Skip to main content
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1997 Apr;150(4):1207–1211.

Frequent expression of the NPM-ALK chimeric fusion protein in anaplastic large-cell lymphoma, lympho-histiocytic type.

S A Pileri 1, K Pulford 1, S Mori 1, D Y Mason 1, E Sabattini 1, G Roncador 1, M Piccioli 1, C Ceccarelli 1, P P Piccaluga 1, D Santini 1, O Leone 1, H Stein 1, B Falini 1
PMCID: PMC1858171  PMID: 9094977

Abstract

The revised European-American lymphoma classification recognizes a subtype of anaplastic large-cell lymphoma (ALCL), termed lympho-histiocytic because of its peculiar cytological composition. As in the case of classical ALCL, this tumor usually occurs in young patients and shows an excellent response to chemotherapy, but some authors have suggested that in reality this is a nonanaplastic T-cell lymphoma rich in histiocytes. In this paper, we show that three of five cases of lympho-histiocytic ALCL stain with anti-ALK antibodies and can therefore be presumed to express the chimeric NPM/ALK protein secondary to (2;5) translocation. These findings further support the inclusion of this as a type of ALCL and not among the nonanaplastic peripheral T-cell lymphomas. Furthermore, they indicate that staining for ALK proteins is a powerful tool for the diagnosis of lympho-histiocytic ALCL, the recognition of which may be difficult on morphological grounds.

Full text

PDF
1207

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agnarsson B. A., Kadin M. E. Ki-1 positive large cell lymphoma. A morphologic and immunologic study of 19 cases. Am J Surg Pathol. 1988 Apr;12(4):264–274. doi: 10.1097/00000478-198804000-00002. [DOI] [PubMed] [Google Scholar]
  2. Bullrich F., Morris S. W., Hummel M., Pileri S., Stein H., Croce C. M. Nucleophosmin (NPM) gene rearrangements in Ki-1-positive lymphomas. Cancer Res. 1994 Jun 1;54(11):2873–2877. [PubMed] [Google Scholar]
  3. Chan J. K., Ng C. S., Hui P. K., Leung T. W., Lo E. S., Lau W. H., McGuire L. J. Anaplastic large cell Ki-1 lymphoma. Delineation of two morphological types. Histopathology. 1989 Jul;15(1):11–34. doi: 10.1111/j.1365-2559.1989.tb03038.x. [DOI] [PubMed] [Google Scholar]
  4. Chott A., Kaserer K., Augustin I., Vesely M., Heinz R., Oehlinger W., Hanak H., Radaszkiewicz T. Ki-1-positive large cell lymphoma. A clinicopathologic study of 41 cases. Am J Surg Pathol. 1990 May;14(5):439–448. doi: 10.1097/00000478-199005000-00003. [DOI] [PubMed] [Google Scholar]
  5. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  6. Falini B., Pileri S., Pizzolo G., Dürkop H., Flenghi L., Stirpe F., Martelli M. F., Stein H. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995 Jan 1;85(1):1–14. [PubMed] [Google Scholar]
  7. Harris N. L., Jaffe E. S., Stein H., Banks P. M., Chan J. K., Cleary M. L., Delsol G., De Wolf-Peeters C., Falini B., Gatter K. C. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994 Sep 1;84(5):1361–1392. [PubMed] [Google Scholar]
  8. Herbst H., Anagnostopoulos J., Heinze B., Dürkop H., Hummel M., Stein H. ALK gene products in anaplastic large cell lymphomas and Hodgkin's disease. Blood. 1995 Sep 1;86(5):1694–1700. [PubMed] [Google Scholar]
  9. Kaneko Y., Frizzera G., Edamura S., Maseki N., Sakurai M., Komada Y., Sakurai M., Tanaka H., Sasaki M., Suchi T. A novel translocation, t(2;5)(p23;q35), in childhood phagocytic large T-cell lymphoma mimicking malignant histiocytosis. Blood. 1989 Feb 15;73(3):806–813. [PubMed] [Google Scholar]
  10. Lopategui J. R., Sun L. H., Chan J. K., Gaffey M. J., Frierson H. F., Jr, Glackin C., Weiss L. M. Low frequency association of the t(2;5)(p23;q35) chromosomal translocation with CD30+ lymphomas from American and Asian patients. A reverse transcriptase-polymerase chain reaction study. Am J Pathol. 1995 Feb;146(2):323–328. [PMC free article] [PubMed] [Google Scholar]
  11. Mason D. Y., Bastard C., Rimokh R., Dastugue N., Huret J. L., Kristoffersson U., Magaud J. P., Nezelof C., Tilly H., Vannier J. P. CD30-positive large cell lymphomas ('Ki-1 lymphoma') are associated with a chromosomal translocation involving 5q35. Br J Haematol. 1990 Feb;74(2):161–168. doi: 10.1111/j.1365-2141.1990.tb02560.x. [DOI] [PubMed] [Google Scholar]
  12. Morgan J. M., Navabi H., Schmid K. W., Jasani B. Possible role of tissue-bound calcium ions in citrate-mediated high-temperature antigen retrieval. J Pathol. 1994 Dec;174(4):301–307. doi: 10.1002/path.1711740410. [DOI] [PubMed] [Google Scholar]
  13. Morris S. W., Kirstein M. N., Valentine M. B., Dittmer K. G., Shapiro D. N., Saltman D. L., Look A. T. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science. 1994 Mar 4;263(5151):1281–1284. doi: 10.1126/science.8122112. [DOI] [PubMed] [Google Scholar]
  14. Pileri S. A., Piccaluga A., Poggi S., Sabattini E., Piccaluga P. P., De Vivo A., Falini B., Stein H. Anaplastic large cell lymphoma: update of findings. Leuk Lymphoma. 1995 Jun;18(1-2):17–25. doi: 10.3109/10428199509064918. [DOI] [PubMed] [Google Scholar]
  15. Pileri S., Bocchia M., Baroni C. D., Martelli M., Falini B., Sabattini E., Gherlinzoni F., Amadori S., Poggi S., Mazza P. Anaplastic large cell lymphoma (CD30 +/Ki-1+): results of a prospective clinico-pathological study of 69 cases. Br J Haematol. 1994 Mar;86(3):513–523. doi: 10.1111/j.1365-2141.1994.tb04781.x. [DOI] [PubMed] [Google Scholar]
  16. Pileri S., Falini B., Delsol G., Stein H., Baglioni P., Poggi S., Martelli M. F., Rivano M. T., Mason D. Y., Stansfeld A. G. Lymphohistiocytic T-cell lymphoma (anaplastic large cell lymphoma CD30+/Ki-1 + with a high content of reactive histiocytes). Histopathology. 1990 Apr;16(4):383–391. doi: 10.1111/j.1365-2559.1990.tb01143.x. [DOI] [PubMed] [Google Scholar]
  17. Pileri S., Sabattini E., Poggi S., Amini M., Falini B., Stein H. Lymphohistiocytic T-cell lymphoma. Histopathology. 1994 Aug;25(2):191–193. doi: 10.1111/j.1365-2559.1994.tb01583.x. [DOI] [PubMed] [Google Scholar]
  18. Rimokh R., Magaud J. P., Berger F., Samarut J., Coiffier B., Germain D., Mason D. Y. A translocation involving a specific breakpoint (q35) on chromosome 5 is characteristic of anaplastic large cell lymphoma ('Ki-1 lymphoma'). Br J Haematol. 1989 Jan;71(1):31–36. doi: 10.1111/j.1365-2141.1989.tb06270.x. [DOI] [PubMed] [Google Scholar]
  19. Shiota M., Fujimoto J., Takenaga M., Satoh H., Ichinohasama R., Abe M., Nakano M., Yamamoto T., Mori S. Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry. Blood. 1994 Dec 1;84(11):3648–3652. [PubMed] [Google Scholar]
  20. Shiota M., Nakamura S., Ichinohasama R., Abe M., Akagi T., Takeshita M., Mori N., Fujimoto J., Miyauchi J., Mikata A. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK: a distinct clinicopathologic entity. Blood. 1995 Sep 1;86(5):1954–1960. [PubMed] [Google Scholar]
  21. Stansfeld A. G., Diebold J., Noel H., Kapanci Y., Rilke F., Kelényi G., Sundstrom C., Lennert K., van Unnik J. A., Mioduszewska O. Updated Kiel classification for lymphomas. Lancet. 1988 Feb 6;1(8580):292–293. doi: 10.1016/s0140-6736(88)90367-4. [DOI] [PubMed] [Google Scholar]
  22. Stein H., Herbst H., Anagnostopoulos I., Niedobitek G., Dallenbach F., Kratzsch H. C. The nature of Hodgkin and Reed-Sternberg cells, their association with EBV, and their relationship to anaplastic large-cell lymphoma. Ann Oncol. 1991 Feb;2 (Suppl 2):33–38. doi: 10.1007/978-1-4899-7305-4_5. [DOI] [PubMed] [Google Scholar]
  23. Stein H., Mason D. Y., Gerdes J., O'Connor N., Wainscoat J., Pallesen G., Gatter K., Falini B., Delsol G., Lemke H. 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. Blood. 1985 Oct;66(4):848–858. [PubMed] [Google Scholar]
  24. Zinzani P. L., Bendandi M., Martelli M., Falini B., Sabattini E., Amadori S., Gherlinzoni F., Martelli M. F., Mandelli F., Tura S. Anaplastic large-cell lymphoma: clinical and prognostic evaluation of 90 adult patients. J Clin Oncol. 1996 Mar;14(3):955–962. doi: 10.1200/JCO.1996.14.3.955. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES