Cancer Review for Medical Students

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CANCER

• IMEC INC
• Quick LearningTechnique

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Some example of factors
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Cancer Incidence

• In 1998 546,000 Deaths
• 100,000 in situ cases of the skin
• Mens rate is rising, women falling
• Men
• Prostate 29,
• Lung 14 ,
• Colon 10
• Women
• Breast 29,
• Lung 13.3,
• Colon 11.1 ,
• Ovary 4.2

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Adenocarcinoma of Lung
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Cancer Deaths

• Men
• Lung 31.6
• Prostate 13.3
• Colon 9.5
• Women
• Lung 24.7
• Breast 16
• Colon 10.5
• Ovary 5.3
• Important Note
• It appears that in males. Prostate Cancer if
  detected early increase morbidity. It also
  appears that Breast cancer in women has the same
  effect.
• Lung Cancer Deaths are rising in women

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Age/Race

• Most Cancers occur after age 55
• Japanese have high incidence of stomach cancer
• Colon cancer is highest in Black males
• Cervical cancer in females is linked to the
  number of sexual partners
• Brain cancer occurs greater in 15-34 YO age group
• Breast Cancer is greatest in 35-54 YO age group

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NEOPLASTIC PROGRESSION

• Normal Cells--? apical differentation
• Cell increase in number?hyperplasia
• Change in size, shape?dysplasia
• In situ?clumped chromatin, have not invaded
  basement membrane
• Cells invade basement membrane using collagenages
  and hydrolases
• Metastatis?spreads (neoplasia)

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GRADE and STAGE

• Grade is the histological appearance of the tumor
• Usually graded (I-IV) based on the degree of
  differentiated
• Stage is based on site and size of the primary
  lesion, and potential to spread
• Remember
• T Size of Tumor
• NNodal Involvement
• MMetastasis

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Cancer Staging

• Cancer staging varies from organ to organ
• Basically
• Hyperplasia-increased cell , Dysplasia-size,shape
  ,oreintation
• In-situ-dysplastic but have not invaded basement
  membrane. High nuclear-cytplasmic ratio
• Invasive-invaded basement membrane using
  colagenasees and hydrolases
• Metastasis-spread to distant organ
• Seed and soil-seedtumor embolus
• soil- target organ
• Refer to CancerNet for each

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Nomenclature

• Oma vs. Sarcoma

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Benign Tumors

• Epithelial---? Adenoma, Papilloma
• Mesenchymal
• Blood Cells
• Blood Vessels-?Hemangioma
• Smooth Muscle?Leiomyoma
• Skeletal Muscle?Rhabdomyoma
• Bone-------------?Osteoma
• Fat--------------?Lipoma
• More than one type of cell
• Mature Teratoma

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Malignant Tumors

• Epithelial-?Adenosarcoma
• Mesenchymal
• Blood Cells?Leukemia, Lymphoma
• Blood Vessels?Angiosarcoma
• Smooth Muscle?Leiomyosarcoma
• Skeletal Muscle?Rhabdomyosarcoma
• Bone--?Osteosarcoma
• Fat-?Liposarcoma
• More than one type of cell
• Immature Teratoma

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Benign tumors

• Well Differentiated
• Highly demarcated (do not invade)
• Note a demarcated Army Unit is well formed, yet
  does not need to proceed to battle.
• Usually progressive yet slow

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Malignant Tumors

• Lack Differentation
• Erratic (slow or fast)
• Locally invasive through basement membrane
• The larger and more UNDIFFERENTIATED, the primary
  they are for metastasis

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Diseases Associated with Neoplasms
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Downs Syndrome

• Associated neoplasm
• Acute LymphoBlastic Leukemia (ALL)
• We all go down together

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Xeroderma Pigmentosum

• Associated neoplasm
• Squamous and Basal Cell of the skin

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Chronic Atrophic Gastritis

• Associated neoplasm
• Gastric Adenosarcoma

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Tubercular Sclerosis

• Associated neoplasm
• Cardiac Rhabdomyolosis
• Astrocytoma

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Actinic Keratosis

• Associated neoplasm
• Squamous Cell Carcinoma of skin

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Barretts Esophagus

• Associated neoplasm
• Esophageal Adenocarcinoma

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Plummer Vinson, (atrophic glottitis, esophageal
webs)

• Associated neoplasm
• Squamous cell of esophagus

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Cirrhosis

• Associated neoplasm
• Hepatocellular Carcinoma
• Ulcerative Colitis

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Ulcerative Colitis

• Associated neoplasm
• Colonic adenosarcoma

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Pagets Disease of Bone

• Associated neoplasm
• Secondary osteosarcoma and fibrosarcoma

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Immunodeficiency States

• Associated neoplasm
• Malignant Lymphomas

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AIDS

• Associated neoplasm
• Non-Hodgkins and Karposis

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Autoimmune disease (Hashimotos, Myastenia Gravis)

• Associated neoplasm
• Benign and Malignant Thymomas

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ACANTHROSIS NIGRICANS

• Associated neoplasm
• VISCERAL MALIGNANCIES Lung, liver, Kidneys, Spleen

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Dysplastic Nevus

• Associated neoplasm
• Malignant Melenoma

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HNPCC

• Hereditary non-polyposis colerectal cancer is
  Autosomal Dominant
• Often happens before the age of 50 years
• 90 are a mismatch in repair of mutations during
  G2 phase of cell cycle
• Female relative are at risk for endometrial
  carcinomas

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ONCOGENES
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ONCOGENES

• GENE ASSOCIATED TUMOR
• C-myc Burkitts Lymphoma
• Bcl-2 Follicular And Undiff Lymphoma
• Erb-B2 Breast, Ovarian, Gastric
• Ras Colon

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Tumor Suppressor Genes

• Gene Chromosome Tumor
• Rb 13b Retinoblastoma
• BRCA-1/2 17q, 13q Breast/Ovarian
• P53 17p Most Human Cancers

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Tumor Markers

• PSA Prostatic CA
• CEA Carcinogenic Antigen
• Very non-specific
• AFP Hepatocellular Carcinomas, Germ Cell of
  testis
• (Yolk sac tumors)
• B-hCG Hyaditaform Moles, Choriocarcinoma,
  Gestational Trophoblablastic tumors
• CA-125 Ovarian Malignant epithelial tumors
• S-100 Melanoma, neural tumors
• Alkaline Phosphatase Pagets
• Tumor markers should not be used to diagnose. May
  be used to confirm diagnosis

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ONCOGENIC VIRUSES

• Virus Associated Cancers
• HTLV-1 Adult T-Cell Leukemia
• HBV, HCV Hepatocellular CA
• EBV Burkitts
• HPV Cervical CA (1618)
• HHV-8 Kaposis

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CHEMICAL CARCINOGENS
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ARSENIC

• SKIN (SQUAMOUS CELL CA)
• LUNG CA
• HEMANGIOSARCOMA
• By product of metal smelting, components of
  alloys, semiconductor devices, herbicides and
  fungicides

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ASBESTOS

• Lung CA
• MESOTHELIOMA
• GI TRACT
• Formally used for the applications because of
  fire, heat, friction resistance. Also used in
  roofing, floor tiles, and brake linings

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BENZENE

• Leukemia
• Hodgkins Disease
• Principle component of light oil. Used in
  lithography and printing. Dry cleaning,
  adhesives, coatings and paints. Used as a very
  strong solvent.

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BERYLLIUM

• Lung CA
• Missile Fuel and space vehicles
• Increased incidence on the east coast of Florida

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CADMIUM

• Prostate
• Found in Soldiers. Used as a phosphor. Also used
  in batteries and metal plating.

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CHROMIUM COMPOUNDS

• Lung
• Component of metal alloys, paints and pigments

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ETHYLENE OXIDE

• Leukemia
• Ripening agent for nuts and fruits. Sterilizes
  hospital equipment

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NICKLE

• Nose
• Lung
• Nickle plating, Component of ferrous alloys,
  ceramics, and batteries
• Stainless steel arch welding

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NITROSAMINES

• Esophageal
• Stomach

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RADON

• Lung
• From decay of minerals containing uranium. Can be
  serious in quarries and mines.

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VINYL CHLORIDE

• ANGIOSARCOMA
• Refrigerant

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CCL4

• LIVER-------CENTROLOBAR NECROSIS

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SKIN CANCER
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Squamous Cell Carcinoma

• Very common.
• Associated with excessive exposure to sunlight
  and arsenic
• Locally invasive
• Rarely Metastisizes
• KERATIN PEARLS
• Actinic Keratosis is a pre-cursor

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Basal Cell Carcinoma

• Most common in
• SUN EXPOSED areas of the body
• Almost never metastasizes

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Melanoma

• Common tumor with significant METS
• FAIR SKINNED INCREASED RISK
• INCREASE IN DEPTH CORRELATES WITH GREATER
  METASTASIS
• NOTE Dysplastic Nevus is a precusor to Melanoma

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PRIMARY BONE TUMORS

• Benign
• Malignant

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BENIGN BONE TUMOR

• Osteochondroma
• MOST COMMON BENIGN TUMOR OF BONE
• Giant Cell Tumor
• MOST COMMON AT EPIPHYSEAL JUNCTION

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Malignant Bone Tumor

• OSTEOSARCOMA-
• MOST COMMON MALIGANT TUMOR OF BONE
• Ewings Sarcoma
• ANAPLASTIC SMALL CELL TUMOR
• BOYS lt 15YO
• Chondrosarcoma
• 30-60YO
• FLAT BONES
• TIBIA
• HUMEROUS

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Primary Brain Tumors

• Adults Peak Incidence

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Meningioma

• 2nd Most Common 1 brain tumor
• Most often occurs in the convex of hemispheres
• Arises from arachnoid cells external to brain
• Psammoma bodies (whorled)

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Glioblastoma Multiform (grade IV astrocytoma)

• MOST COMMON 1 Brain Tumor
• Prognosis VERY POOR
• lt 1 year life expectancy
• Found in Cerebral Hemisphere
• Pseudopalisading tumor cells

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Oligidendrogliomas

• RELATIVELY RARE
• SLOW GROWING
• FRONTAL LOBES
• Fried Egg appearance, Calcified often

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Schwannomas

• 3rd MOST Common
• Acoustic Swannomma
• Swann cells near 8th CN
• Found in NF 2 (Neurofibromatosis 2)
• ANTONI A-Compact Palasading
• ANTONI B-Loose Pattern

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Pituitary Adenoma

• PROLACTIN SECRETING-Most Common
• Bitemporal Hempaniopia (due to pressure in optic
  chiasma)
• Hypopituitarism
• Derive from Rathkes Pouch

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Primary Brain Tumors

• Children Peak Incidence

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Medulloblastoma

• Highly Malignant Cerebellar Tumor
• A form of Primitive Neuroectoderm
• Can compress 4th Ventricle (causing
  hydrocephalus)
• Rosettes or Perivascular Pseudorosettes

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Hemagioblastoma

• Most Often Cerebellar
• Associated with von Hipple-Lindau when found with
  Retinoblastoma
• Foamy cells with high vascularity are
  characteristic
• Can Produce EPO-?2 polycythmia

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Ependymomas

• Most common in 4th Ventricle
• Causing Hydrocephalus
• perivascular rosette pattern
• Rod shaped blepharoblast near nucleus

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Low-grade Astrocytoma

• Diffuse infiltrating glioma
• Most often found near posterior fossa

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Craniopharyngioma

• Confused with pituitary adenoma
• Benign
• Calcifacation is common
• Derived from Rathkes Pouch Remnants

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METS to BRAIN

• Lung
• Breast
• Skin
• Kidneys
• Glia
• Lots of Bad Stuff Kills Glia

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METS to Liver

• Colon
• Stomach
• Pancreas
• Breast
• Lung
• Cancer Sometimes Penetrates Benign Liver

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METS to Bone

• Breast
• Lung
• Thyroid
• Testis
• Kidney
• Prostate
• Very Common
• METS from Breast and Prostate Common

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GROWTH FACTORS

• PDGF-B-Chain
• Protooncogene
• sis - overexpression
• Astrocytomas
• Osteosarcomas

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GROWTH FACTORS

• Fibroblast Growth Factors
• Protooncogene
• Hst-1 over expression
• STOMACH CANCER
• Int-2 Amplification
• Bladder Cancer
• Breast Cancer
• Melanoma

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GROWTH FACTORS RECEPTORS

• EGF-Receptor Family
• Erb-B1---Overexpression
• Squamous Cell Carcinoma of lung
• Erb-B2---Amplification
• Breast, Ovary, Lung, Stomach
• Erb-B3---Overexpression
• Breast Cancer

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GROWTH FACTORS RECEPTORS

• FmsPoint Mutation-?leukemia
• Ret---Multiple Endocrine Neoplasm 2A and 2B (MEN
  TYPE II)
• Familiar medullary thyroid carcinoma

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Proteins Involved in Signal Tranduction

• GTP-binding
• RAS? Point Mutation
• A variety of human cancers

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Proteins Involved in Signal Tranduction

• Non-receptor Tyrosine Kinase
• Abl?Translocation
• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

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Nuclear Regulatory Proteins

• Myc--? Translocation
• BURKITTS

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Nuclear Regulatory Proteins

• N-Myc--?Amplification
• Small cell carcinoma
• Lymphoblastoma

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Cell Cycle Regulators

• CYCLINS
• Cyclin D ?translocation? Mantle cell
• Cyclin D? Amplification? Breast, liver,
  esophageal

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Cell Cycle Regulators

• Cyclin Dependant Kinase
• CDK 4 amplification/point mutation
• Glioblastoma, Melanoma, Sarcoma

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Chronic Myeloid Leukemia

• ( 9 22)
• Philadelphia Chromosome

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Acute Leukemias (ALL AML)

• (411)

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Burkitts Lymphoma

• (814)

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Mantle Cell Lymphoma

• (1114)

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Follicular Lymphoma

• (1418)

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T-Cell Lymphoblastic Leukemia

• (814)
• (1014)

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E-Wings Sarcoma

• (1122)

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Melanoma of Soft Parts

• (1222)

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TUMOR SUPPRESSORS

• Cell Surface
• TGF-B receptor
• Colon
• E-Cadherins
• Stomach
• Breast

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TUMOR SUPPRESSORS

• NF-1
• Inhibits RAS
• SWANNOMMAS

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TUMOR SUPPRESSORS

• NF-2
• NF TYPE 2, Menengiomas

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TUMOR SUPPRESSORS

• CYTOSOL
• Rb-----------cell cycle----retinoblastoma
• P53-----cell cycle----- Li Fraumeni Syndrome
• WT-1---Nuclear Transcript----Wilms Tumor
• p-16-----Regulation CDK---Melenomas
• BRCA-1----DNA Repair---Female Breast
• BRCA-2----DNA Repair--- Male/Female Breast