Singularities in Pediatric Bone Marrow Lymphoid Processes



There are several unique features of hematopoiesis and hematopoietic diseases in children relative to adults. For example, evaluation of lymphoid lesions in the pediatric population is impacted by the fact that lymphoid cells normally comprise a larger percentage of blood and bone marrow cells in children than in adults. The nature of bone marrow lymphoid infiltrates in children differs to some extent from those in adults. In this chapter on singularities in pediatric bone marrow lymphoid processes, the unique characteristics of lymphoid lesions and diseases specific to children will be emphasized. It is important to note that evaluation of lymphoid lesions should include examination of well prepared and stained specimens of the peripheral blood, bone marrow (BM) aspirate smears, touch imprints of the trephine biopsy, and sections of the trephine biopsy and particles/clot. It is often the combination of clues gleaned from the composite of preparations that allows for diagnosis.


Acute Lymphoblastic Leukemia Epstein Barr Virus Hodgkin Lymphoma Anaplastic Large Cell Lymphoma Bone Marrow Involvement 
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  1. 1.
    Comans-Bitter WM, de Groot R, van den Beemd R, Neijens HJ, Hop WCJ, Groeneveld K, et al. Immuno­phenotyping of blood lymphocytes in childhood: reference values for lymphocyte subpopulations. J Pediatr. 1997;130:388–93.CrossRefPubMedGoogle Scholar
  2. 2.
    Rosse C, Kraemer MJ, Dillon TL, McFarland R, Smith NJ. Bone marrow cell populations of normal infants: the predominance of lymphocytes. J Lab Clin Med. 1977;89:1225–40.PubMedGoogle Scholar
  3. 3.
    Miale JB. The bone marrow. Laboratory medicine hematology. 6th ed. St. Louis: C.V. Mosby Co; 1982. p. 219.Google Scholar
  4. 4.
    Downey H, McKinlay CA. Acute lymphadenosis ­compared with acute lymphatic leukemia. Arch Intern Med. 1923;32:82–112.CrossRefGoogle Scholar
  5. 5.
    Reichard K. Bone marrow findings in systemic ­infections. Chap. 33: In: Foucar K, Reichard K, Czuchlewski D, editors. Bone marrow pathology, vol. 2. 3rd ed. Chicago: American Society for Clinical Pathology; 2010. p. 755–6.Google Scholar
  6. 6.
    Tsaparas YF, Brigden ML, Mathias R, Thomas E, Raboud J, Doyle PW. Proportion positive for Epstein-Barr virus, cytomegalovirus, human herpesvirus 6, toxoplasma, and human immunodeficiency virus types 1 and 2 in heterophile-negative patients with an absolute lymphocytosis or an instrument-generated atypical lymphocyte flag. Arch Pathol Lab Med. 2000;124:1324–30.PubMedGoogle Scholar
  7. 7.
    Maeda K, Hyun BH, Rebuck JW. Lymphoid follicles in bone marrow aspirates. Am J Clin Pathol. 1977;67:41–8.PubMedGoogle Scholar
  8. 8.
    Rimsza LM, Larson RS, Winter SS, Foucar K, Chong YY, Garner KW. Benign hematogone-rich lymphoid proliferations can be distinguished from B-lineage acute lymphoblastic leukemia by integration of morphology, immunophenotype, adhesion molecule expression, and architectural features. Am J Clin Pathol. 2000;114:66–75.CrossRefPubMedGoogle Scholar
  9. 9.
    Fisgin T, Yarali N, Duru F, Kara A. CMV-induced immune thrombocytopenia and excessive hematogones mimicking an acute B-precursor lymphoblastic leukemia. Leuk Res. 2003;27:193–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Intermesoli T, Mangili G, Salvi A, Biondi A, Bassan R. Abnormally expanded pro-B hematogones associated with congenital cytomegalovirus infection. Am J Hematol. 2007;82:934–6.CrossRefPubMedGoogle Scholar
  11. 11.
    Guiziry DE, El GW, Farahat N, Hassab H. Phenotypic analysis of bone marrow lymphocytes from children with acute thrombocytopenic purpura. Egypt J Immunol. 2005;12:9–14.PubMedGoogle Scholar
  12. 12.
    Sevilla DW, Emmons FN, Colovai AI, Beaubier NT, Baker C, Bhatia M, et al. Hematogones are markedly reduced in pediatric acquired aplastic anemia: multiparametric flow cytometric analysis. Leuk Lymphoma. 2009;50:1951–7.CrossRefPubMedGoogle Scholar
  13. 13.
    McKenna RW, Washington LT, Aquino DB, Picker LJ, Kroft SH. Immunophenotypic analysis of hematogones (B-lymphocyte precursors) in 662 consecutive bone marrow specimens by 4-color flow cytometry. Blood. 2001;98:2498–507.CrossRefPubMedGoogle Scholar
  14. 14.
    Lucio P, Parreira A, van den Beemd MW, van Lochern EG, van Wering ER, Baars E. Flow cytometric analysis of normal B cell differentiation: a frame of reference for the detection of minimal residual disease in precursor-B-ALL. Leukemia. 1999;13:419–27.CrossRefPubMedGoogle Scholar
  15. 15.
    McKenna RW, Asplund SL, Kroft SH. Immuno­phenotypic analysis of hematogones (B-lymphocyte precursors) and neoplastic lymphoblasts by 4-color flow cytometry. Leuk Lymphoma. 2004;45:277–85.CrossRefPubMedGoogle Scholar
  16. 16.
    Seegmiller AC, Kroft SH, Karandikar NJ, McKenna RW. Characterization of immunophenotypic aberrancies in 200 cases of B acute lymphoblastic leukemia. Am J Clin Pathol. 2009;132:940–9.CrossRefPubMedGoogle Scholar
  17. 17.
    Miale JB. The bone marrow. Laboratory medicine hematology. 6th ed. St. Louis: C.V. Mosby Co; 1982. p. 346.Google Scholar
  18. 18.
    Yamaguchi M, Ohta A, Tsunematsu T, Kasukawa R, Mizushima Y, Kashiwagi H, et al. Preliminary criteria for classification of adult Still’s disease. J Rheumatol. 1992;19:424–30.PubMedGoogle Scholar
  19. 19.
    Mrozek K, Heerema NA, Bloomfield CD. Cytogenetics in acute leukemia. Blood Rev. 2004;18:115–36.CrossRefPubMedGoogle Scholar
  20. 20.
    Schultz KR, Pullen J, Sather HN, Shuster JJ, Devidas M, Borowitz MJ. Risk- and response-based classification of childhood B-precursor acute lymphoblastic leukemia: a combined analysis of prognostic markers from the Pediatric Oncology Group (POG) and Children’s Cancer Group (CCG). Blood. 2007;109:926–35.CrossRefPubMedGoogle Scholar
  21. 21.
    Trigg ME, Sather HN, Reaman GH, Tubergen DG, Steinherz PG, Gaynon PS. Ten-year survival of children with acute lymphoblastic leukemia: a report from the Children’s Oncology Group. Leuk Lymphoma. 2008;49:1142–54.CrossRefPubMedGoogle Scholar
  22. 22.
    Moorman AV, Chilton L, Wilkinson J, Ensor HM, Brown N, Proctor SJ. A population-based cytogenetic study of adults with acute lymphoblastic leukemia. Blood. 2010;115:206–14.CrossRefPubMedGoogle Scholar
  23. 23.
    DeBraekeleer E, Basinko A, Douet-Guilbert N, Morel F, LeBris MJ, Berthou C. Cytogenetics in pre-B and B-cell acute lymphoblastic leukemia: a study of 208 patients diagnosed between 1981 and 2008. Cancer Genet Cytogenet. 2010;200:8–15.CrossRefGoogle Scholar
  24. 24.
    Salzer WL, Devidas M, Carroll WL, Winick N, Pullen F, Hunger SP. Long-term results of the Pediatric Oncology Group studies for childhood acute lymphoblastic leukemia 1984–2001: a report from the Children’s Oncology Group. Leukemia. 2010;24:355–70.CrossRefPubMedGoogle Scholar
  25. 25.
    Olah E, Balogh E, Pajor L, Jakab Z. Ten-year experiences on initial genetic examination in childhood acute lymphoblastic leukaemia in Hungary (1993–2002). Technical approaches and clinical implementation. Pathol Oncol Res. 2011;1:81–90.CrossRefGoogle Scholar
  26. 26.
    Dreyer ZE, Dinndorf PA, Camitta B, Sather H, La MK, Devidas M. Analysis of the role of hematopoietic stem-cell transplantation in infants with acute lymphoblastic leukemia in first remission and MLL gene rearrangements: a report from the Children’s Oncology Group. J Clin Oncol. 2011;29:214–22.CrossRefPubMedGoogle Scholar
  27. 27.
    van der Linden MH, Valsecchi MG, De Lorenzo P, Moricke A, Janka G, Leblanc TM. Outcome of congenital acute lymphoblastic leukemia treated on the Interfant-99 protocol. Blood. 2009;114:3764–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Cimino G, Moir DT, Canaani O, Williams K, Crist WM, Katzav S. Cloning of ALL-1, the locus involved in leukemias with the t(4;11)(q21;q23), t(9;11)(p22;q23), and t(11;19)(q23;p13) chromosome translocations. Cancer Res. 1991;51:6712–4.PubMedGoogle Scholar
  29. 29.
    Pui CH, Kane JR, Crist WM. Biology and treatment of infant leukemias. Leukemia. 1995;9:762–9.PubMedGoogle Scholar
  30. 30.
    Whitlock JA, Sather HN, Gaynon P, Robison LL, Wells RJ, Trigg M. Clinical characteristics and outcome of children with Down syndrome and acute lymphoblastic leukemia: a Children’s Cancer Group Study. Blood. 2005;106:4043–9.CrossRefPubMedGoogle Scholar
  31. 31.
    Bakhshi S, Singh P, Thulkar S. Bone involvement in pediatric non-Hodgkin’s lymphomas. Hematology. 2008;13:348–51.CrossRefPubMedGoogle Scholar
  32. 32.
    Cairo MS, Sposto R, Perkins SL, Meadows AT, Hoover-Regan ML, Anderson JR. Burkitt’s And burkitt-like lymphoma in children and adolescents: a review of the Children’s Cancer Group experience. Br J Haematol. 2003;120:660–70.CrossRefPubMedGoogle Scholar
  33. 33.
    Rubie H, Gladieff L, Robert A, Gaubert I, Huguet F, Rochaix P, et al. Childhood anaplastic large cell lymphoma Ki-1/CD30: clinicopathologic features of 19 cases. Med Pediatr Oncol. 1994;22:155–61.CrossRefPubMedGoogle Scholar
  34. 34.
    Mussolin L, Pillon M, D’Amore ES, Santoro N, Lombardi A, Fagioli F. Prevalence and clinical implications of bone marrow involvement in pediatric ­anaplastic large cell lymphoma. Leukemia. 2005;19:1643–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Brugieres L, Le Deley MC, Pacquement H, ­Meguerian-Bedoyan Z, Terrier-Lacombe MJ, Robert A. CD30+ anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood. 1998;92:3591–8.PubMedGoogle Scholar
  36. 36.
    Quintanilla-Martinez L, Kumar S, Fend F, Reyes E, Teruya-Feldstein J, Kingma DW. Fulminant EBV+ T-cell lymphoproliferative disorder following acute/chronic EBV infection: a distinct clinicopathologic syndrome. Blood. 2000;96:443–51.PubMedGoogle Scholar
  37. 37.
    Sevilla DW, El-Mallawany NK, Emmons FN, Alexander S, Bhagat G, Alobeid B. Spectrum of childhood EBV-associated T-cell proliferations and bone marrow findings. Pediatr Dev Pathol. 2011;14(1):28–37.CrossRefPubMedGoogle Scholar
  38. 38.
    Quintanilla-Martinez L, Kimura H, Jaffe ES. EBV-positive T-cell lymphoproliferative disorders of childhood. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2008. p. 278–80.Google Scholar
  39. 39.
    Zhao XF, Young KH, Frank D, Goradia A, Glotzbecker MP, Pan W. Pediatric primary bone lymphoma – diffuse large B-cell lymphoma: morphologic and immunohistochemical characteristics of 10 cases. Am J Clin Pathol. 2007;127:47–54.CrossRefPubMedGoogle Scholar
  40. 40.
    Glotzbecker MP, Kersun LS, Choi JK, Wills BP, Schaffer AA, Dormans JP. Primary non-Hodgkin’s lymphoma of bone in children. J Bone Joint Surg Am. 2006;88:583–94.CrossRefPubMedGoogle Scholar
  41. 41.
    Qureshi A, Ali A, Riaz N, Pervez S. Primary non-Hodgkin’s lymphoma of bone: experience of a decade. Indian J Pathol Microbiol. 2010;53:267–70.CrossRefPubMedGoogle Scholar
  42. 42.
    Suryanarayan K, Shuster JJ, Donaldson SS, Hutchison RE, Murphy SB, Link MP. Treatment of localized primary Non-Hodgkin’s lymphoma of bone in children: a Pediatric Oncology Group Study. J Clin Oncol. 1999;17:456–9.PubMedGoogle Scholar
  43. 43.
    Bazzeh F, Rihani R, Howard S, Sultan I. Comparing adult and pediatric Hodgkin lymphoma in the surveillance, epidemiology and End results program, 1988–2005: an analysis of 21 734 cases. Leuk Lymphoma. 2010;51:2198–207.CrossRefPubMedGoogle Scholar
  44. 44.
    Niece JA, Roger ZA, Ahmad N, Langevin AM, McClain KL. Hemophagocytic lymphohistiocytosis in Texas: observations on ethnicity and race. Pediatr Blood Cancer. 2010;54:424–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Risdall RJ, McKenna RW, Nesbit ME, Krivit W, Balfour HH, Simmons RL. Virus-associated hemo­phagocytic syndrome. Cancer. 1979;44:993–1002.CrossRefPubMedGoogle Scholar
  46. 46.
    Henter JI, Horne AC, Arico M, Egeler RM, Filipovich AH, Imashuku S. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48:124–31.CrossRefPubMedGoogle Scholar
  47. 47.
    Karandikar NJ, Kroft SH, Yegappan S, Rogers BB, Aquino VM, Lee KM. Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis. Blood. 2004;104:2007–9.CrossRefPubMedGoogle Scholar
  48. 48.
    Yang F, Li Y, Braylan R, Hunger SP, Yang LJ. Pediatric T-cell post-transplant lymphoproliferative disorder after solid organ transplantation. Pediatr Blood Cancer. 2008;50:415–8.CrossRefPubMedGoogle Scholar
  49. 49.
    Swerdlow SH, Webber SA, Chadburn A, Ferry JA. Post-transplant lymphoproliferative disorders. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed. Lyon: International Agency for Research on Cancer (IARC); 2008. p. 343–9.Google Scholar
  50. 50.
    Maecker B, Jack T, Zimmerman M, Abdul-Khaliq H, Burdelski M, Fuchs A. CNS or bone marrow involvement as risk factors for poor survival in post-transplantation lymphoproliferative disorders in children after solid organtransplantation. J Clin Oncol. 2007;25:4902–8.CrossRefPubMedGoogle Scholar
  51. 51.
    Gupta S, Fricker FJ, Gonzalez-Peralta RP, Slayton WB, Schuler PM, Dharnidharka VR. Post-transplant ­lymphoproliferative disorder in children: recent outcomes and response to dual rituximab/low-dose chemotherapy combination. Pediatr Transplant. 2010;14:896–902.CrossRefPubMedGoogle Scholar
  52. 52.
    Manlhiot C, Pollock-Barziv SM, Holmes C, Weitzman S, Allen U, Clarizia NA. Post-transplant lymphoproliferative disorder in pediatric heart transplant recipients. J Heart Lung Transplant. 2010;29:648–57.CrossRefPubMedGoogle Scholar
  53. 53.
    Uribe M, Hunter B, Alba A, Calabran L, Flores L, Soto P. Posttransplant lymphoproliferative disorder in pediatric liver transplantation. Transplant Proc. 2009;41:2679–81.CrossRefPubMedGoogle Scholar
  54. 54.
    Pinho-Apezzato ML, Tannuri U, Tannuri AC, Mello ES, Lima F, Gibelli NE, et al. Multiple clinical presentations of lymphoproliferative disorders in pediatric liver transplant recipients: a single-center experience. Transplant Proc. 2010;42:1763–8.CrossRefPubMedGoogle Scholar
  55. 55.
    Koukourgianni F, Harambat J, Ranchin B, Euvrard S, Bouvier R, Liutkus A. Malignancy incidence after renal transplantation in children: a 20-year single-centre experience. Nephrol Dial Transplant. 2010;25:611–6.CrossRefPubMedGoogle Scholar
  56. 56.
    Caillard S, Dharnidharka V, Agodoa L, Bohen E, Abbott K. Posttranplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression. Transplantation. 2005;80:1233–43.CrossRefPubMedGoogle Scholar
  57. 57.
    Cesaro S, Pegoraro A, Tridello G, Calore E, Pillon M, Varotto S. A prospective study of modulation of immunosuppression for Epstein-Barr virus reactivation in pediatric patients who underwent unrelated hematopoietic stem-cell transplantation. Transplantation. 2010;89:1533–40.CrossRefPubMedGoogle Scholar
  58. 58.
    Abu-Elmagd KM, Mazariegos G, Costa G, Soltys K, Bond G, Sindhi R. Lymphoproliferative disorders and de novo malignancies in intestinal and multivisceral recipients: improved outcomes with new outlooks. Transplantation. 2009;88:926–34.CrossRefPubMedGoogle Scholar
  59. 59.
    Barker JN, Doubrovina E, Sauter C, Jaroscak JJ, Perales MA, Doubrovin M, et al. Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes. Blood. 2010;116:5045–9.CrossRefPubMedGoogle Scholar
  60. 60.
    Koeppen H, Newell K, Baunoch DA, Vardiman JW. Morphologic bone marrow changes in patients with posttransplantation lymphoproliferative disorders. Am J Surg Pathol. 1998;22:208–14.CrossRefPubMedGoogle Scholar
  61. 61.
    Park MA, Li JT, Hagan JB, Maddox DE, Abraham RS. Common variable immunodeficiency: a new look at an old disease. Lancet. 2008;372:489–502.CrossRefPubMedGoogle Scholar
  62. 62.
    Chua I, Quinti I, Grimbacher B. Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol. 2008;15:368–74.CrossRefPubMedGoogle Scholar
  63. 63.
    Sander CA, Medeiros J, Weiss LM, Yano T, Sneller MC, Jaffe ES. Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. Am J Surg Pathol. 1992;16:1170–82.CrossRefPubMedGoogle Scholar
  64. 64.
    Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48.CrossRefPubMedGoogle Scholar
  65. 65.
    Hiel JA, Weemaes CM, van den Heuvel LP, van Engelen BG, Gabreels FJ, Smeets DF. Nijmegen breakage syndrome. The International Nijmegen Breakage Syndrome Study Group. Arch Dis Child. 2000;82:400–6.CrossRefGoogle Scholar
  66. 66.
    Seidemann K, Henze G, Beck JD, Sauerbrey A, Kuhl J, Mann G, et al. Non-Hodgkin’s lymphoma in pediatric patients with chromosomal breakage ­syndromes (AT and NBS): experience from the BFM trials. Ann Oncol. 2000;11 Suppl 1:141–5.CrossRefPubMedGoogle Scholar
  67. 67.
    Mueller BU, Pizzo PA. Cancer in children with primary and secondary immunodeficiencies. J Pediatr. 1995;126:1–10.CrossRefPubMedGoogle Scholar
  68. 68.
    Renedo M, Robledo M, Arranz E, Infantes F, Roman A, Garcia-Yebenes J. Cytogenetic and molecular studies of siblings with ataxia telangiectasia followed for 7 years. Cancer Genet Cytogenet. 1997;95:178–82.CrossRefPubMedGoogle Scholar
  69. 69.
    Taylor AM, Butterworth SV. Clonal evolution of T-cell chronic lymphocytic leukaemia in a patient with ataxia telangiectasia. Int J Cancer. 1986;15:511–6.CrossRefGoogle Scholar
  70. 70.
    Duhrsen U, Uppenkamp M, Uppenkamp I, Becher R, Engelhard M, Konig E. Chronic T cell leukemia with unusual cellular characteristic in ataxia telangiectasia. Blood. 1986;68:577–85.PubMedGoogle Scholar
  71. 71.
    Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R. The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore). 2003;82:373–84.CrossRefGoogle Scholar
  72. 72.
    Petrovic A, Dorsey M, Miotke J, Shepard C, Day N. Hematopoietic stem cell transplatation for pediatric patients with primary immune deficiency diseases at All Children’s Hospital/University of South Florida. Immunol Res. 2009;44:169–78.CrossRefPubMedGoogle Scholar
  73. 73.
    Gulley ML, Chen CL, Raab-Traub N. Epstein-Barr virus related lymphomagenesis in a child with Wiskott-Aldrich syndrome. Hematol Oncol. 1993;11:139–45.CrossRefPubMedGoogle Scholar
  74. 74.
    Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES. Malignant lymphoma in patients with the Wiskott-Aldrich syndrome. Cancer Invest. 1985;3:515–22.CrossRefPubMedGoogle Scholar
  75. 75.
    Perry GS, Spector BD, Schuman LM, Mandel JS, Anderson VE, McHugh RB. The Wiskott-Aldrich syndrome in the United States and Canada (1892–1979). J Pediatr. 1980;97:72–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Spector BD, Perry GS, Kersey JH. Genetically determined immunodeficiency disease (GDID) and malignancy: report from the immunodeficiency-cancer registry. Clin Immunol Immunopathol. 1978;11:12–29.CrossRefPubMedGoogle Scholar
  77. 77.
    Garcia CR, Brown NA, Schreck R, Stiehm ER, Hudnal SD. B-cell lymphoma in severe combined immunodeficiency not associated with the Epstein-Barr virus. Cancer. 1987;60:2941–7.CrossRefPubMedGoogle Scholar
  78. 78.
    Deachey DT, Seif AE, Grupp SA. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). Br J Haematol. 2010;148:205–16.CrossRefGoogle Scholar
  79. 79.
    Oliveira JB, Bleesing JJ, Dianzani U, Fleisher TA, Jaffe ES, Lenardo MJ. Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH international workshop. Blood. 2010;116:35–40.CrossRefGoogle Scholar
  80. 80.
    Dowdell KC, Niemela JE, Price S, Davis J, Hornung RL, Oliveira JB. Somatic FAS mutations are common in patients with genetically undefined autoimmune lymphoproliferative syndrome. Blood. 2010;115:5164–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Lenardo MJ, Oliveira JB, Zheng L, Rao VK. ALPS-ten lessons from an international workshop on a genetic disease of apoptosis. Immunity. 2010;32:291–5.CrossRefPubMedGoogle Scholar
  82. 82.
    Lim MS, Straus SE, Dale JK, Fleisher TA, Stetler-Stevenson M, Strober W. Pathological findings in human autoimmune lymphoproliferative syndrome. Am J Pathol. 1998;153:1541–50.CrossRefPubMedGoogle Scholar
  83. 83.
    Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel RM. Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature. 2002;419:395–9.CrossRefPubMedGoogle Scholar
  84. 84.
    Niemela JE, Lu L, Fleisher TA, Davis J, Caminha I, Natter M. Somatic KRAS mutations associated with a human nonmalignant syndrome of autoimmunity and abnormal leukocyte homeostasis. Blood. 2011;117:2883–6.CrossRefPubMedGoogle Scholar
  85. 85.
    Oliveira JB, Bidere N, Niemela JE, Zheng L, Sakai K, Nix CP, et al. NRAS mutation causes a human autoimmune lymphoproliferative syndrome. Proc Natl Acad Sci USA. 2007;104:8953–8.CrossRefPubMedGoogle Scholar
  86. 86.
    Clementi R, Chiocchetti A, Cappellano G, Cerutti E, Ferretti M, Orilieri E. Variations of the perforin gene in patients with autoimmunity/lymphoproliferation and defective Fas function. Blood. 2006;108:3079–84.CrossRefPubMedGoogle Scholar
  87. 87.
    Purtilo DT, Cassel CK, Yang JPS, Harper R, Stephenson SR, Landing BH. X-linked recessive progressive combined variable immunodeficiency (Duncan’s disease). Lancet. 1975;1:935–40.CrossRefPubMedGoogle Scholar
  88. 88.
    Breier DV, Rendo P, Gonzalez J, Shilton G, Stivel M, Goldztein S. Massive plasmocytosis due to methimazole-induced bone marrow toxicity. Am J Hematol. 2001;67:259–61.CrossRefPubMedGoogle Scholar

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© Springer-Verlag London 2012

Authors and Affiliations

  1. 1.Division of Hematopathology and Division of Molecular Genetics Pathology, Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA
  2. 2.Division of Hematopathology, Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA

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