• Neoplasia literally means ‘’new growth” and the new growth is a neoplasm. • Oncology (Greek oncos = tumour) is the study of tumours or neoplasms. • Cancer is the common term for all malignant tumours (derived from the latin word for crab)

• “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissue and persists in the same excessive manner after cessation of the stimuli that evoked the change”. • Tumour can be benign or malignant and are made up of two basic components: 1. Parenchyma: the proliferating neoplastic cells. 2. Supportive stroma: made up of connective tissue and blood vessels.


Based on parenchymal component
Cells of origin

– –

In general attach the suffix -oma to the cell of origin.
Microscopic architecture & Macroscopic patterns.

Epithelial tissue- -e.g. cysts, papillae & polyp. • Malignant Mesenchymal tissue are usually called sarcomas (Greek sar = fleshy) because they have little connective tissue stroma


Colonic Polyp

Gross appearance of an opened cystic teratoma of the ovary

• Degree of diferentiation : Well; Mod; Poorly differentiated or undifferentiated malignant tumor • Non-classical designations:• Melanomas, seminomas, hepatomas. • choristoma-as • hamartoma -Aberrant differentiation/anomalous development • Specific designations have specific clinical implications.

Tissue of Origin Tumors of mesenchymal origin Connective tissue and derivatives



Nomenclature of Tumors Composed of One Parenchymal Cell Type

Fibroma Lipoma Chondroma Osteoma

Fibrosarcoma Liposarcoma Chondrosarcoma Osteogenic sarcoma Angiosarcoma Lymphangiosarcoma Synovial sarcoma Mesothelioma

Endothelial and related tissues Blood vessels Lymph vessels Synovium Mesothelium Brain coverings Blood cells and related cells Hematopoietic cells Lymphoid tissue Muscle Smooth Striated Leiomyoma Rhabdomyoma Leiomyosarcoma Rhabdomyosarcoma Leukemias Lymphomas Meningioma Hemangioma Lymphangioma

Invasive meningioma

Tumors of epithelial origin Stratified squamous Basal cells of skin or adnexa Epithelial lining of glands or ducts Adenoma Papilloma Cystadenoma Respiratory passages Renal epithelium Liver cells Urinary tract epithelium (transitional) Placental epithelium Testicular epithelium (germ cells) Tumors of melanocytes Nevus Bronchial adenoma Renal tubular adenoma Liver cell adenoma Squamous cell papilloma Squamous cell or epidermoid carcinoma Basal cell carcinoma Adenocarcinoma Papillary carcinomas Cystadenocarcinoma Bronchogenic carcinoma Renal cell carcinoma Hepatocellular carcinoma

Transitional cell papilloma Transitional cell carcinoma Hydatidiform mole Choriocarcinoma Seminoma Malignant melanoma

More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from One Germ Cell Layer Salivary glands Pleomorphic adenoma (mixed tumor of salivary origin) Malignant mixed tumor of salivary gland origin Wilms tumor

Renal anlage

More Than One Neoplastic Cell Type Derived from More Than One Germ Cell Layer-Teratogenous Totipotential cells in gonads or in embryonic rests Mature teratoma, dermoid cyst Immature teratoma, teratocarcinoma

Comparisons Between Benign and Malignant Tumors

Characteristics Differentiation/ana plasia

Benign Well differentiated; structure may be typical of tissue of origin

Malignant Some lack of differentiation with anaplasia; structure is often atypical

Rate of growth

Usually progressive and slow; may come to a standstill or regress; mitotic figures are rare and normal Usually cohesive and expansile well-demarcated masses that do not invade or infiltrate surrounding normal tissues; Encapsulation Absent

Erratic and may be slow to rapid; mitotic figures may be numerous and abnormal

Local invasion

Locally invasive, infiltrating the surrounding normal tissues; sometimes may be seemingly cohesive and expansile Frequently present; the larger and more undifferentiated the primary, the more likely are metastases


Leiomyoma of the uterus

Benign tumor (adenoma) of the thyroid

Malignant tumor (adenocarcinoma) of the colon

Anaplastic tumor showing cellular and nuclear variation in size and shape

Fibroadenoma of the Breast

Invasive carcinoma of the breast

Biology of Tumor Growth
• The natural history of most malignant tumors can be divided into four phases: • (1) malignant change in the target cell, referred to as transformation; • (2) growth of the transformed cells; • (3) local invasion; and • (4) distant metastases

• Differentiation –extent of functional & morphologic resemblance to mature normal cell. • Anaplasia is lack of differentiation • Hallmark of malignant transformation • Xrized by: Pleomorphism; Hyperchromasia; frequent/atypical mitosis; loss of polarity; tumour giant cells; Necrosis

Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma)

Carcinoma in situ

• Loss in the uniformity of the individual cells as well as a loss in their architectural orientation • Disorganized;Pleomorphism; Hyperchromasia; Mitosis • Carcinoma in situ; • Invasion

Factors influencing tumour development
• Tumour development is influenced by many factors that may be considered under three headings: 1. Kinetics of tumour cell growth 2. Tumour angiogenesis and 3. Tumour progression and heterogeneity

Schematic representation of tumor growth

• • • Unequivocal marker of malignancy Exceptions: Gliomas & BCC Pathways of spread:
1. Direct seeding of body cavities 2. Lymphatic spread 3. Haematogenous spread

Figure 7-42 The metastatic cascade. Schematic illustration of the sequential steps involved in the hematogenous spread of a tumor.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2005 11:45 PM) © 2005 Elsevier

A liver studded with metastatic cancer.

• Can give insight to the cause of cancer • Factors in patient & environment. • US residents have 1/5 chances of dying from cancer. • In Nigeria 100,000 new cases occur each year (T. F. Solanke, 2000) • 500,000 in the 21st century • Lung, Breast, prostate C/rectum-death/US



Geography and Environmental Factors

Factors Predisposing to Cancer
• Geog/Environ: Age, Sex, Diet, Lifestyle, Occupation, ambient environ • Genetic: • Nonhereditary conditions: Cx infla; UC, Crohn`s dx, viral hep. Cx pan. Precancerous cond.- CAG/Pernicious anaemia; Solar Keratosis; leukoplakia; adenoma

• Cancer is essentially a genetic disease at the cellular level. • Carcinogenesis, • The process of development of cancer in living tissues, is a complex multistage process at both the phenotypic and the genetic levels. • A malignant neoplasm has several phenotypic attributes, • Such as excessive growth,
• Local invasiveness and the ability to form distant metastases.

• These characteristics are acquired in a stepwise fashion, • A phenomenon called tumour progression. • At the molecular level, progression results from accumulation of genetic lesions. • Such genetic damage [or mutation] may be acquired by the action of environmental agents, • Such as chemicals, Radiation or viruses or it may be inherited in the germ line.

• The genetic hypothesis of cancer also implies that a tumour mass results from the clonal expansion of a single progenitor cell that has incurred the genetic damage – • This is the basis of tumour monoclonality.

Biology of tumor growth

The cell cycle and regulation of cell growth:
 Normal cell division is closely regulated.  Phases of cell cycle include: • -Growth-G-phase-G1,G2; • Synthetic-S-phase and mitotic-M-phase.  After cell division daughter cells may reenter the cycle; • Differentiate into its specialized forms or undergo a programmed cell death (apoptosis).


© 2005 Elsevier

 During the cell cycle, the cell must recognize, detect and repair any DNA alteration or defect that might occur.  Two important classes of genes control cell growth: • Proto-oncogenes; • Tumour suppressor genes.  Many of the cellular changes associated with cancer affect this vital process.

Multiple-hit concept of carcinogenesis
• This involves primary and secondary genetic abnormalities:• 1. Primary abnormalities:  Consistent changes essential in establishing the neoplasm,  Strongly correlated with tumour type. • Features that contribute to their development include: • Environmental factors and genetic factors [hereditary].

 These primary abnormalities [or mutations] effect phenotypic transformation in tumour cells. • Such as: • – loss of capacity for growth arrest. • –loss of contact inhibition of movement • –change in cell morphology and growth habits [anchorage independence] and • - Capacity for indefinite replication [immortality]

Secondary abnormalities:
• These are additional mutations that confer an evolutionary edge on the new clones of tumour cells possessing them, • Causing them to proliferate more vigorously; • Have longer life span and eventually outgrow their neighbours. • These new subsets [tumour heterogeneity] differ in their karyotype, invasiveness, growth rate, hormonal responsiveness, • Metastatic abilities and susceptibility to antineoplastic drugs.

• • • • • •

These secondary genetic changes underlie the phenomenom of tumour progression – Defined as “the acquisition of permanent irreversible qualitative change in one or more characteristics of a neoplasm” Environmental factors: Physical, Chemical & Biological.

Genetic factors.
• Genetic alterations can occur sporadically or may be inherited. • The types of genetic changes seen in tumouriogenes are: • 1. Gene amplification • 2. Gene re-arrangement [e.g. translocations] • 3. Gene mutations and • 4. Deletion of specific genes.

Causes of mutation:
• Exposure to environmental genotoxic agents and stresses, • Gene classes • 5 main classes of genes are involved in the genetic changes underlying carcinogenesis. • i. Oncogenes • ii. Tumour suppressor genes • iii. Metastasis genes • iv. Apoptosis gene . v. DNA repair genes


• • 5. 6. 7. 8.

1. ONCOGENES Cancer causing genes are derived from proto-oncogenes. Proto-oncogenes can exert their functions through production of: Growth factors, Growth factor receptors, Signal tranducers and Transcriptional factors.

Mechanisms of activation of Oncogenes
• • • • • a. Gene amplification – e.g. Small cell lung cancer [L-myc]; b. Loss of control mechanism – e.g. Burkitt’s lymphoma [C-myc] t[8,14]; c. Structural alteration – CML t[9,22] → abl-bcr hybrid gene → a fusion protein. • d. Point mutation in k-ras gene – colorectal cancer

• Their gene products are involved in the negative control of cell proliferation and differentiation, • And their loss or inactivation is associated with carcinogenesis. • E.g. P53, a TSG is the most common genetic alteration found in cancers.• Li fraumeni syndrome, Rb, BRCA, APC genes.

• Ezrin- ERMS & Osteosarcoma • Metastasis Suppressors: NM23 & KAI-1 genes. • The loss or decreases expression of nm23 genes located on 17q 21.3 is associated with high metastatic potential • And poor survival in breast carcinoma.

• Bcl-2 oncogene may rescue cells from apoptosis thus potentiating cellular genetic alteration.

• Mutation in DNA repair genes are known to lead to some cancers e.g. • HNPCC[Hmsh2-(2p16) & Hmlh1-(3p21)] and lymphoid malignancies. • Failure of DNA repair is associated with a group of autosomal recessive disorders comprising: • Bloom syndrome, Xeroderma pigmentosum, Ataxia telangiectasia and Fanconi’s anaemia, all of which are also associated with increased predisposition to cancer.

• A large number of types of cancer, [5-10% or more] including the most common forms show hereditary predisposition in addition to environmental influences. • These include: • 1. Inherited cancer syndromes (Autosomal Dominant): • Retinoblastoma, • Li fraumeni syndrome and FAP, • All associated with TSG.

• 2. Familial cancers – evident familial clustering of cancer, but role of inherited predisposition may not be clear in each case. e.g. • BRCA 1 and 2. • 3. Autosomal recessive syndromes of defective DNA repair [as above]