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Pathology of Solid Tumors

Pathology of Solid Tumors. Megan Troxell, MD/PhD OHSU Pathology troxellm@ohsu.edu 8-1770. Objectives. Diagnostic Techniques Common terminology, definitions in cancer Multi-step carcinogenesis Invasion & Metastasis Tumor grading Tumor staging Newer prognostic/predictive testing.

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Pathology of Solid Tumors

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  1. Pathology of Solid Tumors Megan Troxell, MD/PhD OHSU Pathology troxellm@ohsu.edu 8-1770

  2. Objectives • Diagnostic Techniques • Common terminology, definitions in cancer • Multi-step carcinogenesis • Invasion & Metastasis • Tumor grading • Tumor staging • Newer prognostic/predictive testing

  3. http://www.cancer.org

  4. Histology-morphology ‘Old fashioned’ microscope, H &E slides, formalin fixed paraffin embedded (FFPE) Immunohistochemistry Esp. tumor differentiation, mitotic rate Diagnostic Methods in Tumor Pathology • H=hematoxylin, nucleic acids, purple • E=eosin, protein, pink Undiff. tumor HMB45+ Melanoma

  5. Immunohistochemistry May help subclassify Rarely, may imply specific genetic rearrangement Diagnostic Methods in Tumor Pathology Pediatric Kidney Cancer Loss of PMS2 expression, colon cancer Mismatch repair protein deficient (Lynch) TFE3 +nuclear Argani. AJSP 26:1553-66 Cancer Aberrant TFE3 protein expression as a result of t(X;1)(p11.2;q21) Normal

  6. (courtesy of Helen Lawce) FISH & Cytogenetics Characteristic translocations Diagnostic Methods in Tumor Pathology t(11;22) Ewing’s EWS-FLI1 Breakapart FISH probe

  7. Molecular/PCR Esp. hematopathology T- B-cell clonality Characteristic mutations (Coming: gene arrays, etc) Diagnostic Methods in Tumor Pathology FISH: Her2 amplification (breast cancer) Courtesy Dana Bangs PCR/HPLC (WAVE) for C-kit mutations in GIST Corless Am J Pathol. 2002 160:1567-72

  8. Nomenclature • Hypertrophy: increase in size of cells • Hyperplasia: increase in the # of cells in organ/tissue • Neoplasia: “new growth” • Growth exceeds/uncoordinated with normal tissue • Growth persists after stimulus removed • CLONAL • Benign or malignant • Neoplasm=proliferating cells & associated stroma

  9. Neoplasia: Benign • Cohesive, expansile masses (tumors) • Remain localized • No capacity to invade, metastasize • Slow growing • Often encapsulated • Well differentiated (still resemble normal) • Often named with suffix “-oma” • Chondroma (benign neoplasm of cartilage) • Hemangioma (benign neoplasm of blood vessels) • Leiomyoma (benign neoplasm of smooth muscle) • Adenoma (benign epithelial neoplasm) • Cystadenoma, Papilloma etc

  10. Neoplasia: Malignant • Invade and destroy surrounding tissue • Capacity for metastasis • Spread through blood vessels/lymphatics to distant sites • Higher rate of growth • Pleomorphism (variation in size/shape) • Abnormal nuclear morphology & hyperchromasia • De-differentiation/Anaplasia • Nomenclature: • Malignant epithelial neoplasm: carcinoma • Malignant mesenchyma: sarcoma • Malignant hematolymphoid: leukemia, lymphoma • Malignant melanocytic: melanoma • Malignant germ cell: seminoma, and others

  11. Neoplasia: Benign vs. Malignant Robbins 7-22 Uterus

  12. Normal, Benign, Malignant Normal colon and invasive adenocarcinoma (right, Malignant) Normal colon (lower) & tubular adenoma (benign, upper left)

  13. Adenoma, colon (TVA)

  14. Normal, Benign, Malignant Normal breast Benign hyperplasia Invasive carcinoma

  15. Histologic Features of Malignant Cells http://www.usc.edu/hsc/dental/PTHL312abc/312a/05/Reader/reader.html

  16. Transformation • “Malignant change in the target cell” • What features define a transformed cell? Hanahan and Weinberg. “The Hallmarks of Cancer” Cell. 100:57-70. 2000 And Genomic Instability

  17. Transformation: Darwinian? • “Malignant change in the target cell” Mechanisms & chronology of acquired capabilities vary By organ/tumor type By subtype, etc Hanahan and Weinberg. “The Hallmarks of Cancer” Cell. 100:57-70. 2000

  18. “The Genomic Landscapes of Breast and Colorectal Cancer” Wood et al. Science. 2007 318: 1108-113

  19. “Tumors as Complex Tissues”or, “It takes a village” Hanahan and Weinberg. “The Hallmarks of Cancer” Cell. 100:57-70. 2000

  20. Concept: Carcinoma in situ (CIS) • Malignant cells that have not yet breached the basement membrane (still confined) DCIS & invasive DCIS: breast

  21. Carcinoma In Situ (right) and Invasive carcinoma (left), breast Calponin p63

  22. Carcinoma in situ (CIS) Carcinoma in situ (CIS) Squamous Cell CIS Squamous CIS Invasive SCC

  23. Invasion & metastasis 1’tumor BM Vein Artery Lymph Colon CA in lymphatic channel Platelets ECM Vein Artery Robbins 7-42

  24. Tumor growth and spread Normal cell (Lung) Single tumor cell 30 doublings 1 gm=109 cells Smallest clinically detectable mass 10 doublings 1 kg=1012 cells Maximum mass compatible w/ life Liver mets Robbins 7-12

  25. Tumor angiogenesis Leaky vessels Robbins 7-41

  26. Transformation • Some benignneoplasms have propensity to acquire additional genetic changes and progress to malignancy (precursors) • Example: colonic adenoma carcinoma • Others rarely undergo transformation • Example: Uterine leiomyomas, salivary gland pleomorphic adenomas

  27. Histologic and Molecular Progression:Colon LG dysplasia HG dysplasia Carcinoma P53 18q21 SMAD2,4 Telomerases, etc Kras APC b-cat APC Robbins. 7th ed. Figure 17-60

  28. It’s never that simple… http://www.rr-research.no/wcache/650x_58df157ee0b2a665ce8c99e0dd99e435Adenoma_carcinoma.jpg

  29. http://www.mdconsult.com/das/book/body/128522719-2/0/1492/f4-u1.0-B978http://www.mdconsult.com/das/book/body/128522719-2/0/1492/f4-u1.0-B978 -1-4160-2805-5..50208-1..gr5.jpg from Cecil Medicine 23 ed (Saunders, Elsevier)

  30. Histologic and molecular progression:Breast True precursor? Non-obligate precursor? Infiltrating Carcinoma Florid proliferation Normal ADH DCIS Tissue Invasion Robbins Fig 23-15

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