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