NEOPLASIA

Dr. Salma MansoorLecturer,DCOP,DUHS

Definitions

Neoplasia = new growth

Tumor= swelling due to inflammation

Oncology= oncos is tumor, logy is study

Cancer= malignant tumors (crab)

NEOPLASM

"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"

Facts

2000: 10 million new cases CA 6 million CA deaths worldwide

US: 1.5 million new CA diagnosis 2003, 23% deaths (1500 CA deaths/d) Second COD in US (IHD & atherosclerosis)

Nomenclature

ParenchymaProliferating neoplastic

cells

StromaConnective tissue and

blood vessels

Benign vs. Malignant

Slow growing

Encapsulated

No Metastasis

Well Differentiated

Rapidly growing

Non encapsulated

Metastasis

Well-Poorly differentiated

Benign Tumors

Cell of origin + OMA

Fibroma, chondroma, osteoma

Adenoma: derived from glands/ glandular pattern

Tubular adenoma, colon

Papillomas: architecture finger like projections

Polyp: macroscopic projection of mucosal surface

Malignant tumors

Mesenchymal = sarcomas ( sar, fleshy). Fibrosarcoma, liposarcoma, leiomyosarcoma

Epithelial = carcinomas, glandular – adenocarcinoma, squamous – squamous cell carcinoma

Mixed: epithelial and stromal component, same origin, i.e. pleomorphic adenoma

Teratomas: more than one germ layer

Teratoma, ovaryTeratoma, ovary

Choristoma: ectopic rest of normal tissue

Hamartoma: mass of disorganized but mature specialized cells or tissue native to the particular site

Tissue of origin Benign Malignant

Mesenchymal/ connective tissue FibromaLipomaChondromaOsteoma

FibrosarcomaLiposarcomaChondrosarcomaOsteogenic sarcoma

Endothelial and related tissues HemangiomaLymphangioma

Meningioma

AngiosarcomaLymphangiosarcomaSynovial sarcomaMesotheliomaInvasive meningioma

Hematopoietic LeukemiasLymphomas

Muscle LeiomyomaRhabdomyoma

LeiomyosarcomaRhabdomyosarcoma

Epithelial Squamous papilloma

AdenomaPapillomaCystadenomaBronchial adenomaRenal tubular adenomaLiver cell adenomaTransititonal cell papillomaHydatiform mole

SCC or epidermoid CABCCAdenocarcinomaPapillary carcinomaCystadenocarcinomaBronchogenic carcinomaRenal cell carcinomaTransitional cell carcinomaChoriocarcinomaSeminomaEmbryonal CA

Melanocytes Nevus Malignant melanoma

More than one neoplastic cell- MIXED

Salivary gland Pleomorphic adenoma Malignant mixed tumor of salivary gland origin

Renal Wilms tumor

Teratogenous ( from more than one germ cell layer

Totipotential cells Mature teratoma/ dermoid cyst

Immature teratoma, teratocarcinoma

1. Anaplasia

Lack of differentiation

Hallmark of malignant transformation

Numerous morphologic changes

Pleomorphism: variation in size and shape

Abnormal nuclear morphology: hyperchormatic (abundant DNA), increased N:C ratio (normal 1:4- 1:6)

Mitoses: increased, bizarre

Loss of polarity

Tumor giant cells

Dysplasia: disordered growthLoss of uniformityLoss of architecturePleomorphismHyperchromasiaAbnormal located mitosis

Obesity & Cancer

Relationship b/w BMI & cancer

Mechanism

Hyperinsulinemia

IGF

Steroid hormones

adiponectin

Diet & Cancer

With respect to carcinogenesis 3 aspects of diet are of major concern:

1. The content of exogenous carcinogens

2. The endogenous synthesis of carcinogens fro dietary components

3. Lack of protective factors

Exogenous Substances

Endogenous synthesis

Protective factors

Rates of Growth

How long does it take to produce a clinically overt tumor mass……?????

TUMOR CELL KINETICS

Rate of Growth of Tumor

Growth Fraction

Clinical aspects of neoplasia

1. Local & Hormonal Effects

2. Cancer Cachexia

3. Paraneoplastic Syndrome

Cachexia

PARANEOPLASTIC SYNDROMES

Infrequent but important to recognize.

1. Endocrinopathies

2. Neuromyopathic Paraneoplastic syndromes

3. Dermatologic disorders

4. Osseous, articular & soft tissue changes

5. Vascular & hematologic changes

Endocrinopathies

Cushing syndrome

Hypercalcemia

Neuromyopathic PS

Peripheral neuropathies

Cortical cerebellar degeneration

Polymyopathy

Myasthenia syndrome

Dermatologic Disorders

Acanthosis nigricans

Osteoarthropathy

Vascular & Hematologic

DIC

STAGING OF CANCER

American Joint Committee on Cancer Staging

TNM

T0, T1-T4

N0, N1, N2, N3

M0, M1, M2

DIAGNOSIS OF CANCER

Histologic & Cytologic methods

Immunochemistry

Flow cytometry

Molecular diagnosis

Histology & Cytology

Sample Collection

Adequate

Representative

Properly preserved

Sample Collection Techniques

(1) excision or biopsy

Fine-needle aspiration

Cytologic (Pap) smears

ANTICANCER DRUGS

Principles of Cancer Chemotherapy

Lethal cytotoxic event arrest tumor progression

Treatment Strategies1. Goal of treatment [cure &/or palliation]

2. Indications for treatment [dissminated, supplemental]

3. Tumor susceptibility & the growth cycle:

i. cell-cycle specificity of drugs

ii. Tumor growth rate

Treatment Regimens & Scheduling

1. Log kill (1st order kinetice)

2. Pharmacologic Sanctuaries

3. Treatment protocols:

i. Combination of drugs

ii. Advantages of drug combinations

iii. Treatment protocols (POMP for ALL)

Problems associated with Chemotherapy

1. Resistance

2. Toxicity• Common adverse effects• Minimizing adverse effects

3. Treatment-induced tumors

Anticancer drugs

•Methotrexate, 6-Mercaptopurine, 6-Thioguanine, 5-Fluorouracil, Cytarabine, Gemcitabine

Antimetabolites

•Dactinomycin, Doxorubicin, Daunorubicin, Bleomycin

Antibiotics

•Mechlorethamine, Cyclophosphamide, ifosfamide,Nitrosoureas (carmustine, lomustine)

Alkylating agents

•Vincristine, Vinblastine, TAXOL (Paclitaxel), Docetaxel

Microtubule Inhibitors

•Prednisone, Tamoxifen, Aromatase Inhibitors

Steroid Hormones/Anta

gonist

•Rituximab, Cetuximab

Monoclonal Antibodies

•Platinum complexes, TOPOISOMERASE INHIBITORS (irinotecan, topotecan, etoposide), Interferons

Miscellaneous

References

1. Kumar V, Abbas A, Fausto N. Robbins and Cotran pathologi Basis of Disease. 7th edition. El Servier. 2004; pg 269- 342