Bone marrow findings in autoimmune lymphoproliferative syndrome with germline FAS mutation

被引:13
作者
Xie, Yi [1 ]
Pittaluga, Stefania [1 ]
Price, Susan [2 ]
Raffeld, Mark [1 ]
Hahn, Jamie [3 ]
Jaffe, Elaine S. [1 ]
Rao, V. Koneti [2 ]
Maric, Irina [3 ]
机构
[1] NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA
[2] NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA
[3] NIH, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA
基金
美国国家卫生研究院;
关键词
MASSIVE LYMPHADENOPATHY; DEFECTIVE LYMPHOCYTE; SINUS HISTIOCYTOSIS; APOPTOSIS; PATIENT; IMMUNOGLOBULIN; FEATURES; DISEASE;
D O I
10.3324/haematol.2015.138081
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Autoimmune lymphoproliferative syndrome is a rare genetic disorder characterized by defective FAS-mediated apoptosis, autoimI une disease, accumulation of mature T-cell receptor alpha/beta positive, CD4 and CD8 double-negative T cells and increased risk of lymphoma. Despite frequent hematologic abnormalities, literature is scarce regarding the bone marrow pathology in autoimmune lymphoproliferative syndrome. We retrospectively reviewed 31 bone marrow biopsies from a cohort of 240 patients with germline FAS mutations. All biopsies were performed for the evaluation of cytopenias or to rule out lymphoma. Clinical information was collected and morphological, immunohistochemical, flow cytometric and molecular studies were performed. Bone marrow lymphocytosis was the predominant feature, present in 74% (23/31) of biopsies. The lymphoid cells showed several different patterns of infiltration, most often forming aggregates comprising T cells in 15 cases, B cells in one and a mixture of T and B cells in the other seven cases. Double-negative T cells were detected by immunohistochemistry in the minority of cases (10/31; 32%); significantly, all but one of these cases had prominent double-negative T-lymphoid aggregates, which in four cases diffusely replaced the marrow space. One case showed features of Rosai-Dorfman disease, containing scattered S-100 cells with emperipolesis and double-negative T cells. No clonal B or T cells were detected by polymerase chain reaction in any evaluated cases. Classical Hodgkin lymphoma was identified in three cases. Our results demonstrate that infiltrates of T cells, or rarely B cells, can be extensive in patients with autoimmune lymphoproliferative syndrome, mimicking lymphoma. A multi-modality approach, integrating clinical, histological, immunohistochemical as well as other ancillary tests, can help avoid this diagnostic pitfall. This study is registered at Clinical trials.gov ID # NCT00001350
引用
收藏
页码:364 / 372
页数:9
相关论文
共 37 条
[1]   Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS) Type Ib [J].
Bi, Lilia L. ;
Pan, George ;
Atkinson, T. Prescott ;
Zheng, Lixin ;
Dale, Janet K. ;
Makris, Christopher ;
Reddy, Vishnu ;
McDonald, Jay M. ;
Siegel, Richard M. ;
Puck, Jennifer M. ;
Lenardo, Michael J. ;
Straus, Stephen E. .
BMC MEDICAL GENETICS, 2007, 8
[2]   A homozygous Fas ligand gene mutation in a patient causes a new type of autoirnmune lymphoproliferative syndrome [J].
Del-Rey, Manuel ;
Ruiz-Contreras, Jesus ;
Bosque, Alberto ;
Calleja, Sara ;
Gomez-Rial, Jose ;
Roldan, Ernesto ;
Morales, Pablo ;
Serrano, Antonio ;
Anel, Alberto ;
Paz-Artal, Estela ;
Allende, Luis M. .
BLOOD, 2006, 108 (04) :1306-1312
[3]   Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome [J].
Dowdell, Kennichi C. ;
Niemela, Julie E. ;
Price, Susan ;
Davis, Joie ;
Hornung, Ronald L. ;
Oliveira, Joao Bosco ;
Puck, Jennifer M. ;
Jaffe, Elaine S. ;
Pittaluga, Stefania ;
Cohen, Jeffrey I. ;
Fleisher, Thomas A. ;
Rao, V. Koneti .
BLOOD, 2010, 115 (25) :5164-5169
[4]   DOMINANT INTERFERING FAS GENE-MUTATIONS IMPAIR APOPTOSIS IN A HUMAN AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME [J].
FISHER, GH ;
ROSENBERG, FJ ;
STRAUS, SE ;
DALE, JK ;
MIDDELTON, LA ;
LIN, AY ;
STROBER, W ;
LENARDO, MJ ;
PUCK, JM .
CELL, 1995, 81 (06) :935-946
[5]  
FOUCAR E, 1990, SEMIN DIAGN PATHOL, V7, P19
[6]   Minor dysplastic changes are frequently observed in the bone marrow aspirate in elderly patients without haematological disease [J].
Girodon, F ;
Favre, B ;
Carli, PM ;
Nash, N ;
Desbiolles, N ;
Tatou, E ;
Maynadié, M .
CLINICAL AND LABORATORY HAEMATOLOGY, 2001, 23 (05) :297-300
[7]   Autoimmune lymphoproliferative syndrome with somatic Fas mutations [J].
Holzelova, E ;
Vonarbourg, C ;
Stolzenberg, MC ;
Arkwright, PD ;
Selz, F ;
Prieur, AM ;
Blanche, S ;
Bartunkova, J ;
Vilmer, E ;
Fischer, A ;
Le Deist, F ;
Rieux-Laucat, F .
NEW ENGLAND JOURNAL OF MEDICINE, 2004, 351 (14) :1409-1418
[8]  
Huang Q, 2006, AM J SURG PATHOL, V30, P1189
[9]   Case 27-2013: A 6.5-Month-Old Boy with Fever, Rash, and Cytopenias [J].
Iyengar, Shuba R. ;
Ebb, David H. ;
Yuan, Qian ;
Shailam, Randheer ;
Bhan, Atul K. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 369 (09) :853-863
[10]   Eosinophilia is associated with a higher mortality rate among patients with autoimmune lymphoproliferative syndrome [J].
Kim, Yae-Jean ;
Dale, Janet K. ;
Noel, Pierre ;
Brown, Margaret R. ;
Nutman, Thomas B. ;
Straus, Stephen E. ;
Klion, Amy D. .
AMERICAN JOURNAL OF HEMATOLOGY, 2007, 82 (07) :615-624