1. Neoplasia I
Walter C. Bell, M.D.

2. 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

3. 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

4. Nomenclature Benign neoplasms end in the suffix “-oma” Mesenchymal
Fibroma
Chondroma
Epithelial
Adenoma
Papilloma
Cystadenoma

7. Nomenclature Mesenchymal cancers are called sarcomas
Fibrosarcoma
Chondrosarcoma
Epithelial cancers are called carcinomas
Squamous cell carcinoma
Adenocarcinoma

8. 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)

14. Confusing Terminology (Names that break the rules)
Lymphoma
Mesothelioma
Melanoma
Seminoma
Hepatoma – old terminology for HCC
Choristoma

15. 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

16. 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

20. Benign vs Malignant
Dysplasia – Pre neoplastic change usually in epithelia
May not progress to cancer

22. Differentiation In general, function correlates with differentiation
Unanticipated functions can emerge
Ectopic hormones
Fetal proteins

23. 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

24. Ki-67 in dysplasia
Increased proliferation, disordered

25. 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

28. 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

32. 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

37. 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

39. Epidemiology Age Heredity Acquired preneoplastic disorders
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

40. Clinical Features of Malignancy
Cachexia
Decreased body fat, weakness, anorexia, anemia
Increased infections
Abnormalities of taste, increased metabolic rate
Correlates with size of tumor

41. 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)

42. Cancer Diagnosis Biopsy Fine-Needle aspiration (FNA)
Exfoliative cytology (pap smear)
Biochemical markers (PSA, CEA, Alpha-fetoprotein)

45. 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