Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data)

LYMPHOID TUMORS , , , , ,

AM Kovrigina, LV Plastinina, SK Kravchenko, ES Nesterova, TN Obukhova

Hematology Research Center under the Ministry of Health of the Russian Federation, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Alla Mikhailovna Kovrigina, DSci, Professor, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel: +7(495)612-62-12; e-mail: kovrigina.alla@gmail.com

For citation: Kovrigina AM, Plastinina LV, Kravchenko SK, et al. Diagnosis of Pediatric-Type Follicular Lymphoma in Young Adults (Own Data). Clinical oncohematology. 2017;10(1):52–60 (In Russ).

DOI: 10.21320/2500-2139-2017-10-1-52-60

ABSTRACT

Aim. Pathomorphological, immunophenotypical and clinical characteristics of a new clinico-morphological form of pediatric-type follicular lymphoma (FL) in young adults discovered in 2008 (WHO classification).

Background. FL is a heterogeneous disease according to its morphological, immunophenotypical and molecular-genetic characteristics. FL de novo includes transformed FL, FL without t(14;18), FL with diffuse growth associated with del(1p.36) and TNFRSF14 mutation. Pediatric-type FL in young adults is poorly studied; and it is especially interesting because of its clinical diversity and molecular-genetic heterogeneity of FL, in general.

Methods. Biopsy materials taken from 5 patients (aged 18–25 years; median age: 22 years; the female/male ratio 3:2) were included in the study; all patients were examined, diagnosed and treated in the Hematology Research Center over the period from 2012 to 2016. Clinical stage I with isolated involvement a palatine tonsil or an inguinal lymph node was diagnosed in 4/5 patients; clinical stage II with involvement of a palatine tonsil and cervical lymph node was diagnosed in 1/5 patients. Morphological, immunophenotypical and FISH tests were performed with paraffin blocks.

Results. The morphological pattern was typical for FL 3B (n = 2) and FL 3 with blastoid nucleus morphology (n = 3). Immunophenotypical features demonstrated an intermediate position between FL 3 de novo and transformed FL 3. No BCL-2 rearrangement was detected in any observation.

Conclusion. The comparison of our data on characteristics of pediatric-type FL with those published in the literature demonstrated that lack or weak expression (< 30 % of tumor substrate cells) of MUM1 was the key feature of the experimental group of young adults with pediatric-type FL. This, in turn, indicates the absence of IRF4 rearrangements and possible presence of other genetic abnormalities. The clinical, morphological, and immunophenotypical characteristics broaden the FL heterogeneity spectrum in young adults.

Keywords: pediatric-type follicular lymphoma, follicular lymphoma, young adults, pathomorphology, immunohictochemistry, MUM1.

Received: August 14, 2016

Accepted: November 27, 2016

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REFERENCES

  1. Lennert K, Stein H, Mohri N, et al. Malignant Lymphomas Other than Hodgkin’s Disease: Histology, Cytology, Ultrastructure, Immunology. Berlin, Heidelberg: Springer-Verlag; 1978. 833 p. doi: 10.1016/0092-8674(79)90172-7.
  2. Swerdlow SH, Campo E, Harris NL, et al, eds. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. 4th edition. Lyon: IARC Press; 2008.
  3. Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification. Project Ann Oncol. 1998;9(7):717–20.
  4. Gallagher CJ, Gregory WM, Jones AE, et al. Follicular lymphoma: Prognostic factors for response and survival. J Clin Oncol. 1986;4(10):1470–80.
  5. Bastion Y, Sebban C, Berger F, et al. Incidence, predictive factors, and outcome of lymphoma transformation in follicular lymphoma patients. J Clin Oncol. 1997;15(4):1587–94.
  6. Montoto S, Davies AJ, Matthews J, et al. Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol. 2007;25(17):2426–33. doi: 10.1200/jco.2006.09.3260.
  7. Montoto, S., Fitzgibbon J. Transformation of indolent B-cell lymphomas. J Clin Oncol. 2011;29(4):1827–34. doi: 10.1200/JCO.2010.32.7577.
  8. Hirt C, Weitmann K, Schuler F, et al. Circulating t(14;18)-positive cells in healthy individuals: association with age and sex but not with smoking. Leuk Lymphoma. 2013;54(12):2678–84. doi: 10.3109/10428194.2013.788177.
  9. Weigert O, Kopp N, Lane AA, et al. Molecular ontogeny of donor derived follicular lymphomas occurring after hematopoietic cell transplantation. Cancer Discov. 2012;2(1):47–55. doi: 10.1158/2159-8290.cd-11-0208.
  10. Leich E, Salaverria I, Bea S, et al. Follicular lymphomas with and without translocation t(14;18) differ in gene expression profiles and genetic alterations. Blood. 2009;114(4):826–34. doi: 10.1182/blood-2009-01-198580.
  11. Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122(10):3424–31. doi: 10.1172/jci63186.
  12. Katzenberger T, Kalla J, Leich E, et al. A distinctive subtype of t(14;18)-negative nodal follicular non- Hodgkin lymphoma characterized by a predominantly diffuse growth pattern and deletions in the chromosomal region 1p36. Blood. 2009;113(5):1053–61. doi: 10.1182/blood-2008-07-168682.
  13. Pasqualucci L, Khiabanian H, Fangazio M, et al. Genetics of Follicular Lymphoma Transformation. Cell Reports. 2014;6(1):130–40. doi: 10.1016/j.celrep.2013.12.027.
  14. Bouska A, McKeithan TW, Deffenbacher KE, et al. Genome-wide copy-number analyses reveal genomic abnormalities involved in transformation of follicular lymphoma. Blood. 2014;123(11):1681–90. doi: 10.1182/blood-2013-05-500595.
  15. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959–64. doi: 10.1182/blood.v99.6.1959.
  16. Swerdlow SH. Pediatric follicular lymphomas, marginal zone lymphomas, and marginal zone hyperplasia. Am J Clin Pathol. 2004;122(Suppl 1):S98–S109. doi: 10.1309/4bknake4d7ct3c1b.
  17. Oschlies I, Salaverria I, Mahn F, et al. Pediatric follicular lymphoma—a clinico-pathological study of a population-based series of patients treated within the Non-Hodgkin’s Lymphoma—Berlin-Frankfurt-Munster (NHL-BFM) multicenter trials. Haematologica. 2010;95(2):253–9. doi: 10.3324/haematol.2009.013177.
  18. Liu Q, Salaverria I, Pittaluga S, et al. Follicular lymphomas in children and young adults: a comparison of the pediatric variant with usual follicular lymphoma. Am J Surg Pathol. 2013;37(3):333–43. doi: 10.1097/pas.0b013e31826b9b57.
  19. Louissaint A, Ackerman A, Dias-Santagata D, et al. Pediatric-type nodal follicular lymphoma: an indolent clonal proliferation in children and adults with high proliferation index and no BCL2 rearrangement. Blood. 2012;120(12):2395–404. doi: 10.1182/blood-2012-05-429514.
  20. Guo Y, Karube K, Kawano R, et al. Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances. Leukemia. 2005;19(6):1058–63. doi: 10.1038/sj.leu.2403738.
  21. Katzenberger T, Ott G, Klein T, et al. Cytogenetic alterations affecting BCL6 are predominantly found in follicular lymphomas grade 3B with a diffuse large B-cell component. Am J Pathol. 2004;165(2):481–90. doi: 10.1016/s0002-9440(10)63313-5.
  22. Salaverria I, Siebert R. Follicular lymphoma grade 3B. Best Pract Res Clin Haematol. 2011;24(2):111–9. doi: 10.1016/j.beha.2011.02.002.
  23. Ngan BY, Chen-Levy Z, Weiss LM, et al. Expression in non- Hodgkin lymphoma of the bcl-2 protein associated with the t(14;18) chromosomal translocation. N Engl J Med. 1988;318(25):1638–44. doi: 10.1056/nejm198806233182502.
  24. Adam P, Baumann R, Schmidt J, et al. The BCL2 E17 and SP66 antibodies discriminate 2 immunophenotypically and genetically distinct subgroups of conventionally BCL2-“negative” grade 1/2 follicular lymphomas. Hum Pathol. 2014;44(9):1817–26. doi: 10.1016/j.humpath.2013.02.004.
  25. Lorsbach RB, Shay-Seymore D, Moore J, et al. Clinicopathologic analysis of follicular lymphoma occurring in children. Blood. 2002;99(6):1959–64. doi: 10.1182/blood.v99.6.1959.
  26. Willis SN, Good-Jacobson KL, Curtis J, et al. Transcription Factor IRF4 Regulates Germinal Center Cell Formation through a B Cell–Intrinsic Mechanism. J Immunol. 2014;192(7):3200–6. doi: 10.4049/jimmunol.1303216.
  27. Karube K, Guo Y, Suzumiya J, et al. CD10- MUM1+ follicular lymphoma lacks BCL2 gene translocation and shows characteristic biologic and clinical features. Blood. 2007;109(7):3076–9. doi: 10.1182/blood-2006-09-045989.
  28. Sweetenham JW, Goldman B, LeBlanc ML, et al. Prognostic value of regulatory T cells, lymphoma-associated macrophages, and MUM-1 expression in follicular lymphoma treated before and after the introduction of monoclonal antibody therapy: a Southwest Oncology Group Study. Ann Oncol. 2010;21(6):1196–202. doi: 10.1093/annonc/mdp460.
  29. Xerri L, Bachy E, Fabiani B, et al; LYSA study. Identification of MUM1 as a prognostic immunohistochemical marker in follicular lymphoma using computerized image analysis. Hum Pathol. 2014;45(10):2085–93. doi: 10.1016/j.humpath.2014.06.019.
  30. Salaverria I, Philipp C, Oschlies I, et al. Translocations activating IRF4 identify a subtype of germinal center-derived B-cell lymphoma affecting predominantly children and young adults. Blood. 2011;118(1):139–47. doi: 10.1182/blood-2011-01-330795.
  31. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90. doi: 10.1182/blood-2016-01-643569.
  32. Quintanilla-Martinez L, Sander B, Chan JK, et al. Indolent lymphomas in the pediatric population: follicular lymphoma, IRF4/MUM1+ lymphoma, nodal marginal zone lymphoma and chronic lymphocytic leukemia. Virchows Arch. 2016;468(2):141–57. doi: 10.1007/s00428-015-1855-z.
  33. Jaffe ES. Follicular lymphomas: a tapestry of common and contrasting threads. Haematologica. 2013;98(8):1163–5. doi: 10.3324/haematol.2013.086678.
  34. Martin-Guerrero I, Salaverria I, Burkhardt B, et al. Recurrent loss of heterozygosity in 1p36 associated with TNFRSF14 mutations in IRF4 translocation negative pediatric follicular lymphomas. Haematologica 2013;98(8):1237–41. doi: 10.3324/haematol.2012.073916.
  35. Launay E, Pangault C, Bertrand P, et al. High rate of TNFRSF14 gene alterations related to 1p36 region in de novo follicular lymphoma and impact on prognosis. Leukemia. 2012;26(3):559–62. doi: 10.1038/leu.2011.266.