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Hodgkin lenfoma'da immunhistokimya: Uygulama öncesi ve sonrasında tanı değişiklikleri, morfolojik ve biyolojik grizon lenfomaların tanınabilmesi

Immunhistochemistry of hodgkin lymphoma: Diagnostic differences before and after application of immunhistochemistry determination of morphological and biological gray zone lymphoma

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  1. Tez No: 131767
  2. Yazar: NURAY BAŞSÜLLÜ
  3. Danışmanlar: PROF. NÜKHET TÜZÜNER
  4. Tez Türü: Tıpta Uzmanlık
  5. Konular: Patoloji, Pathology
  6. Anahtar Kelimeler: Belirtilmemiş.
  7. Yıl: 2003
  8. Dil: Türkçe
  9. Üniversite: İstanbul Üniversitesi
  10. Enstitü: Cerrahpaşa Tıp Fakültesi
  11. Ana Bilim Dalı: Patoloji Ana Bilim Dalı
  12. Bilim Dalı: Belirtilmemiş.
  13. Sayfa Sayısı: 81

Özet

ÖZET ve SONUÇLAR Bu çalışmada, İHK kullanılmadan tanı alan ve alt tiplemeleri yapılan HL vakaları ÎHK uygulamasından sonra yeniden değerlendirilerek HL ile NHL arasında ortak yönleri ile kesişen vakalar izole edilmiş ve bunlar HL ile morfolojik ve/veya biyolojik gri zon içinde karışabilen ancak İHK uygulaması ile tam almış ABHL ve THZBHL vakaları da eklenerek değerlendirilmiştir. HL tanısı alan 397 olguda median yaş 31, yaş ortalaması 33,76 ±17,74,yaş sınırları 16-75 dir. Vakaların %67,8'i erkek, %32,2'si kadm olup E/K oram 2,8:1 dir. 508 vaka yeniden değerlendirildiğinde 429 vakadan 397'sinde (%92.5) Hodgkin Lenfoma tanısı kesinlik kazanmıştır. Alt tiplere göre dağılımda en sık görülen tip NS (%43.5) olup bunu Mikst tip (%40) izlemektedir. Lenfositten zengin nodüler HL %3.8 oranında görülürken, Lenfositten zengin klasik HL nın nodüler ve difuz tipleri %2.8 oranındadır. Lenfositten yoksun alt tip oram ise %5.6 dır. 32 olguda (%7.5) ise tam NHL yönünde değişmiştir. İlk tamları NS olan 147 vakadan sadece 3 'ünde HH tanısı NHL olarak değişmiş olup (%2) bu değişim iki vakada ABHL, birinde ise THZBHL şeklindedir.. Vakaların %90'ında alt tip değişmeden NS olarak kalmıştır. Yedi olguda (%4.8) alt tip MH olarak değişirken 4 vakada (%2.7) materyal yetersizliğine bağlı nedenlerle alt tipleme yapılamamıştır. NS gradelendirmesinde ilk tam ile son değerlendirme arasında vakaların sadece %85'inde Grade değişmeden kalmıştır. Grade II içinde yer alan sinsisyal varyant vakaların % 4'ünü oluşturmaktadır İlk tanısı MH olan 201 vakadan 149'unda (%74) alt tip MH olarak kalmıştır. Bu alt tipte NHL olarak tanımlanan olgu sayısı 12 (%6) olup tümü THZBHL tanısı almıştır. MH alt tipindeki değişimler ise 20 vakada (%10) NS, 11 vakada (%5,6) LY, 5 vakada (%2.5) LZKHL bir vakada (%0.5) da NLZHL şeklindedir. İki vakada NLZHL ile THZBHL arasında kesin ayırım yapılamamış, altı vakada ise HH tanısı kesinleşmesine rağmen infiltrasyonun fokal oluşu veya biopsinin insizyonel ve küçük oluşu nedeniyle alt tipleme mümkün olmamıştır. İlk tamlara göre, MH tip bir vakada düşük gradeli B hücreli NHL birlikteliği LY alt tip olarak değişmiştir. 41En fazla tanı değişikliği LY alt tipte gerçekleşmiştir. İlk tanısı LY olarak verilmiş 35 olgunun 21 'inde (%60) HH tanısı değişmezken 13'ünde (%37) tam NHL yönünde değişmiştir. NHL alt tipleri 8 vakada ABHL, 5 vakada ise difuz büyük B hücreli lenfoma şeklindedir. LY alt tip içindeki alt tip değişimleri ise NS (%17), MH (%11.4), sımflandırılamayan (%5.7) şeklindedir. Onbir vakada ise (%31:4) alt tip değişmeden LY olarak kalmıştır. Çalışmamızda bu tip ile en fazla kansan NHL nin ABHL olduğu bunu THZBHL nın izlediği görülmüştür. HL alt tipinde değişim olarak da en sık NS ile karıştığı saptanmıştır İlk tamları nodüler difuz ayırımı yapılmaksızın LZ-HH olarak verilen 15 vakadan beşinde (%33,3) tam MH tip, 4 olguda (%13) biyolojik gri zon olan THZBHL,bir olguda ise (%3) morfolojik gri zon olan PTHL olarak değişmiştir. Bir vakada (%6.6) tam NLZHL, 3 vakada (% 20) LZKHL (1 nodüler, 2 difoz), olarak belirlenmiştir. NLZHH tamsı almış olan 15 vakanın 11 'inde (%73.3) alt tip aynı kalmış, üçünde (%20) LZKHL olarak değişirken bir vakada alt tipleme yapılamamıştır. İlk tanıya göre HH tamsı alan ancak alt tipleme verilmemiş olan 16 vakadan 12'sinde (%75) alt tipleme mümkün olduğu halde 4 vakada alt tipleme yapılamamıştır. KHL tamsı alan vakalarda RS hücreleri CD30 (% 100), CD15(%97,4) ile pozitif olup CD 15 ile + boyanan RS hücrelerinin oram vakadan vakaya değişiklik göstermekteydi. Vakaların %85.4'ünde RS hücrelerinin %50-100'ünde paranüklear ve membran tipi boyanma mevcuttu. Geri kalan HL vakalarında RS hücrelerinin CD 15 boyanma oranlan, vakaların % 7'sinde %10, %6.8'inde %20-50 arasında değişmekteydi. CD15(-) olan vakaların dağılımlan NS (%2.3), MH (%1.3), LY(%4.5) şeklinde olup NLZHL vakalarının tümünde RS hücreleri CD15(-) idi. RS hücrelerinde CD20 ile membran boyanması % 15.6'da saptandı. RS hücrelerinin CD20 ile boyanma oranlan ise vakaların % 24.2'sinde %50 şeklindeydi. ABHL olarak sımflandınlan 50 olguda median yaş 56, yaş ortalaması 51.3±18.8, yaş sınırlan 17-91dir. Vakalann %70 i erkek, %30 u kadm olup E/K oram 2.3:1 dir. İlk tanılan ABHL olan 37 vaka yeniden değerlendirildiğinde ikisinde ABHL ile HL arasında kesin bir ayırıma gidilemedi, birinin tamsı ise B hücreli ABHL olarak değişmiştir. 42ABHL vakalarının %54'ü ALK (-), %40 ı ALK(+) olup, 2 vakada B hücreli ABHL saptandı bunlardan biri ALK+ idi. Üc vakada ise ABHL ile HL arasında kesin ayırım yapılamadı. CD30 tüm olgularda kuvvetli pozitif boyanmaktaydı. EMA vakaların %25'de pozitif bulundu. CD15 olguların % 4.8'de hücrelerin

Özet (Çeviri)

SUMMARY and CONCLUSION In this study, the cases of Hodgkin's lymphoma (HL), diagnosed and subtyped without using immunohistochemistry (IHC) were reinterpreted after the performance of EHC and the cases that share common features with Non Hodgkin Lymphoma (NHL) were isolated. In adition the cases that can be confused with HL in the morphological and/or biological grey zone but diagnosed after IHC as Anaplastic large cell lymphoma (ALCL) and T-cell-rich B-cell lymphoma (TCRBCL) were taken in the study group and together with HL, and all were reevaluated. The median age of 397 HL cases was 31 with an average of 33,76 ±17,74, ranging between 16-75. Among the cases, 67,8 % were male and 32,2 % were female, having a male/female ratio of 2,8:1. After the reinterpretation of 508 cases, the diagnosis of HL was reestablished in 397 cases out of 429 (92,5 %). When the subtypes were considered, the most common one was nodular sclerosis (NS) (43,5 %), and the mixed type (MC) followed (40 %). Lymphocyte rich (LR) nodular HL was seen at a ratio of 3,8 % while lymphocyte rich classic HL (LR-CHL) nodular and diffuse types had a ratio of 2,8 %. Lymphocyte depletion type (LD) HL was seen in 5,6 % of the cases. In 32 cases (7,5 %) the diagnosis was changed to NHL. Out of 147 cases with the initial diagnosis of NS, only in 3 cases, the diagnosis was changed to NHL (2 %), 2 rediagnosed as ALCL and 1 as TCRBCL. In 90 % of the cases the diagnosis remained as NS without any change in the subtype, whereas, 7 cases were reinterpreted as MC (4,8 %). In 4 cases subtyping could not be achieved due to the insufficency of the biopsy material. In grading NS, only 85 % of the cases remained in the same grade as in the initial diagnosis. The sinsitial variant considered in Grade n, was seen in 4 % of the cases. Out of 201 cases with the initial diagnosis of MC,the subtype remained the same in 149 cases (74 %). In this subtype, the number of the cases reinterpreted as NHL was 12 (6 %) and all were rediagnosed as TCRBCL. The changes in subtype were to NS in 20 cases (10 %), LD-HL in 11 cases (5,6 %), LR-CHL in 5 (2,5 %) and nodular lymphocyte predominant HL(NLPHL) in 1 case (0,5 %). In 2 cases the differentiation between NLPHL and TCRBCL couldn't be made properly. Although the diagnosis of HL was confirmed, in 6 cases subtyping couldn't be made since the infiltration was 45focal or the biopsy was either an insitional biopsy or too small. One case with an initial diagnoses of both MC, together with a low grade B cell NHL was rediagnosed as LD subtype. The subtype of HL, in which the diagnosis altered most often after the reevaluation, was LD subtype. Out of 35 cases with the initial diagnosis of LD, the diagnosis remained the same in 21 cases (60 %), whereas, in 13 (37 %) cases, it was changed to NHL. NHL subtypes were ALCL in 8 cases, DLBCL in 5 cases. Changes in subtyping were to NS (17 %) and to MC (11,4 %) while 5,7 % were unclassifiable. In 11 cases (31,4 %) the subtype remained as LD without any change. In our study the most common NHL confused with this subtype was ALCL and the following was TCRBCL. In subtyping of HL, this subtype was most commonly confused with NS. Among the 15 cases diagnosed initially as LR-CHL without pointing out as nodular or diffuse type, 5 cases were reinterpreted as MC (33,3 %), 4 cases (13 %) as TCRBCL which is considered in biological grey zone, and 1 case as PTCL (3 %) which is considered in morphological grey zone. In one case the final diagnosis was designated as NLPHL (6,6 %) and in 3 cases as LR-CHL (20 %) (1 nodular,2 diffuse). Out of 15 cases, initially dignosed as NLPHL, 1 1 cases (73,3 %) remained in the same subtype, while 3 cases (20 %) were rediagnosed as LR-CHL and 1 case couldn't be further classified. Out of the 16 cases diagnosed initially as HL without any subtyping, 12 cases (75 %) could be subtyped during reevaluation. On the other hand, 4 cases still couldn't be subtyped. In CHL, Reed-Sternberg (RS) cells were CD30+ (100 %) and CD15+ (97,4 %). The ratio of CD15+ RS cells varied from case to case. In 85,4 % of the cases, a paranuclear and membranous stanning was seen in 50-100 % of RS cells. In the remaining HL cases, the expression of CD 15 was detected in 10 % of RS cells in 7 % of cases and in 20-50 % of RS cells in 6,8 % of cases. CD15(-) RS cells were seen in some NS (2,3 %), MC (1,3 %), LD (4,5 %) subtypes and in all NLPHL. The membranous stainning with CD20 in RS cells was seen in 15,6 % of the cases. The ratio of the CD20+ RS cells were less than 10 % in 24,2 % of cases, between 10- 30 % in 35,6 % of cases, 30-50 % in 19,4 % of cases and greather than 50 % in 43,5 % of the cases. 46In 50 cases classified as ALCL median age was 56, with an average of 51,3*18,8, ranging between 17-91. Seventy percent of cases were male and 30 % were female with a male/female ratio of 2,3 : 1. Out of 37 cases initially diagnosed as ALCL the differentiation between ALCL and HL couldn't be achieved in 2 cases, and the diagnosis was reestablished as B cell ALCL in one case. Among ALCL, 54 % of cases were ALK(-), whereas, 40 % were ALK+. Two cases were B cell ALCL and one case was ALK+. In 3 cases distinction between ALCL and HL couldn't be done. All cases displayed strong CD30 expression. EMA positivity was detected in 25 %, while CD 15 positivity was seen in less than 10 % of cells in 4,8 % of cases.In 40 % of the cases T cell phenotype was seen. In 3 cases, the differentiation between ALCL and HL couldn't be made with certainty. In these cases, all cells displayed strong positivity with CD30. In the large cells CD 15 expression varied between 10 and 20 % and EMA positivity was detected in 33 %. ALK negativity wasn't seen in T phenotype. The median age of 51 cases of TCRBCL was 44,5, with an average of 45,1±18,8, ranging between 17 and 80. Among them, 62,7 % were male and 32,2 % were female, with a male/female ratio of 1,2: 1. In 31 cases of TCRBCL,the initial diagnosis wasn't changed. Together with the HL cases reinterpreted as TCRBCL, the diagnosis of TCRBCL was established in 51 cases. In 2 cases the differentiation between CD20+ MC-CHL and TCRBCL and in another case the differentiation between NLPHL and TCRBCL couldn't be achieved. In the cases diagnosed as HL without IHC, the most common subtype causing difficulty in the differentiation of TCRBCL was mixed type (12 case) and the followings were lymphocyte rich (4 cases) and lymphocyte depletion types (4 cases). In NS only 1 cases was reinterpreted as TCRBCL. When TCRBCL cases were classified according to their B cell content, large cells with a ratio of less than 10% was seen in 30 cases (58,8 %), 10-20 % in 12 cases (23,5 %) and 20-40 % in 9 cases (17,6 %). Out of 1 1 cases in which the differential diagnosis between HL and NHL couldn't be achieved initially, the diagnosis was established as NHL in 3 cases (27,3 %) and as HL in 7 cases (63,6%) after the reevaluation of the cases. 47Even after the performance of IHC, there were 6 cases in which the exact diagnosis couldn't be made. In 3 cases the differention between ALCL and HL wasn't possible. In all these 3 cases, the morphology was like the common type of ALCL. The large cells were strongly CD30+ while 10-20 % of mononucleer and large cell were CD 15+. EMA was positive in only 1 cases. All of them were ALK(-).In 2 cases, the differentiation between CD20+ MC-CHL and TCRBCL couldn't be achieved. In both of these cases large cells strongly expressed CD30 and the morphology was more alike to HL. CD 15 was negative. Moreover, in 1 case the differentiation between NLPHL and TCRBCL couldn't be made. The grey zone between HL and NHL can either be a biological grey zone as a result of common pathogenesis or it may be a morphological grey zone due to the morphological similarities. With the help of IHC, this type of false diagnosis could be avoided. In conclusion, as the biology and the origin of RS cells were cleared out, the differentiation of HL from other agresive lymphomas such as TCRBCL or ALCL became possible at least to an extend. However, in cases displaying CD 15 negativity and high ratios of CD20 positivity, the differential diagnosis was still troublesome. 48

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