General Pathology (DENF 2701) Topic: Neoplasia

General Pathology (DENF 2701)General Pathology (DENF 2701)

Topic: NeoplasiaTopic: Neoplasia

Fall, 2004; Wednesdays, 10:00-12:00 am; Room 132Fall, 2004; Wednesdays, 10:00-12:00 am; Room 132Course Director: Dr. Jerry BouquotCourse Director: Dr. Jerry Bouquot

Room 3.094B; 713-500-4406; 713-520-1250 (home)Room 3.094B; 713-500-4406; 713-520-1250 (home)

NeoplasiaNeoplasia“New Growth”; From Latin Word for Crab“New Growth”; From Latin Word for Crab

Cancer: Neoplasms are not controlled by the body– Continue to replicate indefinitely– Tumors may flourish, even while the host is wasting away– Cancers induce increased blood supply

Cancer: 2nd leading cause of US deaths-- After cardiovascular disease

Oncology = study of tumors (“oncos” = tumor, “logos” = study of) -- Oncologist = physician who treats cancer exclusively

– Hemoncologist = specializes in leukemias, lymphomas, etc. -- Hematologist = blood doctor, treats leukemias, lymphomas, etc.

– Surgical oncologist; Radiation oncologist Typically monoclonal Malignant (cancers): invade, destroy, metastasize (distant spread) Benign: nonmalignant neoplasm; add suffix “-oma”

Features of NeoplasmsFeatures of NeoplasmsBenign v. MalignantBenign v. Malignant

BenignantBenignant MalignantMalignant

Rate of growthRate of growth SlowSlow RapidRapid

Type of growthType of growth Expansile onlyExpansile only Expansile and/or invasiveExpansile and/or invasive

Similarity to original Similarity to original tissue/cellstissue/cells

Very similarVery similar Not similarNot similar

Uniformity of cellsUniformity of cells UniformUniform Cells vary in shape Cells vary in shape (pleomorphic) and size(pleomorphic) and size

Mitotic rateMitotic rate Low (few mitoses)Low (few mitoses) Medium to high (many Medium to high (many mitoses), may be abnormal mitoses), may be abnormal or in abnormal locationor in abnormal location

Nuclear/cytoplasmic ratioNuclear/cytoplasmic ratio NormalNormal HighHigh

NucleiNuclei Normal, uniformNormal, uniform Enlarged, pleomorphic, Enlarged, pleomorphic, dark (hyperchromatic)dark (hyperchromatic)

NeoplasiaNeoplasiaBenign v. MalignantBenign v. Malignant

Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003; Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995..

LeiomyomaLeiomyomaBenign Smooth Muscle Benign Smooth Muscle

NeoplasmNeoplasm

NeoplasmsNeoplasmsBenign v. MalignantBenign v. Malignant

Photo: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

Thyroid AdenomaThyroid Adenoma

Breast AdenocarcinomaBreast Adenocarcinoma

Breast AdenocarcinomaBreast Adenocarcinoma

Tumor NamesTumor Names

Tissue of OriginTissue of Origin BenignBenign MalignantMalignant

FibrousFibrous FibromaFibroma FibrosarcomaFibrosarcoma

BoneBone OsteomaOsteoma OsteosarcomaOsteosarcoma

CartilageCartilage ChondromaChondroma ChondrosarcomaChondrosarcoma

AdiposeAdipose LipomaLipoma LiposarcomaLiposarcoma

NerveNerve NeurofibromaNeurofibroma NeurofibrosarcomaNeurofibrosarcoma

Smooth muscleSmooth muscle LeiomyomaLeiomyoma LeiomyosarcomaLeiomyosarcoma

Skeletal muscleSkeletal muscle RhabdomyomaRhabdomyoma RhabdomyosarcomaRhabdomyosarcoma

GlandGland AdenomaAdenoma AdenocarcinomaAdenocarcinoma

Squamous Squamous epitheliumepithelium PapillomaPapilloma Squamous cell carcinomaSquamous cell carcinoma

MelanocyteMelanocyte Nevocellular nevusNevocellular nevus Malignant melanomaMalignant melanoma

LymphoidLymphoid Lymphoid hyperplasiaLymphoid hyperplasia LymphomaLymphoma

Well differentiated: cells look mature and similar to original cells-- Grade I = cells are well differentiated-- Grades II and III: moderately differentiated--Grade IV = poorly differentiated

Not very good at prognosis

Poorly differentiated: cells look immature and irregular-- Grade IV; high grade-- Often means worse prognosis

More mature or differentiated cells retain function– e.g. squamous cell carcinoma makes keratin (keratin pearls, epithelial pearls)-- e.g. mucoepidermoid carcinoma makes mucus (mucin)

NeoplasiaNeoplasiaDifferentiation of Cells/TissueDifferentiation of Cells/Tissue

NeoplasiaNeoplasiaDifferentiation of Cells/TissueDifferentiation of Cells/Tissue

Anaplasia (“to form backwards”): very undifferentiated-- Primitive cells

Stem cells of some tumors undergo divergent differentiation – e.g. pleomorphic adenoma (mixed tumor) of salivary glands – e.g. fibroadenoma of breast

Certain tumors induce stromal change (not differentiation)-- Fibrosis (desmoplasia)-- New vessels (angiogenesis)

Squamous Cell CarcinomaSquamous Cell CarcinomaMicroscopic GradingMicroscopic Grading

Grade IGrade I Grade IIIGrade III

Grade IIGrade II Grade IVGrade IV

Loss of Differentiation & MaturityLoss of Differentiation & Maturity

Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995.

Benign neoplasm of colon

Well differentiated adenocarcinoma of colon

Loss of DifferentiationLoss of Differentiation


Poorly differentiated adenocarcinoma of

colon

Anaplastic carcinoma of colon

Signs of DysplasiaSigns of DysplasiaNot Necessarily Associated with CancerNot Necessarily Associated with Cancer

Pleomorphic (abnormal shape) -- Cells and/or nuclei Enlargement...cells or nuclei Reduced cytoplasmic/nuclear ratio

-- Large nucleus compared to cell size-- 1:1 vs. 1:4 - 1:6 for normal

Hyperchromatic nuclei-- Chromatin is course, clumped

Increased mitotic rate -- Numerous mitotic figures Bizarre mitoses: abnormal shape

-- e.g. tripolar/quadripolar mitoses-- e.g. abnormal location

Signs of DysplasiaSigns of DysplasiaNot Necessarily Associated with CancerNot Necessarily Associated with Cancer

Lack of cohesion (detached cells) Prominent, perhaps multiple nucleoli Loss of polarity (no orientation) Bizarre cells

Problem: some dysplasias are not related to cancere.g. Developmental anomalies

Bone dysplasias

Problem: not all dysplasias progress to malignancy (precancer)

Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003.

The Dysplastic CellThe Dysplastic Cell

Photo: J. Bouquot. Pract Perio Aesth Dent, 1995.

Extra Credit QuestionExtra Credit Question

Melanoma is a malignancy of which of the following cells?Melanoma is a malignancy of which of the following cells?

A.A. FibroblastFibroblast

B.B. OsteoblastOsteoblast

C.C. MelanocyteMelanocyte

D.D. Nevus cellNevus cell

E.E. Smooth muscle cellSmooth muscle cell

TeratomaTeratomaA Type of Neoplasm as Well as Developmental AnomalyA Type of Neoplasm as Well as Developmental Anomaly

Usually congenital More than one germ-cell type From multipotential cells

-- Therefore usually found in ovary or testis Usually helter-skelter mix of tissue types

-- May be so mature that small “babies” develop May be benign or malignant Not a hamartoma (mass of disorganized tissue indigenous to the

site) Not a choristoma (congenital anomaly, a heterotopic rest of cells) Cervical teratoma is usually fatal

-- Because it presses on vessels, airways, esophagus

Ovarian TeratomaOvarian Teratoma

Cervical TeratomaCervical Teratoma

Pituitary TeratomaPituitary TeratomaWith TeethWith Teeth

Photo: Dr. J. Bouquot, West Virginia University, Morgantown, West Virginia

Pituitary TeratomaPituitary Teratoma

NeoplasiaNeoplasiaInvasionInvasion

One of two things that most clearly separate benign from cancer– Exceptions: Basal cell carcinoma (skin) Verrucous carcinoma (mouth) Prostate carcinoma-- Exceptions: Hemangioma Lymphangioma Lipoma

Not all benign neoplasms are encapsulated-- Usually a well-defined cleavage plane

After the ability to metastasize, the ability to invade is the most reliable feature of malignancy

Photos: P. Morgan, Guys Hospital, London, England; J. Bouquot, West Virginia University, Morgantown, West Virginia.

Cuniculatum (Verrucous?) Cuniculatum (Verrucous?) CarcinomaCarcinoma

HemangiomaHemangioma

Carcinoma Carcinoma in situin situTop-to-Bottom DysplasiaTop-to-Bottom Dysplasia

Photos: Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003.

Severe DysplasiaSevere Dysplasia

Local InvasionLocal InvasionColonic adenocarcinoma (left) invades into muscle (right)Colonic adenocarcinoma (left) invades into muscle (right)


NeoplasiaNeoplasiaMetastasisMetastasis

Secondary implants of cancer cells separate from 10 tumor The most unique thing about malignancy (v. benignancy) Carcinomas spread via lymphatics to local lymph nodes

– Oral cancer: cervical enlarged, firm, fixed (perhaps matted) lymph nodes

– Breast cancer (usually is in upper outer quadrant): axillary lymph node involvement (perhaps with lymphedema)– Lung cancer: bronchial lymph node involvement

Usually ipsilateral (on same side of body) node-- May be contralateral (opposite side of body)

Sarcomas spread via blood stream-- Therefore: pulmonary mets usually

Usually metastasis is from long-standing, large cancers-- There are exceptions!!

Cellular Events Needed for MetastasisCellular Events Needed for Metastasis


Local Lymphatic InvasionLocal Lymphatic InvasionPara-Aortic Lymph NodesPara-Aortic Lymph Nodes


Main Routes of Tumor SpreadMain Routes of Tumor SpreadCarcinoma of the LungCarcinoma of the Lung


Hilar Lymph NodesHilar Lymph Nodes(cancer = white deposits(cancer = white deposits

Most Common Sites of Distant MetastasisMost Common Sites of Distant Metastasis

Photos: Stevens A, Lowe J. Slide atlas of pathology. Mosby, London, 1995; Kumar, Cotran, Robbins. Robbins Basic pathology, 7th ed., Saunders, Philadelphia, 2003. .

Liver MetastasesLiver Metastases

Epidemiologic TermsEpidemiologic Terms

Incidence rate: number of newly diagnosed cancers/year

Mortality rate: number of patients dying from cancer/year

Prevalence rate: number of cancers diagnosed in a certain population at a given point in time (point prevalence)

Relative frequency rate: proportion of all cancers represented by an individual cancer

Epidemiologic studies (case-control studies, differences in incidence between groups, etc.) are the best “proof” of etiology (cause), but they are very expensive and time-consuming

Incidence of CancerIncidence of CancerMore than 100 Different Types of CancerMore than 100 Different Types of Cancer

Photo: Kumar, Cotran, Robbins. Robbins Basic pathology, 7 th ed., Saunders, Philadelphia, 2003.

CancerCancerAge as an Etiologic FactorAge as an Etiologic Factor

Frequency of cancer generally increases with age Cancers are constantly arising in our bodies, but our immune system

kills them off With increasing age: -- Less effective immune system

-- Less controlled cell division (more mutations)-- More exposure to carcinogens

Young age = sarcomas; old age = carcinomas The major cancer deaths in children under 15 years of age:

-- Leukemia-- CNS tumors-- Lymphomas-- Soft tissue sarcomas-- Bone sarcomas

Cancer Risk Increases with AgeCancer Risk Increases with AgeLong-term exposure & less effective immune systemLong-term exposure & less effective immune system


Trends in Cancer IncidenceTrends in Cancer Incidence1930 - 20001930 - 2000


Oral CancerOral CancerAge- & Gender-Specific Incidence RatesAge- & Gender-Specific Incidence Rates

Photo: Neville, et al. Oral and maxillofacial pathology, 2002.

CancerCancerHereditary FactorsHereditary Factors

Hereditary predisposition toward cancer development is common Inherited cancer syndromes

-- 5-10% of cancers-- Often have specific molecular markers

Familial retinoblastoma: autosomal dominant (AD)-- 40% are familial-- 10,000x more risk

Familial adenomatous polyposis (FAP) of colon (AD)-- Gardner’s syndrome also has jaw osteomas

Colon cancer (other than FAP): familial

CancerCancerHereditary FactorsHereditary Factors

Multiple endocrine neoplasia (MEN) syndrome (AD) Neurofibromatosis types 1 and 2 (AD) Breast cancer: familial; BRCA gene Ovarian cancer: familial Xeroderma pigmentosum: autosomal recessive (AR) Ataxia telangiectasia: AR Bloom syndrome: AR Fanconi anemia: AR

Inherited Syndromes Associated with CancerInherited Syndromes Associated with CancerAssociated Genetic DefectAssociated Genetic Defect

SyndromeSyndrome TumorTumor Genetic DefectGenetic Defect

Multiple endocrine Multiple endocrine neoplasia syndrome neoplasia syndrome (MEN)(MEN)

Tumors of endocrine Tumors of endocrine organsorgans

Mutation, chromosomes Mutation, chromosomes 10 & 1110 & 11

Polyposis coliPolyposis coli Adenomas and Adenomas and adenocarcinomas of adenocarcinomas of coloncolon

Absent tumor Absent tumor suppressor genesuppressor gene

Li-FraumeniLi-Fraumeni Breast carcinoma and Breast carcinoma and sarcomassarcomas

Mutated tumor Mutated tumor suppressor genesuppressor gene

Xeroderma pigmentosumXeroderma pigmentosum Skin carcinomaSkin carcinoma Abnormal DNA repairAbnormal DNA repair

Familial retinoblastomaFamilial retinoblastoma RetinoblastomaRetinoblastoma Absent tumor Absent tumor suppressor genesuppressor gene

Neurofibromatosis, type INeurofibromatosis, type I Neuroma, Neuroma, neurofibroma, neurofibroma, neurofibrosarcomaneurofibrosarcoma

Abnormal tumor Abnormal tumor suppressor genesuppressor gene

Genetically Associated CancersGenetically Associated CancersThe cancer may not be in the mouthThe cancer may not be in the mouth

.

MEN (Multiple Endocrine Neoplasia) IIB or III. Painless yellow-white nodules of the tongue.

Photo: ESTOP.

Acanthosis nigricans Ataxia-Telangiectasia Cowden syndrome Dyskeratosis congenita Gardner’s syndrome Gorlin syndrome (nevoid basal cell carcinoma syndrome) Mucosal neuroma syndrome (MEN IIB, MEN III) Neurofibromatosis Peutz-Jeghers syndrome Trisomy 21 (Downs syndrome) Tuberous sclerosis Xeroderma pigmentosum

Progression of Progression of CancerCancer

PathogenesisPathogenesis


Cancer PhenotypesCancer PhenotypesGenetic RequirementsGenetic Requirements

Self-sufficiency (promotes cell growth without signals)-- Mutated protooncogenes >> oncogenes >> oncoproteins (not regulated)

Cancer cells produce the same growth factors which influence them Cancer cells create excess receptors to these growth factors

-- e.g. excess epidermal growth factor receptors are in 80% of squamous cell carcinomas of lungs

Example: Overexpression of MYC protooncogene-- MYC is in nucleus of all cells-- When overexpressed: increased cyclin-dependent kinases (CDKs) to move cell cycle into an active phase (especially G1 to S)

Example: Mutation of RAS gene--Most common oncogene abnormality in tumors (30%)-- Cell is told to continue to proliferate



Insensitivity to growth-inhibitory signals– TP53 (p53) tumor suppressor gene: exerts antiproliferation effects,

regulates DNA-damage repair, regulates apoptosis; affected by stress

-- TP53 is one of the most common mutations in cancers

Evasion of apoptosis

Limitless replicative potential– Telomere length maintenance is seen in virtually all cancers

Oncogenes in Neoplastic Oncogenes in Neoplastic TransformationTransformation



Increased Expression of Growth Increased Expression of Growth Factor ReceptorsFactor Receptors

Mutation in Transducer Protein GeneMutation in Transducer Protein Gene



Mutant Transcription Factor Mutant Transcription Factor ProductionProduction

Over-Production of Factors that Prevent Cell DeathOver-Production of Factors that Prevent Cell Death




Development of sustained angiogenesis– Cannot metastasize without angiogenesis– When the angiogenic switch is turned on:

cancer proliferations and then metastasis

Ability to invade and metastasize-- Tumor cells must detach from themselves, attach to stroma >> degrade/destroy the stroma (via metalloproteinases) >> migrate

Some tumors show organ tropism (metastases favor certain organs)-- Related to adhesion molecules and receptors

Karyotype Changes in CancerKaryotype Changes in Cancer

Balanced translocations-- Philadelphia chromosome (chronic myelogenous leukemia) -- Usually 22 & 9-- Burkitt lymphoma (usually 8 & 14)-- Follicular B-cell lymphoma (usually 14 & 18)

Deletions (more common in solid tumors)-- Retinoblastoma (13q)-- Colorectal carcinoma (17p, 5q, 18q)

3. Gene amplification-- neuroblastoma-- Breast cancer (N-MYC and HER-2 genes)

CarcinogenesisCarcinogenesis

Major problem: nonlethal genetic damage or mutations Probably “cause” 65% of all cancers

-- Heredity is “cause” of 26-40%

Carcinogens:-- Chemical-- Radiant energy-- Microbial agents

Carcinogenesis is a multistep phenomenon (tumor progression)– Involves genes regulating DNA repair, angiogenesis, invasion, metastasis

CarcinogenesisCarcinogenesis

Three classes of regulatory genes are the main targets:

1) Protooncogenes (promote growth) -- Mutant alleles = oncogenes (dominant genes)

2) Antioncogenes (growth-inhibiting cancer suppressor genes) -- Tumor suppressor genes -- Both alleles must be damaged (recessive oncogenes)

3) Genes controlling apoptosis (programmed cell death)

DNA repair genes affect cell proliferation and survival-- If disabled: widespread mutations


CarcinogenesisCarcinogenesisIonizing RadiationIonizing Radiation


Human Papillomaviruses in Oral LesionsHuman Papillomaviruses in Oral Lesions24 genotypes have been isolated from oral lesions & mucosa24 genotypes have been isolated from oral lesions & mucosa

Lesion Genotype(s) *

Normal mucosaNormal mucosa 6, 7, 11, 16, 18, 31, 33, etc.

Verruca vulgaris (common wart)Verruca vulgaris (common wart) 2 a – e2 a – e, , 4, 6, 40

Papilloma (squamous papilloma)Papilloma (squamous papilloma) 6 a – f6 a – f, 11 a, b , 11 a, b

Condyloma acuminatumCondyloma acuminatum 2,2, 66, , 11 a, b11 a, b, 16, 18, 53, 54, 16, 18, 53, 54

Focal epithelial hyperplasia (Heck’s disease)Focal epithelial hyperplasia (Heck’s disease) 1313, 32, 32

Smokeless tobacco keratosisSmokeless tobacco keratosis 2, 62, 6

Leukoplakia, no dysplasiaLeukoplakia, no dysplasia 2, 6,11,16,18

Leukoplakia with epithelial (koilocytic) dysplasiaLeukoplakia with epithelial (koilocytic) dysplasia 2, 6, 11, 16, 18, 31, 33, 35

Carcinoma in situ 2, 6, 11, 16, 18, 31, 33, 35

KeratoacanthomaKeratoacanthoma 26, 3726, 37

Verrucous carcinoma Verrucous carcinoma 2 a – e, 2 a – e, 6, 11, 16, 18

Squamous cell carcinomaSquamous cell carcinoma 16, 18, 31, 33, 35

* genotypes in bold yellow are isolated in at least 1/3 of all cases with HPV

Herpes simplex virus was a red herring?

CarcinogenesisCarcinogenesisViruses Implicated in Human NeoplasiaViruses Implicated in Human Neoplasia

VirusVirus NeoplasmNeoplasm

Epstein-Barr virus (EBV)Epstein-Barr virus (EBV)

Burkitt’s lymphomaBurkitt’s lymphoma

Nasopharyngeal carcinomaNasopharyngeal carcinoma

Some B-cell lymphomasSome B-cell lymphomas

Some Hodgkin’s diseaseSome Hodgkin’s disease

Hepatitis B virus (HBV)Hepatitis B virus (HBV) Hepatocellular carcinomaHepatocellular carcinoma

Human papillomavirus (HPV)Human papillomavirus (HPV) Cervical carcinomaCervical carcinoma

Human papillomavirus (HPV)Human papillomavirus (HPV)Some skin carcinomasSome skin carcinomas

Some oral and laryngeal Some oral and laryngeal carcinomascarcinomas

HTLV-1HTLV-1 T-cell leukemia/lymphomaT-cell leukemia/lymphoma

NeoplasiaNeoplasiaEnvironmental Etiologic FactorsEnvironmental Etiologic Factors

Carcinogens (chemicals associated with cancer production):– Arsenic (lungs, skin, hemanigiosarcoma) -- e.g. smelting metals, fungicides– Asbestos (lungs, mesothelioma, GI tract) -- e.g. fire retardant, sound insulator – Benzene (leukemia, Hodgkin’s lymphoma) -- e.g. light oils, dry cleaning, solvents– Berylium (lungs) -- e.g.. rocket fuel, nuclear reactors– Cadmium (prostate) -- e.g. yellow dyes including food dyes, batteries

CarcinogenesisCarcinogenesisAssociated ChemicalsAssociated Chemicals

Chromium (lungs) e.g. preservative, metal alloys, pigments Ethylene oxide (leukemia) e.g. ripening of fruits & nuts; rocket fuels, fumigation, sterilizing Nickel (nose, lungs) e.g. metal plating and alloying, ceramics, batteries, stainless steel welding Radon (lungs) e.g. from decay of uranium, in quarries, mines, seeps into home basements Vinyl chloride (liver, angiosarcoma) e.g. refrigerant, monomer for vinyl polymers, plastic adhesive

Causes of Oral CarcinomaCauses of Oral Carcinoma

Tobacco smokingTobacco smoking Tobacco chewingTobacco chewing Betel/pan/areca chewingBetel/pan/areca chewing Alcohol abuseAlcohol abuse PrecancerPrecancer Plummer-Vinson disease Plummer-Vinson disease

(severe Fe deficiency) (severe Fe deficiency) Human papillomavirus 16/18Human papillomavirus 16/18 Chronic infection?Chronic infection? Syphilitic glossitisSyphilitic glossitis History of irradiationHistory of irradiation History of sun damage (lip)History of sun damage (lip) History of H&N carcinomaHistory of H&N carcinoma Increasing ageIncreasing age

The happy, toothless smoker

CancerCancerHost DefensesHost Defenses

Tumor elicits CD8+ cytotoxic T-cell response– e.g carcinoembryonic antigen (CEA)– e.g Oncogenic viruses (EBV, HPV)– e.g Prostate-specific antigen (PSA)

Antitumor effector mechanisms– Cytotoxic T lymphocytes (especially against virus-induced

cancers)– Natural Killer (NK) cells (don’t need prior sensitization; may be first line of defense)– Macrophages (once activated, exhibit selective cytotoxicity against tumor cells)– Humoral mechanisms from complement activation and induction of antibody-dependent cellular cytotoxicity by NK cells

Immunosurveillance– Without it: increased cancer risk (5% in congenitally immunosuppressed patients (usually lymphoma)

NeoplasiaNeoplasiaClinical FeaturesClinical Features

Typically a mass, with or without surface ulceration Compression on surrounding tissues Ulceration with bleeding May produce hormones (even if tumor is from tissue which normally

produces no hormones) Cachexia (wasting syndrome): progressive weight loss and

“wasting”– Usually terminates with fatal infection– Usually correlated with extent of tumor and metastasis– Anorexia is common– May be from TNF and IL-1 from activated macrophages– No good explanation for how this happens

Tumor MarkersTumor MarkersSome tumors create unique molecules -- may be used in diagnosisSome tumors create unique molecules -- may be used in diagnosis

MarkerMarker TumorTumor

Alpha fetoprotein (AFP)Alpha fetoprotein (AFP)Hepatocellular carcinomaHepatocellular carcinoma

Germ cell tumorsGerm cell tumors

Human chorionic gonadotrophin (HCG)Human chorionic gonadotrophin (HCG) Trophoblastic tumorsTrophoblastic tumors

Acid phosphataseAcid phosphatase Prostatic carcinomaProstatic carcinoma

Carcinoembryonic antigen (CEA)Carcinoembryonic antigen (CEA) Gastrointestinal carcinomaGastrointestinal carcinoma

HormonesHormones Endocrine tumorsEndocrine tumors

Precancers and Preneoplastic ConditionsPrecancers and Preneoplastic Conditions

Cancer development is NOT inevitable! Persistent regeneration -- Squamous cell carcinoma at edge of fistula or draining wound

e.g. osteomyelitis-- Hepatocarcinoma in cirrhosis of the liver e.g. alcoholism

Hyperplastic proliferations-- Endometrial carcinoma in atypical endometrial hyperplasia

Dysplastic proliferations-- Bronchogenic carcinoma in dysplastic bronchial mucosa e.g. cigarette smoking-- Colorectal carcinoma


Chronic atrophic gastritis-- Gastric carcinoma in pernicious anemia i.e. vitamin B12 deficiency

Chronic ulcerative colitis-- Colorectal carcinoma

Villous adenoma of colon-- Colorectal carcinoma

Leukoplakia of mouth, vulva, penis-- Squamous cell carcinoma

Precancers and Preneoplastic ConditionsPrecancers and Preneoplastic Conditions

Photo: E. Lalonde, West Virginia University, Morgantown, West Virginia.

Clinical Appearance MattersClinical Appearance MattersVerruciform Leukoplakia, Granular leukoplakia, Verrucous LeukoplakiaVerruciform Leukoplakia, Granular leukoplakia, Verrucous Leukoplakia

HyperkeratosisHyperkeratosisCarcinoma in situCarcinoma in situ

Photo: J. Pindborg, Univ. Copenhagen, Copenhagen, Denmark.

Photo (left): J. Pindborg, Royal College of Dentistry, Copenhagen, Denmark.

ErythroleukoplakiaErythroleukoplakiaSpeckled LeukoplakiaSpeckled Leukoplakia

Corrugated thick and thin leukoplakia of the oral floor andventral tongue, with pink areas surrounded by white.

Oral PrecancersOral PrecancersIncreased Risk (Not 100%!)Increased Risk (Not 100%!)

LeukoplakiaLeukoplakia ErythroplakiaErythroplakia Smokeless tobacco keratosisSmokeless tobacco keratosis Lichen planus (erosive)Lichen planus (erosive) Reverse smoker’s palateReverse smoker’s palate Oral submucous fibrosisOral submucous fibrosis Smooth, red tongue in Plummer-Smooth, red tongue in Plummer-

Vinson diseaseVinson disease Actinic cheilosisActinic cheilosis

Leukoplakia in syphilitic glossitisFrom: Schwimmer, 1876, Budapest

Paraneoplastic SyndromesParaneoplastic Syndromes

No good explanation for how this happens Hypercalcemia

-- Ttumor cells make parathyroid hormone-related protein (PTHrP) Cushing syndrome

-- Tumor cells make ACTH or ACTH-like peptides Nonbacterial thrombotic endocarditis

-- Hypercoagulability state induced by tumor cells Venous thrombosis -- Hypercoagulability Polycythemia

-- Tumor cells make erythropoietin

Staging of CancersStaging of CancersClinical ClassificationClinical Classification

Stage shows severity of clinical features of the tumor Usually staged without sophisticated imaging technologies

-- This may change soon Stage I = small, localized tumor Stage IV = huge or metastatic tumor Not bad at forming prognosis

-- Stage I is good-- Stage IV is very bad

TNM staging system:– T = tumor size, in cm.– N = presence of tumor in local/regional lymph nodes– M = presence of tumor at a distant site (beyond local lymph nodes; e.g. “below the clavicles”)

Tables used to establish the stage, combining the TNM evaluations

The TNM Staging SystemThe TNM Staging System


Tumor size:Tumor size:T0 = no tumorT1 = <2 cm. in sizeT2 = 2-4 cm. in sizeT3 = >4 cm. in size

Lymph node involvement:Lymph node involvement:N0 = no positive nodesN1 = few ipsilateral nodesN2 = many ipsilateral nodes or contralateral nodes

Distant metastasis:Distant metastasis:M0 = no metastasisM1 = metastasis below the clavicleMx = suspected metastasis

Prognosis Varies with Cancer SitePrognosis Varies with Cancer Site5-Year Survival Rates5-Year Survival Rates


CancerCancerOnce Uniformly LethalOnce Uniformly Lethal

Adenocarcinoma at autopsy, circa 1856

1900: <5% survival 1945: 20% survival 1986: 50% survival 2003: 63% survival ACS 2015 goal: 50% reduction in mortality rates ACS 2015 goal: 25% reduction in incidence rates How: prevention, early detection, quality management, research

General Pathology (DENF 2701) Topic: Neoplasia

Documents

Transcript of General Pathology (DENF 2701) Topic: Neoplasia