Tumor Pathology (2)m-learning.zju.edu.cn/G2S/eWebEditor/uploadfile/... · 1. Benign tumors 1....

Tumor Pathology (2)

Zhang Wei （张伟）Associate Professor, Ph.D.

Department of Pathology & Pathophysiology

Zhejiang University, School of Medicine

Zhenjiang University Judicial Evidence & Evaluation Center

zwei72@zju.edu.cn

基础医学导论

二. spread of tumor

（一）. direct spread 直接蔓延

二. spread of tumor

（二）. metastasis (转移）

refers to the process whereby malignant cells spread from

their site of origin(primary tumor) to form other tumors

(secondary tumor) at distant sites.

• Not all cancers have equivalent ability to metastasis, for

example, basal cell carcinoma

• Metastasis are biologic hallmarks of malignancy.

By Three Pathways:

1. lymphatic spread:

Once in the lymphatic vessels, the cancer cells are carried to

the regional draining lymph nodes, where they initially lodge

in the marginal sinus and then extend throughout the node.

Lymph node

metastasis

2.hematogeneous metastasis

By the blood stream, to form secondary tumors in organs

perfused by blood which has drained from a tumor.

Tumor cells systemic veins lung

portal veins liver

pulmonary veins all over the

body( brain, bone, kidney, adrenal gland, et, al.)

3. transcoelomic metastasis（种植转移）：

Seeding in body cavity and surface.

common sites: pericardial , pleural and peritoneal cavities

results in an effusion of fluid into the cavity.

The fluid: rich in protein and may contain the neoplastic cells

cytological examination : important in diagnosing the cause of

effusions into body cavities.

transcoelomic metastasis (seeding)

Krukenberg’ tumors

• Carcinomas tend to favour lymphatic spread

• sarcomas favour hematogenous spread

• However, exceptions to these tendencies are common, and

carcinomas often generate blood-borne metastasis.

1. Invasion of extracellular matrix

two types of extracellular matrix(ECM):

basement membranes

interstitial connective tissue

（三）mechanisms of local and distant

spread in malignant tumors

The sequential steps involved in the local invasion：

detachment 肿瘤细胞彼此分离

↓

attachment 与基底膜粘着增加

↓

degradation 细胞外基质降解

↓

migration 迁移

(1) Detachment of tumor cell from each other

E-cadherin↓ Catenin ↓

(2) Attachment of tumor cells to matrix components

Laminin, Fibronectin + receptors

(3) Degradation of ECM

matrix-degrading enzymes: gelatinases,

collagenases, stromelysins

(4) Migration of tumor cells

autocrine motility factors(AMF)

Schematic illustration of the sequence of events in the

invasion of epithelial basement membranes by tumor cells.

2. metastasis

steps :

1. Invasion of the basement membrane

2. Movement through the extracellular matrix

3. Penetration of vascular or lymphatic channels

4. Survival and arrest within the circulating blood or lymph

5. Exit from the circulation into a new tissue site

6. Survival and growth as a metastasis, a process that involves

angiogenesis

“the seed” and “the soil”

Metastasis

1. heterogenous population of tumor

cells: some break the basement

membrane

2. migration in the mesenchymal tissue,

survival without local growth factors

3. blood vessel invasion

4. survival of the attack by fibrin, NK

cells, complement, antibodies,

thrombocytes, macrophages,

neutrophils, cytotoxic T cells

5. extravasation

6. proliferation

7. angioneogenesis

if you fail in any one of these hurdles,

you will never become a metastasis

三. grading and staging of tumor

grading:

cytologic differentiation

atypia

the number of mitoses

Criteria for the individual grades vary with each form of neoplasia.

gradeⅠ： well differentiated

grade Ⅱ ：moderately differentiated

grade Ⅲ ：poorly differentiated

well differentiated moderately poorly differentiated

staging:

the size of the primary lesion

extent of spread to regional lymph nodes

the presence or absence of metastases

The most generally applicable staging system is the TNM

system：

T: the size of primary tumor T1-T4

N: regional lymph node involvement N0-N3

M: the absence or presence, respectively, of distant metastasis

M0-M1

Section four

Effects of tumor on host

The effects may be local, or occur at distance from the tumor.

一.both benign and malignant tumors

1. Compression

2. Obstruction

3. Hormone production

( more common in benign than in malignant tumors.)

4. Production of bleeding and secondary infections.

二. malignant tumors:

Ulceration, hemorrhage and secondary infecton

Fever

usually the result of tissue necrosis and infection.

Weight loss and cachexia 恶病质

Paraneoplastic syndromes 副肿瘤综合征

Cachexia （恶病质）

refers to the wasting syndrome including progressive loss

of body fat and lean body mass, accompanied by profound

weakness, anorexia, malaise and severe anemia.

no satisfactory treatment for cancer cachexia other than

removal of the tumor.

paraneoplastic syndrome （副肿瘤综合征）：

referred to a syndrome (a set of signs and symptoms) other

than cachexia that appear in patients with cancer and that cannot be readily explained either by the local or distant spread of the tumor or by the elaboration of hormones indigenous to the tissue of origin of the tumor.

Ectopic endocrine syndrome异位内分泌综合征 :

They appear in 10%-15% of patients with cancer.

It is important to recognize them for several

reasons:

1. They may represent the earliest manifestation of an occult

neoplasm.

2. In affected patients they may represent significant clinical

problems and may even be lethal.

3. They may mimic metastatic disease and may, therefore, lead

to inappropriate therapy.

The most common syndromes:

hypercalcemia, cushing syndrome, nonbacterial thrombotic

endocarditis.

The most often associated neoplasms:

bronchogenic carcinoma, breast cancer, and so on.

Paraneoplastic Syndromes

Section 5 comparison of benign and

malignant tumors

Characteristics Benign Malignant

Differentiation/anaplasia Well differentiated; structure

may be typical of tissue of

origin

Some lack of differentiation

with anaplasia; structure is

often atypical

Rate of growth Usually progressive and slow;

may come to a standstill or

regress; mitotic figures are

rare and normal

Erratic and may be slow to

rapid; mitotic figures may be

numerous and abnormal

Local invasion Usually cohesive and

expansile well-demarcated

masses that do not invade or

infiltrate surrounding normal

tissues

Locally invasive, infiltrating

the surrounding normal

tissues; sometimes may be

seemingly cohesive and

expansile

Metastasis Absent Frequently present; the

larger and more

undifferentiated the primary,

the more likely are

metastases

Comparisons Between Benign and Malignant Tumors

Comparison between a benign tumor of the myometrium (leiomyoma)

and a malignant tumor of similar origin (leiomyosarcoma).

Borderline tumors 交界性肿瘤 :

Some tumors defy precise behavioral classification, because

their histology and biological behavior are intermediate

between that associated with benign and malignant tumors.

In certain condition they may transform into malignant

tumors.-----potential malignant

Such as:

some ovarian tumors, pleomorphic adenoma or “mixed

tumor” of salivary gland, papilloma of thyroid.

Section 6 nomenclature and

classification of tumors

一. Nomenclature of tumors

1. Benign tumors

1. site+cell type from which the tumor arises + oma

such as：adenoma of thyroid

2. benign epithelial tumors : more complex.

classified sometimes on the basis of their microscopic ormacroscopic pattern.

such as: papillary cystadenoma

2. Malignant tumors

(1 ) . Malignant neoplasms of epithelial cell origin are called

carcinomas.

site + histogenesis + carcinoma

such as: squamous cell carcinoma of cervix

adenocarcinoma of stomach

transitional cell carcinoma of bladder

(2). Malignant neoplasms arising in mesenchymal tissue

are called sarcomas.

site + histogenesis + sarcoma

such as：osteosarcoma

fibrosarcoma

3. More than one neoplastic cell type usually derived from one

germ layer:

malignant mixed tumor of salivary gland

4. More than one neoplastic cell type derived from more than one

germ layer----immature teratoma

5. Certain additions and exceptions:

Hodgkin’s lymphoma

Ewing’s sarcoma

leukemia

neuroblastoma

clear cell carcinoma

Nomenclature and classification of Tumors

Tissue of Origin Benign Malignant

Composed of One Parenchymal Cell Type

Tumors of epithelial origin

Stratified squamous Squamous cell papilloma Squamous cell or epidermoid carcinoma

Basal cells of skin or adnexa Basal cell carcinoma

Epithelial lining of glands or ducts Adenoma Adenocarcinoma

Papilloma Papillary carcinomas

Cystadenoma Cystadenocarcinoma

Respiratory passages Bronchial adenoma Bronchogenic carcinoma

Renal epithelium Renal tubular adenoma Renal cell carcinoma

Liver cells Liver cell adenoma Hepatocellular carcinoma

Urinary tract epithelium (transitional) Transitional cell papilloma Transitional cell carcinoma

Placental epithelium Hydatidiform mole Choriocarcinoma

Testicular epithelium (germ cells) Seminoma

Embryonal carcinoma

Tumors of melanocytes Nevus Malignant melanoma

Nomenclature and classification of Tumors

Tissue of Origin Benign Malignant

Tumors of mesenchymal origin

Connective tissue and derivatives Fibroma Fibrosarcoma

Lipoma Liposarcoma

Chondroma Chondrosarcoma

Osteoma Osteogenic sarcoma

Endothelial and related tissues

Blood vessels Hemangioma Angiosarcoma

Lymph vessels Lymphangioma Lymphangiosarcoma

Synovium Synovial sarcoma

Mesothelium Mesothelioma Malignant Mesothelioma

Brain coverings Meningioma Invasive meningioma

Blood cells and related cells

Hematopoietic cells Leukemias

Lymphoid tissue Lymphomas

Muscle

Smooth Leiomyoma Leiomyosarcoma

Striated Rhabdomyoma Rhabdomyosarcoma

The WHO Classification of Tumors

Tissue of Origin Benign Malignant

More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from One Germ Cell Layer

Salivary glands Pleomorphic adenoma (mixed tumor of salivary origin) Malignant mixed tumor of salivary gland origin

Renal anlage Wilms tumor

More Than One Neoplastic Cell Type Derived from More Than One Germ Cell Layer-Teratogenous

Totipotential cells in gonads or in embryonic rests Mature teratoma, dermoid cyst Immature teratoma, teratocarcinoma

Not real tumors

aneurysm

Inflammatory pseudotumor

tuberculoma

Hamartoma

ventricular aneurysm

choristoma

A hamartoma is a neoplasm in an organ that is

composed of tissue elements normally found at that

site, but growing in a haphazard mass.

Section 7 Precancerous lesions, dysplasia and

carcinoma in situ

1. precancerous lesions/diseases 癌前病变/疾病：

certain clinical conditions well-recognized predispositions

to the development of malignant neoplasia.

The lesions which have potentially malignant changes, they will change to carcinoma if they exist for long time.

Leukoplakia 粘膜白斑

Atypical ductal hyperplasia of the breast

Villous adenomas of the colon, familial adenomatous

polyposis

Chronic atrophic gastritis with intestinal metaplasia

ulcerative colitis

Chronic skin ulcer

2. dysplasia, atypical hyperplasia

It is a loss in the uniformity of the individual cells,as well as a loss

in their architectural orientation. But it is short of frank

neoplasia.

Dysplastic cell:

pleomorphism(variation in size and shape)

deeply stained(hyperchromatic) and large nuclei

more mitotic figures

architectural anarchy

Mild(<1/3)

moderate(1/3-2/3）

severe (>2/3)

dysplasia

dysplasia

The term ‘intraepithelial neoplasia’, as in cervical

intraepithelial neoplasia (CIN), is used to embrace both

carcinoma in situ and the precursor lesions formerly known

as dysplasia.

3. carcinoma in situ

severe dysplastic changes are almost involved the entire

thickness of the epidermis in skin or squamousepithelium in

mucosa, but do not invade the basement membrane.

a preinvasive stage of carcinoma

It is only at this very early stage that excision of a

carcinoma will guarantee a cure.

The phase of in situ growth may last for several years

before invasion commences.

Carcinoma in situ

子宫颈鳞状上皮内病变、上皮内瘤变和原位癌

(Squamous intraepithelial lesion, SIL)

(cervical intraepitheliar neoplasia, CIN) and Carcinoma in situ

子宫颈上皮异型增生(cervical epithelial dysplasia)：

子宫颈上皮部分被不同程度异型性的细胞所取代，细胞排列紊乱、体积增大、核大

、可见核分裂，属癌前病变。

Ⅰ级：异型细胞局限于上皮下1/3

Ⅱ级: 1/3-2/3

Ⅲ级: 超过2/3，但未累及全层

子宫颈原位癌（carcinoma in situ） ：

异型增生的细胞累及子宫颈鳞状上皮全层，但局限于上皮层内，未突破基底膜。

子宫颈上皮内瘤变（cervical intraepithelial neoplasia, CIN）：

近来认为，子宫颈上皮非典型增生到浸润癌可能是一连续过程，而子宫颈上皮非典型增生

和原位癌属于非浸润性病变，统称为子宫颈上皮内瘤变。

Grade and Pathological change: CIN I: mild dysplasia

atypical cells limited in the basal 1/3 of the epithelium

CIN II: moderate dysplasia

cellular atypia in the lower 2/3 of the epithelium

CIN III: severe dysplasia

atypical cells involve more than 2/3 of the epithelium

CIS

子宫颈鳞状上皮内病变(Squamous intraepithelial lesion, SIL)：

属癌前病变，指子宫颈上皮部分被不同程度异型性的细胞所取代，表现为出现凹空细胞或鳞状

上皮细胞大小形态不一，核增大深染，核浆比例增大，核分裂象增多，细胞极性紊乱。

低级别鳞状上皮内病变 CIN I 轻度非典型增生

（low-grade squamous intraepithelial lesion, LSIL ）

高级别鳞状上皮内病变 CIN II 中度非典型增生

（high-grade squamous intraepithelial lesion, HSIL ） CIN III 重度非典型增生和

原位癌

Section 7 Common tumors

一. Epithelial tumors

1.benign epithelial tumors

papilloma

benign

adenoma

1. papilloma

site：skin,esophagus,larynx,penis

G：exophytic growth, finger-like fronds

M：well-differentiated epithelium

connective tissue axis

Prognosis: good!

exceptions: out-tract of ear, penis, bladder, colon----potential

malignant!

Papilloma of the colon with finger-like projections into the lumen

2. Adenoma

site：thyroid gland, ovary, breast, salivary gland and colon

G：node-like, polyp-like, often circumscribed and

encapsulated

M：(1) crowded glands，uneven distributed

(2) disorder, absence of lobule and duct

(3) well differentiated cells (secretion)

Classified into:

(1) tubular adenoma, villous adenoma

(2) cystadenoma

(3) fibroadenoma

(4) pleomorphic adenoma

(5) polypous adenoma

cystadenoma ：means benign tumor of glandular

epithelium that is largely cystic grossly

Typically in ovary, occasionally in thyroid or pancreas

Grossly: hollow cystic masses

Histologically：serous papillary cystadenoma; mucinous

cystadenoma

cystadenom（ovary）

fibroadenoma

Breasts of young females;

Grossly: solitary, movable mass;

Histologically: a mixture of proliferated ductal

elements (adenoma )embedded in a loose fibrous

connective tissue (fibroma)

pleomorphic adenoma

Mixed tumor of salivary gland origin

Epithelial cells forming ducts + fibromyxoid stroma;

sometimes islands of cartilage or bone

Slow in growth but easy to recurrence

pleomorphic adenoma