Pathologic and Laboratory Diagnosis of Cancer Flashcards
Clinician and pathologist interaction discussion
- 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
Nomenclature of tumor types
- Means by which pathologists communicate a diagnosis to other pathologists and clinicians
- Specific tumor designations carry specific clinical implications
Intraductal Carcinoma of Breast
- ER / PR +
- Sentinel node bx ; no evidence of tumor
Adenocarcinoma of Prostate Gland
- Tumor present up to inked margin
- Perineural invasion
Considerations/practices for most tumors recognized at the macroscopic level
- Adequate sample
- Margins of excision are labeled with indelible ink
- Specimen is opened
- Sections collected (with a scalpel or sharp knife)
Pathologist notes for most tumors recognized at the macroscopic level
- Consistency
- Color
- Extent of neoplastic growth
- Photograph
Macroscopic examination of tissue specimens
- Macroscopic Recognition
- Label Margins
- Open Specimen
- Sections collection
Hematoxylin and Eosin (H&E) staining of sections
- Sufficient to make the Dx with most malignant neoplasms and tissue biopsies
Factors confounding gross and microscopic interpretaiton
- Stage of neoplastic lesion development
- Radiation and/or chemotherapy treatments
- Presence of crush or cautery artifact
- Bordeling or minimal deviation malignancies
Stage of neoplastic lesion development (confounding factor)
- Lacks diagnostic histologic features of malignancy
Radiation and/or chemotherapy treatments (confounding factor)
- Alter the pathologic characteristics of the tissue
Presence of crush or cautery artifact (confounding factor)
- Distort tissue histology
Hematoxylin and Eosin (H&E) staining of sections
- Microscopic Interpretation of Biopsy or Resection Specimens
- Special Stains
Special stains involved in the microscopic interpretation of biopsy of resection specimens
- Features unique to specific tumors are stained to narrow differential or make diagnosis
Stains used in diagnosis
- Alcian Blue
- Periodic Acid-Schiff
- Trichrome
- Congo Red
Alcian Blue stain specificity
- Acid muco-substances
Alcian blue stain sample uses and comments
- Demonstration of stromal mucin production by mesotheliomas
Periodic Acid-Schiff stain specificity
- Glycogen (with appropriate control)
- Neutral mucosubstances
Periodic Acid-Schiff stain sample uses and comments
- Demonstration of mucus or glycogen production
Trichrome stain specificity
- Nuclei
- Cytoplasm
- Collagen
Trichrome stain sample uses and comments
- Nonspecific
- Often can demonstrate immature skeletal muscle cells (myoblasts) in poorly differentiated mesenchymal tumors
Congo red stain specificity
- Amyloid
Congo Red stain sample uses and comments
- Amyloid deposition in neuroendocrine tumors or plasma cell tumors
PAS stain (special stain)
- Germ cell neoplasia of the testis
- Abundant PAS-positive glycogen is present in the cytoplasm of the tumor cells
Tumor markers
- Substances that are produced by cancer cells
- Most tumor markers are made by normal cells
- Cancer cells produce much higher levels
Tumor marker distribution
- Blood
- Urine
- Stool
- Tumor tissue
- Bodily fluids
Most tumor markers are
- Proteins
Patterns of gene expression are classified at
- Tumor markers
DNA changes are classified as
- Tumor markers
Tumor marker use in cancer diagnosis and care
- Supports diagnosis of cancer (along with other test)
- Reflects the stage (extent) of the disease
- Reflect Prognosis
Tumor markers prognosis of cancer diagnosis and care
- Must take periodic measurements
Decrease in tumor marker levels indiactes
- Cancer is responding to treatment
Increase in tumor marker levels indicates
- Cancer is not responding or recurrence
Tumor markers (names)
- Alpha-fetoprotein (AFP)
- Estrogen receptor (ER)/Progesteron receptor (PR)
- CA19-9
- CA-125
- Carcinoembryonic Agent (CEA)
- Cytokeratin Fragments 21-1
Alpha-fetoprotein (AFP)
- 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
Estrogen receptor (ER)/Progesteron receptor (PR)
- Cancer type: Breast cancer
- Tissue analyzed: Tumor
- How used: To determine whether treatment with hormonal therapy (such as tamoxifen) is appropriate
CA19-9
- Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and gastric cancer
- Tissue analyzed: Blood
- How used: To assess whether treatment is working
CA-125
- Cancer type: Ovarian cancer
- Tissue analyzed: Blood
- How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence
Carcinoembryonic Agent (CEA)
- 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
Cytokeratin Fragments 21-1
- Cancer type: Lung cancer
- Tissue analyzed: Blood
- How used: To help in monitoring for recurrence
Tumor marker use in immunochemistry (part 1)
- 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
Tumor marker use in immunochemistry (part 2)
- 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”
Antigens (tumor markers) used in immunocytochemistry
- Cytokeratin
- Epithelial membrane antigen (EMA)
- Prostate-specific antigen (PSA)
- Carcinoembryogenic antigen (CEA)
- CA 19-9
- Estrogen and progesterone receptor (ER/PR)
- Alpha-fetoprotein
Cytokeratin predominant distribution
- Epithelial cells
Cytokeratin common diagnostic uses
- Distinguish carcinoma from lymphoma or melanoma
Epithelial membrane antigen (EMA) predominant distribution
- Epithelial cells
Epithelial membrane antigen (EMA) common diagnostic uses
- Distinguish carcinoma from melanoma
Prostate-specific antigen (PSA) predominant distribution
- Prostatic epithelium
Prostate-specific antigen (PSA) common diagnostic uses
- Identification of metastatic prostatic CA
Carcinoembryonic antigen (CEA) predominant distribution
- Endodermally derived epithelium
Carcinoembryonic antigen (CEA) common diagnostic uses
- Identification of GI and lunch adenocarcinoma
- Distinguish adenocarcinoma from mesothelioma
CA 19-9 predominant distribution
- Alimentary tract epithelium
CA 19-9 common diagnostic uses
- Identification of GI and pancreatic cancer
Estrogen and progesterone receptor (ER/PR) predominant distribution
- Mammary epithelium
Estrogen and progesterone receptor (ER/PR) common diagnostic uses
- Identification of metastatic breast carcinoma
- Prediction of clinical response to hormonal therapy in breast cancer
Alpha-fetoprotein predominant distribution
- Neoplastic hepatocytes
- Selected germ cell tumors
Alpha-fetoprotein common diagnostic uses
- Identification of hepatocellular carcinoma, endodermal sinus tumor, and other germ cell tumors
Other molecules with prognostic or therapeutic significance
- Erb-B2 Oncoprotein (encoded by the HER2/neu oncogene)
- Ki-67
- Estrogen (ER) and progesterone receptor (PR)
- P53
Erb-B2 Oncoprotein (encoded by the HER2/neu oncogene) prognostic/therapeutic significance
- Metastatic breast cancer sensitive to herceptin (trastuzumab)
Estrogen (ER) and progesterone receptor (PR) prognostic/therapeutic significance
- Breast cancer responsive to tamoxifen
Ki-67 prognostic/therapeutic significance
- Proliferating cell nuclear antigen
P53 prognostic/therapeutic significance
- Over-expression = poor prognostic indicator
- Cells carrying mutant p53 resist this response to chemotherapy
Flow cytometry
- Rapid quantitative measurement of cell characteristics
Cell characteristics detected by flow cytometry
- Membrane antigens
- DNA of tumor cells
Identification and classification of neoplasms by flow cytometry
- T and B lymphocytes
- Mononuclear-phagocytic cells
In situ hybridization (fluorescence in situ hybridization - FISH)
- 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
Fluorescent colors when reading FISH
- Green = ABL
- Red = BCR
- Yellow = Fushion gene
Polymerase chain reaction (PCR)
- 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
Examples of target gene sequences amplified by PCR
- KRAS
- BRAF
- Her2
Microarray analysis
- 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
Medical implications of microarray analysis
- Design and tailor treatment strategies targeted directly to each specific type of cancer
Process of microarray analysis
- mRNA → RT PCR (normal and tumor cells)
- Several cDNA copies (label with flourescent dye)
- Combine cDNAs
- Compete for binding to probe
- Analyze binding
Microarray analysis interpretation
- T>N = red
- N>T = green
- N=T = yellow
- Absent = black
Application of microarray analysis
- Malignant melanoma (gene mutations)
Gene mutations seen in malignant melanoma that can be detected by microarray analysis
- BRAF
- MEK
- PTEN
Trametinib (Mekinist)
- MEK inhibitor indicated for melanoma with BRAF mutations
Dabrafenib (Tafinlar)
- BRAF protein kinase inhibitor
