1. The Medical Defense in Mesothelioma Cases Edward M. Slaughter Hawkins Parnell Thackston & Young LLP 4514 Cole Avenue Dallas, TX 75205

2. Overview Mesothelioma: The Basics Stains Malignancy Tissue Digestion

3. MESOTHELIOMA: THE BASICS Pleural –Usually caused by asbestos or some similar fiber, but not always Peritoneal –Maybe caused by asbestos 50% or less Pericardial –Rarely caused by asbestos Testicular mesothelioma –Too uncomfortable to discuss

4. Pleural Mesothelioma

5. Caused by prior radiation therapy at the site Other fibers –Erionite (which is not just in Turkey) –Taconite –Maybe any fiber that that is biopersistent? Spontaneous or ideopathic

6. Peritoneal Mesothelioma Often caused by some other inflammatory process Be on the lookout for: –Prior hernias –Diverticulitis –Hysterectomies –Anything that leads to chronic inflammation

7. Pericardial and Testicular If you ever see one we can talk about then.

8. Types of mesothelioma Epithelial Sarcomatoid Biphasic

9. Epithelial

10. Sarcomatoid

11. Biphasic

12. Extremely Rare Diagnosis Desmoplastic –Really just a rare subtype of sarcomatoid –Hard to diagnose and easily confused with sarcomatoid adenocarcinoma Benign mesothelial hyperplasia –Reactive process that looks like malignant mesothelioma Well differentiated papillary mesothelioma –benign

13. Desmoplastic

14. Old men get Mesothelioma Female mesotheliomas are more often from another cause – maybe 50-50 Really young people usually don’t have sufficient latency If the plaintiff is young look for other causes

15. Take Away #1 – Be Suspicious Mesothelioma in any location other than the pleura (by the lung) is very suspect Mesothelioma diagnosis with extra words is suspect (wdpm, hyperplasia, etc) Mesothelioma in young people and women is suspect. Be suspicious of the diagnosis in these cases.

16. STAINS

17. Stain Limitations Can’t show if process is malignant or benign No single stain can definitively diagnose mesothelioma Glut-1 Caveat

18. Specificity v. Sensitivity LeuM1 Stain Specific to Adenocarcinoma LeuM1 Stain Does Not Have High Sensitivity though, because does not react with all adenocarcinoma EXAMPLE: LeuM1 STAIN

19. Other Common Stains Cytokeratins Glycoproteins Calretinin Thrombomodulin HBME-1 Cadherins TTF-1

20. Stains Used to Diagnose Mesothelioma CK5 - CYTOKERATIN 5/6

21. Stains Used to Diagnose Mesothelioma MESOTHELIN

22. Stains Used to Diagnose Mesothelioma THROMBOMODULIN

23. Stains Used to Diagnose Mesothelioma HBME-1

24. Stains Used to Diagnose Mesothelioma CALRETININ

25. Stains Used to Diagnose Mesothelioma WT-1

26. Take Away #2 – Stains are just a tool IHC stains are NEVER enough for a complete diagnosis They are positive stains and marginally positive stains No one stain is enough Stains cannot distinguish between malignant and benign mesotheliomas

27. Diagnosing Malignancy Invasion Necrosis Clinical Correlation Other factors

28. Stromal Invasion “True stromal invasion is by far the most reliable criterion of mesothelial malignancy” Andrew Churg M.D., et al The Separation of Benign and Malignant Mesothelial Proliferations; The American Journal of Surgical Pathology 24(9):1183

29. …One single slide, 589D4, shows early invasive disease with minimal invasion of fibrous stroma by mesothelial clusters. Minimal Invasion 06/29/05 - Report of Dr. J.F. Legier

30. 6 Days Earlier – Same Pathology 06/23/05 - Report of Dr. J.C. Maddox …based on the clinical history and imaging studies that showed progression of the disease (“malignant mesothelioma on the left with extensive mediastinal invasion…”) … the patient more likely than not had a malignant mesothelioma that caused his death.

31. And Another Opinion 05/21/07 - Report of I. Allen Feingold Despite all of the above hisotpathological and even immunohistochemical evidence against malignancy in this case, it is important to consider the observation of Dr. Robert Viggiano who saw the patient in consultation and follow up…

32. Only Seen 10 Times Q: Okay. And out of those 7- or 800 cases, how many times have you had a difficult diagnosis like this, where you had to compare this sort of a benign, reactive process to a malignant mesothelioma? A: Maybe ten times. Q: Okay. And out of those 7- or 800 cases, how many times have you had a difficult diagnosis like this, where you had to compare this sort of a benign, reactive process to a malignant mesothelioma? A: Maybe ten times. Dr. Jacques Legier, pp. 72-73

33. Clinical Correlation Just fancy talk for “Did the patient seem like a man with mesothelioma?”

34. Necrosis Is there dead or dying tissue?

35. Other Factors Read this: Andrew Churg M.D., et al The Separation of Benign and Malignant Mesothelial Proliferations; The American Journal of Surgical Pathology 24(9):1183

36. Take away #3 – Not all Mesotheliomas are Malignant Stains don’t prove malignancy Invasion, Necrosis, Clinical Correlation do

38. Tissue Selection A whole lung is ideal, but not necessary Autopsy, Pneumonectomy or biopsy Uninvolved tissue (not the tumor) The Bigger, The Better Multiple Sites But as little as a gram can be enough

39. Results of Fiber Burden Analysis Evidence of Fiber Type Amount of Exposure Evidence of Other Exposures Helpful with Alternative Exposure Defenses

40. Take Away # 4 Digestion can be valuable To prove amphibole exposure To suggest an absence of chrysotile To prove a dose estimate

41. All 4 Take Aways or The Big Finale Be Suspicious of unusual mesotheliomas (extra words, people under 60, women) Stains are imperfect and don’t prove malignancy - just differentiate between mesothelioma and other processes Malignancy has to be proven – invasion, necrosis, clinical correlation Digestion can prove fiber type and dose, but not diagnosis