Neoplasia I Walter C. Bell, M.D.
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