Transcript Neoplasia I - UAB - The University of Alabama at Birmingham

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)
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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 “welldifferentiated”
– 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
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Biopsy
Fine-Needle aspiration (FNA)
Exfoliative cytology (pap smear)
Biochemical markers (PSA, CEA, Alphafetoprotein)
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