Oncologic Pathology and Laboratory Medicine

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Oncologic Pathology and Laboratory Medicine

• Paul M. Urie, M.D., Ph.D.
• Surgical Pathologist
• Utah Valley Regional Med Center

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Definitions

• Cancer malignant neoplasm which invades
  surrounding tissues, metastasizes to several
  sites and causes death
• Neoplasm distinct mass of tissue that grows by
  cellular proliferation
• Dysplasia abnormal tissue development

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Electron Microscopy of Idealized Animal Cell
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Benign Cell Diagram
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Malignant Cell Diagram
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Benign versus Malignant Cell
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Cytologic Features of Benign and Malignant Cells
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Chromosomes
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DNA Content by Flow Cytometry
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Nuclear Enlargement in Carcinoma
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Nuclear Pleomorphism and Enlargement
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Mitotic Figures
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Abnormal Mitotic Figures
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Abnormal Mitotic Figures
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Abnormal Mitotic Figures
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Cytologic Features of Benign and Malignant Cells
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Cervical Intraepithelial Neoplasia Grading System
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Uterine Cervix Severe Dysplasia
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Uterine Cervix Severe Dysplasia
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Uterine Cervix Mild Dysplasia
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Uterine Cervix Moderate Dysplasia
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Uterine Cervix Severe Dysplasia
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Uterine Cervix Carcinoma In-Situ
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Uterine Cervix Invasive Carcinoma
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Benign Cells and Cancer Grading
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Atypical Ductal Breast Hyperplasia
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Ductal Breast Carcinoma In-Situ with
Microcalcifications
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Ductal Breast Carcinoma In-Situ
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Ductal Breast Carcinoma In-Situ
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Infiltrating Ductal Breast Carcinoma
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Infiltrating Ductal Breast Carcinoma
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Infiltrating Ductal Breast Carcinoma
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Benign Cells and Cancer Grading
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Prostate Carcinoma Gleason Grading System
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Prostate Carcinoma Gleason Grade 1 low power
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Prostate Carcinoma Gleason Grade 1 high power
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Prostate Carcinoma Gleason Grade 2 low power
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Prostate Carcinoma Gleason Grade 2 high power
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Prostate Carcinoma Gleason Grade 3 low power
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Prostate Carcinoma Gleason Grade 3 high power
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Prostate Carcinoma Gleason Grade 4 low power
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Prostate Carcinoma Gleason Grade 4 high power
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Prostate Carcinoma Gleason Grade 5 low power
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Prostate Carcinoma Gleason Grade 5 high power
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Benign or Malignant?

• Cell Cytologic Features
• Tissue Histologic Architecture

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Final Pathologic Diagnosis

• Benign or Malignant?
• Cell of Origin
• Carcinoma, what kind?
• Sarcoma, what kind?
• Lymphoma, what kind?
• Techniques Other Than Histology
• Electron Microscopy
• Immunoperoxidase Stains

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Immunoperoxidase AE-1/AE-3 Cytokeratin
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Immunoperoxidase AE-1/AE-3 Cytokeratin
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Life Cycle of Cancer

• Induction Phase
• In-Situ Phase
• Invasive Phase
• Dissemination Phase

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Induction Phase

• Variable length of normal cells exposed to
  carcinogens with transformation into cancer cells
• DNA damage
• Oncogenes
• Tumor-suppressor genes

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In-Situ Phase

• Appearance of cancer cells to the time of
  invasion of surrounding tissue
• Best chance for cure

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Invasive Phase

• Spread of malignant cells to adjacent tissues
• Reasonable possibility of cure

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Dissemination Phase

• Malignant cells spread to distant body sites
• Usually 1-5 years in length
• Prognosis is very guarded

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Laboratory Tests

• Sensitivity TP/(TPFN)
• Sensitivity how many subjects known to have
  disease reported as positives
• Specificity TN/(TNFP)
• Specificity how many truly negative subjects
  without the disease

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Criteria of Ideal Tumor Marker

• Easy and inexpensive to measure
• Specific to the tumor studied
• Directly proportional to tumor size
• Detectable in In-Situ or Invasive phase
• Not subject to wild variations
• Level much higher in cancer patients than in
  control patients

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Role of Tumor Markers

• Assess the potential risk for cancer
• Detect or screen for cancer
• Confirm that the patient has cancer
• Identify the type and stage of cancer
• Monitor patients with cancer

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Characteristics of Screening Test

• Type of cancer should be an important health
  problem
• Accepted treatment for patients with the disease
• Facilities for diagnosis and treatment readily
  available
• Recognizable in latent or early symptomatic stage

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Characteristics of Screening Test

• Suitable test or examination
• Test acceptable to the population
• Natural history of the disease understood
• Agreed policy as to whom to treat
• Cost of screening economically balanced
• Ongoing project

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Examples of Screening Tests

• Fecal occult blood for colon cancer
• Pap smear for cervical cancer
• PSA for prostate cancer
• Mammography for breast cancer

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Test to Confirm Cancer

• 100 specificity no false positives
• Examples
• Bone marrow biopsy for leukemia
• AFP for testicular cancer

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Test to Identify Type and Stage

• PSA stage of prostate cancer
• Hormone markers prolactin, calcitonin
• Cellular markers lymphoma, leukemia
• HCG choriocarcinoma

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Test to Monitor Patients

• Recurrence of the tumor
• Response to therapy
• CEA, PSA, AFP, HCG

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Commonly Used Tumor Markers

• CEA colon cancer
• AFP hepatocellular carcinoma and germ cell
  carcinoma
• HCG choriocarcinoma and germ cell carcinoma
• CA-125 epithelial ovarian carcinoma
• PSA prostate carcinoma

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Commonly Used Tumor Markers

• CA-19-9 intra-abdominal carcinoma, especially
  pancreatic carcinoma
• Alk Phos, GammaGT, ALT, 5nucleotidase liver
  metastasis
• Alk Phos bone metastasis
• LD lymphoma and leukemia

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Commonly Used Tumor Markers

• Hormone markers prolactin, calcitonin,
  catecholamines, insulin, etc.
• Cellular markers CD series for lymphomas and
  leukemias
• Genetic markers genetic predisposition for
  breast and ovarian cancer BRCA1 and BRCA2

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Ordering Recommendations

• Never rely on a single test
• When ordering serial testing, be certain to order
  every test from the same lab using the same assay
  kit
• Be certain the tumor marker selected for
  monitoring was elevated in the patient before
  surgery

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Ordering Recommendations

• Consider the half-life of the tumor marker when
  interpreting the test results
• Consider how the tumor marker is metabolized from
  the blood circulation
• Order multiple markers to improve sensitivity and
  specificity for diagnosis

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Ordering Recommendations

• Order nonspecific markers for cost savings and
  high sensitivity
• Be aware of the presence of ectopic tumor markers
• Be aware of the possibility of a hook effect