Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology
Transcript of Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology
![Page 1: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/1.jpg)
NeoplasiaNeoplasia
![Page 2: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/2.jpg)
NEOPLASIA (TUMORS)NEOPLASIA (TUMORS) DefinitionsDefinitions NomenclatureNomenclature Biology of Tumor GrowthBiology of Tumor Growth EpidemiologyEpidemiology Molecular Basis of CancerMolecular Basis of Cancer Molecular Basis of CarcinogenesisMolecular Basis of Carcinogenesis Agents (The Usual Suspects)Agents (The Usual Suspects) Host Defense (Tumor Immunity)Host Defense (Tumor Immunity) Clinical Features of TumorsClinical Features of Tumors
![Page 3: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/3.jpg)
Defnition of NeoplasiaDefnition of Neoplasia
“A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change” - Willis
Genetic changes Autonomous Clonal
![Page 4: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/4.jpg)
Nomenclature – Benign TumorsNomenclature – Benign Tumors -oma = benign neoplasm-oma = benign neoplasm Mesenchymal tumorsMesenchymal tumors
chrondroma: cartilaginous tumorchrondroma: cartilaginous tumor fibroma: fibrous tumorfibroma: fibrous tumor osteoma: bone tumorosteoma: bone tumor
Epithelial tumorEpithelial tumor adenoma: tumor forming glandsadenoma: tumor forming glands papilloma: tumor with finger like projectionspapilloma: tumor with finger like projections papillary cystadenoma: papillary and cystic tumor forming papillary cystadenoma: papillary and cystic tumor forming
glandsglands polyp: a tumor that projects above a mucosal surfacepolyp: a tumor that projects above a mucosal surface
![Page 5: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/5.jpg)
![Page 6: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/6.jpg)
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM)© 2005 Elsevier
![Page 7: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/7.jpg)
Colonic Polyp: Tubular Adenoma
Stalk
Tumor
![Page 8: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/8.jpg)
Nomenclature – Malignant TumorsNomenclature – Malignant Tumors Sarcomas: mesenchymal tumorSarcomas: mesenchymal tumor
chrondrochrondrosarcosarcoma: cartilaginous tumorma: cartilaginous tumor fibrofibrosarcosarcoma: fibrous tumorma: fibrous tumor osteoosteosarcosarcoma: bone tumorma: bone tumor
Carcinomas: epithelial tumorsCarcinomas: epithelial tumors adenoadenocarcinocarcinoma: gland forming tumorma: gland forming tumor squamous cell carcinoma: squamous differentiationsquamous cell carcinoma: squamous differentiation undifferentiated carcinoma: no differentiationundifferentiated carcinoma: no differentiation note: carcinomas can arise from ectoderm, mesoderm, or note: carcinomas can arise from ectoderm, mesoderm, or
endodermendoderm
![Page 9: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/9.jpg)
![Page 10: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/10.jpg)
![Page 11: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/11.jpg)
![Page 12: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/12.jpg)
![Page 13: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/13.jpg)
![Page 14: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/14.jpg)
Tumors with Tumors with mixed differentiationmixed differentiation mixed tumors: e.g. pleomorphic adenoma of salivary glandmixed tumors: e.g. pleomorphic adenoma of salivary gland carcinosarcomacarcinosarcoma
TeratomaTeratoma tumor comprised of cells from more than one germ layertumor comprised of cells from more than one germ layer arise from totipotent cells (usually gonads)arise from totipotent cells (usually gonads) benign cystic teratoma of ovary is the most common teratomabenign cystic teratoma of ovary is the most common teratoma
Aberrant differentiation (Aberrant differentiation (not true neoplasmsnot true neoplasms)) Hamartoma: disorganized mass of tissue whose cell types are Hamartoma: disorganized mass of tissue whose cell types are
indiginous to the site of the lesion, e.g., lungindiginous to the site of the lesion, e.g., lung Choriostoma: ectopic focus of normal tissue (heterotopia), Choriostoma: ectopic focus of normal tissue (heterotopia),
e.g., pancreas, perhaps endometriosis tooe.g., pancreas, perhaps endometriosis too Misnomers?/ExceptionsMisnomers?/Exceptions
hepatoma: malignant liver tumorhepatoma: malignant liver tumor melanoma: malignant skin tumormelanoma: malignant skin tumor seminoma: malignant testicular tumorseminoma: malignant testicular tumor lymphoma: malignant tumor of lymphocyteslymphoma: malignant tumor of lymphocytes
![Page 15: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/15.jpg)
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM)© 2005 Elsevier
![Page 16: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/16.jpg)
![Page 17: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/17.jpg)
![Page 18: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/18.jpg)
Natural History Of Malignant TumorsNatural History Of Malignant Tumors
1.1. Malignant change in the target Malignant change in the target cell, referred to as transformation cell, referred to as transformation
2.2. Growth of the transformed cells Growth of the transformed cells
3.3.Local invasionLocal invasion4.4. Distant metastases. Distant metastases.
![Page 19: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/19.jpg)
DifferentiationDifferentiation WellWell differentiated neoplasm differentiated neoplasm
Resembles mature cells of tissue of originResembles mature cells of tissue of origin PoorlyPoorly diffentiated neoplasm diffentiated neoplasm
Composed of primitive cells with little diffrerentiation, Composed of primitive cells with little diffrerentiation, does NOT resemble tissue of origindoes NOT resemble tissue of origin
Undifferentiated or “anaplastic” tumorUndifferentiated or “anaplastic” tumor Correlation with biologic behaviorCorrelation with biologic behavior
Benign tumors are well differentiatedBenign tumors are well differentiated Poorly differentiated malignant tumors usually have Poorly differentiated malignant tumors usually have
worse prognosisworse prognosis
![Page 20: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/20.jpg)
If cells LOOK BAD, they are probably going to BEHAVE BADLooking “bad” means NOT looking like the orderly
cells they supposedly arose from!
![Page 21: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/21.jpg)
If cells LOOK GOOD, they are probably going to BEHAVE GOOD
Looking “good” means looking like the orderly cells they supposedly arose from!
![Page 22: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/22.jpg)
![Page 23: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/23.jpg)
PleomorphismPleomorphism SizeSize shapeshape
Abnormal nuclear morphologyAbnormal nuclear morphology HyperchromasiaHyperchromasia High nuclear cytoplasmic ratioHigh nuclear cytoplasmic ratio Chromatin clumpingChromatin clumping Prominent nucleoliProminent nucleoli
MitosesMitoses Mitotic rateMitotic rate Location of mitosesLocation of mitoses
Loss of polarity Loss of polarity
““ANAPLASIA” = CANCERANAPLASIA” = CANCER
![Page 24: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/24.jpg)
![Page 25: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/25.jpg)
DysplasiaDysplasia Literally means abnormal growthLiterally means abnormal growth Malignant transformation is a multistep processMalignant transformation is a multistep process In dysplasia some but not all of the features of In dysplasia some but not all of the features of
malignancy are present, microscopicallymalignancy are present, microscopically Dysplasia Dysplasia maymay develop into malignancy develop into malignancy
Uterine cervixUterine cervix Colon polypsColon polyps
Graded as low-grade or high-grade, often prompting Graded as low-grade or high-grade, often prompting different clinical decisionsdifferent clinical decisions
Dysplasia may Dysplasia may NOTNOT develop into malignancy develop into malignancy HIGH grade dysplasia often classified with CISHIGH grade dysplasia often classified with CIS
![Page 26: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/26.jpg)
![Page 27: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/27.jpg)
![Page 28: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/28.jpg)
Tumor Growth RateTumor Growth Rate Doubling time of tumor cellsDoubling time of tumor cells
Lengthens as tumor growsLengthens as tumor grows 30 doublings (1030 doublings (1099 cells) = 1 g cells) = 1 g (months to years)(months to years) 10 more doublings (1 kg) = lethal burden 10 more doublings (1 kg) = lethal burden (“) (“)
Fraction of tumor cells in replicative poolFraction of tumor cells in replicative pool May be only 20% even in rapidly growing tumorsMay be only 20% even in rapidly growing tumors Tumor stem cellsTumor stem cells
Rate at which tumor cells are shed or lostRate at which tumor cells are shed or lost ApoptosisApoptosis MaturationMaturation
Implications for therapyImplications for therapy
![Page 29: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/29.jpg)
“clonal”
![Page 30: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/30.jpg)
Schematic Representation Of Tumor Growth
![Page 31: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/31.jpg)
Features of Malignant TumorsFeatures of Malignant Tumors Cellular featuresCellular features
Local Local invasioninvasion CapsuleCapsule Basement membraneBasement membrane
MetastasisMetastasis Unequivocal sign of malignancyUnequivocal sign of malignancy Seeding of body cavitiesSeeding of body cavities LymphaticLymphatic HematogenousHematogenous
![Page 32: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/32.jpg)
![Page 33: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/33.jpg)
![Page 34: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/34.jpg)
![Page 35: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/35.jpg)
![Page 36: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/36.jpg)
![Page 37: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/37.jpg)
![Page 38: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/38.jpg)
![Page 39: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/39.jpg)
Significance of Nodal MetsSignificance of Nodal Mets Example of breast cancerExample of breast cancer
Halsted radical mastectomyHalsted radical mastectomy Sentinel node biopsySentinel node biopsy
PrognosticPrognostic Number of involved nodes is an important Number of involved nodes is an important
component of TNM staging systemcomponent of TNM staging system TherapeuticTherapeutic
Overall risk of recurrenceOverall risk of recurrence Extent of nodal involvementExtent of nodal involvement Histologic grade and other considerationsHistologic grade and other considerations
““Adjuvant” chemotherapyAdjuvant” chemotherapy
![Page 40: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/40.jpg)
Benign vs Malignant FeaturesBenign vs Malignant Features
FeatureFeature BenignBenign MalignantMalignant
Rate of growthRate of growth Progressive but Progressive but slow. Mitoses few slow. Mitoses few and normaland normal
Variable. Mitoses Variable. Mitoses more frequent and more frequent and may be abnormalmay be abnormal
DifferentiationDifferentiation Well Well differentiateddifferentiated
Some degree of Some degree of anaplasiaanaplasia
LOCAL LOCAL INVASIOINVASIONN
Cohesive growth. Cohesive growth. Capsule & BM Capsule & BM not breachednot breached
Poorly cohesive Poorly cohesive and and
infiltrative!infiltrative!
MetastasisMetastasis AbsentAbsent May occurMay occur
![Page 41: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/41.jpg)
![Page 42: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/42.jpg)
![Page 43: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/43.jpg)
![Page 44: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/44.jpg)
![Page 45: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/45.jpg)
![Page 46: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/46.jpg)
Geographic & Environmental Geographic & Environmental Sun exposureSun exposure
Melanomas 6x incidence New Zealand vs. IcelandMelanomas 6x incidence New Zealand vs. Iceland Blacks have low incidence of melanoma, so do normally Blacks have low incidence of melanoma, so do normally
pigmented areas like areolae on white peoplepigmented areas like areolae on white people Smoking and alcohol abuseSmoking and alcohol abuse Body massBody mass
Overweight = 50% increase in cancerOverweight = 50% increase in cancer Environmental vs. racial factorsEnvironmental vs. racial factors
Japanese immigrants to USAJapanese immigrants to USA Viral exposureViral exposure
Human papilloma virus (HPV) and cervical cancerHuman papilloma virus (HPV) and cervical cancer Hepatitis B virus (HBV) and liver cancer (Africa, Asia)Hepatitis B virus (HBV) and liver cancer (Africa, Asia) Epstein-Barr Virus (EBV) and lymphomaEpstein-Barr Virus (EBV) and lymphoma
![Page 47: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/47.jpg)
Change In Incidence Of Various Cancers With Migration From Japan To The United States
![Page 48: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/48.jpg)
Predisposing Factors for CancerPredisposing Factors for Cancer AgeAge
Most cancers occur in persons ≥ 55 yearsMost cancers occur in persons ≥ 55 years Childhood cancersChildhood cancers
Leukemias & CNS neoplasmsLeukemias & CNS neoplasms Bone tumorsBone tumors
Genetic predispostionGenetic predispostion Familial cancer syndromesFamilial cancer syndromes
Early age at onsetEarly age at onset Two or more primary relatives with the cancer (“soil” theory)Two or more primary relatives with the cancer (“soil” theory) Multiple or bilateral tumorsMultiple or bilateral tumors
Polymorphisms that metabolize procarcinogens, e.g., nitritesPolymorphisms that metabolize procarcinogens, e.g., nitrites Nonhereditary predisposing conditionsNonhereditary predisposing conditions
Chronic inflammation?Chronic inflammation? Precancerous conditionsPrecancerous conditions
Chronic ulcerative colitisChronic ulcerative colitis Atrophic gastritis of pernicious anemiaAtrophic gastritis of pernicious anemia Leukoplakia of mucous membranesLeukoplakia of mucous membranes Immune collapse?Immune collapse?
![Page 49: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/49.jpg)
Defnition of NeoplasiaDefnition of Neoplasia
“A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change” - Willis
Genetic changes Autonomous Clonal
![Page 50: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/50.jpg)
MOLECULAR BASISMOLECULAR BASISof CANCERof CANCER
NON-lethal NON-lethal genetic damage, “usual” suspec.genetic damage, “usual” suspec. A tumor is formed by the clonal expansion A tumor is formed by the clonal expansion
of a single precursor cell (of a single precursor cell (monoclonalmonoclonal)) Four classes Four classes of normal regulatory genesof normal regulatory genes
PROTO-oncogenesPROTO-oncogenes OncogenesOncogenes Oncoproteins Oncoproteins DNA repair genesDNA repair genes Apoptosis genesApoptosis genes
Carcinogenesis is a Carcinogenesis is a multistepmultistep process process
![Page 51: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/51.jpg)
TRANSFORMATION &TRANSFORMATION &PROGRESSIONPROGRESSION
Self-sufficiency in growth signalsSelf-sufficiency in growth signals Insensitivity to growth-inhibiting signalsInsensitivity to growth-inhibiting signals Evasion of apoptosisEvasion of apoptosis Defects in DNA repair: “Spell checker”Defects in DNA repair: “Spell checker” Limitless replicative potential: TelomeraseLimitless replicative potential: Telomerase AngiogenesisAngiogenesis Invasive abilityInvasive ability Metastatic abilityMetastatic ability
![Page 52: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/52.jpg)
![Page 53: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/53.jpg)
Normal CELL CYCLE PhasesNormal CELL CYCLE Phases
INHIBITORS: Cip/Kip, INK4/ARFTumor (really growth) suppressor genes: p53
![Page 54: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/54.jpg)
ONCOGENESONCOGENES Are MUTATIONS of NORMAL genes Are MUTATIONS of NORMAL genes
(PROTO-oncogenes)(PROTO-oncogenes) Growth FactorsGrowth Factors Growth Factor ReceptorsGrowth Factor Receptors Signal Transduction Proteins (RAS)Signal Transduction Proteins (RAS) Nuclear Regulatory ProteinsNuclear Regulatory Proteins Cell Cycle RegulatorsCell Cycle Regulators
Oncogenes code for Oncogenes code for Oncoproteins Oncoproteins
![Page 55: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/55.jpg)
CategoryPROTO- Oncogene
Mode of Activation
Associated Human Tumor
GFs
PDGF-β chain SIS Overexpression Astrocytoma
OsteosarcomaFibroblast growth factors
HST-1 Overexpression Stomach cancer
INT-2 Amplification Bladder cancer
Breast cancerMelanoma
TGFα TGFα Overexpression Astrocytomas
Hepatocellular carcinomas
HGF HGF Overexpression Thyroid cancer
![Page 56: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/56.jpg)
CategoryPROTO- Oncogene
Mode of Activation
Associated Human Tumor
GF ReceptorsEGF-receptor family
ERB-B1 (ECFR)
Overexpression Squamous cell carcinomas of lung, gliomas
ERB-B2 Amplification Breast and ovarian cancers
CSF-1 receptor FMS Point mutation Leukemia
Receptor for neurotrophic factors
RET Point mutation Multiple endocrine neoplasia 2A and B, familial medullary thyroid carcinomas
PDGF receptor PDGF-R Overexpression Gliomas
Receptor for stem cell (steel) factor
KIT Point mutation Gastrointestinal stromal tumors and other soft tissue tumors
![Page 57: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/57.jpg)
CategoryPROTO- Oncogene
Mode of Activation
Associated Human Tumor
“Signal TransductionProteins”GTP-binding K-RAS Point mutation Colon, lung, and pancreatic
tumorsH-RAS Point mutation Bladder and kidney tumors
N-RAS Point mutation Melanomas, hematologic malignancies
Nonreceptor tyrosine kinase
ABL Translocation Chronic myeloid leukemia
Acute lymphoblastic leukemiaRAS signal transduction
BRAF Point mutation Melanomas
WNT signal transduction
β-catenin Point mutation Hepatoblastomas, hepatocellular carcinoma
![Page 58: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/58.jpg)
CategoryPROTO- Oncogene
Mode of Activation Associated Human
TumorNuclear Regulatory ProteinsTranscrip.activators
C-MYC Translocation Burkitt lymphoma
N-MYC Amplification Neuroblastoma, small cell carcinoma of lung
L-MYC Amplification Small cell carcinoma of lung
![Page 59: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/59.jpg)
MYCMYC Encodes for transcription factorsEncodes for transcription factors
AlsoAlso involved with involved with apoptosisapoptosis
![Page 60: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/60.jpg)
P53 and RASP53 and RASp53p53
Activates DNA repair Activates DNA repair proteinsproteins
Sentinel of G1/S Sentinel of G1/S transitiontransition
Initiates apoptosisInitiates apoptosis Mutated in more than Mutated in more than
50% of all human 50% of all human cancerscancers
RASRAS H, N, K, etc., varietiesH, N, K, etc., varieties Single most common Single most common
abnormality of abnormality of dominant oncogenes in dominant oncogenes in human tumorshuman tumors
Present in about 1/3 of Present in about 1/3 of all human cancersall human cancers
![Page 61: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/61.jpg)
![Page 62: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/62.jpg)
Tumor (really “GROWTH”) Tumor (really “GROWTH”) suppressor genessuppressor genes
TGF-TGF-ββ COLON COLON E-cadherinE-cadherin STOMACH STOMACH NF-1,2NF-1,2 NEURAL TUMORS NEURAL TUMORS APC/APC/ββ-cadherin -cadherin GI, MELANOMA GI, MELANOMA SMADsSMADs GI GI RBRB RETINOBLASTOMA RETINOBLASTOMA P53P53 EVERYTHING!! EVERYTHING!! WT-1WT-1 WILMS TUMOR WILMS TUMOR p16 (INK4a) p16 (INK4a) GI, BREAST (MM if inherited) GI, BREAST (MM if inherited) BRCA-1,2BRCA-1,2 BREAST BREAST KLF6KLF6 PROSTATE PROSTATE
![Page 63: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/63.jpg)
Evasion of APOPTOSISEvasion of APOPTOSIS
BCL-2BCL-2p53p53MYCMYC
![Page 64: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/64.jpg)
DNA REPAIR GENE DEFECTSDNA REPAIR GENE DEFECTS DNA repair is like a spell checkerDNA repair is like a spell checkerHNPCCHNPCC ( (HHereditary ereditary NNon-on-PPolyposis olyposis CColon olon
CCancer): TGF-ancer): TGF-ββ, , ββ-catenin, BAX-catenin, BAX Xeroderma Pigmentosum: UV fixing geneXeroderma Pigmentosum: UV fixing gene Ataxia Telangiectasia: ATM geneAtaxia Telangiectasia: ATM gene Bloom Syndrome: defective helicaseBloom Syndrome: defective helicase Fanconi anemiaFanconi anemia
![Page 65: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/65.jpg)
LIMITLESS REPLICATIVE LIMITLESS REPLICATIVE POTENTIALPOTENTIAL
TELOMERES determine the limited TELOMERES determine the limited number of duplications a cell will number of duplications a cell will have, like a cat with nine lives.have, like a cat with nine lives.
TELOMERASETELOMERASE, present in >90% of , present in >90% of human cancers, changes telomeres so human cancers, changes telomeres so they will have UNLIMITED they will have UNLIMITED replicative potentialreplicative potential
![Page 66: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/66.jpg)
TUMOR ANGIOGENESISTUMOR ANGIOGENESIS QQ: How close to a blood vessel must a cell be?: How close to a blood vessel must a cell be? A: 1-2 mmA: 1-2 mm
Activation of VEGF and FGF-bActivation of VEGF and FGF-b
Tumor size is regulated (allowed) by Tumor size is regulated (allowed) by angiogenesis/anti-angiogenesis balanceangiogenesis/anti-angiogenesis balance
![Page 67: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/67.jpg)
TRANSFORMATIONTRANSFORMATIONGROWTHGROWTH
BM INVASIONBM INVASIONANGIOGENESISANGIOGENESISINTRAVASATIONINTRAVASATIONEMBOLIZATIONEMBOLIZATION
ADHESIONADHESIONEXTRAVASATIONEXTRAVASATIONMETASTATIC GROWTHMETASTATIC GROWTH
etc.etc.
![Page 68: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/68.jpg)
Invasion FactorsInvasion Factors DetachmentDetachment ("loosening up") of ("loosening up") of
the tumor cells from each other the tumor cells from each other AttachmentAttachment to matrix components to matrix components DegradationDegradation of ECM, e.g., of ECM, e.g.,
collagenase, etc. collagenase, etc. MigrationMigration of tumor cells of tumor cells
![Page 69: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/69.jpg)
![Page 70: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/70.jpg)
METASTATIC GENES?METASTATIC GENES?
NM23NM23KAI-1KAI-1KiSSKiSS
![Page 71: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/71.jpg)
CHROMOSOME CHANGESin CANCER
TRANSLOCATIONS and INVERSIONS
Occur in MOST Lymphomas/Leukemias Occur in MANY (and growing numbers) of
NON-hematologic malignancies also
![Page 72: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/72.jpg)
Malignancy Translocation Affected GenesChronic myeloid leukemia (9;22)(q34;q11) Ab1 9q34 bcr 22q11Acute leukemias (AML and ALL) (4;11)(q21;q23) AF4 4q21 MLL 11q23 (6;11)(q27;q23) AF6 6q27 MLL 11q23Burkitt lymphoma (8;14)(q24;q32) c-myc 8q24 IgH 14q32Mantle cell lymphoma (11;14)(q13;q32) Cyclin D 11q13 IgH 14q32Follicular lymphoma (14;18)(q32;q21) IgH 14q32 bcl-2 18q21T-cell acute lymphoblastic leukemia (8;14)(q24;q11) c-myc 8q24 TCR-α 14q11 (10;14)(q24;q11) Hox 11 10q24 TCR-α 14q11Ewing sarcoma (11;22)(q24;q12) Fl-1 11q24 EWS 22q12
![Page 73: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/73.jpg)
Carcinogenesis is “MULTISTEP”NO single oncogene causes cancer BOTH several oncogenes AND several tumor
suppressor genes must be involved Gatekeeper/Caretaker concept
Gatekeepers: ONCOGENES and TUMOR SUPPRESSOR GENES
Caretakers: DNA REPAIR GENES Tumor “PROGRESSION”
ANGIOGENESIS HETEROGENEITY from original single cell
![Page 74: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/74.jpg)
Carcinogenesis: The USUAL (3) Suspects
Initiation/Promotion concept: BOTH initiators AND promotors are needed NEITHER can cause cancer by itselfINITIATORS (carcinogens) cause MUTATIONS PROMOTORS are NOT carcinogenic by themselves,
and MUST take effect AFTER initiation, NOT beforePROMOTORS enhance the proliferation of
initiated cells, i.e., HYPERPLASTIC AGENTS!!!
![Page 75: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/75.jpg)
![Page 76: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/76.jpg)
Q: WHO are the usual suspects? Inflammation? Teratogenesis? Immune
Suppression? Neoplasia? Mutations?
![Page 77: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/77.jpg)
A: The SAME 3 that are ALWAYS blamed!
1) ChemicalsChemicals2) RadiationRadiation3) InfectiousInfectious PathogensPathogens
![Page 78: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/78.jpg)
CHEMICAL CARCINOGENS:INITIATORS
DIRECT β-Propiolactone Dimeth. sulfate Diepoxybutane Anticancer drugs
(cyclophosphamide, chlorambucil, nitrosoureas, and others)
Acylating Agents 1-Acetyl-imidazole Dimethylcarbamyl chloride
“PRO”CARCINOGENS Polycyclic and Heterocyclic
Aromatic Hydrocarbons Aromatic Amines, Amides,
Azo Dyes Natural Plant and Microbial
Products Aflatoxin B1 Hepatomas Griseofulvin Antifungal Cycasin from cycads Safrole from sassafras Betel nuts Oral SCC
![Page 79: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/79.jpg)
CHEMICAL CARCINOGENS:INITIATORS
OTHERS Nitrosamine and amides (tar, nitrites) Vinyl chloride angiosarcoma in Kentucky Nickel Chromium Insecticides Fungicides PolyChlorinated Biphenyls (PCBs)
![Page 80: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/80.jpg)
CHEMICAL CARCINOGENS:PROMOTORS
HORMONES PHORBOL ESTERS (TPA), activate kinase C PHENOLS DRUGS, many
“Initiated” cells respond and proliferate FASTER to promotors than normal cells
![Page 81: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/81.jpg)
RADIATION CARCINOGENS UV:UV: BCC, SCC, MM (i.e., all 3) IONIZING:IONIZING: photons and particulate
Hematopoetic and Thyroid (90%/15yrs) tumors in fallout victims
Solid tumors either less susceptible or require a longer latency period than LEUK/LYMPH
BCCs in Therapeutic Radiation
![Page 82: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/82.jpg)
VIRAL CARCINOGENESIS HPV SCC EBV Burkitt Lymphoma HBV Hepatocellular Carcinoma (Hepatoma) HTLV1 T-Cell Malignancies KSHV Kaposi Sarcoma
![Page 83: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/83.jpg)
H. pylori CARCINOGENESIS
100% of gastric lymphomas (i.e., M.A.L.T.-omas)
Gastric CARCINOMAS also!
![Page 84: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/84.jpg)
HOST DEFENSES IMMUNE SURVEILLENCE CONCEPT
CD8+ T-Cells NK cells MACROPHAGES ANTIBODIES
![Page 85: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/85.jpg)
CYTOTOXIC CD8+ T-CELLS are the main eliminators of tumor cells
![Page 86: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/86.jpg)
How do tumor cellsescape immune surveillance?
Mutation, like microbesMutation, like microbes↓ ↓ MHC molecules on tumor cell surfaceMHC molecules on tumor cell surface Lack of CO-stimulation molecules, e.g., Lack of CO-stimulation molecules, e.g.,
(CD28, ICOS), not just Ag-Ab recognition(CD28, ICOS), not just Ag-Ab recognition Immunosuppressive agentsImmunosuppressive agents Antigen maskingAntigen masking Apoptosis of cytotoxic T-Cells (CD8), i.e., Apoptosis of cytotoxic T-Cells (CD8), i.e.,
the damn tumor cell KILLS the T-cell!the damn tumor cell KILLS the T-cell!
![Page 87: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/87.jpg)
Effects of TUMOR on the HOST Location anatomic ENCROACHMENT HORMONE production Bleeding, Infection ACUTE symptoms, e.g., rupture, infarction METASTASES
![Page 88: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/88.jpg)
CACHEXIA Reduced diet: Fat loss>Muscle loss Cachexia: Fat loss AND Muscle loss TNF (α by default) IL-(6) PIF (Proteolysis Inducing Factor)
![Page 89: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/89.jpg)
PARA-Neoplastic SyndromesEndocrine Nerve/Muscle, e.g., myasthenia w. lung ca. Skin: e.g., acanthosis nigricans,
dermatomyositis Bone/Joint/Soft tissue: HPOA (Hypertrophic
Pulmonary OsteoArthropathy) Vascular: Trousseau, Endocarditis Hematologic: Anemias Renal: e.g., Nephrotic Syndrome
![Page 90: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/90.jpg)
ENDOCRINECushing syndrome Small cell carcinoma of lung ACTH or ACTH-like substance Pancreatic carcinoma Neural tumors Syndrome of inappropriate
antidiuretic hormone secretion
Small cell carcinoma of lung; intracranial neoplasms
Antidiuretic hormone or atrial natriuretic hormones
Hypercalcemia Squamous cell carcinoma of lung Parathyroid hormone-related protein (PTHRP), TGF-α, TNF, IL-1
Breast carcinoma Renal carcinoma Adult T-cell leukemia/lymphoma Ovarian carcinoma Hypoglycemia Fibrosarcoma Insulin or insulin-like substance Other mesenchymal sarcomas Hepatocellular carcinoma Carcinoid syndrome Bronchial adenoma (carcinoid) Serotonin, bradykinin Pancreatic carcinoma Gastric carcinoma Polycythemia Renal carcinoma Erythropoietin Cerebellar hemangioma Hepatocellular carcinoma
![Page 91: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/91.jpg)
GRADING/STAGINGGRADING: HOW
“DIFFERENTIATED” ARE THE CELLS?
STAGING: HOW MUCH ANATOMIC EXTENSION? TNM
Which one of the above do you think is more important?
![Page 92: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/92.jpg)
WELL?(pearls)
MODERATE?(intercellular bridges)
POOR?(WTF!?!)
GRADING for Squamous Cell Carcinoma
![Page 93: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/93.jpg)
ADENOCARCINOMA GRADINGLet’s have some FUN!
![Page 94: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/94.jpg)
LAB DIAGNOSISBIOPSYCYTOLOGY: (exfoliative)CYTOLOGY: (FNA, Fine
Needle Aspirate)
![Page 95: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/95.jpg)
IMMUNOHISTOCHEMISTRYCategorization of
undifferentiated tumorsLeukemias/LymphomasSite of originReceptors, e.g., ERA, PRA
![Page 96: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/96.jpg)
TUMOR MARKERS HORMONES: (Paraneoplastic Syndromes) “ONCO”FETAL: AFP, CEA ISOENZYMES: PAP, NSE PROTEINS: PSA, PSMA (“M” = “membrane”) GLYCOPROTEINS: CA-125, CA-195, CA-153 MOLECULAR: p53, RAS
NOTE: These SAME substances which can be measured in the blood, also can be stained by immunochemical methods in tissue
![Page 97: Ch7- - Medical School Pathology · 2017-09-07Ch7- - Medical School Pathology](https://reader036.fdocuments.net/reader036/viewer/2022081812/5aa91a767f8b9a9a188c643e/html5/thumbnails/97.jpg)
MICRO-ARRAYSTHOUSANDS of genes identified from tumors give the cells their own identity and FINGERPRINT and may give important prognostic information as well as guidelines for therapy. Some say this may replace standard histopathologic identifications of tumors.
What do you think?