Ground Glass Opacities

Transcription

1 Ground Glass Opacities A pathologist s perspective Marie-Christine Aubry, M.D. Professor of Pathology Mayo Clinic

2 Objectives Discuss the proposed new pathologic classification of adenocarcinoma with historical perspective Correlate with the radiologic findings of ground glass opacities (GGO)

3 Malignant Epithelial Tumors WHO Classification 2004 Pre-invasive lesions Squamous CIS AAH DIPNECH Invasive Small cell ca (20%) Non-small cell carcinoma (80%) Non small cell carcinoma Adenocarcinoma (40%) Squamous cell ca (30%) Large cell ca (10%) Adenosquamous cell ca Sarcomatoid carcinoma Carcinomas of salivary-gland type Carcinoid tumor

4 Adenocarcinoma WHO Classification Mixed Acinar Papillary Solid with mucin Bronchioloalveolar ca (BAC) Variants Mucinous (colloid) Signet ring Clear cell Fetal

5

6 Acinar Solid

7 Papillary

8 Bronchioloalveolar carcinoma...well-differentiated adenocarcinoma primary in the periphery spread chiefly within the confines of the lung the walls acting as supporting stroma for the neoplastic cells to insist that to be called.grow on unaltered walls of alveoli or without destruction add to confusion since show both to a varying degree Liebow AA Adv Int Med 1960

9 Bronchioloalveolar carcinoma WHO classification 1999 Mucinous, non-mucinous, mixed Pure bronchioloalveolar growth pattern aka lepidic growth pattern No stromal, vascular or pleural invasion

10 BAC

11 Non-mucinous subtype

12 Mucinous subtype

13 Adeno with BAC

14 Small adenocarcinoma Noguchi et al Cancer 1995 Type A BAC 17 Type B BAC with collapse 17 Type C BAC with active fibroblasts 141 Type D Poorly diff adenocarcinoma 44 Type E Tubular adenocarcinoma 9 Type F Papillary adenocarcinoma 8

15 Survival LN met Pleural Vascular Survival Invasion Invasion Type A and B Type C Type D

16 Extent of BAC/invasion Adenocarcinoma with BAC component 5-yr survival 0% BAC 60% 1-49% BAC 57% 50-99% BAC 88% 100% BAC 100% 5 mm 5-yr survival 100% NO LN metastasis Pleura invasion Vascular invasion Intrapulmonary met Higashiyama Ann Thorac Surg 1999 Yokose Lung Cancer 2000 Suzuki Ann Thorac Surg 2000

17 Extent of BAC/invasion 380 adeno 2cm 91 with scar 6mm 3.3% with recurrence 100% alive at 7 yrs Sakurai et al AJSP adeno Stage I and II 4 groups Pure BAC 8 5mm invasion 21 > 5mm 46 Pure invasive 66 Groups 1 and 2 100%survival 10 yrs Yim et al Mod Pathol 2007

18 Cum survival Extent of BAC/invasion BAC Microinvasive adeno 8 BAC 24 MI Adeno ( 5mm) 87 mixed Adeno-BAC 59 pure Adeno Pure invasive Mixed subtypes ,000 4,000 Survival time (days) Borczuk et al Am J Surg Pathol 2009

19 JTO 2011 vol 6 p 244

20 Proposed Classification Pre-invasive Lesions AAH Adenocarcinoma Adenocarcinoma insitu Minimally invasive adenocarcinoma Travis et al JTO 2011 Invasive adenocarcinoma Lepidic predominant Acinar predominant Papillary predominant Micropapillary predominant Solid predominant Variants Mucinous Colloid Fetal Enteric

21 Proposed Classification Pre-invasive Lesions AAH Adenocarcinoma insitu * Minimally invasive adenocarcinoma * Travis et al JTO 2011 Invasive adenocarcinoma Lepidic predominant * Acinar predominant Papillary predominant Micropapillary predominant * Solid predominant Variants Mucinous Colloid Fetal Enteric *

22 Recommendations Discontinue the use of the term BAC strong recommendation, low quality evidence For 3cm, solitary adenocarcinoma with pure lepidic growth pattern recommend AIS that defines patients who should have 100% disease specific survival if completely resected moderate quality evidence Travis et al JTO 2011

23 Recommendations For 3cm, solitary adenocarcinoma with predominant lepidic growth and small foci of invasion measuring 0.5 cm recommend minimally invasive adenocarcinoma to define patients who have near 100% disease specific survival if completely resected low quality evidence Excludes tumors with vascular and pleural invasion and necrosis Travis et al JTO 2011

24 First message For tumors 3cm AIS = BAC MIA = Predominantly lepidic AND invasion 5mm Adenocarcinoma with prominent lepidic growth when > 5 mm invasion Implications for prognosis and treatment

25 Challenges for pathologist What you need to know Determining stromal invasion is difficult Measuring it precisely even more so Thus reproducibility between pathologists not perfect

26 Interobserver variability Concordance of dx Type A to E % Type A/B vs C-E % BAC vs microinvasion vs invasive Κ = 0.49 to 0.64 Borczuck et al AJSP 2009 Noguchi et al Int Pathol 2005

27 Interobserver Agreement Agreement in 237 nodules (80.6%) Disagreement between AIS and MIA: 9 nodules (3%) Disagreement between MIA and IA: 48 nodules (16%) Kappa=0.62 (good) Mean difference in invasion = 3.4 mm Boland et al

28 Case 2: MIA

29 Case 2: MIA Invasion 2mm

30 Case 4: Disagreement between AIS and MIA

31 Case 5: Disagreement between MIA and IA

32 Survival Analysis (OS)

33 Second message Interobserver variability between pathologists for the diagnosis of AIS, MIA, IA

34 AIS/MIA and small biopsies Diagnosis of AIS/MIA requires evaluation of entire tumor since diagnosis based on exclusion of invasion (pleura, vessels and stroma) The terms AIS or MIA should not be diagnosed in small biopsies or cytology specimens. If a non-invasive pattern is present in a small biopsy, it should be referred to as lepidic growth Travis et al JTO 2011

35 What it means for you The diagnosis on TBBX, TTBx will read: Adenocarcinoma with prominent BAC Adenocarcinoma with prominent lepidic growth pattern Well-differentiated adenocarcinoma

36 So if biopsy doesn t tell you AIS/MIA vs invasive how will you know if you have AIS/MIA ie a good prognosis tumor 100% DFS?

37 Ground glass opacities (GGO) Increased opacity with preservation of bronchial and vascular markings Not in the presence of another disease process Persistent

38 Suzuki classification Suzuki et al Ann Thorac Surg 2006

39 Solid nodule = Inv AD = Pure GGO = AIS =

40 Semi-solid Pure GGO Detterbeck and Homer Clinics Chest Med 2011

41 Pure GGO AIS Interobserver variation

42 So if biopsy and radiology doesn t tell you AIS/MIA vs invasive how will you know if you have a good prognosis tumor i.e. Follow? Operate?

43 Maldonado et al

44 N= 37 nodules with 774 areas of interest Maldonado et al

45 Maldonado et al

46 N= 54 nodules P<0.0001

47 Sensitivity 95% Specificity 97%

48 Take Home Messages Changes in terminology for diagnosis of adenocarcinoma BAC replaced by AIS Introduction of MIA Subtyping of adenocarcinoma in predominant pattern i.e. lepidic, acinar.

49 Take Home Messages AIS and MIA predicts for good prognostic tumor with therapeutic implications Diagnosed only on completely resected specimens not on small biopsies Interobserver variation

50 Take Home Messages Imaging with evaluation of GGO Necessary for pre-surgical assessment Limitations with interobserver variation Potential role for computer aided imaging analysis Computer Aided Nodule Assessment and Risk Yield (CANARY)

51 Acknowledgments Physiology&Biomedical Engineering S. Raghunath R. Karwoski R. Robb S. Rajagopalan Radiology B. Bartholman T. Hartman A-M Sykes Epidemiology&Biostatistics P. Yang M. DeAndrade Pulmonary Medicine F. Maldonado T. Peikart Pathology J. Boland J. Yi

52 QUESTIONS?

53 Bronchioloalveolar carcinoma WHO classification 1999 Mucinous, non-mucinous, mixed Pure bronchioloalveolar growth pattern aka lepidic growth pattern No stromal, vascular or pleural invasion In-situ adenocarcinoma