ppt on pathology of lung neoplasm for educational purpose and this ppt have outlined the details of lung cancer pathology

1. Pathology of Lung Neoplasm
Presenter Dr Alemwork.G (GSR1)
Moderator Dr Tesfaye (GS Consultant)
August 2022 1

2. Outline
• Introduction
• Epidemiology and Risk Factors
• Solitary Pulmonary Nodule
• Benign Lung Neoplasm
• Classification of Lung cancer
• Clinical feature of lung cancer
• Diagnosis and Stage of Lung cancer.
2

3. Introduction
• Lung cancer is the leading cause of cancer deaths
worldwide in men, and the second leading cause in
women.
• Lung cancer occurred in 2.1 million patients with estimated
1.8 million deaths worldwide.
• Lung cancer mortality rates in the US is 28.7% of all cancer
mortality.
• overall 5-year survival of only 15%.
• Currently,more than 58% of global lung cancer cases occur
in developing nations.
3

4. Int…
Gender Distribution
Age
Race
4

5. Intr..
• Lung neoplasms can be classified as benign or
malignant.
• Benign lung tumors are < 5% of all resected lung
neoplasms.
• Tobacco smoking causes nearly 90% of lung cancers.
• Most patients are diagnosed at an advanced stage of
disease, so therapy is rarely curative.
5

6. Risk factors
Smoking : The most common risk factor.
• Number of cigarettes smoked and duration of
smoking
• Age at onset of smoking
• Degree of inhalation
• Tar and nicotine content
• Types of cigarettes (filtered vs unfiltered).
• Cigar and pipe smoking
6

7. Cont..
• Smoking cessation
• Smoking reduction
• Secondhand smoke
7

8. Occopatinal and Environmental
• Asbestos — 37.5% of all occupational lung cancer
cases .
• Radon — causes 3%–14% of lung cancer .
• Smoke from cooking and heating — The indoor
burning of unprocessed biomass fuels (wood,
coal) .
• Radiation and Air pollution.
8

9. Solitary Pulmonary Nodule
• A SPN is defined on imaging as a small (≤30 mm), well-
defined lesion surrounded by pulmonary parenchyma.
• An incidental finding in up to 0.2% of CX-rays and around
1% of CT scans.
• 80% of an incidental SPN represents a benign conditions.
• 10 to 20% of patients with lung cancer are presented as
SPN.
9

10. Differential Diagnosis
Malignant
• Adenocarcinoma
• Squamous cell carcinoma
• Large cell carcinoma
• Small cell lung carcinoma
• Metastatic cancer.
• Carcinoid tumors.
Benign
• Infectious granulomas(70-80%)
• Benign tumors(Hamartoma 10%.
• Vascular(PAVM,varix,,infarct).
• Other causes (Developmental,
inflammatory, and traumatic).
10

11. Cont…
11

12. 12

13. Diagnostic Evaluation of SPN
.
13

14. Assessing the risk of malignancy of SPN
The probability of malignancy
in an incidental SPN should be
assessed either :
• Clinically
• Radiographic features
• Quantitative predictive models .
Clinical features:
• Age over 35 year
• History of smoking
• Prior neoplastic disease
• Family history.
• Female
• Emphysema
• Asbestos exposure.
14

15. Quantitative Predictive Models
Brock model
Predictor of malignancy
• older age.
• Female sex.
• Family history of lung cancer.
• Emphysema.
• Nodule size.
• Location of the nodule.
• Nodule type.
• Nodule count and Spiculation.
Probability of Malignancy
• Low probability (<5 %)
• Intermediate probability (5- 65%)
• High probability (>65 %)
15

16. Imaging
• CXR, Non contrast CT, PET/CT.
• CT scan: is the preferred modality for initial evaluation for
malignancy risk.
• CT is the most reliable modality for assessing nodule :
Location
Size Margin morphology
Calcification pattern and growth rate
16

17. Nodular features on CT Scan
• Size — size is an independent predictor for malignancy.
• Nodules <5 mm: <1 percent
• Nodules 5 to 9 mm: 2 to 6 percent
• Nodules 8 to 20 mm: 18 percent
• Nodules >20 mm: >50 percent
17

18. Attenuation
Morphologically,
nodules are classified
as:
 solid
 Subsolid:
 pure ground-glass
nodules.
 partially-solid
nodule
18

19. Growth
• Solid nodules: growth is defined as an increase in size of >2mm or
25% increase in volume.
• Subsolid nodules: growth is an increased attenuation or size or
development of a solid component.
• Volume doubling times(VDT)
–Most malignant nodules have a VDT between 20 and 400
days .
–Nodule that has increased in size over (<20 days) or is
stable for on CT (>2 years) is likely benign.
• Multiplicity : Decrease the probability of malignancy.
19

20. Calcification and fat
Calcification within a
nodule, generally,
suggests a benign lesion
Common patterns of
Benign Calcification are:
• Central
• Diffuse.
• laminated
• Popcorn
20

21. Margin Morphology
 Well-defined,
smooth border.
 Irregular.
 spiculated edges
 Lobulated.
21

22. The corona radiata sign
• Multiple fine striations extend perpendicularly from the surface of the nodule like
the spokes of a wheel
22

23. Nodal location
• Location:
• Upper lobe location is a risk
factor for cancer.
• Location close to a fissure
indicates a benign lymph
node
23

24. PET
• PET is becoming widely used to help differentiate benign
from malignant nodules
• Sensitivity for identifying neoplasms s 97% and its specificity
78%
24

25. Biopsy
• Only a biopsy can definitively diagnose a pulmonary
nodule
– Bronchoscopy
• 20 to 80% sensitivity for detecting Endobronchial
tumors.
– Transthoracic FNA biopsy
• Can accurately identify the status of peripheral
pulmonary lesions in up to 95% of patients
– VATS
25

26. BENIGN LUNG NEOPLASM
• < 5% of all lung tumors
• Most present as asymptomatic solitary pulmonary
nodules, incidentally discovered radiographically.
• The location of these lesion dictates the symptoms.
• About 50% of benign lung neoplasms are hamartomas.
26

27. Classification of Benign Lung Tumors
27

28. Hamartomas
• Pulmonary hamartomas are benign neoplasms composed of cartilage,
connective tissue, muscle and fat.
• Accounts for 8% of all lung neoplasms,
• More common in men (M: F 2 to 3 : 1)
• They typically present in middle age( 30-60).
• Most present as solitary pulmonary nodules.
• Most occur peripherially.
28

29. Cont…
Clinical presentation:
• Pulmonary hamartomas usually
Asymptomatic.
• Prepherial vs Endobronchial
location
Endobronchial Hamartomas
• Bronchial obstruction
• Cough
• Hemoptysis
• Recurrent pneumonia.
Pathophysiology:
• Most are solitary, well-
circumscribed, slightly lobulated
tumors located within the
parenchyma.
• Most measure 1 to 2 cm in
diameter.
• On histologic section, composed
mainly of cartilage and
significant amount of fat.
29

30. cont
30

31. Radiographic Feature
31

32. Papilloma's
Squamous Papilloma
• most often associated with cigarette smoking and human papilloma
virus.
• Most occur in central large airways.
Recurrent Respiratory Papillomatosis
• Also known as juvenile laryngotracheal papillomatosis.
• Associated with human papilloma virus types 11 and 6.
• Lung involvement occurs in 3% of patients.
• Aggressive course, with no effective medical therapy.
• Squamous cell carcinoma is the most feared complication.
32

33. Pulmonary Leiomyoma
• Most common soft tissue tumors of the lung.
• Arise from bronchial wall smooth muscle or the wall of bronchial
arteries. .
• Common in women( F : M, 2:1).
• Mots present as solitary, peripheral, pulmonary nodules.
• Asymptomatic.
• Found incidentally on plain CXR or CT scan.
• No specific characteristics that distinguish this lesion from other
pulmonary nodules.
33

34. Diagnosis
• Most benign pulmonary tumors are asymptomatic.
• Most seen as peripherally located ,solitary nodule.
• Most are incidentally found on routine CX-Ray or CT Scan
performed for other reason.
• Endobronchial location may cause symptoms.
• Imaging , CXR,CT Scan.
• Tissue Biopsy (Bronchoscopy or transthoracic needle biopsy
[TTNB]).
34

35. Malignant Lung Neoplasm
• Broadly divided into 2 main groups :
• Non-small-cell lung carcinoma
• Adenocarcinoma
• Squamous cell carcinoma
• Large-cell carcinoma
• Neuroendocrine tumors
• Typical carcinoid
• Atypical carcinoid
• Large-cell neuroendocrine carcinoma
• Small-cell carcinoma
35

36. 36

37. Adenocarcinoma
• Most frequently diagnosed histologic type of lung cancer.
• Most common subtype in women and nonsmokers.
• Most tumors occur in the periphery.
• ACA grows slowly.
• ACA advanced by the time of diagnosis.
• ACA has an irregularly lobulated border, with a gray-white cut surface.
• Necrosis and hemorrhage are seen only in large lesions (>5 cm).
37

38. The 2021 World Health Organization (WHO)
classification of Adenocarcinoma
• Precursor glandular lesions
• Atypical adenomatous hyperplasia
• Adenocarcinoma in situ
• Adenocarcinoma in situ, non-
mucinous
• Adenocarcinoma in situ,
mucinous
• Minimally invasive
adenocarcinoma
• Minimally invasive
adenocarcinoma, non-
mucinous
• Minimally invasive
adenocarcinoma, mucinous
• Invasive non-mucinous adenocarcinoma
• Lepidic adenocarcinoma
• Acinar adenocarcinoma
• Papillary adenocarcinoma
• Micropapillary adenocarcinoma
• Solid adenocarcinoma
• Invasive mucinous adenocarcinoma
• Mixed invasive mucinous and non-
mucinous adenocarcinoma
• Colloid adenocarcinoma
• Fetal adenocarcinoma
• Adenocarcinoma, enteric-type
• Adenocarcinoma, NOS
38

39. Squamous Cell Carcinoma
• SCLC accounts for 15% of all lung cancer.
• Characterized by keratinization and/or intercellular bridges
on histopathology.
• Strongly associated with cigarette smoking.
• Occurs predominantly in men.
• 60-80% arise in the central airway.
• SCC has an irregular, gray-white cut surface with large area of
central necrosis with cavitation.
39

40. Keratinization in lung cancer
40

41. Large-Cell Carcinoma
• Accounts for 10 to 20% of lung cancers.
• Located centrally or peripherally.
• Undifferentiated malignant epithelial tumors that lack
features of small cell carcinoma and glandular or squamous
differentiation.
• IHC; typically, p40 and thyroid transcription factor 1 [TTF-1])
absent.
• They are characterized by large prominent nucleoli, and a
abundant amount of cytoplasm.
41

42. Pulmonary Neuroendocrine tumors
• Lung NETs) account for 1-2% of all lung cancer in
adult .
• Most common primary lung neoplasm in children.
• Higher incidence in women and white.
• Association between lung NETs and smoking is
unclear.
• Nearly all lung NETs are sporadic; but can rarely
occur in the MEN1.
42

43. 2021 WHO Classification of Lung NET
• Diffuse idiopathic pulmonary neuroendocrine cell
hyperplasia: Preinvasive lesion .
• Low-grade Lung NEC: Typical carcinoid.
• Intermediate-grade lung NEC: Atypical carcinoid.
• High-grade pulmonary neuroendocrine tumor
• Small cell lung cancer.
• Large cell neuroendocrine carcinoma .
43

44. Carcinoid tumors
• Pulmonary carcinoid tumors represent about 1–5% of all lung
malignancies.
• They are mainly of two types, typical and atypical:
• Typical carcinoid: < 2 mitoses per 10HPF and absence of necrosis.
• Atypical carcinoid: well-differentiated NE morphology
• 2- 10 mitoses per 10HPF or presence of
necrosis.
• Usually occur in those who have never smoked.
• About 70% occur centrally.
44

45. Small cell lung carcinoma
• 15% of all lung cancer.
• Most arise in the large central airways.
• Up to 98% of patients with SCLC have a history of smoking.
• The natural history of SCLC is early metastasis and death.
• Unlike NSCLC it is always considered a systemic disease at diagnosis.
• Median survival for disease confined to the chest is 4–6 months
without treatment.
• For metastatic disease, median survival is 5–9 weeks without
treatment.
45

46. Large cell neuroendocrine carcinoma
• High grade NET.
• Commonly located in the peripherally.
• LCNEC has an architecture that
suggests neuroendocrine
differentiation: the cells are arranged in
organoid, trabecular, or palisading
patterns .
• Necrosis is usually prominent and may
be extensive and infarct-like.
46

47. 47

48. Clinical Presentation
Intrathoracic clinical manifestation
• Cough
• Hemoptysis
• Chest pain
• Dyspnea
• Horseness
• Pleural involvement
• Superior vena cava syndrome
• Pancoast syndrome
Extrathoracic clinical manifestation
• Bone
• Adrenal gland
• Liver
• Brain
• Constitutional symptoms
• weight loss.
• Anorexia.
• weakness and fatigue
48

49. Superior vena cava syndrome
• Sensation of fullness in the head
and dyspnea.
• Physical findings
 Dilated neck veins
• Prominent veins on the chest
• Edema of the face, neck and
upper extremities
• Plethoric appearance
49

50. Pancoast syndrome
• Shoulder and arm pain.
• Horner syndrome.
• weakness and atrophy of the
muscles of the hand.
• Most commonly caused by
NSCLC (typically SCC).
• Rarely by SCLC
50

51. Paraneoplastic Syndrome
• Hypercalcemia
 Anorexia
Nausea
 vomiting
Constipation
Lethargy
 polyuria, polydipsia, and
dehydration.
• SIADH secretion — results in
hyponatremia.
• Anorexia.
• Nausea
• Vomiting
• Irritability
• restlessness
• confusion, coma, seizures
• Respiratory arrest.
51

52. Cont…
Lambert-Eaton myasthenic syndrome
• Cerebellar ataxia
• Sensory neuropathy
• Limbic encephalitis
• Ancephalomyelitis
• Autonomic neuropathy
• Retinopathy, and opsomyoclonus
52

53. Hematologic manifestations
• Anemia
• Leukocytosis
• Thrombocytosis
• Eosinophilia
• Hypercoagulable disorders
Superficial thrombophlebitis (Trousseau syndrome)
DVT and thromboembolism
DIC
Thrombotic microangiopathy
Nonbacterial thrombotic endocarditis
53

54. Hypertrophic Pulmonary osteoarthropathy
• characterized by a
symmetrical, painful
arthropathy.
• Long-bone and joint pain.
54

55. Cushing syndrome
• Decreased libido
• Obesity/weight gain
• Plethora
• Round face
• Menstrual changes
• Hirsutism
• Hypertension
• Ecchymoses
• Lethargy, depression
• Dorsal fat pad
• Abnormal glucose tolerance
55

56. Diagnosis, Evaluation, and
Staging
56

57. • Assessment encompasses three areas:
–The primary tumor
–Presence of metastatic disease
–Functional status.
57

58. Assessment of the Primary Tumor
• History
– Pulmonary, metastatic, and paraneoplastic symptoms
• P/E
– Chest
– Voice
– All system.
• Imaging
– Chest X-ray: mass, the widening of the mediastinum ,atelectasis ,
consolidation or pleural effusion
– Contrast CT:
58

59. • Tissue diagnosis
– Bronchoscopy
• Particularly useful for centrally-located tumors
• Methods :
–Brushings and washings for cytology
–Direct forceps biopsy of a visualized lesion
–FNA with a Wang needle of an externally compressing lesion
without visualized endobronchial tumor
–Transbronchial biopsy with the use of forceps guided to the
lesion by fluoroscopy
59

60. – Transthoracic needle aspiration and biopsy
• For peripheral lesions not easily accessible by
bronchoscopy.
• Image guided (CT or Fluoroscopy) FNA or core-needle
biopsy is performed
• The primary complication is pneumothorax (in up to
50% of patients).
• Three biopsy results are possible: malignant, a specific
benign process, or indeterminate
60

61. • Thoracoscopy
– It is potentially a valuable staging tool for assessing
the primary tumor's relationship to contiguous
structures
• Thoracotomy
– Required in cases of:
• A deep-seated lesion that yielded an indeterminate
needle biopsy result or that could not be biopsied
for technical reasons
–FNA, a Tru-Cut biopsy, or preferably an
excisional biopsy is done
61

62. Assessment of Metastatic Disease
• Distant metastases are found in about 40% of patients with newly
diagnosed lung cancer
• History
– Presence or absence of new bone pain, neurologic symptoms, and
new skin lesions
– Constitutional symptoms (Anorexia, Malaise and weight loss) .
• P/E
– Examination of all systems
• Laboratory studies
– LFT, Serum calcium level
62

63. Clinical findings Highly suggesting
metastatic disease
Symptoms elicited in history
• Constitutional - weight loss
>4.5kg
• Musculoskeletal - focal skeletal
pain
• Neurologic - headaches,
syncope, seizures, extremity
weakness, recent change in
mental status
 Signs found on physical exam
• Lymphadenopathy (>1 cm)
• Hoarseness, superior vena cava
syndrome
• Bone tenderness
• Hepatomegaly (>13 cm span)
• Focal neurologic signs,
papilledema
• Soft tissue mass
63

64. cont
Routine laboratory tests
• Hematocrit, <40% in males, and
<35% in females
• Elevated alkaline phosphatase,
ALT,AST.
• Electrolytes
• Calcium
64

65. Clinical directed imaging
• Mediastina Lymph Nodes
– Chest CT
• Most effective method available to assess the mediastinal and
hilar nodes for enlargement.
• Any CT finding of metastatic nodal involvement must be
confirmed histologically.
– PET (more accurate than CT)
– Bronchoscopic FNA of paratracheal lymph nodes
– Mediastinoscopy
• It remains the standard method of tissue staging of the
mediastinum
65

66. • Distant metastases
–Multiorgan scanning
• PET/CT Scan
• Brain MRI
• Abdominal CT
• Bone scan
66

67. Assessment of Functional Status
• Traditional methods
– Ascending (Two flights of stairs)
– Flat surface (6 minutes walk test)
• Pulmonary functions.
• FEV1
• DLCO
• O2max
• Quantitative perfusion scan
– To estimate the functional contribution of a lobe or whole lung
67

68. Lung Cancer Stage
 TNM staging
• To provide a description of the
anatomic extent of cancer that
can be easily communicated to
others.
• Assist in treatment decisions.
• Serve as an indicator of
prognosis.
Four types of staging system
• Clinical-diagnostic staging(cTNM)
• Surgical-pathologic stage(pTNM)
• Retreatment stage
• Autopsy stage
68

69. 69

70. Summary
70

71. Reference
• Pearson’s Thoracic and Esophageal Surgery 3rd Edition
• Shields’ General Thoracic Surgery 2018
• Up To Date 2022
71

72. THANK YOU
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