tumor pathology (2)m-learning.zju.edu.cn/g2s/ewebeditor/uploadfile/... · 1. benign tumors 1....
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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
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