Top

Published in:

01-10-2004 | Original Article

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8⁺ cytotoxic T-cells

Authors: Eva Geissinger, Tobias Odenwald, Seung-Sook Lee, Irina Bonzheim, Sabine Roth, Peter Reimer, Martin Wilhelm, Hans Konrad Müller-Hermelink, Thomas Rüdiger

Published in: Virchows Archiv | Issue 4/2004

Abstract

Nodal peripheral T-cell lymphomas are not well understood, and most of them are classified in the “not otherwise specified group” (PTCL-NOS). Data on their normal cellular derivation are ambiguous. Most peripheral T-cell lymphomas are composed of tumor cells and a (sometimes dominant) reactive background, which also includes resting and activated T-lymphocytes. We defined the phenotype of the tumor cells in 101 PTCL-NOS based on their cytological atypia and using immunohistochemical double stains on paraffin sections with CD4/Ki67 and CD8/Ki67. The results were correlated to clinical presentation and outcome. Lineage could be defined in 98 cases (97%). Tumor cells were CD4⁺ in 43 cases and CD8⁺ in 38. These presented at a younger age but a higher clinical stage compared with the CD4⁺ lymphomas. In 15 cases, the atypical cells were CD4⁻CD8⁻; two cases were CD4⁺CD8⁺. Of 17 lymphoepithelioid (Lennert’s) lymphomas, 15 expressed CD8, one each was CD4⁺ and CD4⁻CD8⁻.

(1982) National Cancer Institute sponsored study of classifications of non-Hodgkin’s lymphomas: summary and description of a working formulation for clinical usage. The Non-Hodgkin’s Lymphoma Pathologic Classification Project. Cancer 49:2112–2135

(1997) A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood 89:3909–3918

Ansell SM, Habermann TM, Kurtin PJ, Witzig TE, Chen MG, Li CY, Inwards DJ, Colgan JP (1997) Predictive capacity of the International Prognostic Factor Index in patients with peripheral T-cell lymphoma. J Clin Oncol 15:2296–2301PubMed

Benharroch D, Meguerian-Bedoyan Z, Lamant L, Amin C, Brugières L, Terrier-Lacombe M-J, Haralambieva E, Pulford K, Pileri S, Morris SW, Mason DY, Delsol G (1998) ALK-positive lymphoma. A single disease with a broad spectrum of morphology. Blood 91:2076–2084PubMed

Boulland ML, Kanavaros P, Wechsler J, Casiraghi O, Gaulard P (1997) Cytotoxic protein expression in natural killer cell lymphomas and in alpha beta and gamma delta peripheral T-cell lymphomas. J Pathol 183:432–439CrossRefPubMed

Chan AC, Ho JW, Chiang AK, Srivastava G (1999) Phenotypic and cytotoxic characteristics of peripheral T-cell and NK-cell lymphomas in relation to Epstein–Barr virus association. Histopathology 34:16–24

Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, Cheung MM, Lau WH (1997) Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 89:4501–4513PubMed

Chaperot L, Bendriss N, Manches O, Gressin R, Maynadie M, Trimoreau F, Orfeuvre H, Corront B, Feuillard J, Sotto JJ, Bensa JC, Briere F, Plumas J, Jacob MC (2001) Identification of a leukemic counterpart of the plasmacytoid dendritic cells. Blood 97:3210–3217CrossRefPubMed

Chott A, Augustin I, Wrba F, Hanak H, Ohlinger W, Radaszkiewicz T (1990) Peripheral T-cell lymphomas: a clinicopathologic study of 75 cases. Hum Pathol 21:1117–1125CrossRefPubMed

10.

de Bruin PC, Kummer JA, van der Valk P, van Heerde P, Kluin PM, Willemze R, Ossenkoppele GJ, Radaszkiewicz T, Meijer CJ (1994) Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization. Blood 84:3785–3791PubMed

11.

Felgar RE, Macon WR, Kinney MC, Roberts S, Pasha T, Salhany KE (1997) TIA-1 expression in lymphoid neoplasms. Identification of subsets with cytotoxic T lymphocyte or natural killer cell differentiation. Am J Pathol 150:1893–1900PubMed

12.

Feller AC, Griesser GH, Mak TW, Lennert K (1986) Lymphoepithelioid lymphoma (Lennert’s lymphoma) is a monoclonal proliferation of helper/inducer T cells. Blood 68:663–667PubMed

13.

Feller AC, Lennert K, Zwingers T (1991) Peripheral T-cell lymphomas. Histopathology 19:481–484

14.

Flamand L, Crowley RW, Lusso P, Colombini-Hatch S, Margolis DM, Gallo RC (1998) Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: implications for HIV pathogenesis. Proc Natl Acad Sci U S A 95:3111–3116CrossRefPubMed

15.

Gisselbrecht C, Gaulard P, Lepage E, Coiffier B, Briere J, Haioun C, Cazals-Hatem D, Bosly A, Xerri L, Tilly H, Berger F, Bouhabdallah R, Diebold J (1998) Prognostic significance of T-cell phenotype in aggressive non-Hodgkin’s lymphomas. Groupe d’Etudes des Lymphomes de l’Adulte (GELA). Blood 92:76–82PubMed

16.

Harris NL, Jaffe ES, Stein H, Banks PM, Chan JKC, Cleary ML, Delsol G, De Wolf Peeters C, Falini B, Gatter KC, Grogan TM, Isaacson PG, Knowles DM, Mason DY, Müller-Hermelink HK, Pileri SA, Piris MA, Ralfkiaer E, Warnke RA (1994) A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood 84:1361–1392PubMed

17.

Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (1999) The World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. Report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November, 1997. Ann Oncol 10:1419–1432CrossRefPubMed

18.

Hastrup N, Hamilton Dutoit S, Ralfkiaer E, Pallesen G (1991) Peripheral T-cell lymphomas: an evaluation of reproducibility of the updated Kiel classification. Histopathology 18:99–105PubMed

19.

Jaffe ES (1999) Hematopathology: integration of morphologic features and biologic markers for diagnosis. Mod Pathol 12:109–115PubMed

20.

Jaffe ES, Harris NL, Diebold J, Müller-Hermelink HK (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues. A progress report. Am J Clin Pathol 111:8–12

21.

Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. IARC Press, Lyon

22.

Kagami Y, Suzuki R, Taji H, Yatabe Y, Takeuchi T, Maeda S, Kondo E, Kojima M, Motoori T, Mizoguchi Y, Okamoto M, Ohnishi K, Yamabe H, Seto M, Ogura M, Koshikawa T, Takahashi T, Kurita S, Morishima Y, Suchi T, Nakamura S (1999) Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients. Am J Surg Pathol 23:1184–1200CrossRefPubMed

23.

Kaplan EL, Meier P (1958) Nonparametric estimation from incomplete observations. J Am Stat Assoc 53:457

24.

Kluin PM, Feller A, Gaulard P, Jaffe ES, Meijer CJ, Muller-Hermelink HK, Pileri S (2001) Peripheral T/NK-cell lymphoma: a report of the IXth Workshop of the European Association for Haematopathology. Histopathology 38:250–270

25.

Kobashi Y, Nakamura S, Sasajima Y, Koshikawa T, Yatabe Y, Kitoh K, Mori S, Ueda R, Yamabe H, Suchi T (1996) Inconsistent association of Epstein–Barr virus with CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract. Histopathology 28:111–120CrossRefPubMed

26.

Krajewski AS, Myskow MW, Cachia PG, Salter DM, Sheehan T, Dewar AE (1988) T-cell lymphoma: morphology, immunophenotype and clinical features. Histopathology 13:19–41PubMed

27.

Lee SS, Rudiger T, Odenwald T, Roth S, Starostik P, Muller-Hermelink HK (2003) Angioimmunoblastic T cell lymphoma is derived from mature T-helper cells with varying expression and loss of detectable CD4. Int J Cancer 103:12–20CrossRefPubMed

28.

Macon WR, Salhany KE (1998) T-cell subset analysis of peripheral T-cell lymphomas by paraffin section immunohistology and correlation of CD4/CD8 results with flow cytometry. Am J Clin Pathol 109:610–617PubMed

29.

Melnyk A, Rodriguez A, Pugh WC, Cabannillas F (1997) Evaluation of the Revised European–American Lymphoma classification confirms the clinical relevance of immunophenotype in 560 cases of aggressive non-Hodgkin’s lymphoma. Blood 89:4514–4520PubMed

30.

Montalban C, Obeso G, Gallego A, Castrillo JM, Bellas C, Rivas C (1993) Peripheral T-cell lymphoma: a clinicopathological study of 41 cases and evaluation of the prognostic significance of the updated Kiel classification. Histopathology 22:303–310PubMed

31.

Nakamura S, Suchi T (1991) A clinicopathologic study of node-based, low-grade, peripheral T-cell lymphoma. Angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma. Cancer 67:2566–2578PubMed

32.

Nakamura S, Koshikawa T, Koike K, Kitoh K, Suzuki H, Oyama A, Motoori T, Kojima M, Ogura M, Kurita S et al (1993) Phenotypic analysis of peripheral T cell lymphoma among the Japanese. Acta Pathol Jpn 43:396–412PubMed

33.

Ng CS, Lo ST, Chan JK (1999) Peripheral T and putative natural killer cell lymphomas commonly coexpress CD95 and CD95 ligand. Hum Pathol 30:48–53PubMed

34.

Ohshima K, Suzumiya J, Sugihara M, Kanda M, Shimazaki K, Kawasaki C, Haraoka S, Kikuchi M (1999) Clinical, immunohistochemical and phenotypic features of aggressive nodal cytotoxic lymphomas, including alpha/beta, gamma/delta T-cell and natural killer cell types. Virchows Arch 435:92–100CrossRefPubMed

35.

Picker LJ, Weiss LM, Medeiros LJ, Wood GS, Warnke RA (1987) Immunophenotypic criteria for the diagnosis of non-Hodgkin’s lymphoma. Am J Pathol 128:181–201PubMed

36.

Reimer P, Rudiger T, Kraemer D, Kunzmann V, Weissinger F, Zettl A, Konrad Muller-Hermelink H, Wilhelm M (2003) What is CD4+CD56+ malignancy and how should it be treated? Bone Marrow Transplant 32:637–646CrossRefPubMed

37.

Rüdiger T, Jaffe ES, Delsol G, deWolf Peeters C, Gascoyne RD, Georgii A, Harris NL, Kadin ME, MacLennan KA, Poppema S, Stein H, Weiss LE, Müller-Hermelink HK (1998) Workshop report on Hodgkin’s disease and related diseases (“grey zone” lymphoma). Ann Oncol 9[Suppl 5]:S31–S38

38.

Rüdiger T, Weisenburger DD, Anderson JR, Armitage JO, Diebold J, MacLennan KA, Nathwani BN, Ullrich F, Müller-Hermelink HK (2002) Peripheral T-cell lymphoma. Results from the Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol 13:140–149CrossRefPubMed

39.

Shih LY, Kuo TT, Dunn P, Liaw SJ (1992) HTLV-I-positive and HTLV-I-negative peripheral T-cell lymphomas in Taiwan Chinese. Int J Cancer 50:186–191PubMed

40.

Shipp MA (1994) Prognostic factors in aggressive non-Hodgkin’s lymphoma: who has “high-risk” disease? Blood 83:1165–1173PubMed

41.

Siegert W, Nerl C, Engelhard M, Brittinger G, Tiemann M, Parwaresch R, Heinz R, Huhn D (1994) Peripheral T-cell non-Hodgkin’s lymphomas of low malignancy: prospective study of 25 patients with pleomorphic small cell lymphoma, lymphoepitheloid cell (Lennert’s) lymphoma and T-zone lymphoma. The Kiel Lymphoma Study Group. Br J Haematol 87:529–534PubMed

42.

Smith JL, Haegert DG, Hodges E, Stacey GN, Howell WM, Wright DH, Jones DB (1988) Phenotypic and genotypic heterogeneity of peripheral T-cell lymphoma. Br J Cancer 58:723–729PubMed

43.

Sng I, Levin A, Jaffe ES, Ng HW, Sim CS, Blattner WB (1992) T-cell lymphoma in Singapore: pathology, clinical findings and association with HTLV-1 antibodies. Histopathology 21:101–113

44.

Stansfeld AG, Diebold J, Noel H, Kapanci Y, Rilke F, Kelenyi G, Sundstrom C, Lennert K, van Unnik JAM, Mioduszewska O, Wright DH (1988) Updated Kiel classification for lymphomas. Lancet 1:292–293CrossRef

45.

Su IJ, Wang CH, Cheng AL, Chen YC, Hsieh HC, Chen CJ, Tien HF, Tsay W, Huang SS, Hu CY et al (1988) Characterization of the spectrum of postthymic T-cell malignancies in Taiwan. A clinicopathologic study of HTLV-1-positive and HTLV-1-negative cases. Cancer 61:2060–2070PubMed

46.

Suchi T, Lennert K, Tu LY, Kikuchi M, Sato E, Stansfeld AG, Feller AC (1987) Histopathology and immunohistochemistry of peripheral T cell lymphomas: a proposal for their classification. J Clin Pathol 40:995–1015PubMed

47.

Takagi N, Nakamura S, Ueda R, Osada H, Obata Y, Kitoh K, Suchi T, Takahashi T (1992) A phenotypic and genotypic study of three node-based, low-grade peripheral T-cell lymphomas: angioimmunoblastic lymphoma, T-zone lymphoma, and lymphoepithelioid lymphoma. Cancer 69:2571–2582PubMed

48.

Trainor KJ, Brisco MJ, Wan JH, Neoh S, Grist S, Morley AA (1991) Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction Blood 78:192–196

49.

Weisenburger DD, Linder J, Armitage JO (1987) Peripheral T-cell lymphoma: a clinicopathologic study of 42 cases. Hematol Oncol 5:175–187PubMed

50.

Yamashita Y, Yatabe Y, Tsuzuki T, Nakayama A, Hasegawa Y, Kojima H, Nagasawa T, Mori N (1998) Perforin and granzyme expression in cytotoxic T-cell lymphomas. Mod Pathol 11:313–323PubMed

51.

Yamashita Y, Nakamura S, Kagami Y, Hasegawa Y, Kojima H, Nagasawa T, Mori N (2000) Lennert’s lymphoma: a variant of cytotoxic T-cell lymphoma? Am J Surg Pathol 24:1627–1633PubMed

Title: Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8+ cytotoxic T-cells
Authors: Eva Geissinger
Tobias Odenwald
Seung-Sook Lee
Irina Bonzheim
Sabine Roth
Peter Reimer
Martin Wilhelm
Hans Konrad Müller-Hermelink
Thomas Rüdiger
Publication date: 01-10-2004
Publisher: Springer-Verlag
Published in: Virchows Archiv / Issue 4/2004
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-004-1077-2

At a glance: The STEP trials

Springer Medicine

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert’s) variant are often derived from CD8⁺ cytotoxic T-cells

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 4/2004

A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumor with a predilection for the fingers

TiA1 in advanced-stage classical Hodgkin’s lymphoma: no prognostic impact for positive tumour cells or number of cytotoxic cells

Epithelioid fibrosarcoma of the ovary

Part of the multiple myeloma-associated microvessels is functionally connected to the systemic circulation: a study in the murine 5T33MM model

Lymphoepithelioma-like carcinoma of the submandibular salivary gland associated with Epstein–Barr virus in a North African woman

Erdheim–Chester disease of the breast associated with Langerhans-cell histiocytosis of the hard palate