Chapter 5
Neoplasia
longjie
Department of Pathology
Neoplasia
Cause of death:
No. 1 Cardiovascular diseases
No. 2 Cancers
Benign tumors
Malignant tumors
cancer
男性
女性
全球肿瘤病人死亡率
Etiology
Pathogenesis
oncology
Dignosis
Treatment
Molecular basis
1. Definition
Tumor means swelling. Currently
tumor is applied solely to neoplastic
masses.
Neoplasm is often referred to as a
tumor.
胃腺癌
革囊胃
Neoplastic proliferation
Nonneoplastic proliferation
良性与恶性增生对照示意图
良性增生
恶性增生
Tumor is a proliferation of cells which is:
1. not related to needs of the body
2. Clonal
3. transformed - loss of normal growth
controls ,abnormal appearance
4.lack of capability of differentiation
5.autonomy-steadily increase in size
肿瘤性增生与非肿瘤性增生的区别
肿瘤性增生
非肿瘤性增生
1 异常增生
反应性增生
2 异常形态代谢和功能
4 机体不需要、有害
为原组织形态结构代谢
改变，或纤维肉芽组织
生理性、修复性、炎症
性
适应需要、有利
5 去除原因后继续增生
去除原因后不再增生
6 细胞基因突变、增殖分
化障碍
7 单克隆
细胞增殖的正常调节
3 良性或恶性
多克隆
Definition
A neoplasm is an abnormal mass of
tissue, the growth of which exceeds and
is uncoordinated with that of the normal
tissues and persists in the same
excessive manner after the cessation of
the stimuli which evoked the change.
肿瘤
局部组织、细胞在致瘤因子作用
下，在基因水平上失去正常调控
而致相对无限制的增生，常常在
局部形成肿块，称肿瘤。
2. Morphology
Grossly:
(1)
Number
(2) Volume
(3)
shape
(4)
colour
(5)
texture
数目：多为一个，也有两个以上。
Follicular adenoma of the
thyroid.
（背部）多发性神经纤维瘤
volume
骶尾部巨大神经纤维瘤
The shape of tumor
The shape of tumor
Colour:
癌组织
脂肪瘤
眼
的
毛
细
血
管
瘤
脚
底
黑
色
素
瘤
texture：
脂肪瘤质软，骨瘤则很硬
capsule：良性瘤多有包膜，恶性瘤没
有包膜或包膜不完整。
大体形态对识别肿瘤的良恶性有很大
意义。
纤维腺瘤（包膜完整）
肺癌（无包膜）
Microscopically:
All tumors, benign and malignant,
have two basic components:
(1) the parenchyma
(2) the stroma (mesenchyma)
PARENCHYMA
STROMA
Squamous cell carcinoma
Parenchyma
1. made up of neoplastic cells.
2. determines biologic behavior of
the tumor.
3. from which the tumor derives its
name.
Stroma
1. made up of connective tissue and
blood vessels.
2. host-derived, non-neoplastic.
3. carries the blood supply to the
parenchymal cells.
4. provides support for the growth
of parenchymal cells.
3. Atypia
The differentiation of
parenchymal cells refers to the
extent to which they resemble
their normal forebears, both
morphologically and functionally.
Malignant neoplasms are characterized
by a wide range of parenchymal cell
differentiation, from well differentiated
to undifferentiated.
Spectrum of malignancy:
High
Moderate
Poor
differentiation-differentiation-differentiation-Undifferentiation
Benign; Lowly
malignant
Moderately
malignant
Highly
malignant
Very highly
malignant
Differentiation of adenocarcinoma
Well
differentiated
Moderate
differentiation
Poorly
differentiated
正常粘膜上皮
高分化恶性增生
粘膜良性增生
低分化恶性增生
腺上皮癌形态与分化程度
高分化
中分化 低分化 未分化
Atypia of neoplasm
The difference of cellular morphology
and tissue structure between the neoplasm
and its original tissue.
肿瘤的异型性
肿瘤组织无论在细胞形态上或
组织结构上都与其起源的正
常组织有不同的程度上的差
异，这种差异称之为异型性
Cellular ~
细胞异型性
atypia
Architectural ~
组织结构异型性
细胞异型性：
1.肿瘤细胞：多数体积较大
2.肿瘤细胞大小、形态不一致，瘤
巨细胞
3.核大深染，核浆比例近1：1。
4. 多核，核深染，
5. 核仁肥大，有病理性核分裂。
肿瘤细胞异型性
病理性核分裂
1，2为
正常核
分裂，
其他为
病理性
核分裂
Abnormal tripolar mitosis (pathologic mitosis)
病理性核分裂
病理性核分裂
组织结构异型性：
肿瘤细胞排列紊乱，无极性和数目
增多。
非肿瘤性增生
肿瘤性增生
（异型性）
4.Nomenclature
classification
Nomenclature
Benign Tumors
Designated by attaching the
suffix “-oma” to the cell or tissue
type from which the tumor arises.
For example: fibroma, myoma,
lipoma, adenoma.
Malignant tumors
Arising in epithelial cell are called
carcinomas
癌
Arising in mesenchymal tissue are called
sarcomas
肉瘤
Carcinosarcoma
癌肉瘤
3 某些肿瘤的特殊命名法：
组织来源不明者，按形态命名：
如腺泡状软组织肉瘤、上皮样肉
瘤；
以人名命名：如尤文瘤（
Ewing’s tumor）、何杰金氏病
（Hodgkin’s disease）；
母细胞瘤：恶性：神经母细
胞瘤、髓母细胞瘤、肾母细胞瘤
等；良性：软骨母细胞瘤、肌母
细胞瘤；
恶性瘤：如恶性畸胎瘤、恶
性黑色素瘤；
习惯命名：白血病、精原细胞瘤
；
内分泌肿瘤：肿瘤细胞分泌激素
名+瘤
如：胃泌素瘤、胰岛素瘤、APUD
瘤
畸胎瘤（teratoma）
Classification of neoplasia
P98
免疫组化标记
Tumor antigens
Tumor-Specific Antigens.
Tumors express unique antigens not expressed
on normal tissues can serve as targets for tumorspecific cytotoxic T cells
Tumor-Associated Antigens
Some tumor antigens are not unique to the
tumors .
They are shared by normal cells from which the
tumor arose. They are also called differentiationspecific antigens. e.g. prostate-specific antigen
(PSA) is expressed on normal as well as cancerous
prostatic epithelium.
5. Growth
Invasion
Growth pattern:
Expansile growth
Exophytic growth
Invasive growth
膨胀性生长
外生性生长
浸润性生长
Rate of growth
Most benign tumors grow slowly.
Most cancers grow much faster to
eventually spread locally and to distant sites
(metastasize).
Some exceptions: Leiomyomas may
rapidly increase in size during pregnancy,
but stop to increase during menopause and
even become small in postmenopause.
Biology of tumor growth
Kinetics of tumor cell growth
1. The doubling time of tumor cells.
2. Growth fraction. Approximately 20%.
3. Cell production and loss. Cell production
exceeds cell loss in tumors
Tumor angiogenesis
Tumor angiogenesis is effected mainly by basic
fibroblast growth factor ( bFGF ) and vascular
endothelial growth factor (VEGF). They stimulate
endothelial cell to grow and to form vessels.
Tumor heterogeneity
As a result of tumor progression, a tumor
contains different subpopulations of cells that
differ with phenotypes, such as invasiveness,
rate of growth, metastatic ability, karyotype,
hormonal responsiveness, and susceptibility
to antineoplastic drugs.
At the molecular level,
tumor progression and associated heterogeneity most
likely result from multiple
mutations that accumulate
independently in different
cells, generating subclones
with different characteristics.
Progression
(演进）
Heterogeneity（异质性）
Local invasion（spreading,infiltrating)
Benign neoplasm:
has no capacity to invade.
does not metastasize to distant sites.
develops an enclosing fibrous capsule (not
all benign neoplasms are encapsulated).
Malignant neoplasm:
progressive growth.
not develop well-defined capsules
infiltrate, destroy the surrounding tissue
Metastasis
Connotes the development of
secondary implants discontinuous with
the primary tumor in remote tissues.
Metastatic pathways:
1) Lymphatic spread.
2) Hematogenous spread
3) Seeding within body cavities
Lymphatic spread
the favored metastasis routin by carcinomas
Lung carcinomas bronchial lymph nodes the
tracheobronchial nodes and hilar nodes
Carcinoma of breast (upper outer quadrant)
the axillary nodes.
.
淋巴道转移模式图
1：外周淋巴管
2：输入淋巴管
3、4：输出淋巴管
淋巴结
双击画面进行播放
淋巴道转移
淋
巴
管
内
癌
栓
淋巴结转移
转
移
的
肿
瘤
组
织
Lymphatic spread
Hematogenous spread
It is the favored pathway for
sarcomas. Via venules.
血道转移：瘤细胞
静脉
肺和
肝等（最多见），形成边缘整齐
、散在、多发的球形结节，中央
常发生坏死，近脏器表面形成“
癌脐”。
血道转移模式图
血管内癌栓
双击画面进行播放
肝血道转移癌
癌脐
(1) Poral venous system
(2) Systemic venous system
肺
血
管
内
的
癌
细
胞
肾上腺腺癌
的肺转移
(3) Pulmonary venous system
Seeding of cancers:
Carcinoma of the colon and ovary
peritoneal
cavity.
Lung cancers
Medulloblastoma
pleural cavities.
cerebral ventricles (carried
by the cerebrospinal fluid and reimplant on the
meningeal surfaces, either within the brain or in
the spinal cord.
6.
Grading
staging
Grading and staging
For clinical use.
Grading: I, II, III, IV
Staging:
T1-T4, N0-N3, M0-M2
Grading of Malignant Neoplasms
Grade Definition
I Well differentiated
II Moderately differentiated
III Poorly differentiated
IV undifferentiated
Grading of adenocarcinoma
I
II
III
IV
TNM-Staging of Bronchial
Carcinoma
 T：Tumor
and
local invasion
 N：lymphatic
spread
 M：
hemologenous
spread
7.
Effect
Effects:
Benign tumor
Malignant tumor
Cachexia
Cancer cachexia
Many cancer patients suffer progressive loss of
body fat and lean body mass, accompanied by
profound weakness, anorexia, and anemia. This
wasting syndrome is referred to as cachexia.
Benign and malignant tumor (cancer)
Benign - Relatively innocent , remain
localized, amenable to removal and patient
survival.
Malignant - Lesion can invade and destroy
adjacent structures. Spread to distant
sites (metastasize). Cause death.
8. Difference
between benign and
malignant tumors
Comparison of benign and malignant tumors
Characteristics
Benign
Malignant
Differentiation/anaplasiaWell-differentiated; Lack of differentiation
Structure may be
with anaplasia; Structure
typical of tissue of is often atypical
origin
Rate of growth
Usually progressive Erratic and may be slow
and slow; may come to rapid; mitotic figures
to a standstill; mitotic may be numerous and
figures are rare
abnormal
Local invasion
Usually expansile,
Locally invasive, infilwell-demarcated
trating the surrounding
masses; not invade
normal tissues; somethe surrounding
times may seem expansile
normal tissues
Metastasis
Absent
Frequently present;
肿瘤的良恶性鉴别
9. Precancerous lesions
dysplasia
Carcinoma in situ
癌前病变
具有癌变潜在可能性的良性
病变。如子宫颈糜烂、粘膜
白斑等。
Dysplasia
A term used to describe disorderly but nonneoplastic proliferation.
1. Principally in the epithelia.
2. Loss in the uniformity of the individual cells.
3. Loss in their architectural orientation.
4. Exhibit pleomorphism.
5. Variation in size and shape.
6. Hyperchromatic nuclei.
7. Mitotic figures are abundant and in abnormal
locations.
When dysplastic changes involve of the
thickness of the epithelium:
less than 1/3
mild atypical proliferation.
less than 2/3
moderate atypical
proliferation.
more than 2/3 severe atypical proliferation.
When dysplastic changes are marked
and involve the entire thickness of the
epithelium, the lesion is referred to as
carcinoma in situ, a preinvasive stage of
cancer.
But dysplasia:
1. not indicate cancer.
2. not necessarily progress to cancer.
3. reversible: Mild to moderate changes of
epithelium may be reversible, and with removal
of the putative inciting causes, the epithelium
may revert to normal.
Intraepithelial neoplasia
10.Pathogenesis
carcinogen
Carcinogenesis
The molecular basis of cancer:
1. Nonlethal genetic damage
May be acquired by the action of carcinogen
May be inherited in the germ line.
2. Three classes of normal regulatory genes
The growth-promoting protooncogenes
The growth-inhibiting cancer suppressor genes
Genes that regulate apoptosis
3. Genes that regulate repair of damaged DNA
A disability in the DNA repair genes can
predispose to widespread mutations in the
genome and hence to neoplastic transformation.
4. Carcinogenesis is a multistep process.
Normal cell
Repair
Acquired environmental
factors:
chemicals
radiation
viruses
Activation of growthpromoting oncogenes
DNA damage
Mutations in
the genome of
somatic cells
Genetic factors
inherited mutation
in genes affecting
cell growth or DNA
repair
Alterations of genes
that regulate apoptosis
Inactive of cancer
suppressor genes
Expression of altered gene products
and loss of regulatory gene products
Clonal expansion
Additional mutations (progression)
Heterogeneity
Malignant neoplasm
Oncogenes and cancer
Acute transforming retroviruses contain
genome which cause rapid induction of tumors
(viral oncogenes or v-oncs)
The normal human cell nucleus contains genes
which code for induction of tumors ( protooncogenes, c-onc).
The oncogenic retroviruses contain genes
(v-onc) which are homologous to the protooncogenes.
Cancer suppressor genes
the products of tumor suppressor genes apply
brakes to cell proliferation.
Rb gene
Two-hit hypothesis:
1. Two mutations (hits) are required to produce
retinoblastoma. These involve the Rb gene.
Both of the normal alleles of the Rb locus must
be inactivated ( two hits ) for the development
of retinoblastoma.
2. In familial cases, children inherit one defective
copy of the Rb gene in the germ line; the other
copy is normal. Retinoblastoma develops when
the normal Rb gene is lost in the retinoblasts as
a result of somatic mutation.
3. In sporadic cases,
both normal Rb alleles
are lost by somatic
mutation in one of the
retinoblasts.
The end result is the
same: a retinal cell that
has lost both normal
copies of the Rb gene
becomes cancerous.
P53
Homozygous loss of the p53 gene is found in
many types of cancer, including carcinomas of
the lung, breast, and colon.
Adenomatous polyposis coli (APC) gene
Patients born with one mutant allele of APC
invariably develop numerous adenomas of the
colon. These adenomas progress to become
malignant.
Genes that regulate apoptosis
A series of three letter words beginning with a
b, (bcl-2, bcl-x, bax, bag, and bad).
The overexpressed bcl-2 protects tumor cells
from apoptosis and allows them to survive for
prolonged periods. bax opposes bcl-2 action and
hence accelerates cell death.
Etilology of cancer:carcinogenic agents
Genetic damage lies at the heart of carcinoge-
nesis. Three classes of carcinogenic agents can be
identified: chemicals, radiant energy, and oncogenic viruses.
Chemical carcinogens
Industry
Aniline dyes
Mineral oil
and tar
Plastics
Insulation
Tumor
Chemical responsible
Bladder cancer Naphthylamine
Skin cancers
Benzpyrene and other
hydrocabons
Angiosarcoma Vinyl chloride
of liver
monomer
Mesothelioma Asbestos(carcinogenic
activity depends on the
physical configuration
of the fibers
Chemical carcinogenesis is a multistep process of
long duration:
(1)Initiation:
Application of Benzpyrene
Skin appears normal but
Normal skin
important changes have
occurred in the cell DNA
(2)Promotion:
co-carcinogens
Papilloma formation
dyspalsia
(3)Appearance of malignant tumor
Breech of basement membrane
invasion
Radiation carcinogenesis
The ionizing activity of X-rays and atomic
radiations produce many changes in the nuclear
DNA ranging from chromosome breakage,
translocations to point mutations. New clones of
mutant cells arise which may produce tumor
growth.
The atomic bombs dropped on Hiroshima
and Nagasaki.
The nuclear power accident at Chernobyl.
Viral Oncogenesis
A large number of DNA and RNA viruses
have proved to be oncogenic in animals. However,
only a few viruses have been linked with human
cancer.
In humans
Human papilloma
DNA Human Skin papilloma
virus (HPV)
and cervical
cancer
Herpes group
DNA Human Burkitts
lymphoma
Epstein-Barr virus
Nasopharyngeal Ca.
(EBV)
Hepatitis B
DNA Human
Liver cancer
Onco-retrovirus
RNA Human Leukemia and
group. Human T
(slow)
lymphoma
cell leukemia
virus (HTLV)
Hepatitis B virus
The oncogenic effect of HBV appears to be
multifactorial.
HBV
infection
HPV
x-protein
Liver cells Liver cell injury inactivation of p53 Aflatoxin
and regeneration activation of oncogenes
Cell mutation
Liver carcinoma
11. exsamples
Benign epithelial tumors
Papilloma
from an epithelial surface.
is thrown into folds.
found in the skin or within ducts (breast).
Papilloma of the colon with
finger-like projections into the
lumen
Papilloma of the skin
Adenoma
derived from the ducts and acini of
glands or solid epithelial organs.
Mucinous cystadenoma of the ovary
Adenoma
cyst forms (cystadenoma).
in a hollow viscus (adenomatous
polyp or papillary adenoma).
in the breast (fibroadenoma).
carcinoma
Squamous cell carcinoma
(1) on the skin and the site covered by stratified
squamous epithelium.
(2) glandular epithelium through metaplastic
transformation. Histologically irregular strands
and columns.
cell nests in the subjacent connective tissue.
keractin pearls and frequent mitotic activity.
Squamous cell carcinoma
Squamous cell carcinoma
(anus)
口唇部鳞状细胞癌
食管鳞状细胞癌（箭头所指）

食管下1/3
食管上1/3
squamous
cell
carcinoma
Squamous cell
carcinoma
Adenocarcinoma
Histologically
1. Adenocarcinoma:
show a varying degree of differentiation with
acinus formation.
2. The carcinoma may be undifferentiated (solid
masses or columns of pleomorphic cells).
3. Mucoid carcinoma: The acini are filled with
mucus.
4. Signet-ring cell carcinoma.
Adenocarcinoma
of stomach
adenocarcinoma
较多见于胃肠、胆囊
、子宫体等处。
1）乳头状腺癌
2）囊腺癌
3）乳头状囊腺癌
adenocarcinoma
癌细胞形成大小
不等、形状不一、
排列不规则的腺样
结构。
endometrial carcinoma
乳头状浆液性囊腺癌
（卵巢）
乳头状浆液性囊腺癌
（卵巢）
Mucoid
carcinoma
又称胶样癌，常见
于胃和大肠。癌组织呈
灰白色，湿润，半透明
如胶冻样，因而得名。
Mucoid carcinoma
镜下，初时黏液聚集在癌细胞内，将
核挤向一侧，使细胞呈印戒状，故称之为
印戒细胞 (signet-ring cell)。
Tubular adenocarcinoma
Carcinoma simplex
Mucoid carcinoma
Signet-ring cell carcinoma
Basal cell carcinoma
common in the face near the eyes and nose.
the surface breaks down and a shallow ulcer is
formed. Cancer cells resemble the basal cells.
is a locally invasive growth almost never
metastasises.
Basal cell carcinoma

transitional
cell
carcinoma
transitional cell carcinoma
箭头所指为肿
瘤，呈菜花
状，并可见
由于肿瘤堵
塞输尿管口
导致两侧输
尿管高度扩
张。
transitional cell carcinoma (I)
transitional cell carcinoma (II)
箭
头
所
指
为
病
理
性
核
分
裂
transitional cell carcinoma (iii)
肿瘤
平滑肌
Benign connective tissue tumors
Fibromas
rare in the soft tissues but in the
ovary and kidney.
Lipoma
in the subcutaneous tissue of
the arms, shoulders and buttocks.
rarely in solid organs.
lobulated.
well-defined.
yellow in color.
Neurofibroma and Schwannoma
derived from the peripheral nerves.
single or multiple.
cause compression effects.
Chondroma
Solitary enchondroma (tubular bones)
causes destruction of the bone by
expansion
and pressure.
Osteoma
Leiomyoma
benign tumors of smooth muscle.
commonly in the uterus.
Hemangioma
1. Capillary angioma
common in the skin as birth-marks.
occasionally in internal organs.
consist of endothelial cells.
2. Cavernous angioma
deep purple and spongy
often in the liver.
Malignant connective tissue tumors
1 The Greek sarcoma means flesh.
2 The most common malignant tumor in
children and young adults.
3 Is a rounded growth with well definite
margins.
4 Hemorrhage and necrosis are frequent.
5 Easily invade the venules and early lung
metastasis are common.
癌与肉瘤的区别
Fibrosarcoma
spindle cells resembling fibroblast
differentiation.
varies degree of malignancy with
frequent mitoses.
Osteosarcoma of the lower end of the femur
1.occur in patients between 10-25 years of age.
2.affect the metaphysial ends of long bones (the upper
end of the tibia, lower end of the femur).
3.Codman triangle formation. highly malignancy.
4.producing metastasis at a early stage.
5.histologically they show irregular calcified bone and
osteoid tissue among masses of pleomorphic cells.
Chondrosarcoma
occurs in older age groups.
arise at the proximal ends of long bones of
the pelvis
slowly grow.
low-grade malignancy.
Liposarcoma
is an uncommon tumor.
arise in connective with simple lipoma.
lobulated and pleomorphic.
liposarcoma
Myosarcoma
1. Leiomyosarcoma:
arise in the deep soft tissues, the stomach
and uterus from pre-existing myomas.
2. Rhabdomyosarcoma:
a rare tumor occurring mainly in children.
may be pleomorphic and frequent mitoses.
highly malignant and poor prognosis.
rhabdomyosarcoma
由不同分化阶段的横纹肌母细胞构成
Mixed tumors
Benign: Mixed parotid tumor (epithelium and
stroma).
Malignant: Carcinosarcoma (a combination
of carcinoma and sarcoma).
Retinoblastoma
Retinoblastoma
菊形团
Malignant melanoma
commonly found in:
(1) skin of face, feet, palms of
hands, legs and trunk.
(2) mucous membranes of
mouth and eye.
Features of malignant melanoma are:
1. Abnormal melanocytes.
2. Invasion of epidermis.
3. Invasion down into dermis.
Teratoma
arise in the gonads or in the mid-line of the
body.
arise from totipotent germ cells.
the most common site of teratoma is in the
ovaries.
1. Benign cystic teratoma:
contains skin and its appendages, neural
tissue, respiratory epithelium, intestinal
epithelium, bone and cartilage.
2. Malignant teratoma:
contains embryonic, fetal and adult tissues.
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