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NeoplasiaNeoplasia
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
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
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
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM)
© 2005 Elsevier
Colonic Polyp: Tubular Adenoma
Stalk
Tumor
Nomenclature – Malignant TumorsNomenclature – Malignant Tumors Sarcomas: mesenchymal tumorSarcomas: mesenchymal tumor
chrondrosarcoma: cartilaginous tumorchrondrosarcoma: cartilaginous tumor fibrosarcoma: fibrous tumorfibrosarcoma: fibrous tumor osteosarcoma: bone tumorosteosarcoma: bone tumor
Carcinomas: epithelial tumorsCarcinomas: epithelial tumors adenocarcinoma: gland forming tumoradenocarcinoma: 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, note: carcinomas can arise from ectoderm,
mesoderm, or endodermmesoderm, or endoderm
Tumors with mixed differentiationTumors with mixed 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 benign cystic teratoma of ovary is the most common
teratomateratoma Aberrant differentiation (not true neoplasms)Aberrant differentiation (not 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 lesionindiginous to the site of the lesion
Choriostoma: ectopic focus of normal tissue (heterotopia)Choriostoma: ectopic focus of normal tissue (heterotopia) MisnomersMisnomers
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
Figure 7-4 A, Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. You do not need a microscope to appreciate this tumor produces both connective tissue as well as epithelial derived elements.
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM)
© 2005 Elsevier
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 cell, referred to as transformation transformation
2.2. Growth of the transformed cells Growth of the transformed cells
3.3. Local invasionLocal invasion
4.4. Distant metastases. Distant metastases.
DifferentiationDifferentiation Well differentiated neoplasmWell differentiated neoplasm
Resembles mature cells of tissue of originResembles mature cells of tissue of origin Poorly diffentiated neoplasmPoorly diffentiated neoplasm
Composed of primitive cells with little Composed of primitive cells with little diffrerentiationdiffrerentiation
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 Poorly differentiated malignant tumors usually
have worse prognosishave worse prognosis
If cells LOOK BAD, they are probably going to BEHAVE BAD
If cells LOOK GOOD, they are probably going to BEHAVE GOOD
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”ANAPLASIA”
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 presentmalignancy are present
Dysplasia Dysplasia maymay develop into malignancy develop into malignancy Uterine cervixUterine cervix Colon polypsColon polyps
Graded as low-grade or high-gradeGraded as low-grade or high-grade Dysplasia may Dysplasia may NOTNOT develop into malignancy develop into malignancy
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
Schematic Representation Of Tumor Growth
Features of Malignant TumorsFeatures of Malignant Tumors
Cellular featuresCellular features Local invasionLocal invasion
CapsuleCapsule Basement membraneBasement membrane
MetastasisMetastasis Unequivocal sign of malignancyUnequivocal sign of malignancy Seeding of body cavitiesSeeding of body cavities LymphaticLymphatic HematogenousHematogenous
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
Benign vs Malignant FeaturesBenign vs Malignant Features
FeatureFeature BenignBenign MalignantMalignant
Rate of growthRate of growth Progressive but Progressive but slow. Mitoses slow. Mitoses few and normalfew and normal
Variable. Mitoses Variable. Mitoses more frequent more frequent and may be and may be abnormalabnormal
DifferentiationDifferentiation Well Well differentiateddifferentiated
Some degree of Some degree of anaplasiaanaplasia
Local invasionLocal invasion Cohesive growth. Cohesive growth. Capsule & BM Capsule & BM not breachednot breached
Poorly cohesive Poorly cohesive and infiltrative.and infiltrative.
MetastasisMetastasis AbsentAbsent May occurMay occur
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 melanomaBlacks have low incidence of melanoma
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)Hepatitis B virus (HBV) and liver cancer (Africa) Epstein-Barr Virus (EBV) and lymphomaEpstein-Barr Virus (EBV) and lymphoma
Change In Incidence Of Various Cancers With Migration From Japan To The United States
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 cancerTwo or more primary relatives with the cancer 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 inflammationChronic 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
MOLECULAR BASISMOLECULAR BASISof CANCERof CANCER
NON-lethal NON-lethal genetic damagegenetic damage 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
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
Normal CELL CYCLE PhasesNormal CELL CYCLE Phases
INHIBITORS: Cip/Kip, INK4/ARFTumor (really growth) suppressor
genes: p53
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
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
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
CategoryPROTO- Oncogene
Mode of Activation
Associated Human Tumor
Signal TransductionProteinsGTP-binding K-RAS Point mutation Colon, lung, and pancreatic
tumors
H-RAS Point mutation Bladder and kidney tumors
N-RAS Point mutation Melanomas, hematologic malignancies
Nonreceptor tyrosine kinase
ABL Translocation Chronic myeloid leukemia
Acute lymphoblastic leukemia
RAS signal transduction
BRAF Point mutation Melanomas
WNT signal transduction
β-catenin Point mutation Hepatoblastomas, hepatocellular carcinoma
CategoryPROTO- Oncogene
Mode of Activation Associated Human
Tumor
Nuclear Regulatory Proteins
Transcrip.activators
C-MYC Translocation Burkitt lymphoma
N-MYC Amplification Neuroblastoma, small cell carcinoma of lung
L-MYC Amplification Small cell carcinoma of lung
MYCMYC Encodes for transcription factorsEncodes for transcription factors Also involved with apoptosisAlso involved with apoptosis
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
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
Evasion of APOPTOSISEvasion of APOPTOSIS
BCL-2BCL-2p53p53MYCMYC
DNA REPAIR GENE DEFECTSDNA REPAIR GENE DEFECTS DNA repair is like a spell checkerDNA repair is like a spell checker
HNPCCHNPCC ( (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
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
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
TRANSFORMATIONTRANSFORMATIONGROWTHGROWTH
BM INVASIONBM INVASIONANGIOGENESISANGIOGENESISINTRAVASATIONINTRAVASATIONEMBOLIZATIONEMBOLIZATION
ADHESIONADHESIONEXTRAVASATIONEXTRAVASATIONMETASTATIC GROWTHMETASTATIC GROWTH
etc.etc.
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
METASTATIC GENES?METASTATIC GENES?
NM23NM23KAI-1KAI-1KiSSKiSS
CHROMOSOME CHANGESin CANCER
TRANSLOCATIONS and INVERSIONS
Occur in MOST Lymphomas/Leukemias Occur in MANY (and growing numbers) of
NON-hematologic malignancies also
Malignancy Translocation Affected Genes
Chronic myeloid leukemia (9;22)(q34;q11) Ab1 9q34
bcr 22q11
Acute leukemias (AML and ALL) (4;11)(q21;q23) AF4 4q21
MLL 11q23
(6;11)(q27;q23) AF6 6q27
MLL 11q23
Burkitt lymphoma (8;14)(q24;q32) c-myc 8q24
IgH 14q32
Mantle cell lymphoma (11;14)(q13;q32) Cyclin D 11q13
IgH 14q32
Follicular lymphoma (14;18)(q32;q21) IgH 14q32
bcl-2 18q21
T-cell acute lymphoblastic leukemia (8;14)(q24;q11) c-myc 8q24
TCR-α 14q11
(10;14)(q24;q11) Hox 11 10q24
TCR-α 14q11
Ewing sarcoma (11;22)(q24;q12) Fl-1 11q24
EWS 22q12
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
Carcinogenesis: The USUAL (3) Suspects
Initiation/Promotion concept: BOTH initiators AND promotors are needed NEITHER can cause cancer by itself
INITIATORS (carcinogens) cause MUTATIONS
PROMOTORS are NOT carcinogenic by themselves, and MUST take effect AFTER initiation, NOT before
PROMOTORS enhance the proliferation of initiated cells
Q: WHO are the usual suspects? Inflammation? Teratogenesis? Immune
Suppression? Neoplasia? Mutations?
A: The SAME 3 that are ALWAYS blamed!
1) ChemicalsChemicals2) RadiationRadiation3) InfectiousInfectious PathogensPathogens
CHEMICAL CARCINOGENS:INITIATORS
DIRECT β-Propiolactone Dimethyl 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
CHEMICAL CARCINOGENS:INITIATORS
OTHERS Nitrosamine and amides (tar, nitrites) Vinyl chloride angiosarcoma in Kentucky Nickel Chromium Insecticides Fungicides PolyChlorinated Biphenyls (PCBs)
CHEMICAL CARCINOGENS:PROMOTORS
HORMONES PHORBOL ESTERS (TPA), activate kinase C PHENOLS DRUGS
“Initiated” cells respond and proliferate FASTER to promotors than normal cells
RADIATION CARCINOGENS
UV:UV: BCC, SCC, MM
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
VIRAL CARCINOGENESIS
HPV SCC EBV Burkitt Lymphoma HBV Hepatocellular Carcinoma (Hepatoma) HTLV1 T-Cell Malignancies KSHV Kaposi Sarcoma
H. pylori CARCINOGENESIS
100% of gastric lymphomas (i.e., M.A.L.T.-omas)
Gastric CARCINOMAS also!
HOST DEFENSES
IMMUNE SURVEILLENCE CONCEPT
CD8+ T-Cells NK cells MACROPHAGES ANTIBODIES
CYTOTOXIC CD8+ T-CELLS are the main eliminators of tumor cells
How do tumor cellsescape immune surveillance?
MutationMutation
↓ ↓ 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)(CD28, ICOS) 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!
Effects of TUMOR on the HOST
Location anatomic ENCROACHMENT HORMONE production Bleeding, Infection ACUTE symptoms, e.g., rupture, infarction METASTASES
CACHEXIA Reduced diet: Fat loss>Muscle loss Cachexia: Fat lost + Muscle loss TNF IL-1 PIF (Proteolysis Inducing Factor)
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
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 lungParathyroid 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
GRADING/STAGING
GRADING: HOW “DIFFERENTIATED” ARE THE CELLS?
STAGING: HOW MUCH ANATOMIC EXTENSION?
Which one of the above do you think is more important?
WELL?
MODERATE?
POOR?
GRADING for Squamous Cell Carcinoma
ADENOCARCINOMA GRADINGLet’s have some FUN!
LAB DIAGNOSISBIOPSYCYTOLOGY: (exfoliative)CYTOLOGY: (FNA, Fine
Needle Aspirate)
IMMUNOHISTOCHEMISTRY
Categorization of undifferentiated tumors
Leukemias/LymphomasSite of originReceptors, e.g., ERA, PRA
TUMOR MARKERS HORMONES: (Paraneoplastic Syndromes) “ONCO”FETAL: AFP, CEA ISOENZYMES: PAP, NSE PROTEINS: PSA, PSMA GLYCOPROTEINS: CA-125, CA-19-5, CA-15-3 MOLECULAR: p53, RAS
NOTE: These SAME substances which can be measured in the blood, also can be stained by immunochemical methods in tissue
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?