Neoplasia By Dr Abiodun Mark A

“The only certain way of avoiding cancer is not to be born; to live is to incur the risk” -Robbins & Cotran PBD.

Introduction. A tumor is an abnormal mass of tissue ,the growth of which Is virtually autonomous and exceeds that of normal tissues. Tumors are classified into 2 broad categories: -Benign -Malignant. The type of neoplasm is based on the characteristics of its parenchyma.

Tumor nomenclature. Tumors have 2 basic components: -The transformed neoplastic cells aka the parenchyma -The supporting component aka the stroma. Benign tumors: the names of this groups of tumor typically(but not uniformly) ends with the suffix “oma.” Malignant tumors are also referred to as cancers and are divided into the following categories: -Carcinomas: from epithelial origin -Sarcomas: from mesenchymal tissues.

Special tumors: Mixed tumors: are derived from one germ layer that differentiates into more than one parenchyma cell type e.g. pleomorphic adenoma. Teratomas: are made up of a variety of parenchmal cells that are derivatives of more than one germ layer(usually 3). Most teratomas are found in the gonads. Choriostoma: Ectopic rests of normal tissues. Harmatomas: Masses of disorganized tissues inherent to a particular site e.g. pulmonary harmatoma.

Pulmonary Harmatoma.

Pulmonary hamartoma The pulmonary hamartoma is seen microscopically to be composed mostly of benign cartilage on the right that is jumbled with a fibrovascular stroma and scattered bronchial glands on the left. A hamartoma is a neoplasm in an organ that is composed of tissue elements normally found at that site, but growing in a haphazard mass.

Misnomers Melanoma Seminoma Glioma Lymphoma Hepatoma Chordoma They are all malignant tumors despite the fact that they all have the suffix “oma”

Identify the slide

Teratoma. Encapsulated tumor with tissue or organ components resembling normal derivatives of more than one germ layer.  Teratomas have been reported to contain hair, teeth, bone and, very rarely, more complex organs or processes such as eyes, torso, and hands, feet, or other limbs

IDENTIFY THE SLIDE? Malignant melanoma: highly metastatic cancer of the skin arising from the melanocytes. Clinical analysis is via: A: ASSYMETRICAL SHAPE. B: BORDERS C: COLOUR. D:DEPTH OF INVASION.

Malignant melanoma. This excision of skin demonstrates a malignant melanoma, which is much larger and more irregular than a benign nevus. From the history provided by the patient, we know that it grew quickly in size in 3 months. In contrast, a benign nevus hardly seems to change at all over many years.

Identify the slide? LIPOMA: A benign tumor of adipocyte origin.

Tumors arising from Adipocytes. LIPOSARCOMA. LIPOMA

Identify the slide? LIPOSARCOMA:A malignant tumor of adipocyte origin.

Squamous papilloma

Squamous papilloma. A Squamous cell papilloma is a generally benign papilloma that arises from the stratified squamous epithelium of the skin, lip, oral cavity,tongue,pharynx, larynx, esophagus, cervix, vagina or anal canal.  Squamous cell papillomas are a result of infection with human papillomavirus(HPV). A papilloma is a benign neoplasm composed of epithelial cells forming finger like projections.

What is the pathology here? Cervical dysplasia: here the normal squamous epithelium(right) merges into the dysplastic epthelium(left)

Carcinoma in situ Here the cancerous cells have not invaded the basement membrane.

Biology of tumor growth. The major differences between a benign and a malignant tumors can be analyzed using this 4 major criteria: -Differentiation vs. Anaplasia -Rate of growth. -Local invasion -Metastases.

Differentiation vs. Anaplasia. Differentiation is the extent to which a tumor cell resembles the original cell thus tumors call be well, moderately or poorly differentiated. Anaplasia refers to the lack of differentiation and it is a hallmark of malignant cells. The following are some qualities of anaplasia: -Nuclear and cellular pleomorphism. -Hyperchromasia. -Nuclear cytoplasmic ratio. -Abnormal mitosis -loss of polarity.

Nuclear Pleomorphism.  Nuclear pleomorphism: Pleomorphism refers to variation in the size and shape of the nuclei in comparison to their neighbors. In this example of a sarcoma, the nuclei vary greatly in size and shape.

Pleomorphism

Rate of growth. Most malignant tumors grow more rapidly than benign tumors. Nevertheless some cancers grow slowly over the years and then enter a rapid growth phase.

Local invasion. Benign tumors: most benign tumors grows as a cohesive mass that develop a rim of expansile but condensed connective tissue or capsule around its periphery. Malignant tumors : are invasive and infiltrative and they destroy normal tissue surrounding them. They also lack a well defined capsule. Surgical treatment of a malignant tissue requires a wide excision.

Metastasis. Metastasis unequivocally marks a tumor as malignant because benign tumors do not metastasize. There are very few exceptions to this rule, Basal cell carcinoma. Gliomas Are malignant tumors that rarely metastasize. The major routes of metastasis are: -Hematogeneous route -Lymphatic spread -Seeding via the body cavities.

FEATURES BENIGN MALIGNANT Structure Resemblance to normal cells (well differentiated) Growth rate Slow Mitoses Few Growth Usually expansive Growth duration May stop growing Encapsulation Usually Metastasis None Effect on host Slight harm, due to location or complication Abnormal; less similarity to normal cells (anaplastic) Rapid Relatively common Invasive Rarely stop growing Rarely Frequent Significant harm, due to invasion & metastasis

Epidemiology A variety of factors predisposes an individual in a population to cancer, they include: Geographic and environmental factors. Age. Genetic predisposition. Precancerous lesions etc.

Molecular basis of cancer. “The literature of the molecular basis of cancer continues to proliferate at such a rapid pace that its easily to get lost in the growing forest of information” Some fundamental principles in the molecular basis of cancer are: Cancer is a genetic disease: here non lethal damage acquired by somatic cells are passed down/inherited. Tumor clonality: A tumor is formed by clonal expansion of a single precursor cell that has incurred a genetic damage.

Molecular basis of cancer. Regulatory genes: the 4 normal regulatory genes are the target of genetic damage: -growth promoting protooncogene. -growth inhibiting tumor suppressor genes. -genes that regulate apoptosis. -genes that regulate DNA repair. And finally carcinogenesis is a multistep process.

DNA repair methods: Nucleotide excision repair Base excision repair DNA repair methods: Nucleotide excision repair Base excision repair. Mismath repair.

Tumor suppressor genes. A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene mutates to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes. Examples are: RB gene. P53. APC/beta catenin pathway. NF1/NF2 WT1.

Essential Changes for Malignancy. Self sufficiency in growth signals. Insensitivity to growth inhibitory signals. Evasion of apoptosis. Defects in DNA repair. Continuous replicative ability(telomerase) Sustained angiogenesis. Ability to invade and metastasize. Ability to escape from immune recognition.

Carcinogens. Carcinogens are simply substances that causes cancer. Carcinogens are either classifieds as: Biologic carcinogens. Chemical carcinogens. Radiant energy.

Chemical carcinogens. Most chemical carcinogens are referred to as procarcinogens because they require a mentabolic activation in vivo to produce ultimate carcinogens. Only a few can act as a direct carcinogen. DNA is the ultimate site of attack by all procarcinogens and direct acting carcinogens. Chemical carcinogens are mutagens that induce changes in the tumor suppressor genes, protooncogenes and the genes that regulate apoptosis.

Scheme of chemical carcinogenesis.

Radiation carcinogenesis. Radiant energy is a form of UV rays and ionizing radiation that causes cancer. UV rays especially from the sun are associated with skin cancers via the following mechanisms: 1)Damage to DNA by formation of pyridine dimers. 2)Immunosupression. Ionizing radiation’s ability to cause cancers is due to the fact that it induces mutations. Miners or radioactive ores are more susceptible to lung cancer.

Biologic carcinogens. A variety of DNA and RNA viruses are known to cause cancer, they include: -Human papilloma virus. -Epstein Barr virus. -Hepatitis B virus. -Kaposi sarcoma. -HTLV. H.pylori is a bacteria associated with gastric cancer and MALTomas.

HPV ROLE IN ONCOGENESIS. E6 binds to p53 and E7 binds to RB, inducing the degradation of these proteins. The net effect of HPV E6 and E7 proteins is to block apoptosis and remove the restrains to cell proliferation

Clinical features of Cancers The utmost importance of neoplasm lies on its effect on its host/patient. Indeed both malignant tumors and benign tumors ma cause problems and they include: -Local impingement on adjacent structures. -Hormonal synthesis and paraneoplastic syndromes. -Bleeding and infection. -Symptoms from rupture and infarction. -Cachexia or wasting.

Summary. Neoplasm are clonal, autonomous, while non neoplastic tumor-like lesions e.g. hamartoma are polyclonal. Carcinogenesis is a multistep process. Early diagnosis goes a long way in determining the prognosis of any cancer. Therapeutic modalities of cancer management are surgery radiotherapy and chemotherapy.

Gracias,Al final.