Neoplasia I

Walter C. Bell, M.D.

Definitions

• Neoplasia = New growth– Loss of responsiveness to normal growth

controls

• Tumor – Swelling, clinically used interchangeably with “neoplasm”

• Oncology – Study of tumors• Benign vs Malignant

– Clinical aggressiveness of neoplasm– A cancer (L. crab) is a malignant neoplasm

Nomenclature

• Tumors are composed of – stroma (supporting connective tissue, blood

supply) – parenchyma (the neoplastic cells which

determines biologic behavior)– Tumor names are derived from the

parenchymal component

Nomenclature

• Benign neoplasms end in the suffix “-oma”

• Mesenchymal– Fibroma– Chondroma

• Epithelial– Adenoma– Papilloma– Cystadenoma

Nomenclature

• Mesenchymal cancers are called sarcomas– Fibrosarcoma– Chondrosarcoma

• Epithelial cancers are called carcinomas– Squamous cell carcinoma– Adenocarcinoma

Neoplasia

• Neoplasms are monoclonal (arise from a single cell which has undergone neoplastic transformation)

• Stem cells may undergo divergent differentiation leading to heterogeneity

• Mixed tumors– Pleomorphic adenoma– Teratoma– Fibroadenoma (appearance only)

Confusing Terminology(Names that break the rules)

• Lymphoma

• Mesothelioma

• Melanoma

• Seminoma

• Hepatoma – old terminology for HCC

• Choristoma

Benign vs Malignant

• Most important clinical question for neoplasms

• Determines appropriate therapy– Conservative vs wide excision– Evaluation of lymph nodes (staging)– Need for chemotherapy or radiation therapy

Benign vs Malignant

• Degree of differentiation– How closely do the parenchymal cells

resemble normal cells of this type– Benign neoplasms are usually “well-

differentiated”– Anaplasia = lack of differentiation (bizarre

nuclei, atypical mitoses, loss of cell polarity)– Determined by microscopic examination

Benign vs Malignant

• Dysplasia – Pre neoplastic change usually in epithelia

• May not progress to cancer

Differentiation

• In general, function correlates with differentiation

• Unanticipated functions can emerge– Ectopic hormones– Fetal proteins

Benign vs Malignant

• Rate of growth– Most benign tumors grow slowly while most

cancers grow fast• Many exceptions

– Rate of growth for malignant tumors correlates with degree of differentiation

– Despite rapid growth, cancers usually take years to become clinically apparent

– Rapid growth may lead to necrosis

Ki-67 in dysplasia

Increased proliferation, disordered

Benign vs Malignant

• Local invasion– Benign neoplasms do not have the capacity to

invade – Invasion is a characteristic of malignancy– Benign neoplasms often develop a fibrous

capsule

Benign vs Malignant

• Metastasis– Metastases are secondary, remote implants of

tumor– Metastatic spread is the most important

hallmark of malignancy– Cancers differ in their ability to metastasize– Methods of metastasis:

• Seeding• Lymphatic spread• Hematogenous spread

Epidemiology

• The study of the relationships of various factors determining the frequency and distribution of diseases in the human community

• Contributes to understanding of risk factors and the origin of cancers

• Smoking – Lung cancer

• Fatty diets – Colon cancer

Epidemiology

• Geographic and environmental factors– Breast cancer – Death rates 4-5x higher in US

and Europe than in Japan– Stomach cancer – Death rates 7x higher in

Japan than in the US– Hepatocellular carcinoma – Uncommon in US,

one of the most common and lethal cancers in some African populations

• Most geographic patterns related to environmental exposures

Epidemiology

• Age– Frequency of cancer increases with age with

peak between ages of 55 and 75– Increased accumulation of somatic mutations

• Heredity– 5-10% of cancers

• Acquired preneoplastic disorders– Dysplasia, colonic adenoma

Clinical Features of Malignancy

• Cachexia– Decreased body fat, weakness, anorexia,

anemia– Increased infections– Abnormalities of taste, increased metabolic

rate– Correlates with size of tumor

Clinical Features of Malignancy

• Paraneoplastic Syndromes– 10-15% of cancer patients– Symptoms that can’t be explained by spread

of the tumor or by indigenous hormones• Endocrinopathies (SIADH, Hypercalcemia)• Nerve and muscle disorders• Vascular and hematologic changes (thrombosis)

Cancer Diagnosis

• Biopsy

• Fine-Needle aspiration (FNA)

• Exfoliative cytology (pap smear)

• Biochemical markers (PSA, CEA, Alpha-fetoprotein)

Grading and Staging

• Grade – Microscopic (degree of differentiation)

• Stage – Pathologic and clinical findings describing the extend of disease

• AJCC Stage – I-IV• Based on T – size and invasiveness of tumor, N

– presence or absence of nodal metastases, M – presence or absence of distant metastases

• Stage is a stronger predictor of prognosis than grade