Dr. Salma Mansoor Lecturer, DCOP, DUHS NEOPLASIA Dr. Salma Mansoor Lecturer, 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: US: 1.5 million new CA diagnosis 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)

Proliferating neoplastic Nomenclature Stroma Connective tissue and blood vessels Parenchyma Proliferating neoplastic cells

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 Tubular adenoma, colon Cell of origin + OMA Fibroma, chondroma, osteoma Adenoma: derived from glands/ glandular pattern

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

Teratomas: more than one germ layer Teratoma, ovary Teratoma, ovary Teratomas: more than one germ layer

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 Fibroma Lipoma Chondroma Osteoma Fibrosarcoma Liposarcoma Chondrosarcoma Osteogenic sarcoma Endothelial and related tissues Hemangioma Lymphangioma Meningioma Angiosarcoma Lymphangiosarcoma Synovial sarcoma Mesothelioma Invasive meningioma Hematopoietic Leukemias Lymphomas Muscle Leiomyoma Rhabdomyoma Leiomyosarcoma Rhabdomyosarcoma Epithelial Squamous papilloma Adenoma Papilloma Cystadenoma Bronchial adenoma Renal tubular adenoma Liver cell adenoma Transititonal cell papilloma Hydatiform mole SCC or epidermoid CA BCC Adenocarcinoma Papillary carcinoma Cystadenocarcinoma Bronchogenic carcinoma Renal cell carcinoma Transitional cell carcinoma Choriocarcinoma Seminoma Embryonal 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 growth Loss of uniformity Loss of architecture Pleomorphism Hyperchromasia Abnormal 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: The content of exogenous carcinogens The endogenous synthesis of carcinogens fro dietary components 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 Local & Hormonal Effects Cancer Cachexia Paraneoplastic Syndrome

Cachexia

PARANEOPLASTIC SYNDROMES Infrequent but important to recognize. Endocrinopathies Neuromyopathic Paraneoplastic syndromes Dermatologic disorders Osseous, articular & soft tissue changes 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 excision or biopsy

Fine-needle aspiration

Cytologic (Pap) smears

ANTICANCER DRUGS

Principles of Cancer Chemotherapy Lethal cytotoxic event  arrest tumor progression

Treatment Strategies Goal of treatment [cure &/or palliation] Indications for treatment [dissminated, supplemental] Tumor susceptibility & the growth cycle: i. cell-cycle specificity of drugs ii. Tumor growth rate

Treatment Regimens & Scheduling Log kill (1st order kinetice) Pharmacologic Sanctuaries Treatment protocols: i. Combination of drugs ii. Advantages of drug combinations iii. Treatment protocols (POMP for ALL)

Problems associated with Chemotherapy Resistance Toxicity Common adverse effects Minimizing adverse effects 3. Treatment-induced tumors

Anticancer drugs Antimetabolites Antibiotics Alkylating agents Methotrexate, 6-Mercaptopurine, 6-Thioguanine, 5-Fluorouracil, Cytarabine, Gemcitabine Antibiotics Dactinomycin, Doxorubicin, Daunorubicin, Bleomycin Alkylating agents Mechlorethamine, Cyclophosphamide, ifosfamide,Nitrosoureas (carmustine, lomustine) Microtubule Inhibitors Vincristine, Vinblastine, TAXOL (Paclitaxel), Docetaxel Steroid Hormones/Antagonist Prednisone, Tamoxifen, Aromatase Inhibitors Monoclonal Antibodies Rituximab, Cetuximab Miscellaneous Platinum complexes, TOPOISOMERASE INHIBITORS (irinotecan, topotecan, etoposide), Interferons

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