TUMORS and NEOPLASM

Neoplasia and Neoplasm

Neoplasm is an abnormal mass of tissue as a result of neoplasia

Neoplasia (new growth in Greek) is the abnormal proliferation of cells.

• Neoplasm is mass of tissue that grows excessively, and keeps growing even if you remove the stimulus that started it off!

• Tumor = neoplasm• Types: BenignBenign tumor and MalignantMalignant tumor

Cancer = Latin for “crab”

• Small• Slow-growing• Non-invasive • Well-differentiated• Stay localized

• Stay where they are.• Can’t invade or

metastasize.

• Large• Fast-growing• Invasive • Poorly-differentiated• Metastasize

• Infiltrate, invade, destroy surrounding tissue.

• Then metastasize to other parts of body.

BenignBenign Tumors MalignantMalignant Tumors

• Usually designated by adding “-oma” to cell type• Adenoma – benign tumor arising from glandular cells• Leiomyoma – benign tumor arising from smooth muscle

cells• Chondroma – benign tumor arising from chondrocytes

• Other benign tumor names• Papilloma – has finger-like projections• Polyp – projects upward, forming a lump• Cystadenoma – has hollow spaces (cysts) inside

Thyroid adenoma Thyroid adenoma Normal thyroid

Oral papilloma Colon polyp Ovarian cystadenoma

• Carcinomas – arise in epithelial tissue• Adenocarcinoma – malignant tumor of glandular cells• Squamous cell carcinoma – malignant tumor of

squamous cells

• Sarcomas – arise in mesenchymal tissue• Chondrosarcoma – malignant tumor of chondrocytes• Angiosarcoma – malignant tumor of blood vessels• Rhabdomyosarcoma – malignant tumor of skeletal

muscle cellsMesenchymal tissue are capable of developing into connective tissue, bone, cartilage, the lymphatic system, and the circulatory system

Neoplasm

Benign Malignant

Carcinoma Sarcoma

AdenomaAngioma

Rhabdomyoma

Squamous cell carcinomaAdenocarcinoma

AngiosarcomaRhabdomyosarcoma

• Differentiation is how much the tumor cells resemble their cells of origin.• well-differentiated – closely resembles• moderately-differentiated – sort of resembles• poorly-differentiated – doesn’t resemble

• Benign tumors are usually well-differentiated• Malignant tumors can’t show any level of differentiation.

• Literally, “to form (-plasia) backwards (ana-)”• Just means cells are very poorly-differentiated• Almost always indicates malignancy

Anaplasia refers to a reversion of differentiation in cells

• Pleomorphism occurrence of two or more structural forms in the size and shape of cells and/or their nuclei

• Hyperchromatic, large nuclei• Unusual nuclear shapes, distinct nucleoli• Lots of mitoses, and atypical mitoses• Architectural disorder

Anaplastic cells show:

Mitosis divides the chromosomes in a cell nucleus.

Anaplastic carcinoma

• “Dysplasia” is used to describe disorderly changes in non-neoplastic epithelial cells.

• Graded as mild, moderate or severe.• Mild-moderate: usually reversible• Severe: usually progresses to carcinoma in situ (CIS).

• Next step after CIS: invasive carcinoma.

Dysplasia = disorderly (dys-) growth (-plasia)

Dysplastic cells show:

Q. Wait a minute, “dysplasia” sounds suspiciously similar to “differentiation” – what’s the difference?

A. Both terms describe whether cells look normal or not!

But:

• “differentiation” is only used with neoplastic cells, and “dysplasia” is only used with non-neoplastic cells!

• “dysplasia” is only used with epithelial cells, but “differentiation” can apply to any cell type.

mild dysplasia

moderate dysplasia

severe dysplasia

carcinoma in situ

Non-neoplastic epithelial cells

well-differentiated

moderately-differentiated

poorly-differentiated

anaplastic

Neoplastic cells

• Malignant tumors grow faster than benign ones.• Poorly-differentiated tumors grow faster than well-

differentiated ones.• Growth is dependent on:

• Blood supply• Hormonal factors• Emergence of aggressive sub-clones استنساخ

Generalizations

Carcinoma in situ

Invasive carcinoma

Invasive carcinoma

Metastasizing carcinoma

Liver with multiple metastases

• Metastasis is development of secondary tumor in distant tissues

• Half of all patients with malignancies have meets at the time of diagnosis!!

• Metastasis depends on:• Type of tumor • Size of tumor• Degree of differentiation of tumor

• Seeding• Lymphatic spread• Hematogenous spread

Three ways tumors metastasize

1. Seeding• Tumor invades body cavity • Bits break off and implant on peritoneal surfaces• Ovarian cancer

2. Lymphatic spread• Tumor spreads to local lymph nodes • Sentinel lymph node first• Moves through thoracic duct• Empties into subclavian vein• Carcinomas like to spread this way

Three ways tumors metastasize

The sentinel lymph node is the hypothetical first lymph node or group of

nodes reached by metastasizing cancer cells

from a primary tumor.

Lymph capillaries converge to become collecting vessels and

end up as either

Thoracic duct or right

lymphatic duct

Thoracic (left lymphatic) duct

Left subclavian vein

Right lymphatic

duct

Right subclavian

vein

Cysterna Chyli

3. Hematogenous spread• Veins are easier to invade than arteries• Liver and lungs are most common metastatic

destinations• Sarcomas like to spread this way (but so do

carcinomas)

Three ways tumors metastasize

Liver seeded with metastatic ovarian carcinoma

Lymphatic spread

Hematogenous spread

• 1.4 million new cases of cancer last year• 565,000 deaths from cancer last year• Cancer is 2nd leading cause of death (after heart

disease)• Most common cancers

• Men: Prostate• Women: Breast

• Deadliest cancers• Men: Lung• Women: Lung

• Decrease in death rates for:• Cervical cancer (pap smears)• Colon cancer (earlier detection)• Breast cancer (earlier detection)• Lung cancer in men (less smokers)• Some types of leukemia (new treatment)

• Increase in death rates for:• Lung cancer in women (more smokers)

Death rates have changed over past 3 years

• Basic underlying cause of cancer: Non-lethal genetic damage • Four kinds of normal genes are damaged:

• Genes that promote growth (“proto-oncogenes”)• Genes that inhibit growth (“tumor-suppressor

genes”)• Genes that regulate apoptosis• Genes involved in DNA repair

• Cancers develop in multiple steps

• Autonomous growth• Insensitivity to growth-inhibitory signals• Evasion of apoptosis• Limitless replication• Sustained angiogenesis• Invasion (infiltration/penetration) and metastasis

“Cancer genes” cause bad things in cells:

• Proto-oncogene: a normal gene whose product promotes cell growth.

• Oncogene: mutated proto-oncogene! Causes cell to grow autonomously!

• Oncoprotein: the product of an oncogene.

1. Chemicals2. Radiation3. Bugs/viruses

• Direct-acting agents• Indirect-acting agents

• Require conversion to become carcinogenic• Examples:

• hydrocarbons (in tobacco, charred meats)• aflatoxin B (from Aspergillus-infected grains, nuts)• nitrites (food preservative)

1- Chemicals

• Ionizing radiation

• Causes chromosome breakage, translocations• Examples: • Unprotected miners: lung cancer• Atomic bomb survivors: leukemia, other cancers• Therapeutic head/neck radiation: thyroid cancer

2- Radiation

Chromosome translocation is a chromosome abnormality caused by rearrangement of parts between nonhomologous chromosomes. A gene fusion may be created when the translocation joins two otherwise separated genes, the occurrence of which is common in cancer.

• HTLV-1: T-cell lymphoma• Human papilloma virus: Cervical cancer• Epstein Bar virus: various lymphomas• Hepatitis B and C: hepatocellular carcinoma• H. pylori: gastric cancer, lymphoma

3- Bugs

1. Define neoplasm and neoplasia? 2. Write the difference between benign and malignant tumor? 3. Give 5 examples of benign tumor and the organs they affect?4. Write the types of malignant tumors with example based on

their origin? 5. Define anaplasia? 6. Write the characteristics of anaplastic cells? 7. Define dysplasia? 8. Write the difference between differentiation and dysplasia?9. Define metastasis? Write the factors on which metastasis

depends on?10. Explain the 3 ways in which the tumors metastasize? 11. What are the 4 kinds of genes that are damaged in cancer? 12. Write the characteristics of cancer genes? 13. Explain different carcinogenic agents responsible for causing

cancer?