bone marrow involvement

Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities

LYMPHOID TUMORS , ,

YaK Mangasarova, AU Magomedova, AM Kovrigina, IE Kostina, ES Nesterova, LG Gorenkova, AE Misyurina, OV Margolin, SK Kravchenko

National Medical Hematology Research Center, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Yana Konstantinovna Mangasarova, MD, PhD, 4a Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: v.k.jana@mail.ru.

For citation: Mangasarova YaK, Magomedova AU, Kovrigina AM, et al. Primary Mediastinal (Thymic) Large B-Cell Lymphoma: Diagnostics of Extramediastinal Lesions and Treatment Opportunities. Clinical oncohematology. 2018;11(3):220–26.

DOI: 10.21320/2500-2139-2018-11-3-220-226

ABSTRACT

Background. Current diagnostic methods and the introduction of molecular investigations into clinical practice allow to improve the understanding of classical primary mediastinal (thymic) large B-cell lymphoma (PMBCL).

Aim. To investigate clinical characteristics of PMBCL patients with extramediastinal lesions.

Materials & Methods. The study was performed from 2007 to 2017 in the National Medical Hematology Research Center and included 157 PMBCL patients. The data of 16 (10.2 %; 4 men and 12 women) patients with extramediastinal lesions were analyzed; the median age was 27 years (range 23–69).

Results. The extramediastinal lesions were found in pancreas (6; 37.5 %), kidneys (5; 31.2 %), ovaries (3; 18.7 %), liver (3; 18.7 %), bone marrow (3; 18.7 %), and breasts (2; 12 %); the lesions in stomach, bones, soft tissues, spleen, adrenals, and small pelvis were observed each in a single case. In 15 of 16 cases extramediastinal lesions were accompanied by involvement of superior mediastinum, and only 1 patient had an isolated lesion in thoracic soft tissues without mediastinal involvement. The samples of 8 out of 16 patients were analyzed using PCR. In all samples overexpression of 2 or more genes (JAK2, TRAF1, MAL, PDL1, PDL2) was determined which allowed to confirm, and in some cases to revise the diagnosis of PMBCL. Overall 5-year survival (93 %) of patients with classical PMBCL with thoracic involvement was similar to the cohort with extramediastinal lesions. All unfavourable events (progression/relapse) were identified at an early stage, i.e. within a year after the completion of therapy.

Conclusion. PMBCL patients can have not only superior mediastinum involvement, but extramediastinal lesions as well, including bone marrow. The spreading of the disease beyond superior mediastinum should be differentiated from diffuse large B-cell lymphoma using standard evaluation methods, and molecular analysis in some cases.

Keywords: primary mediastinal (thymic) large B-cell lymphoma, extramediastinal lesions, bone marrow involvement.

Received: January 22, 2018

Accepted: April 15, 2018

Read in PDF 

REFERENCES

  1. Lichtenstein AK, Levine A, Taylor CR, et al. Primary mediastinal lymphoma in adults. Am J Med. 1980;68(4):509–14. doi: 10.1016/0002-9343(80)90294-6.
  2. Cazals-Hatem D, Lepage E, Brice P, et al. Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA (“Groupe d’Etude des Lymphomes de l’Adulte”) study. Am J Surg Pathol. 1996;20(7):877–88. doi: 10.1097/00000478-199607000-00012.
  3. Rosenwald A, Wright G, Leroy K, et al. Molecular diagnosis of primary mediastinal B cell lymphoma identifies a clinically favorable subgroup of diff use large B cell lymphoma related to Hodgkin lymphoma. J Exp Med. 2003;198(6):851–62. doi: 10.1084/jem.20031074.
  4. Zhang B, Wang Z, Li T, et al. NF-kappaB2 mutation targets TRAF1 to induce lymphomagenesis. Blood. 2007;110(2):743–51. doi: 10.1182/blood-2006-11-058446.
  5. Meier C, Hoeller S, Bourgau C, et al. Recurrent numerical aberrations of JAK2 and deregulation of the JAK2-STAT cascade in lymphomas. Mod Pathol. 2009;22(3):476–87. doi: 10.1038/modpathol.2008.207.
  6. Steidl C, Gascoyne RD. The molecular pathogenesis of primary mediastinal large B-cell lymphoma. Blood. 2011;118(10):2659–69. doi: 10.1182/blood-2011-05-326538.
  7. Joos S, Granzow M, Holtgreve-Grez H, et al. Hodgkin’s lymphoma cell lines are characterized by frequent aberrations on chromosomes 2p and 9p including REL and JAK2. Int J Cancer. 2003;103(4):489–95. doi: 10.1002/ijc.10845.
  8. Мангасарова Я.К., Мисюрин А.В., Магомедова А.У. и др. Молекулярная диагностика первичной медиастинальной В-клеточной лимфомы и диффузной В-крупноклеточной лимфомы с первичным вовлечением лимфатических узлов средостения. Клиническая онкогематология. 2011;4(2):142–5.
    [Mangasarova YaK, Misyurin AV, Magomedova AU, et al. Molecular diagnostics of primary mediastinal B-cell lymphoma and diffuse large B-cell lymphoma with primary involvement of mediastinal lymph nodes. Klinicheskaya onkogematologiya. 2011;4(2):142–5. (In Russ)]
  9. Twa DD, Chan FC, Ben-Neriah S, et al. Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014;123(13):2062–5. doi: 10.1182/blood-2013-10-535443.
  10. Bentz M, Barth TF, Bruderlein S, et al. Gain of chromosome arm 9p is characteristic of primary mediastinal B-cell lymphoma (MBL): comprehensive molecular cytogenetic analysis and presentation of a novel MBL cell line. Genes Chromos Cancer. 2001;30(4):393–401. doi: 1002/1098-2264(2001)9999:9999<::aid-gcc1105>3.0.co;2-i.
  11. Huang J, Sanger G, Greiner T, et al. The t(14;18) defines a unique subset of large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood. 2002;99(7):2285–90. doi: 10.1182/blood.v99.7.2285.
  12. Barans S, Connor S, Evans P, et al. Rearrangement of the BCL-6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. Br J Hematol. 2002;117(2):322–32. doi: 1046/j.1365-2141.2002.03435.x.
  13. Ковригина А.М., Пробатова Н.А. Лимфома Ходжкина и крупноклеточные лимфомы. М.: МИА, 2007; 108–24.
    [Kovrigina AM, Probatova NA. Limfoma Khodzhkina i krupnokletochnye limfomy. (Hodgkin’s lymphoma and large cell lymphomas.) Moscow: MIA Publ.; 2007. pp. 108–24. (In Russ)]
  14. Yuan J, Wright G, Rosenwald A, et al. Identification of Primary Mediastinal Large B-cell Lymphoma at Nonmediastinal Sites by Gene Expression Profiling. Am J Surg Pathol. 2015;39(10):1322–30. doi: 10.1097/PAS.0000000000000473.
  15. Bishop PC, Wilson WH, Pearson D, et al. CNS involvement in primary mediastinal large B-cell lymphoma. J Clin Oncol. 1999;17(8):2479–85. doi: 10.1200/jco.1999.17.8.2479.
  16. Магомедова А.У., Фастова Е.А., Ковригина А.М. и др. Поражение костного мозга при первичной медиастинальной В-крупноклеточной лимфоме. Терапевтический архив. 2017;89(7):65–8. doi: 10.17116/terarkh201789765-68.
    [Magomedova AU, Fastova EA, Kovrigina AM, et al. Bone marrow involvement in primary mediastinal B-cell lymphoma. Terapevticheskii arkhiv. 2017;89(7):65–8. doi: 17116/terarkh201789765-68. (In Russ)]