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Recent Developments in Pathological Diagnosis and Classification of Lung Cancer

Recent Developments in Pathological Diagnosis and Classification of Lung Cancer. Serpil Dizbay Sak Ankara ÜTF, Patoloji ABD 15. Toraks Kongresi Nisan 2012/ A ntalya. Conflict of Interest : NONE TO DECLARE. Topics. “ Old ” classification Why do we need change ?

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Recent Developments in Pathological Diagnosis and Classification of Lung Cancer

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  1. RecentDevelopments in PathologicalDiagnosisandClassification of LungCancer Serpil Dizbay Sak Ankara ÜTF, Patoloji ABD 15. Toraks Kongresi Nisan 2012/Antalya

  2. Conflict of Interest:NONE TO DECLARE

  3. Topics • “Old” classification • Why do weneedchange? • Thenew (proposed) classification

  4. OLD CLASSIFICATION

  5. TC Sağlık Bakanlığı

  6. Türkiye’nin Akciğer Kanseri Haritası Projesi Türk Toraks Derneği/ Akciğer ve Plevra Maligniteleri Çalışma Grubu T.C. Sağlık Bakanlığı Kanserle Savaş Dairesi

  7. 2004 • Writtenbypathologistsforpathologists • Surgicalresectionspecimens

  8. İNVAZİV 1.Yassı hücreli karsinoma 2.Küçük hücreli karsinoma 3. Adenokarsinoma 4. Büyük hücreli karsinoma 5. Adenoskuamöz karsinoma 6. Sarkomatoid karsinoma 7. Karsinoid tümör 8.Tükrük bezi tipi karsinomalar PREKÜRSÖR-ÖNCÜ 9.Preinvaziv lezyonlar Displazi- CIS AAH DIPNECH Akciğerin malign epitelyal tümörleri (WHO 2004)

  9. WHO 2004 Adenocarcinoma(25-40%) ↑ SCC (25-40%) ↓ Smallcell (20-25%) Largecell (%10-25)

  10. 1.Yassı hücreli karsinoma a.       Papiller b.       Şeffaf (berrak) hücreli c.       Küçük hücreli d.       Bazaloid 2.Küçük hücreli karsinoma Kombine küçük hücreli karsinoma 3. Adenokarsinoma a.       Asiner b.       Papiller c.       Bronkioloalveolarkarsinoma: müsinöz/nonmüsinöz/mikst d.       Müsin bulunduran solid e.       Mikstadenokarsinoma Varyantlar: Fetal Müsinözkarsinom Müsinözkistadenokarsinom Taşlı yüzük hücreli karsinom Berrak hücreli karsinom 4. Büyük hücreli karsinoma a. Büyük hücreli nöroendokrin karsinoma b.Bazoloid karsinoma c.Lenfoepitelyoma benzeri karsinoma d. Şeffaf (berrak) hücreli karsinoma g.  Rabdoid fenotipli büyük hücreli karsinoma 5. Adenoskuamöz karsinoma 6. Sarkomatoid karsinomalar a.       Pleomorfik karsinoma b.       İğsi hücreli karsinoma c.       Dev hücreli karsinoma b.       Karsinosarkoma c.       Pulmoner blastoma 7. Karsinoid tümör a.Tipik karsinoid b.Atipik karsinoid 8.Tükrük bezi tipi karsinomalar a.       Mukoepidermoid karsinoma b.       Adenoid kistik karsinoma c.       Epitelyal-myoepitelyal 9.Preinvaziv l ezyonlar a.İn situ yassı hücreli karsinoma b.Atipik adenomatöz hiperplazi c. Diffüz idiyopatik pulmoner nöroendokrin hücre hiperplazisi Akciğerin malign epitelyal tümörleri Mevcut Sınıflama (WHO2004) 3. Adenokarsinoma a.       Asiner b.       Papiller c.       Bronkioloalveolarkarsinoma: müsinöz/nonmüsinöz/mikst d.       Müsin bulunduran solid e.       Mikstadenokarsinoma

  11. WHO 2004

  12. WHO 2004

  13. Adenokarsinoma a.       Asiner b.       Papiller c.       Bronkioloalveolarkarsinoma d.       Müsin bulunduran solid adenokarsinoma e.       Mikstadenokarsinoma %90 Mikst tipte (asiner, papiller ve BAK patterni bulunduran) adenokarsinoma

  14. Stage of NSCLC bythe time of diagnosis 72.6 % Türkiye’nin Akciğer Kanseri Haritası Projesi Türk Toraks Derneği/ Akciğer ve Plevra Maligniteleri Çalışma Grubu T.C. Sağlık Bakanlığı Kanserle Savaş Dairesi

  15. Onlysmallbiopsyandcytologyspecimensareavailable in advanceddisease

  16. Classification is difficult in smallspecimen • Necrosis • Artefacts • Lack of differantiation • Tumorheterogeneity

  17. Smallcellcarcinoma • Non-smallcellcarcinoma • Adenocarcinoma • SCC • Largecell

  18. Simple • Reproducable • Sufficientforpatientmanagement • Chemoforsmallcell • Surgeryorcytotoxictherapyfor NSCLC

  19. CHANGE, WHY?

  20. WhyChange? New andTargetedtherapies Prognosticinformation on smallBAC’s Excellentprognosis of pure BAC and BAC with minimal invasion • Molecularcharacterization of lungcancer • New agentsforadenocarcinoma • Histologiceligibilitycriteriaforsomenewdrugs DEMISE OF NSCLC NEED FOR NEW PROGNOSTIC CATEGORIES

  21. WhyChange? New andTargetedtherapies Prognosticinformation on smallBAC’s Excellentprognosis of pure BAC and BAC with minimal invasion • Molecularcharacterization of lungcancer • New agentsforadenocarcinoma • Histologiceligibilitycriteriaforsomenewdrugs DEMISE OF NSCLC NEED FOR NEW PROGNOSTIC CATEGORIES

  22. Noguchi M, Morikawa A, Kawasaki M, et al. Smalladenocarcinoma of the lung. Histologic characteristics andprognosis. Cancer. 1995;75:2844–2852. Lungadenocarcinomameasuring 2 cm orless • A Lokalized BAC • B LokalizedBAC-focalalveolarcollapse • C LokalizedBAC-focalaktvefibroblastic proliferation 4. D Poorlydifferentiated AC • E Tubularadenocarcinoma • F Papillaryadenocarcinomawith compressive anddestructivegrowth

  23. Aoyagi Y, Yokose T, Minami Y, et al. Accumulation of lossesof heterozygosity and multistep carcinogenesis in pulmonaryadenocarcinoma. CancerRes. 2001;61:7950–7954. • LOH in tumorsupressorgenes: • Noguchi A (BAC): 17% • NoguchiB (BAK-focalalveolarcollapse):40% • NoguchiC (BAK-focalactivefibroblastic proliferation): 96%

  24. Koga T, Hashimoto S, Sugio K, et al. Clinicopathological andmolecular evidence indicating the independence of bronchioloalveolarcomponents from other subtypes of human peripherallung adenocarcinoma. Clin Cancer Res. 2001;7:1730–1738. P53 mutation • In-situadenocarcinoma: BAC 0 % • Earlyinvaziveadenocarcinoma (Minimallyinvaziveadenocarcinoma) : Mixttypeadenocarcinomawith a major BAC component11% • Lateadenocarcinoma: Otheradenocarcinomas48%

  25. In-situadenocarcinoma • Earlyinvaziveadenocarcinoma (Minimallyinvaziveadenocarcinoma) • Lateadenocarcinoma

  26. WhyChange? New andTargetedtherapies Prognosticinformation on smallBAC’s Excellentprognosis of pure BAC and BAC with minimal invasion • Molecularcharacterization of lungcancer • New agentsforadenocarcinoma • Histologiceligibilitycriteriaforsomenewdrugs DEMISE OF NSCLC NEED FOR NEW PROGNOSTIC CATEGORIES

  27. New Agents Etkinlik Toksisite Etkinlik NSCLC is not enoughnow

  28. NEW (PROPOSED) CLASSIFICATION

  29. 2011 • Multidisciplinaryapproach • Smallspecimens

  30. WHAT İS NEW?ReSECTIONS

  31. StrongRecommendations For nonmucinousadenocarcinomas previously classifiedas mixed subtype where the predominant subtype consists of the former nonmucinous BAC, the use of the term LPA and discontinuing the term “mixed” subtype In patients with early-stage adenocarcinoma, the addition of “micropapillary predominant adenocarcinoma” as a major histologicsubtype due to its association with poor prognosis • Discontinuing the use of the term“BAC” • For small (3 cm), solitary adenocarcinomas with pure lepidic growth, the use of term “Adenocarcinomain situ” • For small (3 cm), solitary, adenocarcinomas with predominant lepidic growth and small foci of invasionmeasuring 0.5 cm, theuse of a new concept: “Minimallyinvasiveadenocarcinoma”

  32. OtherRecommendations • For invasive adenocarcinomas, comprehensivehistologicsubtyping be used to assess histologicpatternssemiquantitatively in 5% increments, choosing a single predominant pattern. Individualtumors be classified according to the predominant pattern • In patients with multiple lung adenocarcinomas, comprehensive histologicsubtyping in thecomparison of the complex, heterogeneous mixtures ofhistologic patterns to determine whether the tumorsare metastases or separate synchronous or metachronous primaries

  33. WHO 2004

  34. 100 % DFS

  35. Micropapillary Solid Lepidic Aciner Papillary

  36. Micropapillarypattern: Poorprognosis

  37. Örnek: • İNVAZİV ADENOKARSİNOMA, ASİNER TİP BASKIN ( % 50 ASİNER, %25 PAPİLLER, %25 LEPİDİK TİP) • İNVAZİV ADENOKARSİNOMA, MÜSİN OLUŞTURAN SOLİD TİP BASKIN ( % 70 MÜSİN OLUŞTURAN SOLİD , %30 ASİNER TİP) • İNVAZİV ADENOKARSİNOMA, MİKROPAPİLLER TİP BASKIN ( % 80 MİKROPAPİLLER, % 15 PAPİLLER, %5 ASİNER TİP)

  38. Limited (Sublobar) resections • For a limitedresectionto be adequate: • A preciseintraoperativediagnosis • Evaluation of resectionmargins • Evaluation of lymphnodes FROZEN SECTIONS

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