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Non Small Cell Lung Cancer New Pathological Staging System

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Non Small Cell Lung Cancer New Pathological Staging System

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    1. Non Small Cell Lung Cancer New Pathological Staging System Oscar Nappi Anatomia Patologica AORN A. Cardarelli - Napoli

    2. Nella nuova classificazione TNM dei tumori polmonari,la presenza di noduli separati nello stesso lobo si indica con la sigla M1 M0+ T4 T2c T3

    3. Nella nuova classificazione TNM dei tumori polmonari la sigla T1a configura Tumore inferiore o uguale a 3 cm Tumore inferiore o uguale a 2 cm Tumore compreso tra due e tre cm Tumore superiore a 3 cm Tumore compreso tra 1 e 3 cm

    4. Nella nuova classificazione TNM dei tumori polmonari, un tumore che presenta anche noduli pleurici omolaterali o versamento pleurico “maligno” si indica con la sigla M1b M1 T4 M1a T4a

    7. TNM Clinical cTNM or TNM Pathologic pTNM Retreatment rTNM Autopsy aTNM

    12. Proposed changes for lung cancer staging 7th edition of TNM T component Tumour size Multiple tumours Pleural invasion N component No changes in N component M component Minimal but significant change

    13. Proposed changes for lung cancer staging 7th edition of TNM T component Tumour size Multiple tumours Pleural invasion

    14. TNM T1

    15. T1 ( 6th ed ) Tumour < 3 cm in greatest dimension , surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus ( i.e. not in the main bronchus )

    16. T1 6th Edition Tumour < 3 cm 7th Edition T1a Tumour < 2 cm T1b Tumour > 2 but < 3 cm

    17. T2 6th edition Tumor with any of the following features of size or extent : • more than 3 cm in greatest dimension • involves main bronchus, 2 cm or more distal to the carina • invades the visceral pleura • associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung

    18. T2 7th edition Tumor >3 cm but < 7 cm T2a - Tumor >3 cm but < 5 cm T2b - Tumor >5 cm but < 7 cm Tumor with any of the following features: * Involves main bronchus, 2 cm distal to carina * Invades visceral pleura * Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung

    19. T2 6th Edition Tumor > 3 cm 7th Edition T2a Tumor > 3 cm but <5 cm Tumour between 3 and 7cm T2b Tumor > 5 cm but <7cm

    20. T3 6th edition Tumor of any size that directly invades any of the following: chest wall (including superior sulcus tumors),diaphragm,mediastinal pleura,parietal pericardium Tumor of any size in the main bronchus less than 2 cm distal to the carina but without involvement of the carina Tumor of any size associated atelectasis or obstructive pneumonitis of the entire lung

    21. T3 7th edition Tumour >7 cm Direct invasion of any of the following: chest wall, diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium, Tumour in the main bronchus <2 cm from carina (without involvement of carina) Atelectasis or obstructive pneumonitis of the entire lung Separate tumor nodules in the same lobe

    22. 6th ed T4 7th ed Tumor of any size that invades any of the following • mediastinum • heart • great vessels • trachea • esophagus • vertebral body * carina Tumor of any size that invades any of the following mediastinum heart great vessels trachea esophagus, vertebral body carina Recurrent laryngeal nerve

    23. 6th ed T4 7th ed * Tumor of any size with satellite tumor nodule(s) within the primary tumor lobe * Tumor of any size with a malignant pleural effusion * Separate tumor nodules in a different ipsilateral lobe

    25. Tumour size Summary Size cut off 3 cm ( T1 ) 6th ed New size cut off 2 cm ( T1a ) 7th ed 5 cm ( T2a ) 7 cm ( T2b )

    26. Hsu PK, Huang HC, Hsich CC et al Effect of formalin fixation on tumor size determination in stage I non-small cell lung cancer Ann Thorac Surg 84 : 1825 – 1829, 2007 After formalin fixation 20% of tumours > 3 cm shrank by an average of 1cm ! Downstaged ! Size should be recorded from the unfixed specimen

    33. Multiple tumours It is important the communication between Surgeon and Pathologist ! Some tumours are more difficult to find for the Pathologist than the Radiologist ( i.e. Broncho-Alveolar Carcinoma )

    34. Small cell carcinoma Shepherd FA, Crowley J, Van HP et al The International Association for the Study of lung cancer staging project : proposal regarding the clinical staging of small cell lung cancer in the fothcoming ( seventh ) edition of the tumor, node, metastasis classification for lung cancer J Thoracic Oncol 2 : 1067 – 1077, 2007

    35. Carcinoid tumours The IASLC Staging Committee has reccomended that in the 7th edition that the TNM be applied to pulmonary carcinoid tumours

    38. Main changes in stage groupings T2b N0M0 from IB to IIA T2a N1M0 from IIB to IIA T4 N0 ( N1) M0 from IIIB to IIIA

    39. 5 years survival IA 50% IB 47% IIA 36% IIB 26% IIIA 19% IIIB 7% IV 2%

    41. NSCLC Squamous cell carc. Adenocarcinoma Large cell carcinoma Adenosquamous carc. Sarcomatoid carc.

    42. Renewed interest in lung cancer histotype The advent of effective targeted therapies ! Anti EGFR ( Erlotinib, Gefinitib ) Anti VEGF ( Bevacizumab ) New chemotherapic agents

    44. Pathologists and Lung cancer 2/3 of lung cancer are unresectable/advanced Diagnosis of lung cancer is achieved on cytology ( even effusion ) or small biopsies Goal : To optimize the tumour tissue 1. Diagnosis 2. Possible biological markers ( EGFR,k-ras,ERCC1 etc… )

    45. Diagnostic IHC in confirming and subtyping primary lung cancer TTF 1 P 63

    46. Diagnostic IHC in confirming and subtyping primary lung cancer

    47. Pathologist’s Role At present Any effort has to be made in order to typizing Squamous Cell Carcinoma and Adenocarcinoma. A diagnosis of NSCLC - NOS should be avoided

    49. IHC in distinguish SCC and AC in poorly differentiated tumours

    50. Large Cell Carcinoma WHO 2004 poorly differentiated NSCLC that lacks cytologic and architectural features of SCLC and glandular or squamous differentiation 5 variants: LCNEC Large Cell Neuroendocrine Carcinoma Basaloid Lymphoepithelioma-like Clear cell Large cell with rhabdoid phenotype

    51. Large Cell Carcinoma sec WHO 2004 Does it exist ? It should be considered a “container “ of tumor patterns with different immuno- ( and geno ) typing profiles Today, in order to planning a correct therapy, it should be necessary to identify the clone of origin

    52. LCNEC

    53. LCNEC - immunohistochemistry

    54. LCNEC – molecular biology LCNEC and SCLC seem to share common molecular alterations: ? p53 ? cell-cycle proteins (Rb, Cyclin D1, p16) ? apoptosis regulation- bax/bcl2 ? assessment of LOH by microsatellite markers

    56. Tumours with NE morpholohy WHO 2004 Typical carcinoid Atypical carcinoid Small cell carcinoma ( SCLC ) Large cell NEC ( LCNEC )

    57. Should SCLC and LCNEC be included in the same category (as high-grade NE carcinomas) ? Differential diagnosis may be difficult Similar prognosis Identical IHC profile Very similar molecular profile, such as cell cycle regulatory proteins alterations (Rb/P16/Ciclina D1), p53, bcl2 Similar prognosis is not definitively proven It is not well-demonstrated that patients with LCNEC have the same clinical benefit from the therapeutical regimens adopted in SCLC

    59. Large Cell Carcinoma WHO 2004 poorly differentiated NSCLC that lacks cytologic and architectural features of SCLC and glandular or squamous differentiation 5 variants: LCNEC Large Cell Neuroendocrine Carcinoma Basaloid Lymphoepithelioma-like Clear cell Large cell with rhabdoid phenotype

    60. Lung carcinomas with a basaloid pattern: a study of 90 cases focusing on their poor prognosis. Moro-Sibilot D, Lantuejoul S, Diab S, Moulai N, Aubert A, Timsit JF, Brambilla C, Brichon PY, Brambilla E. Basaloid carcinoma is a unique entity ( Variant of SCC + Variant of LCC ) Compared with NSCLC, in Stage I – II patients, its overall survival is significantly lower ( 29 vs 49 % ) as well as its 5 years survival rate ( 27% vs 44% )

    61. Large Cell Carcinoma WHO 2004 poorly differentiated NSCLC that lacks cytologic and architectural features of SCLC and glandular or squamous differentiation 5 variants: LCNEC Large Cell Neuroendocrine Carcinoma Basaloid Lymphoepithelioma-like Clear cell Large cell with rhabdoid phenotype

    62. Lymphoepitelioma-like True entity but very rare Cases EBV – probably are Adenocarcinomas LCC with Rhabdoid phenotype * Rhabdoid pattern is a phenotype, never an entity. * It is very rare in the lung but it is a powerful adverse prognostic factor

    63. Large Cell Carcinoma WHO 2004 poorly differentiated NSCLC that lacks cytologic and architectural features of SCLC and glandular or squamous differentiation 5 variants: LCNEC Large Cell Neuroendocrine Carcinoma Basaloid Lymphoepithelioma-like Clear cell Large cell with rhabdoid phenotype

    64. Clear cell carcinoma It is not an Entity It is a pattern of SCC or Adenoca need to defining the origin clone by IHC DD Metastatic from other organs

    66. Large Cell Carcinoma sec WHO 2004 Does it exist ? It should be considered a “container “ of tumor patterns with different immuno- ( and geno ) typing profiles Today, in order to planning a correct therapy, it should be necessary to identify the clone of origin : “ Squamous “, “Adenoca” , “Neuroendocrine” Immunophenotypes

    70. EMT refers to the loss of epithelial cell traits and the acquisition of a mesenchymal phenotype by cells with motile properties EMT is pivotal in a variety of conditions including normal ontogenesis, fibrosis, wound healing, inflammation and tumor progression (with invasiveness and metastasis formation) EPITHELIAL-MESENCHYMAL TRANSITION (EMT)

    71. Sarcomatoid carcinoma It is not an Entity but a Phenotype secondary to selection of aggressive cellular clones arising in SCC or Adenocarcinoma The EMT ( epithelial- mesenchymal transition ) patway is involved , probably by the upregulation of c-Jun gene Implication in therapy

    72. Grazie

    73. Nella nuova classificazione TNM dei tumori polmonari,la presenza di noduli separati nello stesso lobo si indica con la sigla M1 M0+ T4 T2c T3

    74. Nella nuova classificazione TNM dei tumori polmonari, un tumore che presenta anche noduli pleurici omolaterali o versamento pleurico “maligno” si indica con la sigla M1b M1 T4 M1a T4a

    75. Nella nuova classificazione TNM dei tumori polmonari la sigla T1a configura Tumore inferiore o uguale a 3 cm Tumore inferiore o uguale a 2 cm Tumore compreso tra due e tre cm Tumore superiore a 3 cm Tumore compreso tra 1 e 3 cm

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