A prostatarák patológiája

Átírás

1 A prostatarák patológiája Székely Eszter S.E. II.Path. Int.

2 Prostata carcinoma incidencia Morbiditás Mortalitás

3 Prosztata carcinoma Relevancia (?)

4 Legfontosabb kihívások a patológiai diagnosztikában Daganatot utánzó eltérések elkülönítése a Daganattól

5 A patológus feladata a daganat - Jelenlétének igazolása - Grade-jének meghatározása - Kiterjedtségének meghatározása Ehhez szükség van

6 Megfelelő Mintára Technikai feltételek megvalósulására Klinikai adatokra

7 Legfontosabb kihívások a patológiai diagnosztikában Megfelelni (+ alkalmazkodni) a folyamatosan változó szabályoknak(hoz)!

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9 2016 WHO Szemelvények, új entitások Intraductalis carcinoma Microcystic carcinoma Pleomorph giant cell carcinoma Large cell neuroendocrine carcinoma

10 Intraductalis carcinoma jelentősége 90 %-ban invazív HG ACC mellett látni (nem akkora tragédia, ha nem ismerjük fel, vagyis nem a nevén nevezzük) 10%-ban azonban nincs invazív componens és a prostatectomia 100%-os gyógyulást jelent

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13 Intraductalis carcinoma Dense cribriform Loose cribriform Micropapillary pattern +/- comedonecrosis PIN-szerű, de annál durvább cytol. eltérések Marked nuclear atypia Ált HG inv. hagyományos ACC mellett

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25 Ductal ACC vs Intraductal Pr.Cc Ductal ACC endometrioid Cribriform with slitlike spaces Pseudostratified columnar cells Papillary fronds Basal cells variably present Intraductal Pr.Cc Cribriform with rounded lumina Cuboidal cells Micropapillary fronds Basal cells always present

26 Léteznek intermediair formák, amikor e két típus egyszerre látható

27 Prostatic duct ACC (Endometrioid) Papillary Solid papillary Solid nests Cribriform PIN-like Individual glands (mimicking colonic ACC) (Ritkán lehet CDX2+!)

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37 Cribriform Acinar ACC vs Cribriform Intraductal Pr.CC. Cribriform Acinar ACC Cribriform Intraductal Pr.CC Lacks branching glands Much larger than normal glands May have branching glands Can be larger than normal glands Irregular infiltrative borders ABSENCE OF BASAL CELLS Rounded circumscribed glands BASAL CELLS PRESENT

38 Intraductal Urothelial Carcinoma vs Intraductal Carcinoma of the prostate Intraductal Urothelial Carcinoma Rarely associated with glands Often solid nests Intraductal Carcinoma of the prostate Often glandular or cribriform Occasional solid nests Often marked pleomorphism Occasional marked pleomorphism Prostatic markers negative Uroth. Markers positive (GATA3, thrombomodulin, P63, HMWCK) Protate markers positive (PSA, Prostein, PSMA, Erg) Urothelial markers negative

39 Bal oldali minta 61 éves PSA 3.03 ng/ml Diónyi izomtapintatú prosztata, jobb oldalon kis göbbel

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42 Ez egy másik eset, urothel Az eredeti eset

43 A beteg mintája a jobb lebenyből

44 Microcystic carcinoma Deceptively benign Dilatált cysticus mirigyek, hagyományos ACC mirigyméretének 10-szerese AMACR +, BCK- Gleason Grade ált: 3 (Pseudohpl., ill. pseudoatrophiás cc. variáns )

45 Pleomorph giant cell carcinoma Közölt esetek száma: 10! Ált hagyományos tu kezelése hormon-sugár th. után alakul ki

46 Large cell neuroendocrine carcinoma Hagyományos prosztata ACC hormonterápiája után Közölt esetek száma szintén nagyon alacsony Morfológiája egyezik más szervek hasonló daganataival

47 Prosztata ACC variánsok, grademeghatározásuk A prosztata ACC variánsokat a mintázatuk alapján soroljuk be, a kissejtes cc. kivételével. Pl. mucinosus: ha 25% : ACC mucinosus jelleggel Gleason grade: a mirigyek mintázata alapján, nem minden mucinosus Gl4! (A mikroszkópos képből kivonjuk a mucint.) Variants are typically graded on the basis of their underlying architectural pattern, with the exception of small cell carcinoma. Mucinous (colloid) carcinoma of the prostate should be graded on the basis of underlying growth patterns (rather than all as pattern 4) If less than 25% mucinous: ACC with mucinous features

48 ACC pecsétgyűrű-sejtes jelleggel (Ez a régi signet ring cell ) Nincs inracytoplasmaticus mucin Mintázat meghatározás : Kivonjuk a vacuolumokat, és a structurát osztályozzuk. ACC with signet ring cell like features No IC mucin Grade should be assigned based on the underlying architectural pattern as if the IC vacuoles were not present ACC with signet ring cell like features No IC mucin Grade should be assigned based on the underlying architectural pattern as if the IC vacuoles were not present

49 Basal sejtes carcinoma - Ki67 %-t, - nagy szolid fészkek jelenlétét, - necrosis meglétét meg kell említeni, mert ez rosszabb prognózissal jár.

50 Gleason történelem

51 GleasonGRADE

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53 Legújabb.

54 Fentiekből következően több lett a Gleason score 7 eset, a Gleason 6 score esetek jobb prognózisúak mint korábban.

55 Legújabb Eggyel korábbi

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57 2016 WHO Újdonságok 2014-es consensus meeting eredménye 2016-os WHO könyv új.. szabályai

58 2016 WHO GRADE GROUPING (2014 ISUP conferencia óta bevezetett ajánlás )

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60 Az új, Grade Group meghatározás mellett a Gleason score-t is meg kell adni a leletben! A new prostate cancer grading system initially to be used in parallel to the Gleason system has been developed that is simpler and more accurately reflects prognosis. Rationale: Despite the above changes to the Gleason system, there are still significant deficiencies in its reporting that are described below that have led to a new grading system for prostate cancer.

61 Tűbiopsziában NEM DIAGNOSZTIZÁLUNK Gl 3+3 alatti tumort! Gleason scores 2-4 are no longer assigned on needle biopsy and Gleason scores 2-5 are virtually never diagnosed on other types of prostate samples. (2000 never 2005 rarely if ever 2014 never)

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64 - cribriform - a rosszul formált (purely formed) és a - glomeruloid mirigyek Gleason 4 mintázatba tartoznak

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66 Mucinosus fibroplasia (collagen micronodulusok) esetén - a mirigyek formája, - fúzió jelenléte/hiánya határozza meg a Gleason mintázatot

67 Ha ép mirigyek között rosszul formált mirigyeket látunk, sorozatmetszeten kell vizsgálni, hogy technikai ok vagy mirigyfúzió-e az elváltozás. Bizonytalanság esetén Gl. 3.

68 Kezelt prosztata ACC Sem irradiatio, sem hormon th után nem adunk Gleason score-t, mert a kép félrevezető lehet. Ha a terápiás válasznak nincs szöveti jele, (puffadt cpl-jú, vagy zsugorodott sejtek), azt meg kell említeni a leletben.

69 Intraductalis carcinoma Nem adunk Gleason grade-t, de ha nincs invazív komponens, meg kell említeni a leletben, hogy ez a tumor agresszívabb tumorral együtt szokott előfordulni. Intraductal carcinoma of the prostate in the absence of invasive component should not be graded but should be commented on in the report to alert clinicians of its consistent association with aggressive cancer Intraductal carcinoma of the prostate (IDC-P) should not be assigned a Gleason grade, yet it is typically associated with aggressive disease. Rationale: IDC-P usually represents extension of high-grade invasive carcinoma into ducts and is typically seen with Gleason scores 7 or higher cancer. However, uncommonly, IDC-P can represent a precursor lesion without adjacent invasive cancer. in the latter situation, it would be inaccurate to assign a Gleason score to a precursor lesion in which the cure rate is 100% if completely removed. Consequently, IDC-P is not given a grade. However, in the uncommon setting in which there is only IDC-P on biopsy in the absence of infiltrating carcinoma, a note is added to the pathology report stating that IDC-P is typically associated with high-grade invasive carcinoma and it is justified to treat these patients definitively with surgery or radiation therapy.

70 HG tumor esetén egy kis területen - 5% - előforduló jobban differenciált tumor nem számolandó a Gleason score-ba. In the setting of high-grade cancer, one should ignore lower-grade patterns if they occupy less than 5% of the area of the tumor. Rationale: When a tumor is almost entirely high grade, it is expected that the tumor will be aggressive, even if there is a very small focus of lowergrade cancer. For example, a needle biopsy composed of 99% Gleason pattern 4 with just a few well-formed glands of Gleason pattern 3 would be graded as Gleason score = 8.

71 Ha tűbiopsziában 3 féle mintázat van, a legnagyobb és a legrosszabbul differenciált terület száma adja a score-t, akármilyen kis terület is a legrosszabbul differenciált! In the setting of three patterns on needle biopsy (i.e., patterns 3-5), the most common pattern is added to the highest grade pattern. Rationale: On needle biopsy, it is thought that any pattern 5 on needle biopsy, even if it is the third most common pattern, is significant and should be incorporated into the Gleason score; it would likely not be so limited if it was not for undersampling on needle biopsy.

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74 Gleason matek 1. Legnagyobb Legnagyobb Legrosszabb 5 5 5

75 Ugyanez prosztatectomiás anyagban: Ha a tertiair Grade Gleason 5 ~ de 5%, az minor HG mintázatnak számít, a leletben megemlítendő, de a score-ba nem számoljuk ~ 3+4 esetén Gleason score 7, GG2+, 4+3 esetén GG3+ ~ de 5%, akkor a score-ba adjuk, hiába tertiair grade In the settings of three patterns in a radical prostatectomy nodule (i.e., patterns 3-5), if pattern 5 is the least common pattern yet occupies more than 5% of the tumor, then pattern 5 is included in the Gleason score. If pattern 5 is the least common pattern and occupies less than 5% of the tumor, then it is recorded as a tertiary pattern. (Minor HG pattern!) The only time tertiary patterns should be reported in prostate specimens is in the setting of = 7 with tertiary pattern (Minor HG pattern!) 5 or (GG2+) = 7 with tertiary pattern (Minor HG pattern!) 5 (GG3+) Rationale: When the entire cancer is evaluable on radical prostatectomy without the sampling artifact on needle biopsy, a small amount of pattern 5 in a Gleason score 7 cancer worsens the prognosis yet not as bad as the next highest grade. A Gleason score = 7 with tertiary (<5%) pattern 5 has a prognosis in between and A Gleason score = 7 with tertiary (<5%) pattern 5 has a prognosis in between and

76 Ugyanez Gl 4-nél kicsit másképp ajánlott: Tűbiopsziában ha van Gl 4, akármennyi is, az a score része (nincs különbség a Gl 5-tel). RP mintában is jobb lenne ez, mint az 5% +/- t nézni. Ajánlás: Gl3+4, 4-et %-ban megadva

77 Reporting of percentage of Gleason 4 component in Gleason score 7 (particularly Gleason score =3+4) tumors is also a major recommendation, as it may have major impact on treatment decisions - surveillance

78 Radicalis prostatectomia Két különálló, különböző score-t mutató tumor-góc Grade-jét külön kell megadni 4+4 Different tumor nodules in a radical prostatectomy specimen are assigned different Gleason scores. Rationale: For example, if there is a Gleason score = 8 in the left posterior lobe and a larger separate Gleason score = 6 in the right posterior lobe, there is no rationale that the = 6 tumor would make the = 8 less aggressive. Consequently, in this example, each tumor nodule would be graded separately and the highest grade (4 + 4 = 8) would be the grade assigned to the patient, rather than adding all tumors together that would have resulted in an inappropriately low grade of = 7. Experts in prostate pathology have used this grading rule in the past with outcome studies demonstrating that grading each major nodule separately correlates well with prognosis. 3+3

79 RP-ban pozitív RV esetén meg kell adni az infiltralt terület hosszát, és az infiltráló tumor Gl mintázatát

80 Tűbiopsziás mintában Minden hengernek saját score-t kell adni, - ha külön tartályban érkezik, - ha egy tartályba dobálták valamennyi hengert, akkor opcionális, - hogy egyenként adunk score-t, - vagy globális score-t adunk-e meg ssign individual Gleason scores to separate cores if as long as the cores are submitted in separate containers In case there are different undesignated cores with different grades in the same specimen container it is optional whether to assign individual grades to different cores or a global grade to the specimen container

81 Tűbiopsziás mintában Ha egy tartályban széttöredezett anyag van, globális score-t adunk Ha külön tartályban érkezett hengereknek individuális score-t adunk, opcionális, hogy a végén adunk-e egy átlagolt score-t In cases with multiple fragmented cores in a jar, give a global Gleason score to that jar In addition to giving separate cores individual Gleason scores, one has the option to also give an overall score at the end of the case

82 További posztulátumok The present and future of prostate cancer histopathology Jess K. McKenney Vol.27. No.5 Sep.2017

83 Quantitative gleason grading Gleason mintázat százalékos megemlítése a grade group és a score megadása mellett

84 + Cribriform mintázat megadásának jelentősége Gl 4 cribriform rosszabb prognózisú, mint a többi Gl 4, ezért ezt meg kell említeni a leletben Stromogén cc desmoplasticus szintén rosszabb prognózissal jár, ezt is meg kell említeni

85 Javaslat még nem parancs Score számát emelni, hogy jobban jelezze számmal a prognózist befolyásoló negatív tényező jelenlétét Pl.: Ha 3+4 mintázatban cribriform mirigyek vannak, akkor az a GG2-t GG3-ra, 4+3 mintázat esetén GG3-t GG4-re emeli..

86 Immunhisztokémia alkalmazása Core biopszia Ha egy fókuszban Gl3+3, további potenciális kiterjedtség miatt a további 3+3 gyanús többi területen IGEN (Csak akkor nem, ha tudjuk, hogy kezelés szempontjából irreleváns)

87 Immunhisztokémia alkalmazása Core biopszia Ha egy fókuszban Gl3+4 vagy magasabb grade tumor van, további potenciális kiterjedtség megítélése miatt 3+3 gyanús többi területen nem szükséges, mert nincs jelentősége

88 Immunhisztokémia alkalmazása Differenciálatlan tumor- metastasisban UCC-tól elkülönítendő PSA (monoclonalis specificus polycl.-hólyag ACC-ban+) PSAP Újabbak: ERG specifikus de nem szenzitív P501S prostein elég jó NKX3.1 (PSMA) elég jó P63 (pr.acc-ban nem spec. + lehet) GATA3 Uroplakin (nem elég szenzitív HG UCC-ban) Thrombomodulin (értumor, SQCC, mesoth + lehet)

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90 pros & cons A rendszer úgy gondolkodik, mintha a mintavétel, és a score meghatározás teljesen objektív és megfellebezhetetlen tényeken alapulna, pedig..

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92 pros & cons A rendszer úgy gondolkodik, mintha a mintavétel, és a score meghatározás teljesen objektív és megfellebezhetetlen tényeken alapulna, pedig

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103 pros & cons Patológus

104 J Magn Reson Imaging Jul 8. doi: /jmri [Epub ahead of print] Accuracy and agreement of PIRADSv2 for prostate cancer mpmri: A multireader study. Greer MD 1,2, Brown AM 1,3, Shih JH 4, Summers RM 5, Marko J 6, Law YM 7, Sankineni S 1, George AK 8, Merino MJ 9, Pinto PA 8, Choyke PL 1, Turkbey B 1. Author information Abstract PURPOSE: Multiparametric MRI (mpmri) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theprostate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpmri. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. MATERIALS AND METHODS: Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpmri using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy wholemount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. RESULTS: Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS 3 and 90% for PIRADS 4. Specialists performed better only for PIRADS 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. CONCLUSION: By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. J. Magn. Reson. Imaging International Society for Magnetic Resonance in Medicine.

105 Eur Urol Feb;69(2): doi: /j.eururo Epub 2015 Jun 10. Current Histopathologic and Molecular Characterisations of Prostate Cancer: Towards Individualised Prognosis and Therapies. Santoni M 1, Scarpelli M 2, Mazzucchelli R 2, Lopez-Beltran A 3, Cheng L 4, Epstein JI 5, Cascinu S 1, Briganti A 6, Catto JW 7, Montorsi F 8, Montironi R 9. Author information Abstract Data on TMPRSS2-ERG and AR-V7 may pave the way for personalised therapy for prostate cancer (PCa) patients. Comprehensive molecular profiling can help identify multiple PCa subtypes and driving alterations. Translating these findings into clinical practice is still challenging.

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107 Külön köszönet Dr. Tőkés Annamária

108 Eur Urol Jul;70(1): doi: /j.eururo Epub 2016 Mar 17. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Humphrey PA 1, Moch H 2, Cubilla AL 3, Ulbright TM 4, Reuter VE 5. Differential Immunohistochemical Profiles for Distinguishing Prostate Carcinoma and UrothelialCarcinoma. Oh WJ, Chung AM, Kim JS, Han JH, Hong SH, Lee JY, Choi YJ. J Pathol Transl Med Sep;50(5): doi: /jptm Epub 2016 Aug 7. Am J Surg Pathol Aug;38(8):e6-e19. Best practices recommendations in the application of immunohistochemistry in the prostate: report from the International Society of Urologic Pathology consensus conference. Epstein JI 1, Egevad L, Humphrey PA, Montironi R; Members of the ISUP Immunohistochemistryin Diagnostic Urologic Pathology Group. Arch Pathol Lab Med Oct;140(10): doi: /arpa SA. Epub 2016 Jan 12. Prostate Cancer Grading: A Decade After the 2005 Modified Gleason Grading System. Kryvenko ON 1, Epstein JI. LETTERS TO THE EDITOR Prostate Cancer Grading: A Decade After the 2005 Modified Gleason Grading System Brett Delahunt, MD, FRCPA 1 ; David J. Grignon, MD 2 ; Hemamali Samaratunga, MBBS, FRCPA 3 ; John R. Srigley, MD, FRCPC 4 ;Katia R. M. Leite, MD 5 ; Glen Kristiansen, MD, PhD 6 ; Andrew J. Evans, MD 7 ; James G. Kench, MBBS, FRCPA 8 ; Lars Egevad, MD, PhD 9 Asian J Androl Aug 4. doi: /aja.aja_24_17. [Epub ahead of print] Contemporary grading of prostate cancer: 2017 update for pathologists and clinicians. Gasparrini S 1, Cimadamore A 1, Scarpelli M 1, Massari F 2, Doria A 1, Mazzucchelli R 1, Cheng L 3, Lopez-Beltran A 4, Montironi R 1. Am J Surg Pathol Apr;41(4):e1-e7. doi: /PAS Contemporary Gleason Grading of Prostatic Carcinoma: An Update With Discussion on Practical Issues to Implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma. Epstein JI 1, Amin MB, Reuter VE, Humphrey PA. Curr Opin Urol Sep;27(5): doi: /MOU The present and future of prostate cancer histopathology. McKenney JK 1. Biopsy interpretation of the prostate: Fifth edition Jonathan I. Epstein, George J. Netto School of Medicine

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