Summary
We investigated for rearrangements of the immunoglobulin (Ig) heavy and light chain genes and of the T cell receptorγ (TCRTγ) andβ (TCrβ) genes 45 biopsy samples from a variety of lymphoproliferative disorders. They were diagnosed histopathologically and immunophenotypically as non-Hodgkin's lymphomas (NHLs) of the B cell type (19 cases), NHLs of the T cell type (3 cases), NHLs of “undetermined“ cell type (3 cases), atypical lymphoid proliferation (1 case) and AIDS-related lymphadenopathies with florid polyclonal follicular hyperplasia (19 cases). A monoclonal proliferation of B cells was shown by DNA analysis in all 19 B cell NHLs. In two immunohistologically determined T cell NHLs (both diagnosed as mycosis fungoides) the cells had rearrangements of TCrβ gene, whereas in the third case (lymphoblastic NHL) the cells had rearrangements of Ig heavy chain and TCrγ and TCrβ genes. None of the B cell NHLs exhibited TCrγand TCrβ gene rearrangement bands. All the “undetermined” cell NHLs demonstrated rearrangements of Ig heavy chain gene associated with the germ line TCrγand TCrβ genes; in two cases light chain gene rearrangements were also found. The atypical lymphoid proliferation, in which the differential diagnosis was between a reactive or malignant process, and two out of 19 cases of florid polyclonal follicular hyperplasia showed a clonal B cell population by DNA analysis. This study indicates that there was a strong correlation between the rearrangements of specific genes and the immunophenotype of the NHL; moreover, DNA analysis of tissue biopsy specimens from phenotypically “undetermined” cell NHLs and from equivocal lymphoid proliferation using Ig and TCR gene probes yelded an answer in the cases analyzed. The significance of clonal B cell expansions found in two AIDS-related lymphadenopathies should be interpreted with caution.
Similar content being viewed by others
References
Arnold A, Cossman J, Bakhski A, Jaffe ES, Waldmann TA, Korsmeyer SJ (1983) Immunoglobulin-gene rearrangements as unique clonal markers in human lymphoid neoplasms. N Engl J Med 309:1593–1599
Asou N, Matsuoka M, Hattori T, Kawano F, Maeda S, Shimada K, Takatsuki K (1987a) T cellγ gene rearrangements in hematologic neoplasms. Blood 69:968–970
Asou N, Matsuoka M, Hattori T, Nishimura H, Ishii T, Takatsuki K (1987b) Genotypic analysis of lymph node cells from patients with phenotypically undetermined cell lymphoma. Leukemia 1:725–729
Bentley DL, Rabbitts TH (1983) Evolution of immunoglobulin V genes: evidence indicating that recently duplicated human V sequences have diverged by gene conversion. Cell 32:181–189
Bertness V, Kirsch I, Hollis G, Johnson B, Bunn PA (1985) T-cell receptor gene rearrangements as clinical markers of human T-cell lymphomas. N Engl J Med 313:534–538
Burke JS, Sheibani K, Nathwani BN, Winberg CD, Rappaport H (1987) Monoclonal small (well differentiated) lymphocytic proliferations of the gastrointestinal tract resembling lymphoid hyperplasia: a neoplasm of uncertain malignant potential. Hum Pathol 18:1238–1245
Carbone A, Manconi R, Poletti A, Tirelli U, De Paoli P, Santini G, Diodato S, Manconi PE, Grigoletto E, Santi L, Volpe R (1985) Lymph node immunohistology in intravenous drug abusers with persistent generalized lymphadenopathy. Arch Pathol Lab Med 109:1007–1012
Carbone A, Poletti A, Manconi R, Gloghini A, Volpe R (1987) Heterogeneous in situ immunophenotyping of follicular dendritic reticulum cells in malignant lymphomas of B-cell origin. Cancer 60:2919–2926
Carbone A, Manconi R, Poletti A, Gloghini A, De Paoli P, Volpe R (1988) Expression of Leu-8 surface antigen in B-cell lymphomas. Correlation with other B-cell markers. J Pathol 154:133–140
Ceccherini-Nelli L, De Re V, Viel A, Molaro G, Zilli L, Clemente C, Boiocchi M (1987) Ha-ras-1 restriction fragment length polymorphism and susceptibility to colon adenocarcinoma. Br J Cancer 56:1–5
Cleary ML, Chao J, Warnke R, Sklar J (1984) Immunoglobulin gene rearrangement as a diagnostic criterion of B-cell lymphoma. Proc Natl Acad Sci USA 81:593–597
Cossman J, Uppenkamp M, Sundeen J, Coupland R, Raffeld M (1988) Molecular genetics and the diagnosis of lymphoma. Arch Pathol Lab Med 112:117–127
Davey MP, Bongiovanni KF, Kaulfersch W, Quertemous T, Seidman JG, Hershfield MS, Kurtzberg J, Haynes BF, Davis MM, Waldmann TA (1986) Immunoglobulin and T-cell receptor gene rearrangement and expression in human lymphoid leukemia cells at different stages of maturation. Proc Natl Acad Sci USA 83:8759–8763
Flanagan JG, Rabbitts TH (1982) The sequence of a human immunoglobulin epsilon heavy chain constant region gene, and evidence for three non-allelic genes. EMBO J 5:655–660
Flug F, Pelicci PG, Bonetti F, Knowles DM II, Dalla-Favera R (1985) T-cell receptor gene rearrangements as markers of lineage and clonality in T-cell neoplasms. Proc Natl Acad Sci USA 82:3460–3464
Furley AJ, Mizutani S, Weilbaecher K, Dhaliwal HS, Ford AM, Chan LC, Molgaard HV, Toyonaga B, Mak T, van den Elsen P, Gold D, Terhorst C, Greaves MF (1986) Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex. Cell 46:75–87
Gerard-Marchant R, Hamlin I, Lennert K, Rilke F, Stansfeld AG, Van Unnik JAM (1974) Classification of non-Hodgkin's lymphomas. Lancet 2:406–408
Gonzalez-Crussi F, Mangkornkanok M, Hsueh W (1987) Large cell lymphoma: diagnostic difficulties and case study. Am J Surg Pathol 11:59–65
Griesser H, Feller A, Lennert K, Minden M, Wak TW (1986) Rearrangement of theβ chain of the T cell antigen receptor and immunoglobulin genes in lymphoproliferative disorders. J Clin Invest 78:1179–1184
Knowles DM II, Neri A, Pelicci PG, Burke JS, Wu A, Winberg CD, Sheibani K, Dalla Favera R (1986) Immunoglobulin and T-cell receptorβ-chain gene rearrangement analysis of Hodgkin's disease: implications for lineage determination and differential diagnosis. Proc Natl Acad Sci USA 83:7942–7946
Lefranc MP, Rabbits TH (1985) Two tandemly organized human genes encoding the T-cellγ constant-region sequences show multiple rearrangement in different T-cell types. Nature 316:464–466
Lennert K, Mohri N, Stein H, Kaiserling E (1975) The histopathology of malignant lymphoma. Br J Haematol (Suppl) 31:193–203
Lippman SM, Volk JR, Spier CM, Grogan TM (1988) Clonal ambiguity of human immunodeficiency virus-associated lymphomas: similarity to posttransplant lymphomas. Arch Pathol Lab Med 112:128–132
Nathwani BN (1979) A critical analysis of the classifications of non-Hodgkin's lymphomas. Cancer 44:347–384
National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas. Summary and description of a working formulation for clinical usage (1982) Cancer 49:2112–2135
Neri A, Jakobiec FA, Pelicci PG, Dalla Favera R, Knowles DM II (1987) Immunoglobulin and T cell receptorβ chain gene rearrangement analysis of ocular adnexal lymphoid neoplasms: clinical and biologic implications. Blood 70:1519–1529
Norton AJ, Isaacson PG (1987) Detailed phenotypic analysis of B-cell lymphoma using a panel of antibodies reactive in routinely fixed wax-embedded tissue. Am J Pathol 128:225–240
O'Connor NTJ, Gatter KC, Wainscoat JS, Crick J, Jones DB, Delsol G, Ralfkiaer E, De Wolf-Peeters C, Angus B, Mason DY (1987) Practical value of genotypic analysis for diagnosing lymphoproliferative disorders. J Clin Pathol 40:147–150
O'Murchadha MT, Wolf BC, Neiman RS (1987) The histologic features of hyperplastic lymphadenopathy in AIDS-related complex are nonspecific. Am J Surg Pathol 11:94–99
Pelicci PG, Knowles DM II, Arlin ZA, Wieczorek R, Luciw P, Dina D, Basilico C, Dalla Favera R (1986) Multiple monoclonal B cell expansions and c-myc oncogene rearrangements in acquired immune deficiency syndrome-related lymphoproliferative disorders: implications for lymphomagenesis. J Exp Med 164:2049–2076
Picker LJ, Weiss LM, Medeiros LJ, Wood GS, Warnke RA (1987) Immunophenotypic criteria for the diagnosis of nonHodgkin's lymphoma. Am J Pathol 128:181–201
Rabbitts TH, Forster A (1983) The breakpoint of the Philadelphia chromosome 22 in chronic myeloid leukaemia is distal to the immunoglobulin lambda light chain constant region genes. Mol Biol Med 1:11–19
Sheibani K, Winberg C (1987) A systematic approach to the immunohistologic classification of lymphoproliferative disorders. Hum Pathol 18:1051–1062
Sheibani K, Wu A, Ben-Ezra J, Stroup R, Rappaport H, Winberg C (1987) Rearrangement of K-chain and T-cell receptorβ-chain genes in malignant lymphomas of “T-cell” phenotype. Am J Pathol 129:201–207
Sims JE, Tunnacliffe A, Smith WJ, Rabbitts TH (1984) Complexity of human T-cell antigen receptorβ-chain constant-and variable-region genes. Nature 312:541–545
Smith WJ, Garson JA, Bourne SP, Kemshead JT, Coakham HB (1988) Immunoglobulin gene rearrangement and antigenic profile confirm B cell origin of primary cerebral lymphoma and indicate a mature phenotype. J Clin Pathol 41:128–132
Turner RR, Meyer PR, Taylor CR, Gill PS, Hofman FM, Nichols P, Rasheed S, Levine AM (1987) Immunohistology of persistent generalized lymphadenopathy: evidence for progressive lymph node abnormalities in some patients. Am J Clin Pathol 88:10–19
Waldmann TA, Korsmeyer SJ, Bakhshi A, Arnold A, Kirsh IA (1985) Molecular genetic analysis of human lymphoid neoplasms. Ann Intern Med 102:497–510
Warnke R, Miller RA, Grogan T, Pederson M, Dilley J, Levy R (1980) Immunologic phenotype of 30 diffuse large cell lymphomas: possible clinical relevance. N Engl J Med 303:293–300
Weiss LM, Wood GS, Trela M, Warnke RA, Sklar J (1986) Clonal T-cell populations in lymphomatoid papulosis. N Engl J Med 315:475–479
Williams ME, Innes DJ, Borowitz MJ, Lovell LA, Swerdlow SH, Hurtubise PE, Brynes RK, Chan WC, Byrne GE jr, Whitcomb CC, Thomas CY (1987) Immunoglobulin and T cell receptor gene rearrangements in human lymphoma and leukemia. Blood 69:79–86
Wright DH (1987) Recent advances in the study of malignant lymphomas. J Pathol 151:177–178
Author information
Authors and Affiliations
Additional information
This work was supported in part by a Grant No 86.00644.44 from the Consiglio Nazionale delle Ricerche, Progetto Finalizzato “Oncologia”, Rome, and by the Associazione Italiana per la Ricerca sul Cancro, Milan, Italy
Rights and permissions
About this article
Cite this article
Carbone, A., De Re, V., Gloghini, A. et al. Immunoglobulin and T cell receptor gene rearrangements and in situ immunophenotyping in lymphoproliferative disorders. Vichows Archiv A Pathol Anat 414, 223–230 (1989). https://doi.org/10.1007/BF00822026
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00822026