The IASLC Lung Cancer Staging Project: Proposals for the TNM Stage Groupings in the Eighth Edition of the TNM Classification for Lung Cancer

1. Neil A. Abrahams, MD
Memorial Regional Hospital
Memorial Cancer Institute
Hollywood, Florida
Department of Pathology
The IASLC Lung Cancer Staging
Project: Proposals for the TNM
Stage Groupings in the Eighth
Edition of the TNM Classification
for Lung Cancer

2. Four Step Approach to Understanding the
TNM
1. WHO Classification of Lung Cancer
– Terminology and definitions
2. TNM 7Th Edition
– Problems and controversial areas
3. TNM Proposed 8th Edition
– Changes compared to 7th Edition
4. TNM Proposed 8th Edition
– Were the controversies from the 7th Edition addressed in the
8th Edition ?

3. World Health Organization (WHO)
Classification of Lung Cancer
 WHO Classifications of 1967, 1981 and 1999
developed by pathologists for pathologists
 WHO 2004 revised Classification first attempt to
incorporate genetics and clinical information
 6 year collaboration towards a multidisciplinary
classification based on
– Molecular biology (EGFR tyrosine kinase inhibitors)
– Need for uniform criteria to exclude squamous histology to
avoid toxicity with bevacizumab (Avastin)
– Radiologic correlations (solid, ground glass etc.)
– Larger percentage of small biopsy samples used for
definitive treatment decisions

5. • Oncologists
• Pulmonologists
• Pathologists
• Radiologists
• Molecular biologists
• Thoracic surgeons
International Association for the Study of
Lung Cancer/ American Thoracic
Society/European Respiratory Society
International Multidisciplinary Classification
of Lung Adenocarcinoma (2011)

6. Journal of Thoracic Oncology 2011, 6:244-285

7. IASLC/ATS/ERC
Classification of
Lung AdCa in
resection
specimens

8. IASLC/ATS/ERC
Classification of
Lung AdCa in
biopsy/cytology
specimens
Emphasis on
patterns

9. Atypical Adenomatous Hyperplasia (AAH)
Criteria: Localized, small proliferation of mild to moderately
atypical type II Pneumocytes lining alveolar walls.
LESS THAN 5.0 MM IN SIZE

10. Adenocarcinoma in situ (formerly BAC)
< 3.0 cm, solitary tumor, pure lepidic growth: 100% disease specific survival

12. Adenocarcinoma in situ (formerly BAC)
 Diagnostic Criteria
– Less than 3.0 cm in size
– No Invasion of underlying stroma
– No Pleural Invasion
– No Vascular Invasion
– Pure lepidic growth pattern
– No Micropapillary or Papillary
– No Intra-alveolar cells
– Solitary lesion, mucinous and non-mucinous (more frequent)

13. Minimally Invasive Adenocarcinoma
<3.0 cm, solitary, predominant lepidic , less than 0.5 cm invasion: NEAR 100% survival

15. Minimally Invasive Adenocarcinoma
 Diagnostic Criteria
– Less than 3.0 cm in size
– No more than 5.0 mm of invasion in stroma or
– Non-lepidic growth patterns can be measured (pap, micropap)
– AUTOMATIC EXCLUSION CRITERIA
– Pleural Invasion
– Vascular Invasion
– Tumor necrosis

16. Invasive Adenocarcinoma: Pattern
Predominant
 Lepidic
 Acinar
 Mucinous
 Solid
 Papillary
 Micropapillary
 Fetal
 Enteric

17. Invasive AdCa: Acinar predominant
Cribriform arrangement

18. Invasive AdCa: Acinar predominant

19. Invasive AdCa: Lepidic growth predominant
>5.0 mm invasion
Invasion
Lepidic growth

20. Invasive AdCa: Papillary predominant

21. Invasive AdCa: Papillary predominant
True fibrovascular core

22. Invasive AdCa: Micropapillary
Poor prognosis; aerogenous spread, multifocal

23. Invasive AdCa: Micropapillary predominant:
Aerogenous spread

24. Mixed Papillary and Micropapillary
Invasive Adenocarcinoma (Most frequent)
Papillary: True fibrovascular core
Micropapillary

25. Invasive AdCa: Solid predominant with or
without mucin production

26. Invasive Mucinous AdCa

27. AdCa with mixed histologic subtypes:
describe patterns present

28. Squamous Cell Carcinoma
Preferred Terminology Biopsies
“Non-small cell carcinoma favor squamous cell carcinoma”
COMMENT: IHC markers. Percentage of squamous. Discussed with oncologist.
Tumor board review. Exclude large cell NE carcinoma

29. Squamous Cell Carcinoma of the Lung

30. Squamous Cell Carcinoma of the Lung
p40

31. Discouraged/Outdated Terminology
 The term BAC (Brochioloalveolar carcinoma) is
STRONGLY discouraged
– Used to describe broad spectrum of tumors with distinct
survival rates
 Non Small Cell Lung Carcinoma (NSCLC) should be
avoided as a single diagnostic line
– Does not relay any clinical or pathologic relevant information
 Nonsquamous cell carcinoma is NOT a pathologic term
rather a clinical/oncology subgroup

32. TNM 7Th Edition
Problems and controversial areas
2

33. TNM 7th Edition

34. TNM 7Th Edition
Problems and controversial areas
 pTis: Carcinoma In Situ
– Squamous carcinoma in situ ?
– Adenocarcinoma in Situ criteria ?
– “AIS less than 3 cm, no invasion, No LVI, No Pleural Invasion,
No Papillary, No Micropapillary
– Invasion is subjective (collapse ? Atelectasis ?)
– NOT a biopsy diagnosis
– One papillae ?
– Intra alveolar tumor cells shedding ?

35. Adenocarcinoma in situ (formerly BAC)

36. TNM 7Th Edition
Problems and controversial areas
 pT2a: Tumor 5 cm or less in greatest dimension with any
of the following features of extent: involves main bronchus,
2 cm or more distal to the carina; invades the visceral
pleura…
– Tumor breaches the elastic layer (VPI)
– How much VPI
– Need elastic stains which are not reliable
– Can over interpret VPI at interlobular septa or lobar fissures
– What about tumor invading hilar tissue where there is NO
pleura ?

37. Visceral Pleural Invasion
Taken from CAP Tumor Staging Protocols. http://www.cap.org/web/oracle/webcenter
Elastic
layer
Elastic
layer
Tumor at
pleural
surface: pT2
No
pleural
invasion

38. TNM 7Th Edition
Problems and controversial areas
 pT3: Tumors of any size with separate tumor nodule(s) in
same lobe
 pT4: Tumor of any size with separate tumor nodule(s) in a
different lobe of ipsilateral lung
 pM1a: Separate tumor nodule(s) in contralateral lung
– How do you determine multifocal synchronous primary
tumors from intralobar and contralateral "metastases”
– Staged as multiple T1a (multifocal BAC) versus T4 or M1
based on ………..

40. Differentiating Synchronous Primaries
from Intrapulmonary Metastasis
 Martini and Melamed: Sync Primaries
– Similar histology BUT have CIS component
– No LVI
– Based on Squamous cell Ca
 Girard et al. to differentiate looked at
– Histologic type
– Growth pattern (lepidic, acinar etc.)
– Stromal features (desmoplasia) and cytological features
(nuclear shape)
 THESE ARE POOR SUBJECTIVE CRITERIA

41. A staging system that relies heavily on size does
not take into account tumor size shrinkage (up
to 20%) in post formalin fixed lobectomies
Clinically T2 stage. Radiographic measurement
3.5 cm
Pathologic pT1b stage. Gross post fixation
measurement 2.8 cm

42. TNM Proposed 8th Edition
Changes compared to 7th Edition
3

43. TNM 7th Edition
T Grouping
 pTis: Carcinoma in situ
 pT1a: Tumor 2 cm or less, surrounded by lung or visceral pleura,
without bronchoscopic evidence of invasion more proximal than the lobar or
Superficial spreading tumor of any size with its invasive component limited
to the bronchial wall, which may extend proximally to the main bronchus
 pT1b: Tumor greater than 2 cm, but less than 3 cm surrounded by
lung or visceral pleura, without bronchoscopic evidence of invasion more
proximal than the lobar bronchus
 pT2a: Tumor greater than 3 cm, but less than 5 cm or tumor 5
cm or less in greatest dimension with: involves main bronchus, 2 cm or more
distal to the carina; invades the visceral pleura; associated with atelectasis or
obstructive pneumonitis
 pT2b: Tumor greater than 5 cm, but 7 cm or less in greatest
dimension
 pT3: Tumor greater than 7 cm in greatest dimension; or
 Tumor of any size that directly invades any of the
following: parietal pleural chest, diaphragm, phrenic nerve, mediastinal
pleura, parietal pericardium; or
 Tumor of any size in the main bronchus less than 2 cm distal to the or
 Tumor of any size associated with atelectasis or obstructive
pneumonitis of the entire lung; or
 Tumors of any size with separate tumor nodule(s) in same lobe
 pT4: Tumor of any size that invades any of the following:
mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve,
esophagus, vertebral body, carina; or
 Tumor of any size with separate tumor nodule(s) in a different lobe
of) effusion
TNM 8th Edition
T Grouping

44. Proposed TNM 8th Edition Emphasis on
tumor size. Why ?
 Use of larger cohort of cases from Asia (Mostly Japan)
with smaller tumors being validated in larger numbers
 Progressive degradation of survival was identified for each
1-cm cut point
 3.0 cm is still valid for separating T1 and T2
 Introduction of CIS and MIA Concepts
– Expect less T3 and T4 cases ?
– Clinical upstaging from T1 to T2

45. Proposed TNM 8th Edition Emphasis on
tumor size. Why ?

46. Changes to the N grouping from 7th to 8th
Proposals (No real change)
Regional Lymph Nodes (pN)
pNX: Cannot be assessed
pN0: No regional lymph node metastasis
pN1: Metastasis in ipsilateral peribronchial and/or ipsilateral hilar
lymph nodes, and intrapulmonary nodes, including involvement
by direct extension
pN2: Metastasis in ipsilateral mediastinal and/or subcarinal lymph
node(s)
pN3: Metastasis in contralateral mediastinal, contralateral hilar,
ipsilateral or contralateral scalene, or supraclavicular lymph
node(s)

47. Changes to the M grouping from7th to 8
Edition TNM
pM1a: Separate tumor
nodule(s) in contralateral
lung; tumor with pleural
nodules or malignant
pleural (or pericardial)
effusion
pM1b: Distant metastases
7th Edition 8th Edition

48. Changes to the M grouping based on
Oligometastases

49. Notable changes to the TNM 8th Edition
 Data driven revision shows the larger the tumor the worse
the prognosis.
– Most changes affect T1 and T2 categories (need a cheat
sheet !!)
– Cut off T1 to T2 is STILL 3.0 cm
 Tumors involving main bronchus behave like T2
regardless of distance to carina
 Tumors invading diaphragm = T4
 Deleted category of mediastinal pleural invasion
 M category. One metastasis (M1b) better outcome
compared to multiple metastases (M1c)

50. 1.
TNM Proposed 8th Edition
Controversies addressed ?
4

51. Some gray areas persist and are magnified
in the TNM 8th Edition others have new
guidelines
1. Size cut offs for tumor stage proliferate but no guideline
on how to deal with tumor shrinkage
1. Use CT size ?
2. Add 20% to gross size?
2. Synchronous primaries from metastases ?
1. PUBLISHED GUIDELINES
2. Use genomic testing
3. Interobserver studies on MIA ?
1. Multiple areas of invasion all less than 5.0 mm

52. Some gray areas persist and are magnified
in the TNM 8th Edition others have new
guidelines
1. Visceral pleural invasion ?
1. One section ? Better stain than elastic stain ?
2. Invasion of hilar region where there is no pleura
1. How to stage ?
2. Sub stratification of Multifocal CIS (Multifocal BAC)
1. New Guidelines published

53. ACKNOWLEDGEMENTS
 Luis Raez MD, Thoracic Oncology MHS, Hollywood, FL
 Samuel Yousem MD, Professor Pathology UPMC
Pittsburgh, PA
 Departments of Thoracic Oncology and Surgery Memorial
Health Care System, Hollywood,
QUESTIONS

54. TTF-1
CK 7