#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Detection of the t(14;18) chromosomal translocation from fine-needle aspiration in follicular lymphoma and the significance of so called molecular nodal remission


Authors: A. Janíková-Obořilová;  J. Mayer;  L. Křen;  I. Kroupová 1;  J. Šmardová 1;  D. Dvořáková 1;  P. Mejstřík;  J. Neubauer;  I. Vášová 2
Authors‘ workplace: Interní hematoonkologická klinika FN Brno, 1Patologicko anatomický ústav FN Brno, 2Radiodiagnostická klinika FN Brno
Published in: Transfuze Hematol. dnes,13, 2007, No. 2, p. 79-87.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

Aim:
To prove, if fine needle aspiration (FNA) is sufficient for detection of t(14;18) in lymph node infiltrated by follicular lymphoma (FL). To determine value of molecular remission in lymph node in patients in complete and molecular remission.

Methods:
First we tested t(14;18) in paired-specimens taken by FNA and by classical biopsy (from autopsies and operation biopsies). We continued to perform FNAs guided by ultrasound (US) in patients with easy accessible lymphadenopathy, t(14;18) was tested by FISH (fluorescent in situ hybridization) and by PCR (polymerase chain reaction). FNA of near the same lymph node was repeated in suitable patients in complete (CR) and molecular remission.

Results:
We tested for t(14;18) 22 paired samples (FNA vs. biopsy). 1/22 (4.5 %) FNA was negative compared to the biopsy. 31 FNA of lymph node guided by US were done, success of FNA was 100 % in advanced FL. FISH identified t(14;18) in 89 %, PCR in 67 %. 12 cases of FNA were done in CR (CT and PET) and molecular remission in blood (PCR): in 4/12 cases samples were not taken for technical reason, in 3/12 FNA fibrosis was detected. 6/7 patients with non-diagnostic FNA are in remission (median 19 months), 1 patient relapsed. 5/12 FNA were diagnostic (in 4 patients), t(14;18) was identified in 5/5 (100%) cases. 3 patients relapsed 3, 6 and 12 months later, 1 patient remains in remission (>20 months), in spite of repeated FNA identified t(14;18) after 12 months again.

Conclusion:
FNA is potentially suitable for detection t(14;18) in lymph nodes in FL. Persistence of t(14;18) in lymph node in CR is relatively frequent and this could be considered as real minimal residual disease. Further study is needed to define its biological importance, because persistence of t(14;18) in lymph node does not mean clinical relapse. Key words: t(14;18), follicular lymphoma, fine needle aspiration, minimal residual disease, FISH, PCR


Sources

1. Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocation: t(14;18) and 3q27 are mutually exclusive. Blood 2003; 101: 1149–1154.

2. Horsman DE, Okamoto I, Ludkovski O, et al. Follicular lymphoma lacking the t(14;18) (q32;q21): identification of two disease subtypes. Br J Haematol 2003; 120: 424–433.

3. Jardin F, Gaulard P, Buchmnont G, et al. Follicular lymphoma without t(14;18) and with bcl-6 rearrangement: a lymphoma subtype with distinct pathological, molecular and clinical characteristics. Leukemia 2002; 16: 2309–2317.

4. Tilly H, Rossi A, Stamatoullas A, et al. Prognostic value of chromosomal abnormalities in follicular lymphoma. Blood 1994; 84: 1043–1049.

5. Meijerink JPP. T (14;18), a journey to eternity. Leukemia 1998; 11: 2175–87.

6. Aster JC, Kobayashi Y, Shiota M, et al. Detection of the t(14;18) at similar frequencies in hyperplastic lymphoid tissues from American and Japanese patients. Am J Pathol 1992; 141: 291–299.

7. Delage R, Roy J, Jacques L, et al. Multiple bcl-2/Ig gene rearrangements in persistent polyclonalB-cell lymphocytosis. Br J Haematol 1997; 97: 589–595.

8. Dölken G, Illerhaus G, Hirt C, et al. BCL-2/JH rearrangements in circulating B cells of healthy blood donors and patients with nonmalignant diseases. J Clin Oncol 1996; 14: 1333–1344.

9. Ladetto M, Drandi D, Compagno M, et al. PCR-detectable nonneoplastic Bcl-2/IgH rearrangement are common in normal subjects and cancer patients at diagnosis but rare in subjects treated with chemotherapy. J Clin Oncol 2003; 21: 1398–1403.

10. Tsimberidou AM., McLaughlin P., Younes A, et al. Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma. Blood 2002; 100: 4351–4357.

11. Tsujimoto Y, Finger LR, Yunis J, et al. Cloning of the chromosome breakpoint of neoplastic B cells with t(14;18) chromosomal translocation. Science 1984; 226: 1097–1099.

12. Tsujimoto Y, Cossman J, Jaffe E, et al. Involvement of the bcl- 2 gene in human follicular lymphoma. Science 1985; 228: 1440–1443.

13. Cleary ML, Sklar J. Nucleotide sequence of t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of breakpoint- cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci USA 1985; 82: 7439–7443.

14. Cleary ML, Galili N, Sklar J. Detection of second t(14;18) breakpoint cluster region in human follicular lymphomas. J Exp Med 1986; 164: 315–320.

15. Akasaka T, Akasaka H. Yonetani N, et al. Refinement of the Bcl2/imunoglobulin heavy chain fusion gene in t(14;18)(q32;q21) by polymerase chain reaction amplification for long targets. Genes Chromosomes cancer 1998; 21: 17–29.

16. Tsujimoto Y, Bashir MM, Givol I, et al. DNArearrangements in human follicular lymphoma can involve the 5’ or the 3’region of the bcl-2 gene. Proc Natl Acad Sci USA 1987; 84: 1329–1331.

17. Gribben JG, Freedman AS, Woo SD, et al. All advanced stage Non-Hodgkin’s lymphomas with a polymerase chain reaction amplifiable breakpoint of bcl-2 have residual cells containing the bcl-2 rearrangement at evaluation and after treatment. Blood 1991; 78: 3275–3280.

18. Horsman DE, Gascoyne RD, Coupland RW, et al. Comparison of cytogenetic analysis, southern analysis and polymerase chain reaction for detection of t(14;18) in follicular lymphoma. Am J Clin Pathol 1995; 103: 472–478.

19. van Dongen JM, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: Report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia 2003; 17: 2257–2317.

20. Vaandrager JW, Schuuring E, Raap T, et al. Interphase FISH detection of BCL2 rearragement in follicular lymphoma using breakpoint-flanking probes. Genes, Chromosomes Cancer 2000; 27: 85–94.

21. Godon A, Moreau A, Talmant P, et al. Is t(14;18) (q32;q21) a constant finding in follicular lymphoma? In interphase FISH study on 63 patients. Leukemia 2003; 17: 255–259.

22. Yao-Shan F, Rizkalla K. Comprehensive cytogenetic analysis including multicolor spectral karyotyping and interphase fluorescence in situ hybridization in lymphoma diagnosis: a summary of 154 cases. Cancer Genetics and Cytogenetics 2003; 27: 85–94.

23. López-Guillermo A, Cabanillas F, McLaughlin P, et al. The clinical significance of molecular response in indolent follicular lymphoma. Blood 1998; 8: 2955–2960.

24. López-Guillermo A, Cabanillas F, McLaughlin P, et al. Molecular response assessed by PCR is the most important factor predicting failure-free survival in indolent follicular lymphoma: Update of the MDACC series. Annals of Oncology 2001; 11 (Suppl.1): S137–140.

25. Montoto S, López-Guillermo A, Colomber D, Esteve J, et al. Incidence and and clinical significance of bcl-2/IgH rearrangements in follicular lymphoma. Leuk Lymphoma 2003; 44: 71–76.

26. Apostolidis J, Gupta R, Grenzelias D, et al. High-dose therapy with autologous bone marrow support as consolidation of remission in follicular lymphoma: long-term clinical and molecular follow- up. J Clin Oncol 2000; 18: 527–536.

27. Freedman A, Gribben J, Neuberg D, et al. High-dose therapy and autologous bone marrow transplantation in patients with follicular lymphoma during first remission. Blood 1996; 88: 2780–2786.

28. Ladetto M, Corradini P, Vallet S, et al. High rate of clinical remissions in follicular lymphoma patients receiving high-dose sequential chemotherapy and autografting at diagnosis: a multicenter prospective study by Gruppo Italiano Trapianto Midollo Osseo (GITMO). Blood 2002; 100: 1559–1565.

29. Hirt C, Dölken G. Quantitative detection of t(14;18)-positive cells in patients with follicular lymphoma before and after autologous bone marrow transplantation. BMT 2000; 25: 419–426.

30. Meijerink JPP, Goverde GJ, Smetsers TFCM, et al. Quantitation of follicular non-Hodgkin’s lymphoma cells carrying t(14;18) in a patient before and after allogeneic bone marrow transplantation. Annals of Oncology 1994; 5(Suppl 1): S43–S45.

31. Foran JM, Gupta RK, Cunningham D, et al. A UK multicenter phase II study of rituximab (chimaeric anti-CD20 monoclonal antibody) in patients with follicular lymphoma, with PCR monitoring of molecular response. Br J Haematol 2000; 109: 81–88.

32. Mandingers CMPW, Meijerink JPP, Mensink EJBM, et al. Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma. Blood 2001; 98: 940–944.

33. Lambrechts A, Hupkes P, Dorssers L, et al. Clinical significance of t(14;18)-positive cells in the circulation of patients with stage III or IV follicular non-Hodgkin’s lymphoma during first remission. J Clin Oncol 1994; 12: 1541–1546.

34. Price C, Meerabux J, Murtagh S, et al. The significance of circulating cells carrying t(14;18) in long remission from follicular lymphoma. J Clin Oncol 1991; 9: 1527–1532.

35. Gribben JG, Neuberg D, Barber M, et al. Detection of residual lymphoma cells by polymerase chain reaction in peripheral blood is significantly less predictive for relapse than detection in bone marrow. Blood 1994; 83: 3800–3807.

36. Rambaldi A, Carlotti E, Oldani E, et al. Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma. Blood 2005; 105: 3428–3433.

37. Summers KE, Davise AJ, Matthews J, et al. The relative role of peripheral blood and bone marrow for monitoring molecular evidence of disease in follicular lymphoma by quantitative real-time polymerase chain reaction. British Journal of Haematology 2002; 118: 563–566.

38. Steward FW. The diagnosis of tumors by aspiration. Am J Pathol 1933; 9: 801–815.

39. Das DK. Value and limitations of fine-needle aspiration cytology in diagnosis and classification of lymphomas: A Review Diagn Cytopathol 1999; 21: 240–249.

40. Jeffers MD, Milton J, Herriot R, McKean M. Fine needle aspiration cytology in the investigation of non-Hodgkin’s lymphoma. J Clin Pathol 1998; 51: 189–196.

41. Gong Y, Caraway N, Gu J, et al. Evaluation of interphase fluorescence in situ hybridization for the t(14;18)(q32;q21) translocation in the diagnosis of follicular lymphoma on fine-needle aspirates. Cancer (Cancer Cytopathol) 2003; 99: 385–393.

42. Mayall F, Darlington A, Harrison B. Fine needle aspiration cytology in the diagnosis of uncommon types of lymphoma. J Clin Pathol 2003; 56: 821–825.

43. Wakely PE. Fine-needle aspiration cytopathology in diagnosis and classification of malignant lymphoma: Accurate and reliable? Diagn Cytopathol 2000; 22: 120–125.

44. Cheson B, Horning S, Coiffier B, et al. Report of international workshop to standardize response criteria for non-Hodgkin’s lymphomas. J Clin Oncol 1999; 17: 1244–1253.

45. Dolken L, Schuler F, Dolken G. Quantitative detection of t(14;18)-positive cells by real-time quantitative PCR using fluorogenic probes. Biotechniques 1998; 25: 1058–1064.

46. Chiu RW, Murphy MF, Fidler C, et al. Determination of RhD zygosity: comparison of a double amplification refractory mutation system approach and a multiplex real-time quantitative PCR approach. Clinical Chemistry 2001; 47: 667–672.

47. Shaminie J, Peh SC, Tant MJA. Improvement in the detection rate of t(14;18) translocation on paraffin embedded tissue: a combination approach using PCR and FISH. Pathology 2003; 35: 414–421.

48. Schmitt C, Grundt A, Buchholtz C, et al. One single dose of rituximab added to a standard regimen of CHOP in primary treatment of follicular lymphoma appears to result in a high clearance rate from circulating bcl-2/IgH positive cells: Is the end of molecular monitoring near? Leuk Res 2006; 9: in press.

49. Czuczman MS, Grillo-Lopez AJ, McLaughlin P, et al. Clearing of cells bearing the bcl-2 [ t(14;18)] translocation from blood and marrow of patients treated with rituximab alone or in combination with CHOP chemotherapy. Ann Oncol 2001; 12: 109–114. 50. Hart J, Turner AR, Larratt LM, et al. Transmission of a follicular lymphoma by allogeneic bone marrow transplantation – evidence to support the existence of a lymphoma progenitor cell. Blood 2006; 108: 683a (Abstract No 2415).

Labels
Haematology Internal medicine Clinical oncology

Article was published in

Transfusion and Haematology Today

Issue 2

2007 Issue 2

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#