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1. Chapter 5. Neoplasia
Xu HT

2. 病 例病 例
ＸＸＸ，女， 21岁
主诉：近半年左下肢膝关节附近疼痛，活动后
加重，一个月前发现左股骨下端局部隆
起，逐渐长大，疼痛难忍，来诊。
查体：左股骨下端局部肿物，压痛（＋）
处置：1. 左股骨下端 X线正侧位像
2. 胸部X线正侧位像
3. 左股骨下端肿物穿刺活检

3. 检查结果检查结果
1.左股骨下端 X线正位像
：
左股骨下端占位病变，
骨皮质破坏 ,骨膜反应。
2.胸部X线正侧位像：
未见明显异常

4. 临床诊断：恶性骨肿瘤？
活检病理诊断：骨肉瘤

5. 治疗原则治疗原则
1.手术切除
2.化 疗
3.放 疗
4.支持疗法

6. 1.什么是肿瘤？具有哪些特性？
2.肿瘤有哪些种类、各自特点？
3.肿瘤生物学行为如何？对机体有何影响
？
4.肿瘤的结局如何？
5.肿瘤是如何发生发展的？如何防治？
思 考 题思 考 题

7. Chapter 5. Neoplasia
Tumors is common diseases.
Bad news: Malignant tumor (cancer) is the
second leading cause of death in some countries.
(The first leading cause is cardiovascular
diseases.)
According to American Cancer Society estimates,
in 2003, about 23% of all deaths in the United
States (1500 cancer deaths per day).

8. Good news:
The rapid progress has been made in
understanding the molecular basis and
biological behavior of cancer and cancer
therapy. Many cancers can be cure or
arrested.
For example: breast cancer, cervical cancer
But many problems still need to be solved!

9. Section 1. Definition and morphologySection 1. Definition and morphology
Two question:
What is tumor? Definition
What are tumors look like? Morphology

10. ※※DefinitionDefinition
Neoplasia literally means the process of
“new growth” and a new growth is called
a neoplasm.
tumor was originally applied to the
swelling caused by inflammation.
Oncology is the study of tumors or
neoplasms.
Cancer is the common term for all
malignant tumors.

11. Neoplasia
In 1953, The eminent British oncologist Willis had
given neoplasia a famous 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
cessation of the stimuli which evoked the change.”
A more scientific difinition: “Neoplasia is genetic
disease, in which the growth of tumors is loss of
responsiveness to normal growth control, and shows
an excessive hyperplasia with abnormal
differentiation.”

12. Tumor (neoplasm):
under the stimulation of tumorgenic
agents
a single cell of local tissue loss the
controlling to its growth at the gene level
excessive proliferation to form neoplasm

13. Distinguish between neoplastic and Distinguish between neoplastic and
non-neoplastic hyperplasianon-neoplastic hyperplasia
Neoplastic Non-neoplastic
Monoclonality Polyclonality
Abnormal morphology Normal morphology
and function and function
Abnormal differentiation Matured differentiation
Persistent, autonomous Limited
Harmful Beneficial

14. ※※Morphology and structureMorphology and structure

Number and Size: various

Shape: sessile, papillary, nodular, lobular,
cystic, fungating, ulcerated, and infiltrating

Color: dependent on histogenesis and
secondary changes (hemorrhage, necrosis)

Consistency: Parenchyma-stroma ratio,
Secondary changes

Capsule: benign with intact capsule

Secondary changes: hemorrhage, necrosis
Macropathology: The gross appearance of tumors is
varied, reflecting the nature of the tumor to some extent.

15. Number and size:
various
Fibroadenoma
Polypous adenoma

16. papillary
polypous
Shape: relate to histogenesis,
site and biologic behavior
Papilloma
Polypous adenoma
Benign

17. Nodular or lobular
cystic
Lipoma Fibroadenoma
Mucinous cystadenoma粘液性囊腺瘤
Benign

18. Fungating（菜花） Ulcerated Infiltrative
Malignant

19. Color:

The color of a benign tumor resembles that of the normal tissue from
which it derived.

The color of the cut surface of a malignant tumor may be gray-
white, and often varied due to secondary changes (hemorrhage,
degeneration and necrosis).

20. Capsule
•The benign tumor is usually circumscribed by a clearly
defined border and often encapsulated by thin fibrous capsule.
•The malignant tumor is invasive and poorly circumscribed.
Fibroma Carcinoma of stomach

21. Consistency


Resembles the normal tissue
it derived from

Tumors are usually firmer than
surrounding tissues

Proportion of parenchyma
and stroma

Secondary changes
Adipose tissue  Lipoma: soft
Cartilage  Chondroma: hard

22. ScirrhousScirrhous
硬癌硬癌
carcinomacarcinoma
Consistency
Parenchyma-stroma ratio
stroma>Parenchyma
hard

23. Medullary carcinoma Medullary carcinoma
髓样癌髓样癌
Consistency
Parenchyma>Stroma
soft

24. Secondary changes
Necrosis
Hemorrhage

25. Histological structureHistological structure
All tumors have basic two components:
1. Parenchyma
Major component of tumor: neoplastic cell
Determine the biologic nature and specificity
2. Stroma
Composed of CT and BV →support the tumor
Growth speed depend on the stroma blood supply
LC infiltration →immune reaction to tumor

26. Parenchyma Stroma

27. Stromal BVStromal BV
Fibrosarcoma

28. NO stromal BVNO stromal BV

29. What is neoplastic atypia?
The atypia of tissue architecture
The atypia of neoplasic cells
Section 2. Neoplastic atypiaSection 2. Neoplastic atypia

30. ※※What is atypia?What is atypia?
Atypia: Neoplastic tissue has various extent of
differences with its originated normal tissue,
both cell morphologically and tissue
architecturally.
Differentiation: The degree to which a neoplasic
cells resembles its originated normal mature
cells, both morphologically and functionally.

31. 
Anaplasia（未分化） : Lack of
differentiation of malignant neoplastic
cell, with obviously atypia.

Anaplastic tumor: composed of
undifferentiated cell.
Pleomorphism: obvious
variation in size, shape
obviously atypia

32. Atypia of tissue architectureAtypia of tissue architecture
Refers to difference between neoplastic
tissue and its originated normal tissue

The arrangement of neoplastic tissue

The polarization of neoplastic tissue

the relationship with stroma

33. Intestinal adenoma
Adenocarcinoma

35. Squamous cell carcinoma

36. Atypia of neoplastic cells
◆Pleomorphism of neoplastic cells
1. Variation in size and shape
2. Generally larger than normal cells
→tumor giant cells

37. ◆ Pleomorphism of nucleusPleomorphism of nucleus
1. Increased nucleus:
The nuclear- to - cytoplasmic ratio may
approach 1:1 instead of the normal 1:4 - 6.

38. 2. Variation in size, color and shape of
nucleus:

①
Size: Huge, two or more nuclei, bizarre nuclei,
large nucleoli are usually present.

②
Color: The nuclei contain an abundance of
DNA and are extremely dark staining

39. ③ Shape :
i) The shape is usually extremely variable,
the chromatin is coarsely clumped

40. ii) Increased mitotic figures :
Atypical, bizarre mitotic figures producing
tripolar, quadripolar, or multipolar spindles.

42. Normal structureAdenocarcinoma

43. ◆

◆
Changes of Changes of
cytoplasm cytoplasm
1. Cytoplasm:
Basophilic →nucleoprotein increased
2. Abnormal products or secretion:
Mucus, glycogen, lipid
helpful to determine histogenesis of tumor

44. Mucoid carcinoma

45. Squamous cell carcinomaSquamous cell carcinoma

46. Melanoma（黑色素瘤） of the skin

48. Ultrastructural changes Ultrastructural changes (electron microscope)(electron microscope)
Organelles : signs of histogenesis
Neuroendocrine granules
→neuroendocrine tumor
Tonofilament and desmosomes
→squamous cell carcinoma
Myofilament and dense body →SMC

49. Section 3. Growth and spread of tumorSection 3. Growth and spread of tumor
Growth pattern of tumor
Biology of tumor growth
Spread of neoplasms (Invasion
and metastasis)
Mechanisms of invasion and
metastasis
Grading and staging of tumor

50. 1. The growth of tumor1. The growth of tumor
I. Growth pattern of tumor
1.Expansive growth
2.Exophytic growth
3.Infiltrating growth

51. ◆ Growth pattern of tumor
1. Expansive
growth:
The mode of most
benign tumor
nodular
intact capsule
Leiomyoma

52. (1) Sites: surface of body, body cavities
or tract organs.
(2) Shape: papillary, polypoid, cauliflower
(3) Growth pattern of both benign (has a
pedicle) and malignant tumor (also grow by
infiltrating)
2. Exophytic growth:

53. Exophytic growth

54. The mode of most malignant tumor
absence of capsule, infiltrate and destroy
surrounding tissue
3. Infiltrating growth

55. II. Biology of tumor growthII. Biology of tumor growth
1. Monoclonality: Tumor is formed by a
transformed cell proliferation
2. The natural history of most malignant tumors
can be divided into four phases:
(1) Malignant transformation in the target cell
(2) Clonal growth of the transformed cells
(3) Local invasion
(4) Distant metastasis

56. 3. The multiple factors that influence
tumor growth are considered under
three headings:
(1) kinetics of tumor cell growth
(2) Tumor angiogenesis
(3) Tumor progression and heterogeneity

57. ◆

◆
Kinetics of tumor cell growthKinetics of tumor cell growth
Doubling time of tumor cells
Growth fraction
Tumor cell production and loss

58. Doubling time of tumor cells:
In reality, cell cycle time for many tumors
equal to or longer than that of
corresponding normal cells
growth of tumor is not associated with a
shortening of cell doubling time

59. Growth fraction: the proportion of cells
within the tumor population that are in the
proliferative pool ( S + G2 phase ).

①
Early stage →vast majority of
transformed cell are in the proliferative
pool →high growth fraction

②
As tumors continue to grow →cell leave
the replicative pool →by differentiating
and by reversion to Go →in rapidly
growing tumors → approximately 20%

60. Tumor cell production and loss:
Growth of tumors are determined by the
excess of cell production over cell loss.
 The rate of tumor growth depends on:
Growth fraction
Degree of imbalance between cell
production and cell loss

61. High grow fraction:
Clinical course is rapid (lymphoma)
susceptibility to chemotherapy
Low grow fraction (cell production exceeds
cell loss by only about 10%):
Grow at a much slower pace (car. of colon)
no susceptibility to chemotherapy

62. ◆

◆
Tumor angiogenesisTumor angiogenesis
Angiogenesis is a necessary biologic
correlate of malignancy: tumors cannot
enlarge beyond 1 to 2 mm in diameter or
thickness unless they are vascularized.
Angiogenesis is requisite not only for
continued tumor growth, but also for
metastasis.

63.  Neovascularization has dual effect:

①
Perfusion supplies nutrients and oxygen
② Newly formed endothelial cell
secreting polypeptides such as
insulin-like GF, PDGF
stimulate the growth of tumor cell

64. 
How do growing tumors develop How do growing tumors develop
a blood supply? a blood supply?

①
Tumor associated angiogenesis factors
produced by tumor cells
infiltrated inflammatory cells

VEGF, FGF, PDGF

65. ②
Tumor induce antiangiogenesis molecules:

WP53 →induce thrombospondin 1
→ inhibit formation of BV
P53 gene mutation →thrombospondin 1↓→BV↑
Plasminogen, collagen, transthyretin Plasminogen, collagen, transthyretin
→ →proteolytic cleavage proteolytic cleavage
→ →angiostatin, endostatin, vasculostatin, angiostatin, endostatin, vasculostatin,
→ →potent angiogenesis inhibitorspotent angiogenesis inhibitors

66. ◆

◆
Tumor progression and heterogeneityTumor progression and heterogeneity
1. Tumor progression
Malignant tumor become more aggressive in
the process of growth
accelerated growth
local invasion
distant metastasis

67. 2. 2. Tumor heterogeneityTumor heterogeneity
In the process of growth, monoclonal tumor cells
generate subclones with different characteristics


3. Mechanism:
Mutant additional genes damage（突变附
加基因损伤）
Invasiveness, rate of growth
hormonal responsiveness
susceptibility to antineoplastic drugs

68. 2. Spread of neoplasms
Local invasion (direct spread)
Metastasis
Lymphatic metastasis
Hematogeneous metastasis
Transcoelomic metastasis
(Metastasis in body cavities)
(seeding)

69.  Spread of neoplasms
1. Direct spread
Malignant tumor C →infiltrate tissue,
lymphatic, BV, nervous tissue
2. Metastasis
Malignant cells from primary site invade
into lymphatics, BVs and body cavities and
reach distant site continues growth to form
the same type tumor with primary tumor

70. ①
The most common pathway for the
initial dissemination of carcinoma

②
Sarcoma（肉瘤） may also use this route

③
The most common site:
Lung
Gastrointestinal tract
Arm pit, groin, cervical glands
（臂窝，腹股沟，宫颈腺）
(1) Lymphatic metastasis:
Left
supraclavicular
LN

71. Afferent lymphatics
Tumor emboli
Subcapsular sinus
Efferent lymphatics
Retrograde
metastasis
Primary tumor
Lymphatic nodule

72. Lymphatic metastasis

73. Lymphatic metastasis

74. (2) Hematogeneous metastasis

①
The favored pathway of sarcoma.

②
Metastatic pathway:
Caval blood lung
Portal blood liver
Pulmonary v(cap) brain, bone, kidney
Vertebral vein paravertebral plexus
brain ( Prostate, thyroid)

③
Common sites: lung (most), liver, bone

75. ④
Features of hematogeneous metastatic tumor:
multiple, rounded nodules with clear border,
scattered in distribution, close to surface of organ.
Choriocarcinoma

76. ⑤
Carcinoma umbilicus （癌脐）
Hematogeneous metastatic tumor located
surface of the organ forms umbilication because
of central hemorrhage and necrosis

77. (3) Transcoelomic metastasis
(Metastasis in body cavities or Seeding)

①
Definition: Malignant tumor cell of an
organ in body cavity penetrate into the surface
of the organ and break off to seed in the
surface of the organs of body cavity and form
metastatic tumor.

78. Transcoelomic metastasis
Colloid carcinoma of stomach
seed in
the surface
of intestine

79. ②
krukenberg tumor:
Gastric carcinoma destroy gastric wall
and tumor cell seed in the ovaries to form
metastatic tumor

③
Sites peritoneal cavity (most common)
pleural, pericardial,
subarachnoid, joint space

④
Surgical instruments: rare
an artificial mode of dissemination

80. 
The mechanisms of invasion andThe mechanisms of invasion and
metastasis metastasis
The mechanism of local invasion
Vascular dissemination and homing
of tumor cells
Molecular genetics of metastasis

81. ◆ The mechanism of local invasion
(1) Detachment of the tumor cells from each other :
Down-regulation of E-cadherin (CAM) expression
(2) Attachment to matrix components:
Integrin (epithelium) binding to laminin (BM)
(3) Degradation of extracellular matrix:
Tumor cell secrete proteolytic enzymes
induce host cell to elaborate proteases
(4) Migration of tumor cells: Mediated by
Tumor cell derived motility factors
Cleavage products of matrix components

83. ◆◆ Vascular dissemination and homing of
tumor cells
Single tumor cell is destroyed
by nature killer cell (NKC)
Formation of platelet-tumor aggregate
Enhance the survival and implantability
Tumor emboli involve adhesion
to endothelium cells (EC)
Egress through the basement membrane (BM)

85. prostate to boneprostate to bone
lung to adrenal, brain lung to adrenal, brain
breast to lung, liver, bone breast to lung, liver, bone
(1) Tumor cell express the adhesion molecules
whose ligands are expressed on the EC of
the target organs.
(2) Some target organs may liberate
chemoattractants to recruit tumor cell
to the site.
(3) Some organs may be an unfavorable
soil for the growth of tumor seeding:
such as spleen, heart, skeletal muscle
Organ Organ
tropismtropism

86. ◆
Molecular genetics of metastasis
1.No single metastasis gene has been found.
2.The gene that encode E-cadherin,
inhibitors of metalloproteinases, nm23,
etc. is considered metastasis suppressor
genes.

87. III. Grading and staging of tumorIII. Grading and staging of tumor
◆ Grading of tumor:
According to degree of differentiation
and the number of mitoses:
Grade : well-differentiated
Ⅰ
Grade : moderately-differentiated
Ⅱ
Grade : poorly-differentiated
Ⅲ
Grade : undifferentiated
Ⅳ

88. Well-differentiated Moderately-differentiated
Poorly-differentiated Undifferentiated

89. ◆◆ Staging of tumor:Staging of tumor:
Based on size of the primary lesion,
its extent of spread to LN
distant metastasis:
UICC (international union against cancer)
TNM classification of malignant tumours
T: primary tumor, T1~T4 →increasing size
N: Regional LN involved, N
0
→no involved; N1-N3
M: distant metastasis, M
0→no; M1-M2

90. Section 4. Effects of tumor on host
Benign tumor: less effects
Local oppression and obstruction:
Relate to site and secondary change
Important organs: intestinal, brain→hernia(疝)
Tumor of endocrine glands: systemic symptoms
Acidophilic adenoma of hypophysis（垂体） cerebri:
gigantism or acromegaly
Adenoma of pancreatic islets: fatal hypoglycemia

91. 
Malignant tumorMalignant tumor
1. Local compression + obstruction + pain
2. Constitutional symptoms:
Fever, infection, night sweat
3. Cachexia（恶病质） :
Refer to the state of progressive loss of
weight, anemia, weakness and systemic
failure.

92. 4. Paraneoplastic syndrome 4. Paraneoplastic syndrome ( PNS )( PNS )
 Neoplastic product (ectopic异位 hormones)
 Abnormal immune reaction (cross immune,
autoimmune, immune complex )
 Other unclear causes

Lead to lesions of endocrine, nervous, digestive
system and so on

93. (1) Ectopic endocrine syndrome:
Some non-endocrine tumors elaborate
hormones or hormone-like substance cause
endocrine disorder.

①
Hypercalcemia: parathormone -like substance
elaborated by carcinoma of lung, kidney

②
Hypoglycemia: elaboration of insulin-like
substance by fibrosarcoma, mesothelioma

94. (2) Hypertrophic osteoarthropathy:
Formation of bone, arthritis of the
adjacent joint and clubbing of the digits.
(3) Vascular and hematologic syndrome:
Migratory thrombophlebitis,
endocarditis

95. Section 6. Differences between
Benign and malignant tumor ※

96. Degree of well poorly
differentiation structure is typical obvious atypia
Mitotic figure rare and normal increased

no pathologic mitotic pathologic mitotic
Rate of growth slow rapid
Growth pattern expansive infiltrative
exophytic exophytic
well demarcated poorly
demarcated
Benign malignant

※
Difference between benign and malignant tumor
(Part I)

97. Secondary rare common
changes ( hemorrhage, necrosis)
Local invasive noninvasive locally invasive
Metastasis absent common
Recurrence rare common
Effects compression cachexia
on host obstruction metastasis
Benign malignant

※
Difference between benign and malignant tumor
(Part
II)

98. Section 3. Nomenclature and
classification

99. 
NomenclatureNomenclature

◆
Benign tumor:
(1) Cells of origin + “oma”
Fibroma, adenoma, fibroadenoma
(2) Cells of origin + morphologic feature
Adenoma + cystic囊 cystadenoma
+ papillary papillary cystadenoma

100. ◆

◆
Malignant tumorMalignant tumor
(1) Carcinoma: Arising in epithelial cell
Squamous cell carcimnoma
Adenocarcinoma
Transitional cell carcinoma
(2) Sarcoma: Arising in mesenchymal tissue
Cells of origin + “sarcoma”
Fibrosarcoma, liposarcoma,
Leiomyosarcoma, rhabdomyosarcoma平滑肌，
横纹肌
(3) Carcinosarcoma:
Carcinoma + sarcoma

101. (1) Arising in totipotential cells:
Teratoma (benign, malignant): Made up of a variety
parenchymal cell type of more than one germ layer
(2) -blastoma: Neuroblastoma, medulloblastoma,
(3) Malignant-: Malignant melanoma, meningioma
(4) Custom: Leukemia, seminoma
(5) Name: Ewing’s sarcoma, Hodgkin’s lymphoma
(6) Tumor cell morphology: Clear (oat ) cell sarcoma
(7) -omatosis: Neurofibromatosis, lipomatosis

◆
Others

102.  Classification
Tissue of origin Benign Malignant
Epithelial tumors
Stratified squamous squamous cell squamous cell or
papilloma epidermoid carcinoma
Basal cells of skin or adnexa basal cell carcinoma
Epithelial lining
Glands or ducts adenoma adenocarcinoma
papilloma papillary carcinoma
cystadenoma cystadenocarcinoma
pleomorphic adenoma malignant mixed tumor
(mixed tumor of salivary origin) of salivary gland origin
Urinary tract epithelium Transitional cell Transitional cell
(transitional) papilloma carcinoma

103. Mesenchymal tumors
Connective tissue fibroma fibrosarcoma
lipoma liposarcoma
Smooth muscle leiomyoma leiomyosarcoma
Striated muscle rhabdomyoma rhabdomyosarcoma
Blood vessels hemangioma angiosarcoma
Lymph vessels lymphangioma lymphangiosarcoma
osteoma osteogenic sarcoma
chondroma chondrosarcoma
Synovium synovil sarcoma
Mesothelium mesothelioma malignant mesothelioma
Tissue of origin Benign Malignant

104. Lymphoid tissue malignant lymphomas
Hematopoietic cells leukemias
Brain coverings meningioma invasive meningioma
Melanin cell nevus malignant melanoma
Placental epithelium Hydatidiform mole choriocarcinoma
(trophoblast)
Testicular epithelium seminoma
(germ cells) embryonalcarcinoma
Totipotential cells in gonads mature teratoma immature teratoma
or in embryonic rests dermoid cyst teratocarcinoma
Tissue of origin Benign Malignant

105. Assignments
•Concept explanation:
•Neoplasia
•Atypia
•Differentiation
•Cachexia

106. Questions:
How tumor growth? (growth pattern)
How neoplasms Spread? (Invasion and metastasis)
Try to explain The process of tumor cells
local invasion?
Difference between benign and malignant
tumor？