internal medicine

1. lung cancer
( 肺 癌 )

2. Prevalence
Epidemic report in 1999: 1,000, 000 new
cases worldwidely
Rapid increase in population of youth and
females
Death rate: 1st in male cancer patients, 3 rd
in female; In China, 3rd in cancer patients –
1st in urban, 4th in rural area
A report from WHO predict that lung cancer &
AIDS are the first TWO of the most severe D
in this century

3. Etiology & Mechanisms
( 病因和发病机制 )

4. 1. Smoking
One of the most important risk factors
Smoking closely related to squamous & small
cell lung cancer
of lung cancer patients: smokers have 10-13
times higher Death rate than nonsmokers
The more the smoking, the longer the course,
the earlier the initiation, the younger the death
The passive smokers have even more
impairment than active ones

5. Smoking & histological changes
↓ Ciliary cells
Epithelial cells hyperplasia
Metaplasia to squamous cell
Atypical hyperplasia

6. Industrial waste air
Tail gas excreted by auto
Pitchy waste on highway
Benzopyrene
2. Air pollution

7. 3. Pollution in family
passive smoking
Incomplete burning of coal
Radon

8. 4. Occupational factors
Confirmed by WHO
Exposure to asbestos, inorganic Arsenate,
radon, Nickel, etc
Other possible factors include acrylamidine,
acrolein resin, chlorovynilic products, etc

9. 5. Ionizing radiation
Lung is sensitive
Occurrence increased after atomic attacks in
Japan and radiation therapy
More related to small cell carcinoma
Nosocomial radiation is much more, among
which, 36.7% from X-ray
Natural radiation in special area

10. 6. Diets & Nutrition
Deficiency of vitamin A or its derivatives,
vitamin C, B2 & E
Deficiency of selenium or zinc

11. Other factors
Bronchial carcinoma may be related to
chronic bronchitis, lung TB, or other chronic
respiratory D
TB scar tends to develop into Cancer
Genetic correlation remains to be proven

12. Pathogenesis

13. Anatomic classification
Central bronchial carcinoma: segmental
or larger bronchi, account for ¾ cases,
consist of squamous and small cell lung
cancer
Peripheral: small bronchi or
bronchioles, account for ¼
cases ， adenocarcinoma is the main
histological type

14. Histological classification
(WHO)
1980
Squamous cell
well, medium or badly differentiated
Small undifferentiated cell
lymphocyte-like ( avenine cell )
intermediate cell (fusiform cell, polyhedral cell, etc)
Adenocarcinoma
well, medium or badly differentiated, bronchoalveolar/papillary
Large cell
accompanied with mucus differentiation
accompanied with multilamellar structure
cytomegalic, megalocyte
hyalocyte

15. Biobehavioral classification
Small cell lung cancer (SCLC): 25%
Non-small cell lung cancer (NSCLC):
75%, including squamous lung cancer,
adenocarcinoma, and adeno-squamous
lung cancer

16. Clinical features

17. Small cell carcinoma
Originated from Kultschitzky (K cell) or
argyrophilic cell in mucus gland of airway
Evidence from immunohistochemistry and
special tumor markers indicate SCLC has
characters of neuroendocrinal tissues
Paraneoplastic syndrome: serotonin, histamine,
kinin, catecholamine, etc
Polymorphic: avenine, lymphoid, and fusiform

19. Accounts for 25% of all lung cancer cases,
increase rapidly recently
Most malignant
Occur commonly at age of 40-50
Closely related to history of smoking
90% in a central location
Sensitive to radiation & chemical therapy

20. Rapidly growth
Earlier local infiltration: blood vessel, hilum of
lung, or mediastinal lymph node
Earlier metastasis: 22-28% in liver, 17-30% in
bone marrow, 8-15% in CNS, 11% in
postperitonum

21. Non-small cell lung carcinoma
（非小细胞肺癌）

22. Squamous cell （鳞癌）
Originated mainly from segmental or
subsegmental bronchi
Intraluminal growth
Cancerous cavity & abscess is more common
Medium or badly differentiated: cancerous
nest, keratinization, intercellular bridge
Neural granule rarely seen

24. Commonly occurrence
In the elder male persons
Closely related to smoking
Mostly in a central location
Slow growth, late metastasis, more
opportunity to be eradicated
Insensitive to radiation & chemical
therapy

25. Adenocarcinoma ( 腺癌 )
Acinar, papillary, mucoserous or mucus
cell carcinoma
Originated from peripheral bronchiole
mucoserous glands
Peripheral lung cancer
Extraluminal growth

27. more commonly in Females
Irrelevant to smoking
Early local infiltration & early metastasis
Infiltrate to pleura→ pleural effusion
Metastasis to liver, brain and bones

28. Bronchoalveolar cancer
( 细支气管肺泡癌 )
A subtype of lung adenocarcinoma
Peripheral region
Single nodule, multiple nodule or diffused distribution
Slow growth, especially for single nodule
Infiltrates to several lobe for diffuse ones
Well differentiated
Originated from Clara cell, type alveolar epithelialⅡ
cells or mucus cells

31. Large cell lung cancer
Megalocyte, polygonal or presented as
clear cytoplasm,
May be central, but more occurs
peripherally
Malignant
Neuroendocrinal granules
Metastasis is a little later than SCLC, so
more opportunity for surgery

33. Clinical manifestations

34. Symptoms caused by
primary tumors
cough
hemoptysis
gasping
Dyspnea or short of breath
Loss of body weight
fever

35. Cough
One of the early symptoms
Stimulating Without sputum or with a little
mucus sputum
Large quantity of sputum was seen in
bronchoalveolar LC
Obstructive cough: persistent, high-pitch,
metal-like sound
Exuberant purulent sputum seen in those
accompanied with secondary infection

36. Hemoptysis
More commonly in central LC
A little amount of blood in sputum, large
amount of bleeding is rare

37. Gasping or asthma
Partly obstruction of airway induced by
tumor
Typical presentation: localized gasping

38. Dyspnea, short of breath
Possible mechanisms
1. Bronchial narrowing induced by intraluminal
growth of tumor
2. Extraluminal oppression by Metastasis of
hilar lymph node
3. Large amount of pleural effusion
4. Large amount of pericardium effusion
5. Diaphragmatic paralysis, obstruction of
superior cava vein, diffuse infiltration

39. Loss of body weight
Tumor toxin
Increased consumption
Infection
Dyspepsia caused by unendurable pain

40. Fever
Tumor necrosis, lower than 38.5ºC
Secondary infection

41. Symptoms caused by local
infiltration
Chest pain: infiltrated to pleura, ribs or
thoracic wall
Dyspnea: big airway oppressed
Dysphagia: esophagus infiltrated, or
bronchoesophageal fistula
Aphasia: recurrent laryngeal nerve
infiltrated

42. Superior cava vein syndrome
Mechanism: Mediastinal infiltration →S.
cava V oppressed →blood flow obstructed
Manifestations: Edema on face, neck
and upper limbs
Varices and haemostasis on chest
Headache and dizziness

44. Horner syndrome
Also termed as Pancoast tumor, superior sulcus
tumor
In the apex or upper lobe near brachial plexus and
cervical sympathetic ganglion
Oppression on the latter →ipsilateral drooped eyelid,
myosis (retracted pupil), inward eyeball, little or no
sweating on ipsilateral forehead and chest
The former oppressed →ipsilateral pain radiated to
inside upper limb, exacerbated at night

46. Symptoms caused by distal
metastasis
Metastasis to brain and CNS
Bone
Liver
Lymph node: such as supraclavicular
ones

48. Paraneoplastic syndrome
• In SCLC, Endocrinal disorders: serotonin,
histamine, kinin, catecholamine, etc
Male mammary development caused by ↑
secretion of human chorionic
gonadotrophin (hCG)
Cushing syndrome caused by ↑ secretion
of adrenocorticotrophic hormone (ACTH)

49. Secretion of anti-diuretic hormone (ADH)
1. Diluted hyponatremia
2. Dyspepsia
3. Fatigue, somnolence
Hypercalcemia caused by parathyroid
hormone- related hormone, more in
squamous LC

50. Neuromuscular syndrome
Mechanism is not clear
More commonly in SCLC, but seen in
all histological types of LC
Irrespective to site and metastasis
Characteristic manifestations: proximal
limb muscle weakness & fatigue

51. Carcinoid syndrome
Excessive secretion of serotonin
Occur in SCLC (avenine cell LC) and
adenocarcinoma
Clinical manifestations:
1. Bronchial spasm →gasping or asthma
2. Paroxysmal tachycardia
3. Watery diarrhea
4. Skin flush

52. Digital clubbing & hypertrophic
oesteoarthropathy
More commonly in squamous lung cancer,
next is adenocarcinoma, least in SCLC
Distal side of long bone of limbs
Acropachy and oesteoarthropathy
Disappear after successful surgery, but
appear with recurrence of tumor

54. Imaging
Thoracic X-ray– most important
examination
1. Thoracic perspective
2. Posterioanterior and lateral X-RAY
imaging
3. CT
4. MRI

55. PA & lateral X-RAY imaging
Central LC
1. Mass or shadow near to hilum with
irregular margin
2. Multiple lobe
3. Coexistent of atelectasis, obstructive
pneumonia & localized emphysema

56. Peripheral LC
1. Bronchoalveolar LC
2. Nodular or diffuse type

57. CT
Have advantage in diagnosis of LC in
special sites: posterior to heart, near to
spine, capitulum costae or diaphragm,
on apex
Discern metastasis to hilar or
mediastinal LN
Helix CT: ＞ 3mm discernable

58. MRI
Compared with CT
1. Have advantage in discern the infiltration to
large blood vessels
2. But no advantage in the diagnosis of small
tumors

59. Histology
Sampling means
1. Bronchoscopy – most important ,90-93%
sensitive to central LC
2. CT-guided subcutaneous needle aspiration
3. Mediastinoscopy
4. Biopsy in surgery
5. Exfoliative cytology in sputum, more
sensitive for NSCLC, 70-80%

60. Scintigraphic Imaging
Tumorphilic chemicals labeled with Radioactive
isotypes
Tumor marker-specific Ab labeled with
Radioactive isotypes –radioimmunography
Administered intravenously or by inhalation,
image obtained with a gamma camera
＜ 1cm LC or LN metastasis can be discerned
by PET

61. Tumor markers in use
CEA, NSE ( 神经原特异性烯醇化酶 ),
SCC ( 麟癌细胞抗原 ), TPA ( 组织多肽
抗原 )
Not sensitive and specific enough

62. Diagnosis

63. 1. > 40, longtime persistent heavy smokers (smoking
index >400 per year)
2. Stimulant cough without prominent trigger, little or
no response to therapy; Characters of cough
Varied in patients with chronic respiratory D
3. Persistent or recurrent hemoptysis, not interpreted
by other respiratory D
4. Recurrent localized pneumonia, esp. segmental
pneumonia
5. Lung abscess, without toxic presentations, no
exuberant purulent sputum, no inhalation of foreign
body, no response to antibiotics

64. 1. Limb articulate pains or acropachy
2. Localized emphysema, or segmental,
lobar atelectasis
3. Solitary round loci, ipsilateral hilar
enlargement
4. New alterations of Stable TB loci
5. Pleural effusion, especially
haemothorax with progressively
increase of effusion

65. Differentiation Diagnosis
Lung TB
Pneumonia
Lung abscess
Tubercular effusion pleurisy

66. Lung TB
TB tuberculoma from central LC: more
common in youth, asymptomatic, with clear
margin & integral envelope, high density
→calcified loci, invariable with follow-ups
Hilus TB from metastasis to hilar LN: more
common in childhood & aging, well
responded to tuberculocides
Acute miliary TB from peripheral
bronchoalveolar LC: homogenous size,
evenly distributed, low density; while the latter
with uneven distributed loci, high density,
progressively enlargement

67. Pneumonia
Abrupt onset
Respond well to antibiotics
Curable, loci can completely disappear

68. Lung abscess
Primary Lung abscess: abrupt onset, fever, &
other significant toxic symptoms, ↑ WBC &
neutral granulocyte counting; thinner cavity
wall with liquid plane & inflammatory changes
Cancerous cavity: centrifugal cavity within a
cancerous mass, thick & rough wall. May
complicated with secondary infection→ fever,
production of purulent sputum

69. Tubercular effusion pleurisy
Malignant effusion: haemothorax,
increase rapidly
↑CEA &LDH
No response to tuberculocides
Cytology examine in pleural precipitates

70. Clinical staging
TNM staging standard for LC
Cryptic Tx N0 M0 (or invisible )
0 Tis tumor in situ
Ⅰ T1N0M0 T2N0M0
Ⅱ T1N1M0 T2N1M0
Ⅲa T3N0M0 T3N1M0 T1-3N2M0
Ⅲb N3M0 with any T, T4 and M0 with any N
Ⅳ M1 with any T, any N

71. Interpretations for TNM staging
T: primary tumor
1. T0: no evidence of tumor
2. Tx: cytology findings, but not confirmed by X-ray
or bronchoscopy, termed as cryptic tumor
3. Tis: tumor in situ
4. T1: φ≤3cm, enveloped by lung tissue or visceral
layer of pleura, no infiltration to proximal lobar
bronchi
5. T2: φ >3cm, or infiltrated to visceral layer of
pleura, or obstructive pneumonia or atelectasis;
hilar infiltration, but less than 2cm from carina;
6. T3 ： infiltration to chest wall, diaphragm,
mediastinum, pleura or pericardium, hilar
infiltration, more than 2cm from carina
7. T4: Invades heart, great vessels, esophagus,
trachea, carina, vertebrae, or malignant effusion

72. N: infiltration to local LN
1. N0: no infiltration findings
2. N1: infiltration around bronchi, or ipsilateral
hilar infiltration, or bilateral infiltration
3. N2: metastasis to ipsilateral mediastinal LN
or those below carina
4. N3: metastasis to contralateral hilar,
mediastinal LN of the other side; ipsilateral
or contralateral metastasis to supraclavicular
or scalenus ( 斜角肌 ) LN
5. M: distal metastasis
M0: no evidence; M1: proved metastasis

73. Treatment
NSCLC
1. Stage - a: surgery centered integralⅠ Ⅲ
intervention
2. Stage b: chemical therapy centeredⅢ
integral treatment
3. Stage : chemical therapy with supportiveⅣ
measurements
SCLC ： chemical therapy centered,
assisted by surgery and/or radiation
Immune regulations
TCM

74. Surgery
Pneumonectomy
Lobectomy
Limited resections
Carinal resection & sleeve Pneumonectomy
Monitor, Supportive therapy & chemical
therapy before & after operation

75. Chemical therapy
SCLC
1. EP project: Etoposide + cisplatin
2. CAO project: cytoxan +adriamycina +
vincristine
NSCLC
1. EP project
2. ICE project: ifosfamide + etoposide +
carboplatin

76. Prognosis
Good prognosis benefits from early
diagnosis and early intervention
Cryptic lung cancer is curable
Squamous better than
adenocarcinoma, the latter better than
small cell undifferentiated cancer