A practical approach to the understanding and diagnosis of lymphoma: An assessment of the WHO classification based on immunoarchitecture and immuno-ontogenic principles

Pathology

Volumn 41, Issue 4, 2009, Pages 305-326

  Tan, Leonard Hwan Cheong ^a  

^a SINGAPORE GENERAL HOSPITAL   (Singapore)

Author keywords

Compartmentalisation; Germinal centre; Immuno ontogeny; Immunoarchitecture; Lymphoma negation principle; Post germinal centre

Indexed keywords

COMMON ACUTE LYMPHOBLASTIC LEUKEMIA ANTIGEN; CXCL13 CHEMOKINE; INTERFERON REGULATORY FACTOR 4; PROTEIN BCL 6; SYNDECAN 1;

B CELL LYMPHOMA; BURKITT LYMPHOMA; CANCER DIAGNOSIS; CHRONIC LYMPHATIC LEUKEMIA; CLASSICAL HODGKIN LYMPHOMA; CLINICAL ASSESSMENT; FOLLICULAR CARCINOMA; GENOTYPE; HUMAN; LARGE CELL LYMPHOMA; LYMPHOMA; MANTLE CELL LYMPHOMA; MARGINAL ZONE LYMPHOMA; MORPHOLOGY; NODULAR LYMPHOCYTE PREDOMINANT HODGKIN LYMPHOMA; PHENOTYPE; PLASMACYTOMA; PRIMARY EFFUSION LYMPHOMA; REVIEW; SOMATIC HYPERMUTATION; T CELL LYMPHOMA; WORLD HEALTH ORGANIZATION; CLASSIFICATION; IMMUNOLOGY;

HUMANS; LYMPHOMA; WORLD HEALTH ORGANIZATION;

EID: 68849095832     PISSN: 00313025     EISSN: 14653931     Source Type: Journal    
DOI: 10.1080/00313020902884501     Document Type: Article

References (130)

1. Swerdlow SH, Campo E, Harris NL, et al. Pathology and Genetics. Tumours of Haematopoeitic and Lymphoid Tissues. World Health Organisation Classi.cation of Tumours. Lyon: International Agency for Research on Cancer, 2008.
2. Marafioti T, Hummel M, Foss HD, et al. Hodgkin and Reed- Sternberg cells represent an expansion of a single clone originating from a germinal center B-cell with functional immunoglobulin gene rearrangements but defective immunoglobulin transcription. Blood 2000; 95: 1443-1450
3. Marafloti T, Hummel M, Anagnostopoulos I, et al. Origin of nodular lymphocyte-predominant Hodgkin disease from a clonal expansion of highly mutated germinal-center B cells. N Engl J Med 1997; 337: 453-458
4. Hall PA. Differentiation, stem cells and tumour histogenesis. In: Anthony PP, MacSween RNM, editors. Recent Advances in Histopathology. Vol 15. Edinburgh: Churchill Livingstone, 1992; 1-16.
5. Graham CF. Tumour cell Differentiation and control. In: Mc Gee JO'D, Isaacson PG, Wright NA, editors. Oxford Textbook of Pathology. Vol 1. Oxford: Oxford University Press, 1992; 597-607.
6. Wynford-Thomas D. Telomeres, tumour-suppressors and lifespan checkpoints: Implications for tumour pathology. In: Kirkham N, Lemoine NR, editors. Progress in Pathology. Vol 4. Edinburgh: Churchill Livingstone, 1998; 79-97.
7. Kadin ME. Hodgkin disease: Cell of origin, immunobiology and pathogenesis. In: Knowles DM, editor. Neoplastic Hematopathology. Philadelphia: Williams and Wilkins, 2001; 667-690
8. Müller G, Hopken UE, Stein H, et al. Systemic immunoregulatory and pathogenetic functions of homeostatic chemokine receptors. J Leukoc Biol 2002; 72: 1-8.
9. Falini B, Fizzotti M, Pucciarini A, et al. A monoclonal antibody (MUM1p) detects expression of the MUM1/IRF4 protein in a subset of germinal center B cells, plasma cells and activated T cells. Blood 2000; 95: 2084-2092
10. Calame C, Lin K-I, Tunyaplin C. Regulatory mechanisms that determine the development and function of plasma cells. Annu Rev Immunol 2003; 21: 205-230
11. Rappaport H, Winter WJ, Hicks EB. Follicular lymphoma. A reevaluation of its position in the scheme of malignant lymphoma, based on a survey of 253 cases. Cancer 1956; 9: 792-821.
12. Brill NE, Baehr G, Rosenthal N. Generalized giant follicle hyperplasia of lymph nodes and spleen. A hitherto undescribed type. J Am Med Assoc 1925; 84: 668-671
13. Symmers D. Follicular lymphadenopathy with splenomegaly: A newly recognized disease of the lymphatic system. Arch Pathol 1927; 3: 816-820
14. Anagnostopoulos I, Hansmann ML, Franssila K, et al. European Task Force on Lymphoma project on lymphocyte predominance Hodgkin disease: histologic and immunohistologic analysis of submitted cases reveals two types of Hodgkin disease with a nodular growth pattern and abundant lymphocytes. Blood 2000; 96: 1889-1899
15. Kadin ME, Glatstein E, Dorfman RF. Clinicopathologic studies of 117 untreated patients subjected to laparotomy for the staging of Hodgkin disease. Cancer 1971; 27: 1277-1294
16. Van Parys G, de Wolf-Peeters C, van den Oord JJ, et al. Lymph node architecture in Hodgkin disease: Evidence for the role of the composite nodule in nodular sclerosing Hodgkin disease. Hematol Oncol 1987; 5: 147-154
17. Cabone A, Gloghini A, Gaidano G, et al. Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin disease. Blood 1998; 92: 2220-2228
18. Falini B, Bigema B, Pasqualucci L, et al. Distinctive expression pattern of the BCL-6 protein in nodular lymphocyte predominance Hodgkin disease. Blood 1996; 87: 465-471
19. Carbone A, Gloghini A, Aldinucci D, et al. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin disease. Br J Haematol 2002; 117: 366-372
20. Poppema S. The nature of the lymphocytes surrounding Reed- Sternberg cells in nodular lymphocyte predominance and in other types of Hodgkin disease. Am J Pathol 1989; 135: 351-357
21. Frizzera G, Moran EM, Rappaport H. Angio-immunoblastic lymphadenopathy with dysproteinaemia. Lancet 1974; 1: 1070-1073
22. Attygalle A, Al-Jehani R, Diss TC, et al. Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10. Blood 2002; 99: 627-633
23. Attygalle A, Diss TC, Munson P, et al. CD10 expression in extranodal dissemination of angioimmunoblastic T-cell lymphoma. Am J Surg Pathol 2004; 28: 54-61.
24. De Leval L, Savilo E, Longtine J, et al. Peripheral T-cell lymphoma with follicular involvement and a CD4p/bcl-6pphenotype. Am J Surg Pathol 2001; 25: 395-400.
25. Jones D, Jorgensen JL, Shahsafaei A, et al. Characteristic proliferations of reticular and dendritic cells in angioimmunoblastic lymphoma. Am J Surg Pathol 1998; 22: 956-964
26. Lee S-S, Rudiger T, Odenwald T, et al. Angioimmunoblastic T-cell lymphoma is derived from mature T-helper cells with varying expression and loss of detectable CD4. Int J Cancer 2003; 103: 12-20.
27. Grogg K, Attygalle A, Macon WR, et al. Angioimmunoblastic T-cell lymphoma: A neoplasm of germinal-center T-helper cells. Blood 2005; 106: 1501-1502
28. Dupuis J, Boye K, Martin N, et al. Expression of CXCL13 by neoplastic cells of angioimmunoblastic T-cell lymphoma (AITL). A new diagnostic marker providing evidence that AITL derives from follicular helper T-cells. Am J Surg Pathol 2006; 30: 490-494
29. Krenacs L, Schaerii P, Kis G, et al. Phenotype of neoplastic cells in angioimmunoblastic T-cell lymphoma is consistent with activated follicular B helper T cells. Blood 2006; 108: 1110-1111
30. De Leval L, Rickman DS, Thielen C, et al. The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. Blood 2007; 109: 4952-4963
31. Ottensmeier CH, Thompsett AR, Zhu D, et al. Analysis of VH genes in follicular and diffuse lymphoma shows ongoing somatic mutation and multiple isotype transcripts in early disease with changes during disease progression. Blood 1998; 91: 4292-4299
32. Bräuninger A, Wacker H-H, Rajewsky K, et al. Typing the histogenetic origin of the tumor cells of lymphocyte-rich classical Hodgkin lymphoma in relation to tumor cells of classical and lymphocyte-predominance Hodgkin lymphoma. Cancer Res 2003; 63: 1644-1651
33. Chapman CJ, Wright D, Stevenson FK. Insight into Burkitt's lymphoma from immunoglobulin variable region gene analysis. Leuk Lymphoma 1998; 30: 257-267 (Pubitemid 28391042)
34. Brauninger A, Spieker T, Willenbrock K, et al. Survival and clonal expansion of mutating 'forbidden' (immunoglobulin receptorde .cient) Epstein-Barr virus-infected B cells in angioimmunoblastic T-cell lymphoma. J Exp Med 2001; 194: 927-940
35. Knecht H, Berger C, Rothenberger S, et al. The role of Epstein-Barr virus in neoplastic transformation. Oncology 2001; 60: 289-302.
36. Ambinder RF. Epstein-Barr virus-associated lymphoproliferations in the AIDS setting. Eur J Cancer 2001; 37: 1209-1216
37. Dalla-Favera R, Migliazza A, Chang CC, et al. Molecular pathogenesis of B cell malignancy: The role of BCL-6. Curr Top Microbiol Immunol 1999; 246: 257-263
38. Wang F, Gregory C, Sample C, et al. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are e.ectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23. J Virol 1990; 64: 2309-2318
39. Strickler JG, Fedeli F, Horwitz CA, et al. Infectious mononucleosis in lymphoid tissue. Histopathology, in situ hybridization, and Differential diagnosis. Arch Pathol Lab Med 1993; 117: 269-278
40. Ye BH, Cattoretti G, Shen Q, et al. The BCL-6 proto-oncogene controls germinal-centre formation and Th2-type in.ammation. Nat Genet 1997; 16: 161-170
41. Lam N, Sugden B. CD40 and its viral mimic, LMP1: similar means to Different ends. Cell Signal 2003; 15: 9-16.
42. Uchida J, Yasui T, Takaoka-Shichijo Y, et al. Mimicry of CD40 signals by Epstein-Barr virus LMP1 in B lymphocyte responses. Science 1999; 286: 300-303
43. Yasui T, Muraoka M, Takaoka-Shichijo Y, et al. Dissection of B cell Differentiation during primary immune responses in mice with altered CD40 signals. Int Immunol 2002; 14: 319-329
44. Qin J, Konno H, Ohshima D, et al. Developmental stage-dependent collaboration between the TNF receptor-associated factor 6 and lymphotoxin pathways for B cell follicle organization in secondary lymphoid organs. J Immunol 2007; 179: 6799-6807
45. Kersten MJ, van Gorp J, Pals ST et al. Expression of Epstein-Barr virus latent genes and adhesion molecules in AIDS-related non- Hodgkin lymphomas: Correlation with histology and CD4-cell number. Leuk Lymphoma 1998; 30: 515-524
46. Gabarre J, Raphael M, Lepage E, et al. Human immunode.ciency virus-related lymphoma: Relation between clinical features and histologic subtypes. Am J Med 2001; 111: 704-711
47. Carbone A, Gaidano G, Gloghini A, et al. Differential expression of BCL-6, CD138/Syndecan-1, and Epstein-Barr virus-encoded latent membrane protein-1 identifies distinct histogenetic subsets of acquired immune de.ciency syndrome-related non-Hodgkin lymphomas. Blood 1998; 91: 747-755
48. Carbone A, Gaidano G, Gloghini A, et al. BCL-6 protein expression in AIDS-related non-Hodgkin lymphomas: Inverse relationship with Epstein-Barr virus-encoded latent membrane protein-1 expression. Am J Pathol 1997; 150: 155-165
49. Anagnostopoulos I, Hummel M, Kreschel C, et al. Morphology, immunophenotype and distribution of latently and/or productively Epstein-Barr virus-infected cells in acute infectious mononucleosis: Implications for the interindividual infection route of Epstein-Barr virus. Blood 1995; 85: 744-750
50. Niedobitek G, Herbst H, Young LS, et al. Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue. Blood 1992; 79: 2520-2526
51. Kurth J, Hansmann ML, Rajewsky K, et al. Epstein-Barr virusinfected B cells expanding in germinal centers of infectious mononucleosis patients do not participate in the germinal center reaction. Proc Natl Acad Sci USA 2003; 100: 4730-4735
52. Zhou Y, Attygalle AD, Chuang SS, et al. Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load. Br J Haematol 2007; 138: 44-53.
53. Willenbrock K, Bräuninger A, Hansmann ML. Frequent occurrence of B-cell lymphomas in angioimmunoblastic T-cell lymphoma and proliferation of Epstein-Barr virus-infected cells in early cases. Br J Haematol 2007; 138: 733-739
54. Polack A, Hortnagel K, Pajic B, et al. C-myc activation renders proliferation of Epstein-Barr virus (EBV)-transformed cells independent of EBV nuclear antigen 2 and latent membrane protein 1. Proc Natl Acad Sci USA 1996; 93: 10411-10416
55. Jochner N, Eick D, Zimber-Strobl U, et al. Epstein-Barr virus nuclear antigen 2 is a transcriptional suppressor of the immunoglobulin m gene: Implications for the expression of the translocated c-myc gene in Burkitt's lymphoma cells. EMBO J 1996; 15: 375-382
56. Isaacson PG. Extranodal lymphomas: The MALT concept. Verh Dtsch Ges Pathol 1992; 76: 14-23.
57. Isaacson PG, Norton AJ. Extranodal Lymphomas. Edinburgh: Churchill Livingstone, 1994.
58. Isaacson PG. Malignant lymphomas with a follicular growth pattern. Histopathology 1996; 28: 487-495
59. Lalani E-N, Stamp GWH. Role of the stroma in neoplastic growth and progression. In: Kirkham N, Lemoine NR, editors. Progress in Pathology. Vol.3. New York: Churchill Livingstone, 1997; 102-124
60. Addis BJ, Hyjek E, Isaacson PG. Primary pulmonary lymphoma: A reappraisal of its histogenesis and its relationship to pseudolymphoma and lymphoid interstitial pneumonia. Histopathology 1988; 13: 1-17.
61. Schmid U, Eckert F, Griesser H, et al. Cutaneous follicular lymphoid hyperplasia with monotypic plasma cells. A clinicopathologic study of 18 patients. Am J Surg Pathol 1995; 19: 12-20.
62. Lukes RJ. Criteria for involvement of lymph node, bone marrow, spleen, and liver in Hodgkin disease. Cancer Res 1971; 31: 1755-1767
63. Kadin ME, Glatstein E, Dorfman RF. Clinicopathologic studies of 117 untreated patients subjected to laparotomy for the staging of Hodgkin disease. Cancer 1971; 27: 1277-1294
64. Van Parys G, de Wolf-Peeters C, van den Oord JJ, et al. Lymph node architecture in Hodgkin disease: Evidence for the role of the composite nodule in nodular sclerosing Hodgkin disease. Hematol Oncol 1987; 5: 147-154
65. Ashton-Key M, Thorpe PA, Allen JP, et al. Follicular Hodgkin disease. Am J Surg Pathol 1995; 19: 1294-1299
66. Schwarting R, Gerdes J, Durkop H, et al. A new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood 1989; 74: 1678-1689
67. Carbone A, Gloghini A, Aldinucci D, et al. Expression pattern of MUM1/IRF4 in the spectrum of pathology of Hodgkin disease. Br J Haematol 2002; 117: 366-372
68. Carbone A, Gloghini A, Gaidano G, et al. Expression status of bcl-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin disease. Blood 1998; 92: 2220-2228
69. Carbone A, Gloghini A, Larocca LM, et al. Human immunode.ciency virus-associated Hodgkin disease derives from post-germinal center B-cells. Blood 1999; 93: 2319-2326
70. Hopken UE, Foss H-D, Meyer D, et al. Up-regulation of the chemokine receptor CCR7 in classical but not in lymphocytepredominant Hodgkin disease correlates with distinct dissemination of neoplastic cells in lymphoid organs. Blood 2002; 99: 1109-1116
71. Alkan S, Ross CW, Hanson CA, et al. Epstein-Barr virus and bcl-2 protein overexpression are not detected in the neoplastic cells of nodular lymphocyte predominance Hodgkin disease. Mod Pathol 1995; 8: 544-547
72. Kim SH, Shin YK, Lee I-S, et al. Viral latent membrane protein 1 (LMP-1)-induced CD99 down-regulation in B cells leads to the generation of cells with Hodgkin and Reed-Sternberg phenotype. Blood 2000; 95: 294-300.
73. Kim SH, Choi EY, Shin YK, et al. Generation of cells with Hodgkin and Reed-Sternberg phenotype through downregulation of CD99 (Mic2). Blood 1998; 92: 4287-4295
74. Tindle BH, Parker JW, Lukes RJ. 'Reed-Sternberg cells' in infectious mononucleosis? Am J Clin Pathol 1972; 58: 607-617
75. Childs CC, Parham DM, Berard CW. Infectious mononucleosis. The spectrum of morphologic changes simulating lymphoma in lymph nodes and tonsils. Am J Surg Pathol 1987; 11: 122-132
76. Mao Z, Quintanilla-Martinez L, Ra.eld M, et al. IgVH mutational status and clonality analysis of Richter's transformation: diffuse large B-cell lymphoma and Hodgkin lymphoma in association with B-cell chronic lymphocytic leukemia (B-CLL) represent 2 Different pathways of disease evolution. Am J Surg Pathol 2007; 31: 1605-1614
77. Tzankov A, Fong D. Hodgkin disease variant of Richter's syndrome clonally related to chronic lymphocytic leukemia arises in ZAP-70 negative mutated CLL. Med Hypotheses 2006; 66: 577-579
78. Ma Y, Visser L, Blokzijl T, et al. The CD4pCD26- T-cell population in classical Hodgkin lymphoma displays a distinctive regulatory T-cell profile. Lab Invest 2008; 88: 482-490
79. Lukes RL, Tindle BH. Immunoblastic lymphadenopathy: A hyperimmune entity resembling Hodgkin disease. N Engl J Med 1975; 292: 1-8.
80. Hertel CB, Zhou XG, Hamilton-Dutoit SJ, et al. Loss of B cell identity correlates with loss of B cell-specific transcription factors in Hodgkin/Reed-Sternberg cells of classical Hodgkin lymphoma. Oncogene 2000; 21: 4908-4920
81. Theil J, Laumen H, Marafloti T, et al. Defective octamer-dependent transcription is responsible for silenced immunoglobulin transcription in Reed-Sternberg cells. Blood 2001; 97: 3191-3196
82. Su W, Spencer, Wotherspoon AC. Relative distribution of tumour cells and reactive cells in follicular lymphoma. J Pathol 2001; 193: 498-504.
83. Adam P, Katzenberger T, Eifert M, et al. Presence of preserved reactive germinal centers in follicular lymphoma is a strong histopathologic indicator of limited disease stage. Am J Surg Pathol 2005; 29: 1661-1664
84. Freedman AS, Saporito L, Rhynhart K, et al. Adhesion of follicular lymphoma cells to lymphoid geminal centers-a potential mechanism of tumor cell homing following autologous transplantation. Leuk Lymphoma 1994; 13: 47-52.
85. Fan Z, Natkunam Y, Bair E, et al. Characterization of variant patterns of nodular lymphocyte predominant Hodgkin lymphoma with immunohistologic and clinical correlation. Am J Surg Pathol 2003; 27: 1346-1356
86. Kojima M, Nakamura S, Itoh H, et al. Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: A clinicopathological and immunohistochemical study of 10 cases. APMIS 2001; 109: 699-706.
87. Ree HJ, Kadin ME, Kikuchi M, et al. Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers. Am J Surg Pathol 1998; 22: 643-655
88. Ree HJ, Kadin ME, Kikuchi M, et al. Bcl-6 expression in reactive follicular hyperplasia, follicular lymphoma, and angioimmunoblastic T-cell lymphoma with hyperplastic germinal centers: heterogeneity of intrafollicular T-cells and their altered distribution in the pathogenesis of angioimmunoblastic T-cell lymphoma. Hum Pathol 1999; 30: 403-411
89. Tan LHC, Chiu LL, Koay ESC. Diagnostic impact of molecular lineage analysis on para.n-embedded tissue in hematolymphoid neoplasia reclassified by current WHO criteria. Mol Diagn Ther 2007; 11: 29-53.
90. Du M, Diss TC, Xu C, et al. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia 1996; 10: 1990-1997
91. Aarts WM, Willemze R, Bende RJ, et al. VH gene analysis of primary cutaneous B-cell lymphomas: Evidence for ongoing somatic hypermutation and isotype switching. Blood 1998; 92: 3857-3864
92. Tan SY. Cell Populations in Normal and Neoplastic Lymphoid Tissues. Oxford: University of Oxford, Nu.eld Department of Clinical Laboratory Sciences, 2007: 175-200.
93. Lynch RG. Components of immune function studied with lymphoid tumors. Int Rev Immunol 1986; 1: 335-348
94. Janz M, Dörken B, Mathas S. Reprogramming of B lymphoid cells in human lymphoma pathogenesis. Cell Cycle 2006; 5: 1057-1061
95. Müller-Hermelink HK, Zettl A, Pfeifer W, et al. Pathology of lymphoma progression. Histopathology 2001; 38: 285-306.
96. Johansson B, Mertens F, Mitelman F. Secondary chromosomal abnormalities in acute leukemias. Leukemia 1994; 8: 953-962
97. Kwon MS, Go JH, Choi JS, et al. Critical Evaluation of bcl-6 protein expression in diffuse large B-cell lymphoma of the stomach and small intestine. Am J Surg Pathol 2003; 27: 790-798
98. Omonishi K, Yoshino T, Sakuma I, et al. Bcl-6 protein is identified in high-grade but not low-grade mucosa-associated lymphoid tissue lymphomas of the stomach. Mod Pathol 1998; 11: 181-185 (Pubitemid 28144154)
99. Uherova P, Ross CW, Finn WG, et al. Peripheral T-cell lymphoma mimicking marginal zone lymphoma. Mod Pathol 2002; 15: 420-425
100. Rudiger T, Ichinohasama I, Ott MM, et al. Peripheral T-cell lymphoma with distinct perifollicular growth pattern. A distinct subtype of T-cell lymphoma? Am J Surg Pathol 2000; 24: 117-122
101. Lai R, Lefresne SV, Franko B, et al. Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome. Mod Pathol 2006; 19: 1498-1505
102. Nakamura N, Abe M. Histogenesis of CD5-positive and CD5- negative B-cell neoplasms on the aspect of somatic mutation of immunoglobulin heavy chain gene variable region. Fukushima J Med Sci 2003; 49: 55-67.
103. Bahler DW, Aguilera NS, Chen CC, et al. Histological and immunoglobulin VH gene analysis of interfollicular small lymphocytic lymphoma provides evidence for two types. Am J Pathol 2000; 157: 1063-1070
104. Farinha P, Gascoyne R. Molecular pathogenesis of mucosaassociated lymphoid tissue lymphoma. J Clin Oncol 2005; 23: 6370-6378
105. Gonzá lez D, van der Burg M, García-Sanz R, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood 2007; 110: 3112-3121
106. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000; 403: 503-511
107. Berglund M, Thunberg U, Amini RM, et al. Evaluation of immunophenotype in diffuse large B-cell lymphoma and its impact on prognosis. Mod Pathol 2005; 18: 1113-1120
108. Chang CC, McClintock S, Cleveland RP, et al. Immunohistochemical expression patterns of germinal center and activation B-cell markers correlate with prognosis in diffuse large B-cell lymphoma. Am J Surg Pathol 2004; 28: 464-470
109. Huang JZ, Sanger WG, Greiner TC, et al. The t(14;18) de.nes a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood 2002; 99: 2285-2290
110. Fang J-M, Finn WG, Hussong JW, et al. CD10 antigen expression correlates with the t(14;18)(q32;q21) major breakpoint region in diffuse large B-cell lymphoma. Mod Pathol 1999; 12: 295-300.
111. Davies AJ, Rosenwald A, Wright G, et al. Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms. Br J Haematol 2007; 136: 286-293
112. Eshoa C, Perkins S, Kampalath B, et al. Decreased CD10 expression in Grade III and in interfollicular in.ltrates of follicular lymphomas. Am J Clin Pathol 2001; 115: 882-967
113. Dierlamm J, Penas EMM, Bentink S, et al. Gain of chromosome region 18q21 including the MALT1 gene is associated with the activated B-cell-like gene expression subtype and increased BCL2 gene dosage and protein expression in diffuse large B-cell lymphoma. Haematologica 2008; 93: 688-696
114. Brown PJ, Ashe SL, Leich E, et al. Potentially oncogenic B-cell activation-induced smaller isoforms of FOXP1 are highly expressed in the activated B cell-like subtype of DLBCL. Blood 2008; 111: 2816-2824
115. Sagaert X, de Paepe P, Libbrecht L, et al. Forkhead box protein P1 expression in mucosa-associated lymphoid tissue lymphomas predicts poor prognosis and transformation into diffuse large B-cell lymphoma. J Clin Oncol 2006; 24: 2490-2497
116. Calvo KR, Traverse-Glehen A, Pittaluga S, et al. Molecular profiling provides evidence of primary mediastinal large B-cell lymphoma as a distinct entity related to classic Hodgkin lymphoma. Implications for mediastinal gray zone lymphomas as an intermediate form of B-cell lymphoma. Adv Anat Pathol 2004; 11: 227-238
117. Leithäuser F, Bäuerle M, Huynh MQ, et al. Isotype-switched immunoglobulin genes with a high load of somatic hypermutation and lack of ongoing mutational activity are prevalent in mediastinal B-cell lymphoma. Blood 2001; 98: 2762-2770
118. Willemze R, Ja.e ES, Burg G, et al. WHO-EORTC classi.cation for cutaneous lymphomas. Blood 2005; 105: 3768-3785
119. Shen D-F, Doukhan L, Kalams S, et al. High-resolution analysis of T-cell receptor b-chain repertoires using DNA heteroduplex tracking: generally stable, clonal CD8pexpansions in all healthy young adults. J Immunol Methods 1998; 215: 113-121
120. Manfras BJ, Rudert WA, Trucco M, et al. Analysis of the a/b T-cell receptor repertoires by competitive and quantitative familyspeci .c PCR with exogenous standards and high resolution .uorescence based CDR3 size imaging. J Immunol Methods 1997; 210: 235-249
121. Cochet M, Pannetier C, Regnault A, et al. Molecular detection and in vivo anaysis of the specific T-cell response to a protein antigen. Eur J Immunol 1992; 22: 2639-2647
122. Dunon D, Courtois D, Vainio O, et al. Ontogeny of the immune system g/d and a/b T cells migrate from thymus to the periphery in alternating waves. J Exp Med 1997; 186: 977-988
123. Deusch K, Luling F Reich K, et al. A major fraction of human intraepithelial lymphocytes simultaneously expresses the g/d T cell receptor, the CD8 accessory molecule and preferentially uses the Vd1 gene segment. Eur J Immunol 1991; 21: 1053-1059
124. Falini B, Flenghi L, Pileri S, et al. Distribution of T cells bearing Different forms of the T cell receptor g/d in normal and pathological human tissues. J Immunol 1989; 143: 2480-2488
125. Asna. V, Beldjord K, Boulanger E, et al. Analysis of TCR, pTa, and RAG-1 in T-acute lymphoblastic leukemias improves understanding of early human T-lymphoid lineage commitment. Blood 2003; 101: 2693-2703
126. Langerak AW, van den Beemd R, Wolvers-Tettero ILM, et al. Molecular and .ow cytometric analysis of the Vb repertoire for clonality assessment in mature TCRab T-cell proliferations. Blood 2001; 98: 165-173
127. Przybylski GK, Wu H, Macon WR, et al. Hepatosplenic and subcutaneous panniculitis-like g/d T cell lymphomas are derived from Different Vd subsets of g/d T lymphocytes. J Mol Diagn 2000; 2: 11-19
128. De Wolf-Peeters C, Achten R. gd T-cell lymphomas: A homogeneous entity? Histopathology 2000; 36: 294-305.
129. Pagels HR. Perfect Symmetry. Toronto: Bantam Books, 1986.
130. Müschen M, Küppers R, Spieker T, et al. Molecular singlecell analysis of Hodgkin and Reed-Sternberg cells harbouring unmutated immunoglobulin variable region genes. Lab Invest 2001; 81: 289-295