l Neoplasm A

8/12/2019 l Neoplasm A

1/90


2/90

NON-NEOPLASTIC PROLIFERATION

H M Nadjib Dahlan Lubis

Bag.Patologi Anatomi

Fak Kedokteran USU/UISU Medan


3/90

Control of GrowthNet balance: - Proliferation Proto-oncogen

- Differentiation Death

Abnormal Growth

Atrophy: size: tissue, organ size, number- normally formed

- distinct from: agenesis, aplasia, hypoplasia (abn

organ development)

Hypertrophy: size size of individula cells

Hyperplasia: size number of component cells


4/90

Causes of Atrophy-

cytoplasm,

number of organelles

Types

Disuse - Immobilized skletal muscle & bone: - cast

- bed restBone: Reabs > formation size trabecuae

osteoporosis

Denervation damage to lower motor neuron

Loss of trohic hormon: Endometrium, breast, endocrine

Lack of nutrients Protein-calorie malnutrition (marasmus)Ischemia: Cereb Vasc dis Cereb atrophy

Senile: brain, heart ischemia

Pressure: spinal cord, vertebrae neop spinal canal


5/90

Causes of Hypertrophy & Hyperplasia

- Phy: cardiac demand

- Path: - stimulus of demand (-)

- - Myocardian hypertrophy: Hypertension, valv, cong HD (-)

- - Endometrial hyperplasia estrogen (near menopause)

- - Bilat adr hyperplasia ACTH

- - Thyroid: Graves dis TSH auto Ab + TSH rec

- - Prostate Androgen


6/90

Hypertrophy


7/90


8/90

Metaplasia = abn cell diff: mature cells is replaced by diff type of mature

cell (not normal for the tiss involved)

Reversible, most common: epithelium: potential for diff in stem

cell chronic physical, chemical irritation

Squamous Metaplasia= Nonsqu pse str coll / cuboid squ epithelium

Loc: - Endocervix

- Bronchial mucosa

- Endometrium, urinary bladder


9/90

Mucous secreting Squamous Fibrous Bone


10/90

Glandular Metaplasia Esophagus: squamous glandular, mucus secreting acid

reflux

Stomach, intestine: gastric mucosa intestinal mucosa

(intestinal metaplasia vice versa (gastric metaplasia)

Ovary: serous & mucinous cyst

Mesenchym: scar, fibroblastic prolif osseous metaplasia

Clinical Significance

Little

Loss of cilia & mucus (bronchi) predispose: infection

No increased risk cancer

However: dysplastic changes (often present) cancer :

SCC in bronchus

Adenoca in esophagus


11/90


12/90


13/90


14/90

Dysplasia= Abn of differentiation & maturation

A. Nuclear

- size nucleus: - absolute

- relative: to cyto (N/C ratio- Hyperchromatism ( chromatine content)- Abn chr distribution (coarse clumping)

- Nuc memb irregularities: thickening, wrinkling

B. Cytoplasmic

Failure of normal diff: - lack of keratinization in squ cells

- lack of mucin in gl epit


15/90

C. Rate of cell multiplication- mitotic in many layer (N: mitotic in basal layer)- Individual mitoses: N

D. Disordered Maturation

- Retain resemblance to basal stem cells as move upward

- Keratin production: fail

Grading - Mild

- Moderate- Severe


16/90

SignificancePremalignant one step short of cancer

= Cervical Intraepithelial Neoplasia (CIN)

Carcinoma in situ (CIS) is included in CIN, however:

- True neoplasm with all of features of malignant exc invasiveness

SevereDysplasia = CIS : - Clinical significance

- Treatment

Riskof dysplasia to develope invasive cancer

- Grade

- Duration

- Site


17/90

Differences: Dysplasia & CancerInvasiveness

Dysplasia & CIS: - do not invade BM

- do not spread cb lymphatics (-), bl ves (-)

Cancer: invade BM

spread lymphatic, bl ves excision

Reversibility

Dysplasia: - may return to normal

- severe dysp may be irreversible

Cancer: irreversible,


18/90


19/90

Microscopic exam

Cytology must be confirmed by biopsy

Nuclear & cytoplasmic features diag & grading

Well established: - cervix

- urinary bladder

- lung

Other sites: GIT, Breast: difficult infl & regeneration

atypia

Papanicolaou: - early detection & therapy of cervical dysplasia

- cancer of cervix past 20 years


20/90

NEOPLASTIC

PROLIFERATION


21/90

Neoplasia (New growth)Abn of cell diff, maturation, & control of growth

Formation of masses of abnor tissue (tumors)

Tumor applied to any swelling, now: suspected neoplasm

Benign/Malignant ? Depend on spread.

Benign remain localized

Cancer = Mal neo, grips surrounding (claw like crab)

Rupert Willis (1950s): Abn mass of tiss, growth exceeds,

uncoordinated, persist after cessation o/t stimuli


22/90

Biologic Behavior 2 extremes

Benign: - grow slowly, do not invade surr or spread

- rarely live threatening

so: - hormon secr

- critical location: cranial nerve & compress med

Malignant: - grow rapidly

- infiltrate & destroy surr, metastasize lethal

Intermediate: - locally invasive, low metastatic potential

- called locally aggressive neo ( low-grade neo): BCC


23/90

Basis for Classification

Site

Biologic behavior

Cell (tissue) of origin (histogenetic Classification) Embryologic derivation

Differentiation potential of cell of origin

Etilogy

Gross or microscopic feature


24/90

Prediction of Biol Behavior by Path. ExamTreatment: based on biol behavior

Benign: excision

Locally aggressive: excising + wide margin

Malignant: - local wide removal

- freg + reg LN

- + systemic treatment for met neo cells

Pathologist Ben/Mal ? : - Hist & Cyto feature

- Cumulative clinicopath of neo. Type

- No absolute criteria


25/90

Benign MalignantGross Smooth surface

Fibrotic cap

Compressed surr

Irregular surface

Encaps (-)

Destruct surr

Size Small to largeVery large

Small to large

Growth Slow Rapid

Fatal Rarely Fatal: untreated


26/90

Benign MalignantGrowth Compression Invasion

Differentiation

Resembling to normal

tiss of orig

High

+

Well/poor

- (anaplasia)

Similarity To N, one another

uniform

Cyto abn, enlarged,

hyperchr, irr nuc, large

nucl, pleomorphism

Mitosis Few, N , abn, bizarre mitotic

Blood vessels Well formed Numerous, poorly formed

Lack endot lining

Necrosis Unusual, degenerative -+ + hemorrhage: common

Distant spread

(Metastasis)

- +


27/90

Abnormal Mitosis


28/90

Benign Malignant

DNA content N Degree of

DifferentiationAdditional Chr

Karyotype N Aneuploidy

Polyploidy

Clonal genetic

abn


29/90

Rate of GrowthAssessment of growth rate: clinical information: serialMic: - number of mitotic

- met activ of nuclei: - enlarged

- dispersed chromatin

- large nucleoli

Size

No bearing

Carcinoid of appendix: ben, unless > 2 cm

- < 2 cm: do not met- Ben & malignant: his identical


30/90

Degree of DifferentiationDegree to which a neoplastic cell resembles the normal

mature cells

Benign: fully (well) diff closely resembleN tissue

Malignant: variable degree of diff, littleresemblance to N

poorly diff.

Anaplasia:noresemblance to N

More cellular

Higher mitotic rate:- smooth muscle uterus relevance

- pheochromocytoma (adr med) little relevance

Cytologic feature of malignancy


31/90

D. Changes in DNAAbn DNA content Neoplasm. Abn Degree of Mal Deg

Hyperchromatism: crude assessment of DNA content

Malignant cells: Hyperchromatic

Flow cytometry: DNA content mal cell degree of mal:

- Malignant Lymphoma

- Bladder tumor

- Astocytic neo

Cytogenetic: aneuplidy & polyploidy indicative ofmalignancy

Molecular techniques: clonal deletion, translocations, abnoncogen exp


32/90

E. Infiltration & InvasionBen: - noninfiltrative, capsule: compressd & fibr N tiss

Mal: - infiltrating margin

Exception: Ben: - granular cell T

- dermatofibroma lack caps, + inf margin- carcinoid T

F. Metastasis

Non contiguous / distant growthIdentification: difficult the only evidence is metastasis

90% pheochromocytoma: ben, no criteria for identifying the10% that will metastasize.


33/90

HistogenesisTotipotent Cells

= capable of differentiating (maturing) any cell type = zygote

Zygote embryo fetus

Postnatal: the only totipotent cells = germ cells:

- gonad (most commonly)

- retroperit, mediast, pineal

Germ cell neo

- minimal diff

- mal primitive germ cells: seminoma & embryonal ca

- develop variety of tiss: - trophoblast (chorioca.)

- yolk sac (yolk sac ca)

- somatic (teratoma)

Teratoma

- somatic diff: 3 germ layer: endo, ecto, mesoderm brain, resp, intes muc,cartilage, bone, skin, teeth, hair


34/90

Embryonic Pluripotent Cells

Pluripotent cells mature different cell types

Neo renal anlage cells (nephroblastoma) diff renal tubulusor muscle, cartilage, & bone Embryoma/Blastoma

Emb pluripot cells: fetal & first few years occur early childhood,

rarely in adult


35/90

Differentiated CellsPost natal: differentiated, adult type cells

Most neo from differentiated cell

Nomenclature

Epithelial N

- Ben: Adenoma, Papilloma

- Mal: Carcinoma: - Adenoca (gland)

- SCC & Transit ca (epithel)

Mesenchymal N

Ben: cell of origin + oma

Mal: cell of origin + sarcoma


36/90

Adenoma


37/90

Skin Papilloma: Common Wart

Papilloma within duct


38/90


39/90

Papilloma + Adenoma = Adenomatous Polyp


40/90


41/90

Lipoma


42/90

Chondroma in tubular bones o/t hand


43/90


44/90

Leiomyoma


45/90

Carcinoma o/t Glandular Organ


46/90

Sarcomas


47/90

Benign Cystic Teratoma


48/90

Spread of Tumor

Spread of Tumor


49/90

Spread of Tumor

E ti


50/90

ExceptionsSound benign but really malignant

Lymphoma, plasmacytoma, melanoma, glioma, astrocytoma

Sound malignant but really benign

Osteoblastoma, chondroblastoma, because of + blastoma

Leukemia

Mixed T: > 1 neoplastic cell type

Mal Mixed T: - Adenosquamous ca

- Mal fibrous histiocytoma

- Carcinosarcoma (lung), Mal Mixed Mullerian T (uterus)- 2 separate cell line ?

- 1 multipotent cell type

Cell of origin is unknown: - Wilms T nephroblastoma

- Grawitzs renal adenoca.


51/90

Hamartoma & ChoristomaTumor like developmental anomaly

Not true N

Abn, disorganized, prol masses of several different adult cell type

Hamartoma

Tissue normally present in the organ

Lung: bronchial ep & cartilage

Choristoma

Tissue not normally present

Smooth muscle & pancreatic acini & duct in the wall of

stomach

Incidence & Distribution


52/90

Incidence & DistributionIncidence & Mortality Rates (1996)

Indonesia Medan

1. Cervix 1. Breast

2. Breast 2. Cervix

3. Lymph nodes 3. Skin

4. Skin 4. Lymphnodes

5. Nasopharynx 5. Nasopharynx

6. Ovary 6. Liver

7. Rectum 7. Soft tissue

8. Soft tissues 8. Thyroid

9. Thyroid 9. Other sites

10. Colon 10. Lung


53/90

Age : Male: 55-64

Female : 45-54Male+ Female: 45-54

Cause of death

US: 1. IHD 2. Cancer: 500.000 annually

Ind: 1. Infection 2. IHD/Cancer


54/90


55/90

Occupational, Social, & GeographicCigarette smokingTobacco sewing

Borne several children, breast feeding lower inc breast

cancer, Nun >< EBV Burkit L, HPV Tumor

Natural Killer Cells

IL-2 active NK

Cl I def escape T-cell recog

ADCC

Macrophages

T- cell IFN active mac oxyg metabolit

NK cell TNF

Humoral: - activation compl

- induction of ADCC by NK cells


84/90

Tumor Immunity

Gen Alteration Surface Ag (nonself by imm sys)

Tumor Antigen

Tumor-specific Ag (TSA) only tumor cells, normal(- )

Tumor-associated Ag (TAA) tum cells & normal cell

TSA (peptides within tumor cells) presented surface byClass I MHC cytotoxic T-cell response


85/90

Tumor Antigen Tumor-Specific Shared Ag: - MAGE, GAGE,

- BAGE, RAGE

Tissue-Specific Ag: tumor cell & normal untransf

Ag Resulting from Mutations: peptides derived from

mutated p53, K-ras, CDK4, bcr-c-abl

Overexpressed Ag: c-erbB2 (or neu) protein

Viral: E7 protein of HPV-16

Other Tumor Ag


86/90

Other Tumor Antigen

TAA, normal self prot not imm resp

Detection Diagnosis

Ab against useful for imm the

Oncofetal Ag: - AFP, CEA

Differentiation Ag:

- CD10 (CALLA): early B Lcy & B-cell Leu , Loma

- Prostate-Specific Ag: normal & cancer


87/90

Immunotherapy of Human Tumor Adoptive Cellular Therapy atients bloodLcy cultured w IL2 in vitroLymphokine-activated Killer LAK), antitumorreinfused Tum spe CTC enriched among Tumor Infiltrating Lcy Lcy harvested f resected tumor cultured in IL-2

reinfused


88/90

H


89/90

HD

A

A


90/90

Documents

l Neoplasm A