Pathologic and Laboratory Diagnosis of Cancer Flashcards

1
Q

Clinician and pathologist interaction discussion

A
  • Prior history of patient
  • Past or recent Dx procedures
  • Availability of Previous slides
  • Intraoperative frozen sections
  • Quantity of tissue required for Dx
  • Special processing requirements
  • Adjunctive pathologic analyses
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2
Q

Nomenclature of tumor types

A
  • Means by which pathologists communicate a diagnosis to other pathologists and clinicians
  • Specific tumor designations carry specific clinical implications
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3
Q

Intraductal Carcinoma of Breast

A
  • ER / PR +

- Sentinel node bx ; no evidence of tumor

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4
Q

Adenocarcinoma of Prostate Gland

A
  • Tumor present up to inked margin

- Perineural invasion

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5
Q

Considerations/practices for most tumors recognized at the macroscopic level

A
  • Adequate sample
  • Margins of excision are labeled with indelible ink
  • Specimen is opened
  • Sections collected (with a scalpel or sharp knife)
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6
Q

Pathologist notes for most tumors recognized at the macroscopic level

A
  • Consistency
  • Color
  • Extent of neoplastic growth
  • Photograph
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7
Q

Macroscopic examination of tissue specimens

A
  • Macroscopic Recognition
  • Label Margins
  • Open Specimen
  • Sections collection
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8
Q

Hematoxylin and Eosin (H&E) staining of sections

A
  • Sufficient to make the Dx with most malignant neoplasms and tissue biopsies
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9
Q

Factors confounding gross and microscopic interpretaiton

A
  • Stage of neoplastic lesion development
  • Radiation and/or chemotherapy treatments
  • Presence of crush or cautery artifact
  • Bordeling or minimal deviation malignancies
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10
Q

Stage of neoplastic lesion development (confounding factor)

A
  • Lacks diagnostic histologic features of malignancy
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11
Q

Radiation and/or chemotherapy treatments (confounding factor)

A
  • Alter the pathologic characteristics of the tissue
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12
Q

Presence of crush or cautery artifact (confounding factor)

A
  • Distort tissue histology
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13
Q

Hematoxylin and Eosin (H&E) staining of sections

A
  • Microscopic Interpretation of Biopsy or Resection Specimens
  • Special Stains
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14
Q

Special stains involved in the microscopic interpretation of biopsy of resection specimens

A
  • Features unique to specific tumors are stained to narrow differential or make diagnosis
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15
Q

Stains used in diagnosis

A
  • Alcian Blue
  • Periodic Acid-Schiff
  • Trichrome
  • Congo Red
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16
Q

Alcian Blue stain specificity

A
  • Acid muco-substances
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17
Q

Alcian blue stain sample uses and comments

A
  • Demonstration of stromal mucin production by mesotheliomas
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18
Q

Periodic Acid-Schiff stain specificity

A
  • Glycogen (with appropriate control)

- Neutral mucosubstances

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19
Q

Periodic Acid-Schiff stain sample uses and comments

A
  • Demonstration of mucus or glycogen production
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20
Q

Trichrome stain specificity

A
  • Nuclei
  • Cytoplasm
  • Collagen
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21
Q

Trichrome stain sample uses and comments

A
  • Nonspecific

- Often can demonstrate immature skeletal muscle cells (myoblasts) in poorly differentiated mesenchymal tumors

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22
Q

Congo red stain specificity

A
  • Amyloid
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23
Q

Congo Red stain sample uses and comments

A
  • Amyloid deposition in neuroendocrine tumors or plasma cell tumors
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24
Q

PAS stain (special stain)

A
  • Germ cell neoplasia of the testis

- Abundant PAS-positive glycogen is present in the cytoplasm of the tumor cells

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25
Q

Tumor markers

A
  • Substances that are produced by cancer cells
  • Most tumor markers are made by normal cells
  • Cancer cells produce much higher levels
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26
Q

Tumor marker distribution

A
  • Blood
  • Urine
  • Stool
  • Tumor tissue
  • Bodily fluids
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27
Q

Most tumor markers are

A
  • Proteins
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28
Q

Patterns of gene expression are classified at

A
  • Tumor markers
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29
Q

DNA changes are classified as

A
  • Tumor markers
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30
Q

Tumor marker use in cancer diagnosis and care

A
  • Supports diagnosis of cancer (along with other test)
  • Reflects the stage (extent) of the disease
  • Reflect Prognosis
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31
Q

Tumor markers prognosis of cancer diagnosis and care

A
  • Must take periodic measurements
32
Q

Decrease in tumor marker levels indiactes

A
  • Cancer is responding to treatment
33
Q

Increase in tumor marker levels indicates

A
  • Cancer is not responding or recurrence
34
Q

Tumor markers (names)

A
  • Alpha-fetoprotein (AFP)
  • Estrogen receptor (ER)/Progesteron receptor (PR)
  • CA19-9
  • CA-125
  • Carcinoembryonic Agent (CEA)
  • Cytokeratin Fragments 21-1
35
Q

Alpha-fetoprotein (AFP)

A
  • Cancer types: Liver cancer and germ cell tumors
  • Tissue analyzed: Blood
  • How used: diagnosis liver cancer and follow response to treatment; to assess stage, prognosis, and response to treatment of germ cell tumors
36
Q

Estrogen receptor (ER)/Progesteron receptor (PR)

A
  • Cancer type: Breast cancer
  • Tissue analyzed: Tumor
  • How used: To determine whether treatment with hormonal therapy (such as tamoxifen) is appropriate
37
Q

CA19-9

A
  • Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancer
  • Tissue analyzed: Blood
  • How used: To assess whether treatment is working
38
Q

CA-125

A
  • Cancer type: Ovarian cancer
  • Tissue analyzed: Blood
  • How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence
39
Q

Carcinoembryonic Agent (CEA)

A
  • Cancer types: Colorectal cancer and breast cancer
  • Tissue analyzed: Blood
  • How used: To check whether colorectal cancer has spread; to look for breast cancer recurrence and assess response to treatment
40
Q

Cytokeratin Fragments 21-1

A
  • Cancer type: Lung cancer
  • Tissue analyzed: Blood
  • How used: To help in monitoring for recurrence
41
Q

Tumor marker use in immunochemistry (part 1)

A
  • Prepared and applied directly to paraffin embedded sections
  • Based on an indirect, antibody-enzyme method (immunoperoxidase procedure)
  • Differentiate between 2 or more histologically similar neoplasms
42
Q

Tumor marker use in immunochemistry (part 2)

A
  • Categorization of undifferentiated malignant tumors
  • Determination of site of origin of metastatic tumors
  • Detection of molecules that have prognostic or therapeutic significance
  • Highlight distinguishing features of a tumor to aid in diagnosis
  • “Picking the needle out of the haystack”
43
Q

Antigens (tumor markers) used in immunocytochemistry

A
  • Cytokeratin
  • Epithelial membrane antigen (EMA)
  • Prostate-specific antigen (PSA)
  • Carcinoembryogenic antigen (CEA)
  • CA 19-9
  • Estrogen and progesterone receptor (ER/PR)
  • Alpha-fetoprotein
44
Q

Cytokeratin predominant distribution

A
  • Epithelial cells
45
Q

Cytokeratin common diagnostic uses

A
  • Distinguish carcinoma from lymphoma or melanoma
46
Q

Epithelial membrane antigen (EMA) predominant distribution

A
  • Epithelial cells
47
Q

Epithelial membrane antigen (EMA) common diagnostic uses

A
  • Distinguish carcinoma from melanoma
48
Q

Prostate-specific antigen (PSA) predominant distribution

A
  • Prostatic epithelium
49
Q

Prostate-specific antigen (PSA) common diagnostic uses

A
  • Identification of metastatic prostatic CA
50
Q

Carcinoembryonic antigen (CEA) predominant distribution

A
  • Endodermally derived epithelium
51
Q

Carcinoembryonic antigen (CEA) common diagnostic uses

A
  • Identification of GI and lunch adenocarcinoma

- Distinguish adenocarcinoma from mesothelioma

52
Q

CA 19-9 predominant distribution

A
  • Alimentary tract epithelium
53
Q

CA 19-9 common diagnostic uses

A
  • Identification of GI and pancreatic cancer
54
Q

Estrogen and progesterone receptor (ER/PR) predominant distribution

A
  • Mammary epithelium
55
Q

Estrogen and progesterone receptor (ER/PR) common diagnostic uses

A
  • Identification of metastatic breast carcinoma

- Prediction of clinical response to hormonal therapy in breast cancer

56
Q

Alpha-fetoprotein predominant distribution

A
  • Neoplastic hepatocytes

- Selected germ cell tumors

57
Q

Alpha-fetoprotein common diagnostic uses

A
  • Identification of hepatocellular carcinoma, endodermal sinus tumor, and other germ cell tumors
58
Q

Other molecules with prognostic or therapeutic significance

A
  • Erb-B2 Oncoprotein (encoded by the HER2/neu oncogene)
  • Ki-67
  • Estrogen (ER) and progesterone receptor (PR)
  • P53
59
Q

Erb-B2 Oncoprotein (encoded by the HER2/neu oncogene) prognostic/therapeutic significance

A
  • Metastatic breast cancer sensitive to herceptin (trastuzumab)
60
Q

Estrogen (ER) and progesterone receptor (PR) prognostic/therapeutic significance

A
  • Breast cancer responsive to tamoxifen
61
Q

Ki-67 prognostic/therapeutic significance

A
  • Proliferating cell nuclear antigen
62
Q

P53 prognostic/therapeutic significance

A
  • Over-expression = poor prognostic indicator

- Cells carrying mutant p53 resist this response to chemotherapy

63
Q

Flow cytometry

A
  • Rapid quantitative measurement of cell characteristics
64
Q

Cell characteristics detected by flow cytometry

A
  • Membrane antigens

- DNA of tumor cells

65
Q

Identification and classification of neoplasms by flow cytometry

A
  • T and B lymphocytes

- Mononuclear-phagocytic cells

66
Q

In situ hybridization (fluorescence in situ hybridization - FISH)

A
  • Technique for detecting and locating a specific DNA sequence on a chromosome
  • Exposing chromosomes to a small DNA sequence called a probe that has a fluorescent molecule attached
  • Probe sequence binds to its corresponding sequence on the chromosome
67
Q

Fluorescent colors when reading FISH

A
  • Green = ABL
  • Red = BCR
  • Yellow = Fushion gene
68
Q

Polymerase chain reaction (PCR)

A
  • Used to amplify DNA sequences
  • Primers to select the portion of the genome to be amplified
  • Enzyme directed DNA replication of target sequence
  • Billions of copies of the target sequence in a few hours
69
Q

Examples of target gene sequences amplified by PCR

A
  • KRAS
  • BRAF
  • Her2
70
Q

Microarray analysis

A
  • Examine how active thousands of genes are at any given time
  • Determine gene expression and activity in normal and tumor cells
  • Differences in gene activity between untreated and treated tumor cells
71
Q

Medical implications of microarray analysis

A
  • Design and tailor treatment strategies targeted directly to each specific type of cancer
72
Q

Process of microarray analysis

A
  • mRNA → RT PCR (normal and tumor cells)
  • Several cDNA copies (label with flourescent dye)
  • Combine cDNAs
  • Compete for binding to probe
  • Analyze binding
73
Q

Microarray analysis interpretation

A
  • T>N = red
  • N>T = green
  • N=T = yellow
  • Absent = black
74
Q

Application of microarray analysis

A
  • Malignant melanoma (gene mutations)
75
Q

Gene mutations seen in malignant melanoma that can be detected by microarray analysis

A
  • BRAF
  • MEK
  • PTEN
76
Q

Trametinib (Mekinist)

A
  • MEK inhibitor indicated for melanoma with BRAF mutations
77
Q

Dabrafenib (Tafinlar)

A
  • BRAF protein kinase inhibitor