Neoplasia (1 of 6)

Introduction

= new growth

• Oncology = study of neoplasia

• Genetic/epigenetic basis

• Neoplasms are clonal

• Accumulation of mutations…more are accumulated in malignant ones

See next slide

With accumulation of mutations, features of malignancy are produced • More dysregulated autonomous growth (self-sufficiency in growth signals)

• More lack of response to inhibitory signal

• Evasion of apoptosis

• Limitless replicative potential

• More development of angiogenesis

• Ability to invade surrounding tissues

• Reprograming metabolic pathways

• Evasion of the immune system

Hamartomas and choristomas

Well-differentiated Anaplastic

-more N/C ratio -more nuclear pleomorphism -more hyperchromasia -more mitoses -more abnormal mitoses -more large (giant) cells -more bizarre cells -less structures resembling original tissue -more coarse clumped chromatin

What is dysplasia?

Benign Malignant Less mutations More mutations

Better differentiation (more resemblance to original tissue)

Worse differentiation (less resemblance to original tissue)…more to be anaplastic (anaplasia = total undifferentiation) than benign

Less mitoses More mitoses Mitoses are more likely to be abnormal than in benign

Stroma for supply is present Stroma for supply is also present *Note: some cancers have abundant fibrous stroma (= desmoplasia)

Slower growth…with some exception like? Faster growth

No invasion Invasion

Some with a capsule Mostly no capsule

More circumscribed (well-defined) Less circumscribed (ill-defined)…infiltrative

No metastasis Metastasis

Metastasis and dissemination

• Basal cell carcinomas…almost always non-metastatic

…also primary tumors of the central nervous system

• Bone sarcomas…usually already spread to lungs at diagnosis

• with differentiation and size…with exceptions

• 3 ways of dissemination

Metastasis and dissemination, cont’d

• Medulloblastoma or ependymoma…through CSF in ventricles to meningeal surfaces of brain/spinal cord

• Carcinoma…lymphatics, not only through lymphatics

• Sarcoma…blood, not only through blood

• Lung carcinomas regional bronchial lymph nodes tracheobronchial and hilar nodes

Metastasis and dissemination, cont’d

• Breast:

…usually upper outer quadrant axillary lymph nodes

…medial breast lesions nodes along internal mammary artery

• Sentinel lymph node???

• Enlargement of nodes near cancer are not necessarily involved by the cancer

both may seed supraclavicular or infraclavicular nodes

Metastasis and dissemination, cont’d

• Veins are penetrated easier than arteries

• The liver and lungs are the most frequently involved secondary sites in hematogenous dissemination

• Vertebral metastases of thyroid and prostate cancers…through the paravertebral plexus

• Renal cell carcinoma…renal vein…may then spread through IVC

• Prostatic carcinoma…bone

• Lung…adrenals and brain

• Neuroblastoma…liver and bones

• Skeletal muscles are rare sites for metastasis

Epidemiology of cancer Started to decline

Cervical cancer deaths markedly

Epidemiology of cancer, cont’d

• Some geographic areas are with high incidence of smoking & alcoholism

• Dietary fat and fibers colon cancer…differences between the West & Africa

• Death rates from breast cancer are about four to five times higher in the United States and Europe than in Japan

• The death rate for stomach carcinoma in men and women is about seven times higher in Japan than in the United States

• Liver cell carcinoma is relatively infrequent in the United States but is the most lethal cancer among many African populations

• Cervical cancer and its risk factors

Environmental more than genetic

Epidemiology of cancer, cont’d

• Most cancer deaths occur between ages 55 and 75

• The major lethal cancers in children are leukemias, tumors of the central nervous system, lymphomas, and soft tissue and bone sarcomas

…also retinoblastoma occurs mainly in pediatric age group

Epidemiology of cancer, cont’d

Occupational hazards

Epidemiology of cancer, cont’d

Inherited predisposition to cancer

40% of retinoblastoma cases are hereditary

-early age at onset -tumors arising in two or more close relatives of the index case -sometimes multiple or bilateral tumors -not associated with specific marker phenotypes

no more than 5% to 10% of all human cancers fall into one of these three categories

Epidemiology of cancer, cont’d

• Acquired preneoplastic lesions

…some are due to chronic tissue injury or inflammation

…their removal or reversal may prevent the development of a cancer

…examples: -Squamous metaplasia and dysplasia of the bronchial

mucosa…smokers

-Endometrial hyperplasia

-Leukoplakia of the oral cavity, vulva, or penis

-Adenomas of the colon