue

102 Bone – Osteogenic – Chondrosarcoma – Ewing sarcoma Soft tissue – Liposarcoma – Rhabdosarcoma – Synovial sarcoma – Fibrosarcoma – Malignant fibrous histiocytoma – Angiosarcoma

103 What is the characteristic age range for osteogenic sarcoma, chondrosarcoma, and ewing sarcoma

104 Osteogenic – Teens and young adults – Adults over 60 in association with pagets Chondrosarcoma – Adults > 40 Ewing – Childhood – Young adulthood

105 What are the radiographic findings for osteogenic sarcoma

106 Spiculated mass about the knee

107 What are the radiographic findings of chondrosarcoma

108 Irregularly destructive lesion within bone Lytic areas Soft tissue extension with speckled calcifications

109 What are the radiographic findings of Ewing Sarcoma

110 Irregularly destructive, lytic lesions often with disproportionately large soft tissue mass relative to the bone involvement

111 Differentiate Osteogenic sarcoma, chondrosarcoma, and ewing sarcoma histologically

112 Osteogenic – Bone – Malignant osteoblasts Chondro – Cartilage Ewing – Small round blue cell tumor

113 What genetic change is characteristic of Ewing sarcoma

114 T(11:22)

115 What are the common locations and age of presentation of the soft tissue sarcomas

116 Age Liposarcoma40+Retroperitoneum Deep tissues of the thigh RhabdomyosarcomaChildrenHead and neck Urogenital Deep soft tissues (adults) Synovial sarcomaAdults < 50 Lower extremity typically the knee Malignant fibrous histiocytoma 40+Lower extremity Angiosarcoma FibrosarcomaDeep soft tissues of extremities

117 Identify the histology of the soft tissue sarcomas

118 LiposarcomaFat in cells Myxoid variant = gelatinous Round cell variant similar to lymphoma and ewing RhabdomyosarcomaEmbryonal – 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 sarcomaGlandular epithelial cells mixed with spindle cells that may express cytokeratin Malignant fibrous histiocytoma Mixed spindle cells and polygonal cells Angiosarcoma FibrosarcomaCells arranged with nuclei parallel to each other in herringbone pattern

119 What are the gene transformations in Ewing, liposarcoma, and synovial sarcoma?

120 Ewing = t(11;22) FLI1-EWS Liposarcoma = t(12,16) CHOP/TLS Synovial = t(X:18) SYT-SSX

121 What are the important features for grading sarcomas

122 Degree of differentiation Cellularity Mitotic activity Pleomorphism Extent of necrosis

123 Differentiate wegener, goodpastures, and microscopic poly arteritis

124 All are vasculidities that can affect small vessels WegenerGoodpastureMicroscopic GranulomaYesNo Antibodiesc-ANCAAnti-GBMp-ANCA Affected areaKidney Lungs Upper respiratory tract Kidney lower respiratory tract Skin Others?

125 If vasculitis is suspected, why must a relatively long segment of affected vessel be biopsied?

126 Vasculitis often skips segments within an affected vessels so a short biopsy may not contain diagnostic information.

127 What is acute necrotizing vasculitis?

128 A rapidly destructive vasculitis that results from rejection in transplant patients

129 What is the target in temporal arteritis?

130 Giant cell destruction of the elastic lamina.

131 List several common markers used to localize liver injury

132 Hepatocyte damage – AST – ALT Bile duct damage – Alkaline phosphatase Bilirubin – Direct – Indirect Not yet conjugated by hepatocytes

133 What diseases cause microvesicular steatosis

134 Reye syndrome Fatty liver of pregnancy Also – Tetracycline – Aflotoxin

135 What antibody is associated with primary biliary cirrhosis?

136 Anti-mitochondrial antibody

137 What are he principle mechanisms by which hepatitis B is spread

138 Vertical Sexual contact IVDA/needle sharing

139 Why can disruption of hypothalamus function cause a rise in prolactin

140 Prolactin secretion is inhibited by dopamine (prolactin inhibitory factor) released from the hypothalamus. Removing this negative modulator allows prolactin secretion.

141 List several common causes of hypercalcemia

142 CHIMPS Cancer Hyperparathyroidism Intoxication with vitamin D Milk alkalai syndrome Pagets disease Sarcoidosis

143 Distinguish parathyroid hormone from parathyroid hormone related peptide

144 PTH is secreted by the parathyroid glands PTH-rp is secreted by cancers.

145 List several common cancers that may secrete PTH-rp

146 Squamous cell carcinoma – most common Adult T-cell leukemia Adenocarcinoma – Breast – Esophagus – Colon

147 Decreased renal blood flow will cause increases in what hormones

148 Renin Angiotensin I/II Aldosterone

149 Distinguish the gross pathology of a pheochromocytoma from a adrenal adenoma

150 Pheo – beefy red Adenoma – golden yellow due to steroids

151 What are the two types of malignant gliomas and what are their common ages of presentation

152 anaplastic astrocytoma (grade III), 45 year olds glioblastoma (grade IV), 64 year olds,

153 What is the only proven risk factor for malignant gliomas

154 Ionizing radiation

155 What are symptoms of malignant glioma

156 increased intra-cranial pressure and mass effect – Headache – Mental status changes/behavior changes – Papilledema – Vomiting – Diploplia Focal – Motor deficits – Sensory deficits – Agnosia – Aphsia – Apraxia – Ataxia

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