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 nonneoplastic 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!