Epidemiology 242: Cancer Epidemiology

Epidemiology 242: Cancer Epidemiology

Epidemiology 242: Pathology Basis of Caner Jian-Yu Rao, MD Professor of Pathology and Epidemiology Fall, 2009 OBJECTIVES

To learn basic histopathological terminology. To know different types of tumor. Tumor is a disorder of cells

A neoplasm (Greek, Neo-New, plasma, thing formed) is the autonomous growth of tissue that have escaped the normal restraints on cell proliferation and exhibit varying degrees of fidelity to their precursors. It is usually appears as a tumor ( a swelling) made of mass of cells.Abnormal growth of

cells, Unlimited growth of cells. What is the difference between tumor vs cancer Tumor Either benign or malignant Cancer Usually malignant

Classification of Tumors -Based on histological origin (epithelial, mesenchyme, etc..) -Based on biological behavior (benign vs malignant)

PATHOLOGICAL REPORT Tumor histological type. Tumor stage. Tumor grade. Other features (size, % necrosis, lymphovascular invasion)

CANCER HISTOLOGICAL TYPE Three Major Categories: Epithelial Carcinoma Mesenchyme Sarcoma Hematopoitic Leukemia/Lymphoma Other Minor Categories:

Nevocytic Melanoma Germ cell Teratoma, Seminoma, Yolk sac tumor, Choriocarcinoma, etc Endocrine/Neuro Carcinoid/Insulinoma/small cell carcinoma, etc

CARCINOMA Squamous Squamous Cell Carcinoma. Glandular - Adenocarcinoma. Transitional Transitional Cell Carcinoma.

Small cell Small cell carcinoma SARCOMA Muscle Smooth muscle: Leiomyosarcoma Skeletal muscle: Rhabdomyosarcoma

Fat Liposarcoma Skeleton Osteosarcoma Cartilage Chondrosarcoma Classification of tumor according to their morphologic features (histology)

Morphologic classification refers to the histologic classification made by pathologist based on microscopic examination. Benign vs Malignant Tumor

The main distinction between benign and malignant tumor is: Malignant tumor has invasion and metastatic potential whereas benign tumor does not. Malignant tumor has features of abnormal cellular differentiation

whereas benign tumor usually not. Why histologic classification is important in cancer epidemiology? Cancer is not ONE disease Different cancer types of same organ may have different exposure

etiology, pathogenesis, as well as behavior, i.e., HETEROGENEITY Carcinoma Carcinoma (Cancer of the epithelium) 85% Epithelium is the term applied to the

cells that cover the external surface of the body or that line the internal cavities, plus those cells derived from the linings that form glands. Why most common cancers are epithelial origin? These cells are the first point of contact

of the body with environmental substances, either directly (squamous cells) or indirectly (glandular cells). Epithelial cells usually have fast turn over rate, i.e., fast cell division, and their DNA can be damaged by carcinogens more often than non-dividing cells.

Carcinoma: Squamous cell Originates from stratified squamous epithelium of the skin, mouth, esophagus, and vagina, as well as from areas of squamous metaplasia, as in the bronchi or squamocolumnar

junction of the uterine cervix. SCC is marked by the production of keratin. Skin Cancer Squamous Cell Carcinoma Carcinoma, Transitional Cell

Transitional cell carcinoma - arise from the transitional cell epithelium of the urinary tract, such as bladder. transitional cell carcinoma of the urothelium is shown here at low power to reveal the frond-like papillary projections of the tumor above the surface to the left. It is differentiated enough to resemble urothelium, but

is a mass. No invasion to the right is seen at this point. TCC at high power Carcinoma: Adenocarcinoma Adenocarcinoma - is carcinoma of

glandular epithelium and includes malignant tumors of the gastrointestinal mucosa, endometrium, and pancreas; and is often associated with desmoplasia, tumor-induced proliferation of non-neoplastic fibrous connective tissue, particularly in adenocarcinoma of the breast, pancreas, and prostate.

Prostate Ca Ovarian Ca Sarcoma Sarcoma is a malignant tumor of

mesenchymal origin Sarcoma is often used with a prefix that denotes the tissue of origin of the tumor, as in osteosarcoma (bone), leiomyosarcoma (smooth muscle), rhabdomyosarcoma (skeletal muscle), and liposarcoma (fatty tissue).

Classification of tumor according to stage Stage -is clinical assessment of the degree of localization or spread of the tumor. -generally correlated better with prognosis

than dose histopathologic grading. -is examplified by the generalized TNM system, which evaluates size and extent of tumor (T), lymph node involvement (N), and metastasis (M). -different staging systems (WHO, TNM, etc), sometimes oriented toward specific tumors, e.g., Dukes system for colorectal

carcinomas. Classification of Tumor according to its differentiation (grade) Grade of Disease Grading is histo-pathologic evaluation of

the lesion based on the degree of cellular differentiation and nuclear features: Well Differentiated (Grade I) more resemble to normal tissue/cell Moderately differentiated (Grade II) - less resemblance of normal tissue/cell Undifferentiated (Grade III)

- lost resemblance to normal tissue/cell Gleason's breakthrough was to develop a reproducible description of the glandular architecture, to which one assigns a score from 1 to 5. The pathologist looks for a major pattern and a minor pattern

to give a Gleason sum between 2 and 10. On the left is a picture adapted from Gleason's 1977 article demonstrating the changes in gland pattern as one goes from grade 1 to grade 5 cancer. The glands in grade 1 cancer are small and round. Grade 5 cancer is

hardly forming glands at all. Gleason Grade 1 Prostate Cancer At right is Gleason 3 CaP. The glands are irregularly shaped. They are mixed in with some normal glands.

This tumor is infiltrating the prostate. At higher magnification, there are nests of glands with no intervening stroma. This is characteristic of

higher grade CaP Here is Gleason 5, or poorly differentiated cancer. You can see that it is invading the

seminal vesicle (stage T4) The cells are not organized into glands, but are infiltrating the prostate as cords.

Precursors from intraepithelial neoplasia (INs) to carcinoma in situ (CIS) NORMAL

CIN 1 NORMAL LGSIL CIN 2

HG SIL CIN 3 HGSIL Important for Epidemiologist Study nature history of disease progression

Study genetic/environmental factors associate with disease progression Develop tools for risk assessment/early detection Targets for chemoprevention Exposure to Carcinogen Birth

Precancerous Intraepithelial Lesions, (PIN, CIN, PaIN..)e Additional Molecular Event

Cancer Surrogate End Point Markers Genetic Suscep. Marker Markers for

Exposure Markers of Effect CHEMOPREVENTION Tumor

Markers SUMMARY The key is to understand tumor hetergeneity: Human cancer is not one disease , but many different types of diseases (Disease heterogeneity). The same type/stage/grade of tumor may behave differently in different person (Behavior

heterogeneity). Even within the same tumor, there are may be different histological appearances and molecular expressions/changes (Expression heterogeneity). As an epidemiologist, we should know the basic features of the disease, and design studies accordingly

Thank You!

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