In this article, we describe the morphologic and immunophenotypic features of 75 cases of pediatric anaplastic large cell lymphoma (ALCL). According to the World Health Organization classification, 49 cases were common subtype ALCL, and respectively, 3, 6, and 17 cases were small cell, lymphohistiocytic, or mixed histologic variants. Anaplastic lymphoma kinase positivity was detected in 90.7% of the tumors and, using a panel of 9 T-cell surface markers, 88% could be assigned to the T-cell lineage. A molecular analysis for the T-cell receptor γ (TCR- γ) and the heavy chain of the immunoglobulin H rearrangements was performed on 6/9 ALCLs with a null immunophenotype, and a TCR clonal pattern was detected in 5/6 cases. In addition, 94.1% were immunoreactive for 1 or more cytotoxic proteins (Tia1, granzyme B, or perforin), and 15% expressed CD56. Clusterin, CD83, and Pax5, respectively, expressed in 91.3%, 1.7%, and 0% of the ALCLs, were useful biomarkers for the differential diagnosis with Hodgkin's lymphomas.
SteinHMasonDYGerdesJ. The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood1985;66:848–858.
2.
MorrisSWKirsteinMNValentineMB. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science1994;263:1281–1284.
3.
BullrichFMorrisSWHummelMPileriSSteinHCroceCM. Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res1994;54:2873–2877.
4.
FaliniBPulfordKPucciariniA. Lymphomas expressing ALK fusion protein(s) other than NPM-ALK. Blood1999;94:3509–3515.
5.
HarrisNLJaffeESSteinH. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood1994;84:1361–1392.
6.
JaffeESHarrisNLSteinHVardimanJW. World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Hematopoietic and Lymphoid Tissues. Lyon, France: IARC Press, 2001.
7.
PileriSAPiccalugaAPoggiS. Anaplastic large cell lymphoma: update of findings. Leuk Lymphoma1995;18:17–25.
ChanJKBuchananRFletcherCD. Sarcomatoid variant of anaplastic large-cell Ki-1 lymphoma. Am J Surg Pathol1990;14:983–988.
11.
CheukWHillRWBacchiCDiasMAChanJK. Hypocellular anaplastic large cell lymphoma mimicking inflammatory lesions of lymph nodes. Am J Surg Pathol2000;24:1537–1543.
12.
KinneyMCCollinsRDGreerJPWhitlockJASioutosNKadinME. A small-cell-predominant variant of primary Ki-1 (CD30)+ T-cell lymphoma. Am J Surg Pathol1993;17:859–868.
13.
JaffeES. Anaplastic large cell lymphoma: the shifting sands of diagnostic hematopathology. Mod Pathol2001;14:219–228.
14.
VassalloJLamantLBrugieresL. ALK-positive anaplastic large cell lymphoma mimicking nodular sclerosis Hodgkin's lymphoma: report of 10 cases. Am J Surg Pathol2006;30:223–239.
15.
TzankovABourgauCKaiserA. Rare expression of T-cell markers in classical Hodgkin's lymphoma. Mod Pathol2005;18:1542–1549.
16.
SteinHJohrensKAnagnostopoulosI. Non-mediastinal grey zone lymphomas and report from the workshop. Eur J Haematol2005;75(suppl 66):42–44.
17.
SeitzVHummelMMarafiotiTAnagnostopoulosIAssafCSteinH. Detection of clonal T-cell receptor gamma-chain gene rearrangements in Reed-Sternberg cells of classic Hodgkin disease. Blood2000;95:3020–3024.
18.
KononenJBubendorfLKallioniemiA. Tissue microarrays for high-throughput molecular profiling of tumor specimens. Nat Med1998;4:844–847.
AchilleAScarpaAMontresorM. Routine application of polymerase chain reaction in the diagnosis of monoclonality of B-cell lymphoid proliferations. Diagn Mol Pathol1995;4:14–24.
21.
MurphySB. Classification, staging and end results of treatment of childhood non-Hodgkin's lymphomas: dissimilarities from lymphomas in adults. Semin Oncol1980;7:332–339.
22.
BenharrochDMeguerian-BedoyanZLamantL. ALK-positive lymphoma: a single disease with a broad spectrum of morphology. Blood1998;91:2076–2084.
23.
ChanJK. Anaplastic large cell lymphoma: redefining its morphologic spectrum and importance of recognition of the ALK-positive subset. Adv Anat Pathol1998;5:281–313.
24.
ShiotaMFujimotoJTakenagaM. Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood1994;84:3648–3652.
25.
PulfordKLamantLMorrisSW. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood1997;89:1394–1404.
26.
FaliniB. Anaplastic large cell lymphoma: pathological, molecular and clinical features. Br J Haematol2001;114:741–760.
27.
FaliniBPileriSZinzaniPL. ALK+ lymphoma: clinicopathological findings and outcome. Blood1999;93:2697–2706.
28.
PerkinsSLPickeringDLoweEJ. Childhood anaplastic large cell lymphoma has a high incidence of ALK gene rearrangement as determined by immunohistochemical staining and fluorescent in situ hybridisation: a genetic and pathological correlation. Br J Haematol2005;131:624–627.
29.
BrugieresLDeleyMCPacquementH. CD30(+) anaplastic large-cell lymphoma in children: analysis of 82 patients enrolled in two consecutive studies of the French Society of Pediatric Oncology. Blood1998;92:3591–3598.
30.
GascoyneRDAounPWuD. Prognostic significance of anaplastic lymphoma kinase (ALK) protein expression in adults with anaplastic large cell lymphoma. Blood1999;93:3913–3921.
31.
ten BergeRLde BruinPCOudejansJJOssenkoppeleGJvan der ValkPMeijerCJ. ALK-negative anaplastic large-cell lymphoma demonstrates similar poor prognosis to peripheral T-cell lymphoma, unspecified. Histopathology2003;43:462–469.
32.
ArrowsmithERMaconWRKinneyMC. Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification. Leuk Lymphoma2003;44:241–249.
33.
WeisenburgerDDAndersonJRDieboldJ. Systemic anaplastic large-cell lymphoma: results from the non-Hodgkin's lymphoma classification project. Am J Hematol2001;67:172–178.
34.
ZhangWSloan-LancasterJKitchenJTribleRPSamelsonLE. LAT: the ZAP-70 tyrosine kinase substrate that links T cell receptor to cellular activation. Cell1998;92:83–92.
35.
FacchettiFChanJKZhangW. Linker for activation of T cells (LAT), a novel immunohistochemical marker for T cells, NK cells, mast cells, and megakaryocytes: evaluation in normal and pathological conditions. Am J Pathol1999;154:1037–1046.
36.
FossHDAnagnostopoulosIAraujoI. Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules. Blood1996;88:4005–4011.
37.
DukersDFten BergeRLOudejansJJ. A cytotoxic phenotype does not predict clinical outcome in anaplastic large cell lymphomas. J Clin Pathol1999;52:129–136.
38.
KagamiYSuzukiRTajiH. Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients. Am J Surg Pathol1999;23:1184–1200.
39.
FelgarRESalhanyKEMaconWRPietraGGKinneyMC. The expression of TIA-1+ cytolytic-type granules and other cytolytic lymphocyte-associated markers in CD30+ anaplastic large cell lymphomas (ALCL): correlation with morphology, immunophenotype, ultrastructure, and clinical features. Hum Pathol1999;30:228–236.
40.
LanierLLTestiRBindlJPhillipsJH. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med1989;169:2233–2238.
41.
SuzukiRKagamiYTakeuchiK. Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype. Blood2000;96:2993–3000.
42.
ChanJK. Peripheral T-cell and NK-cell neoplasms: an integrated approach to diagnosis. Mod Pathol1999;12:177–199.
43.
KinneyMC. The role of morphologic features, phenotype, genotype, and anatomic site in defining extranodal T-cell or NK-cell neoplasms. Am J Clin Pathol1999;111(1suppl 1):S104–118.
44.
PetrellaTComeauMRMaynadieM. ‘Agranular CD4+ CD56+ hematodermic neoplasm’ (blastic NK-cell lymphoma) originates from a population of CD56+ precursor cells related to plasmacytoid monocytes. Am J Surg Pathol2002;26:852–862.
45.
Van CampBDurieBGSpierC. Plasma cells in multiple myeloma express a natural killer cell-associated antigen: CD56 (NKH-1; Leu-19). Blood1990;76:377–382.
46.
HammerRDVnencak-JonesCLManningSSGlickADKinneyMC. Microvillous lymphomas are B-cell neoplasms that frequently express CD56. Mod Pathol1998;11:239–246.
47.
PinkusGSPinkusJLLanghoffE. Fascin, a sensitive new marker for Reed-Sternberg cells of Hodgkin's disease: evidence for a dendritic or B cell derivation?Am J Pathol1997;150:543–562.
48.
FanGKotyloPNeimanRSBrazielRM. Comparison of fascin expression in anaplastic large cell lymphoma and Hodgkin disease. Am J Clin Pathol2003;119:199–204.
49.
WellmannAThieblemontCPittalugaS. Detection of differentially expressed genes in lymphomas using cDNA arrays: identification of clusterin as a new diagnostic marker for anaplastic large-cell lymphomas. Blood2000;96:398–404.
50.
SafferHWahedARassidakisGZMedeirosLJ. Clusterin expression in malignant lymphomas: a survey of 266 cases. Mod Pathol2002;15:1221–1226.
51.
NascimentoAFPinkusJLPinkusGS. Clusterin, a marker for anaplastic large cell lymphoma: immunohistochemical profile in hematopoietic and nonhematopoietic malignant neoplasms. Am J Clin Pathol2004;121:709–717.
ZhouLJTedderTF. Human blood dendritic cells selectively express CD83, a member of the immunoglobulin superfamily. J Immunol1995;154:3821–3835.
54.
BrownePPetrosyanKHernandezAChanJA. The B-cell transcription factors BSAP, Oct-2, and BOB.1 and the pan-B-cell markers CD20, CD22, and CD79a are useful in the differential diagnosis of classic Hodgkin lymphoma. Am J Clin Pathol2003;120:767–777.
55.
KuppersRSchweringIBrauningerARajewskyKHansmannML. Biology of Hodgkin's lymphoma. Ann Oncol2002;13(suppl 1):11–18.
56.
KanzlerHKuppersRHansmannMLRajewskyK. Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells. J Exp Med1996;184:1495–1505.
57.
KanavarosPBoullandMLPetitBArnulfBGaulardP. Expression of cytotoxic proteins in peripheral T-cell and natural killer-cell (NK) lymphomas: association with extranodal site, NK or Tgammadelta phenotype, anaplastic morphology and CD30 expression. Leuk Lymphoma2000;38:317–326.
58.
OudejansJJKummerJAJiwaM. Granzyme B expression in Reed-Sternberg cells of Hodgkin's disease. Am J Pathol1996;148:233–240.
59.
MuschenMRajewskyKBrauningerA. Rare occurrence of classical Hodgkin's disease as a T cell lymphoma. J Exp Med2000;191:387–394.
