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. 1996 Aug;149(2):699–705.

Expression of perforin in nasal lymphoma. Additional evidence of its natural killer cell derivation.

N Mori 1, Y Yatabe 1, K Oka 1, T Kinoshita 1, T Kobayashi 1, T Ono 1, J Asai 1
PMCID: PMC1865304  PMID: 8702007

Abstract

Eight patients with nasal lymphoma in whom fresh-frozen tissues were available were studied to elucidate the nature of the lymphoma cells. Two cases were diagnosed as diffuse, large cell lymphoma, and the remaining six cases as diffuse, mixed cell types. Immunohistochemical studies revealed that all of the cases were positive for perforin, which is a specific marker for cytotoxic T or natural killer (NK) cells. As all of the cases were CD8 negative, the perforin-positive finding further confirmed the concept that nasal lymphoma is a distinct neoplastic entity derived from NK or NK-related cells. Light microscopic immunohistochemical studies revealed that these nasal lymphoma cases could be classified into Leu19(CD56)+Leu4(CD3)+ (two cases) and Leu19(CD56)+Leu4(CD3)- (six cases) types according to the phenotypes of the proliferating cells. However, simultaneous staining for perforin and Leu4 (CD3) using immunoelectron microscopy on the Leu19+Leu4+ cases showed that the perforin-positive cells were different from the Leu4-positive cells. This finding suggests that the Leu4-positive cells are not neoplastic NK cells but reactive T cells. Six cases were positive for EBER-1 by in situ hybridization analysis. This finding reconfirms the previous studies that Epstein-Barr virus plays a significant role in the pathogenesis of nasal lymphoma.

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Selected References

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

  1. Aozasa K., Ohsawa M., Tajima K., Sasaki R., Maeda H., Matsunaga T., Friedmann I. Nation-wide study of lethal mid-line granuloma in Japan: frequencies of wegener's granulomatosis, polymorphic reticulosis, malignant lymphoma and other related conditions. Int J Cancer. 1989 Jul 15;44(1):63–66. doi: 10.1002/ijc.2910440112. [DOI] [PubMed] [Google Scholar]
  2. Arber D. A., Weiss L. M., Albújar P. F., Chen Y. Y., Jaffe E. S. Nasal lymphomas in Peru. High incidence of T-cell immunophenotype and Epstein-Barr virus infection. Am J Surg Pathol. 1993 Apr;17(4):392–399. [PubMed] [Google Scholar]
  3. Borisch B., Hennig I., Laeng R. H., Waelti E. R., Kraft R., Laissue J. Association of the subtype 2 of the Epstein-Barr virus with T-cell non-Hodgkin's lymphoma of the midline granuloma type. Blood. 1993 Aug 1;82(3):858–864. [PubMed] [Google Scholar]
  4. Chan J. K., Ng C. S., Lau W. H., Lo S. T. Most nasal/nasopharyngeal lymphomas are peripheral T-cell neoplasms. Am J Surg Pathol. 1987 Jun;11(6):418–429. doi: 10.1097/00000478-198706000-00002. [DOI] [PubMed] [Google Scholar]
  5. Chan J. K., Tsang W. Y., Pau M. Y. Discordant CD3 expression in lymphomas when studied on frozen and paraffin sections. Hum Pathol. 1995 Oct;26(10):1139–1143. doi: 10.1016/0046-8177(95)90277-5. [DOI] [PubMed] [Google Scholar]
  6. Chang K. L., Chen Y. Y., Shibata D., Weiss L. M. Description of an in situ hybridization methodology for detection of Epstein-Barr virus RNA in paraffin-embedded tissues, with a survey of normal and neoplastic tissues. Diagn Mol Pathol. 1992 Dec;1(4):246–255. [PubMed] [Google Scholar]
  7. Chott A., Rappersberger K., Schlossarek W., Radaszkiewicz T. Peripheral T cell lymphoma presenting primarily as lethal midline granuloma. Hum Pathol. 1988 Sep;19(9):1093–1101. doi: 10.1016/s0046-8177(88)80092-3. [DOI] [PubMed] [Google Scholar]
  8. Fox W. M., 3rd, Hameed A., Hutchins G. M., Reitz B. A., Baumgartner W. A., Beschorner W. E., Hruban R. H. Perforin expression localizing cytotoxic lymphocytes in the intimas of coronary arteries with transplant-related accelerated arteriosclerosis. Hum Pathol. 1993 May;24(5):477–482. doi: 10.1016/0046-8177(93)90159-e. [DOI] [PubMed] [Google Scholar]
  9. Gaulard P., Henni T., Marolleau J. P., Haioun C., Henni Z., Voisin M. C., Divine M., Goossens M., Farcet J. P., Reyes F. Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Evidence for a monoclonal T-cell lymphoproliferative disorder. Cancer. 1988 Aug 15;62(4):705–710. doi: 10.1002/1097-0142(19880815)62:4<705::aid-cncr2820620410>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  10. Griffiths G. M., Mueller C. Expression of perforin and granzymes in vivo: potential diagnostic markers for activated cytotoxic cells. Immunol Today. 1991 Nov;12(11):415–419. doi: 10.1016/0167-5699(91)90145-J. [DOI] [PubMed] [Google Scholar]
  11. Hamilton-Dutoit S. J., Rea D., Raphael M., Sandvej K., Delecluse H. J., Gisselbrecht C., Marelle L., van Krieken H. J., Pallesen G. Epstein-Barr virus-latent gene expression and tumor cell phenotype in acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma. Correlation of lymphoma phenotype with three distinct patterns of viral latency. Am J Pathol. 1993 Oct;143(4):1072–1085. [PMC free article] [PubMed] [Google Scholar]
  12. Harabuchi Y., Yamanaka N., Kataura A., Imai S., Kinoshita T., Mizuno F., Osato T. Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma. Lancet. 1990 Jan 20;335(8682):128–130. doi: 10.1016/0140-6736(90)90002-m. [DOI] [PubMed] [Google Scholar]
  13. Ho F. C., Choy D., Loke S. L., Kung I. T., Fu K. H., Liang R., Todd D., Khoo R. K. Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases. Hum Pathol. 1990 Oct;21(10):1041–1050. doi: 10.1016/0046-8177(90)90254-3. [DOI] [PubMed] [Google Scholar]
  14. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  15. Ishii Y., Yamanaka N., Ogawa K., Yoshida Y., Takami T., Matsuura A., Isago H., Kataura A., Kikuchi K. Nasal T-cell lymphoma as a type of so-called "lethal midline granuloma". Cancer. 1982 Dec 1;50(11):2336–2344. doi: 10.1002/1097-0142(19821201)50:11<2336::aid-cncr2820501120>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  16. Kanavaros P., Lescs M. C., Brière J., Divine M., Galateau F., Joab I., Bosq J., Farcet J. P., Reyes F., Gaulard P. Nasal T-cell lymphoma: a clinicopathologic entity associated with peculiar phenotype and with Epstein-Barr virus. Blood. 1993 May 15;81(10):2688–2695. [PubMed] [Google Scholar]
  17. Kern W. F., Spier C. M., Hanneman E. H., Miller T. P., Matzner M., Grogan T. M. Neural cell adhesion molecule-positive peripheral T-cell lymphoma: a rare variant with a propensity for unusual sites of involvement. Blood. 1992 May 1;79(9):2432–2437. [PubMed] [Google Scholar]
  18. Laeng R. H., Gerber H. A., Schaffner T., Bürki K. H. Heterogeneous malignant non Hodgkin's lymphomas as a causative disorder in lethal midline granuloma. Virchows Arch A Pathol Anat Histopathol. 1989;415(3):265–273. doi: 10.1007/BF00724914. [DOI] [PubMed] [Google Scholar]
  19. Lanier L. L., Chang C., Spits H., Phillips J. H. Expression of cytoplasmic CD3 epsilon proteins in activated human adult natural killer (NK) cells and CD3 gamma, delta, epsilon complexes in fetal NK cells. Implications for the relationship of NK and T lymphocytes. J Immunol. 1992 Sep 15;149(6):1876–1880. [PubMed] [Google Scholar]
  20. Lanier L. L., Spits H., Phillips J. H. The developmental relationship between NK cells and T cells. Immunol Today. 1992 Oct;13(10):392–395. doi: 10.1016/0167-5699(92)90087-N. [DOI] [PubMed] [Google Scholar]
  21. Liang R., Todd D., Chan T. K., Chiu E., Choy D., Loke S. L., Ho F. C. Nasal lymphoma. A retrospective analysis of 60 cases. Cancer. 1990 Nov 15;66(10):2205–2209. doi: 10.1002/1097-0142(19901115)66:10<2205::aid-cncr2820661027>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  22. Martin A. R., Chan W. C., Perry D. A., Greiner T. C., Weisenburger D. D. Aggressive natural killer cell lymphoma of the small intestine. Mod Pathol. 1995 Jun;8(5):467–472. [PubMed] [Google Scholar]
  23. McLean I. W., Nakane P. K. Periodate-lysine-paraformaldehyde fixative. A new fixation for immunoelectron microscopy. J Histochem Cytochem. 1974 Dec;22(12):1077–1083. doi: 10.1177/22.12.1077. [DOI] [PubMed] [Google Scholar]
  24. Mishima K., Horiuchi K., Kojya S., Takahashi H., Ohsawa M., Aozasa K. Epstein-Barr virus in patients with polymorphic reticulosis (lethal midline granuloma) from China and Japan. Cancer. 1994 Jun 15;73(12):3041–3046. doi: 10.1002/1097-0142(19940615)73:12<3041::aid-cncr2820731224>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  25. Nakamura S., Suchi T., Koshikawa T., Kitoh K., Koike K., Komatsu H., Iida S., Kagami Y., Ogura M., Katoh E. Clinicopathologic study of CD56 (NCAM)-positive angiocentric lymphoma occurring in sites other than the upper and lower respiratory tract. Am J Surg Pathol. 1995 Mar;19(3):284–296. doi: 10.1097/00000478-199503000-00006. [DOI] [PubMed] [Google Scholar]
  26. Ng C. S., Chan J. K., Lo S. T. Expression of natural killer cell markers in non-Hodgkin's lymphomas. Hum Pathol. 1987 Dec;18(12):1257–1262. doi: 10.1016/s0046-8177(87)80410-0. [DOI] [PubMed] [Google Scholar]
  27. Ohno T., Yamaguchi M., Oka K., Miwa H., Kita K., Shirakawa S. Frequent expression of CD3 epsilon in CD3 (Leu 4)-negative nasal T-cell lymphomas. Leukemia. 1995 Jan;9(1):44–52. [PubMed] [Google Scholar]
  28. Phillips J. H., Hori T., Nagler A., Bhat N., Spits H., Lanier L. L. Ontogeny of human natural killer (NK) cells: fetal NK cells mediate cytolytic function and express cytoplasmic CD3 epsilon,delta proteins. J Exp Med. 1992 Apr 1;175(4):1055–1066. doi: 10.1084/jem.175.4.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Ratech H., Burke J. S., Blayney D. W., Sheibani K., Rappaport H. A clinicopathologic study of malignant lymphomas of the nose, paranasal sinuses, and hard palate, including cases of lethal midline granuloma. Cancer. 1989 Dec 15;64(12):2525–2531. doi: 10.1002/1097-0142(19891215)64:12<2525::aid-cncr2820641220>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  30. Strickler J. G., Meneses M. F., Habermann T. M., Ilstrup D. M., Earle J. D., McDonald T. J., Chang K. L., Weiss L. M. Polymorphic reticulosis: a reappraisal. Hum Pathol. 1994 Jul;25(7):659–665. doi: 10.1016/0046-8177(94)90298-4. [DOI] [PubMed] [Google Scholar]
  31. Suzumiya J., Takeshita M., Kimura N., Kikuchi M., Uchida T., Hisano S., Eura Y., Kozuru M., Nomura Y., Tomita K. Expression of adult and fetal natural killer cell markers in sinonasal lymphomas. Blood. 1994 Apr 15;83(8):2255–2260. [PubMed] [Google Scholar]
  32. Takeuchi Y., Nishimura T., Gao X. H., Watanabe K., Akatsuka A., Shinkai Y., Okumura K., Habu S. Perforin is expressed in CTL populations generated in vivo. Immunol Lett. 1992 Feb;31(2):183–187. doi: 10.1016/0165-2478(92)90144-d. [DOI] [PubMed] [Google Scholar]
  33. Tao Q., Chiang A. K., Srivastava G., Ho F. C. TCR-CD56+CD2+ nasal lymphomas with membrane-localized CD3 positivity: are the CD3+ cells neoplastic or reactive? Blood. 1995 May 15;85(10):2993–2996. [PubMed] [Google Scholar]
  34. Tao Q., Ho F. C., Loke S. L., Srivastava G. Epstein-Barr virus is localized in the tumour cells of nasal lymphomas of NK, T or B cell type. Int J Cancer. 1995 Jan 27;60(3):315–320. doi: 10.1002/ijc.2910600306. [DOI] [PubMed] [Google Scholar]
  35. Taylor C. R. An immunohistological study of follicular lymphoma, reticulum cell sarcoma and Hodgkin's disease. Eur J Cancer. 1976 Jan;12(1):61–75. doi: 10.1016/0014-2964(76)90125-0. [DOI] [PubMed] [Google Scholar]
  36. Tokunaga M., Imai S., Uemura Y., Tokudome T., Osato T., Sato E. Epstein-Barr virus in adult T-cell leukemia/lymphoma. Am J Pathol. 1993 Nov;143(5):1263–1269. [PMC free article] [PubMed] [Google Scholar]
  37. Tsunoda R., Terashima K., Takahashi K., Kojima M. An ultrastructural study with enzyme-labeled antibody technique on immunoglobulin-containing cells in human tonsils, especially in germinal centers. Acta Pathol Jpn. 1978 Jan;28(1):53–75. doi: 10.1111/j.1440-1827.1978.tb01250.x. [DOI] [PubMed] [Google Scholar]
  38. Wong K. F., Chan J. K., Ng C. S., Lee K. C., Tsang W. Y., Cheung M. M. CD56 (NKH1)-positive hematolymphoid malignancies: an aggressive neoplasm featuring frequent cutaneous/mucosal involvement, cytoplasmic azurophilic granules, and angiocentricity. Hum Pathol. 1992 Jul;23(7):798–804. doi: 10.1016/0046-8177(92)90350-c. [DOI] [PubMed] [Google Scholar]
  39. Wu T. C., Mann R. B., Epstein J. I., MacMahon E., Lee W. A., Charache P., Hayward S. D., Kurman R. J., Hayward G. S., Ambinder R. F. Abundant expression of EBER1 small nuclear RNA in nasopharyngeal carcinoma. A morphologically distinctive target for detection of Epstein-Barr virus in formalin-fixed paraffin-embedded carcinoma specimens. Am J Pathol. 1991 Jun;138(6):1461–1469. [PMC free article] [PubMed] [Google Scholar]
  40. Yamaguchi M., Ohno T., Oka K., Nishii K., Kawakami K., Miwa H., Kita K., Shirakawa S. Discordant reaction of Leu4 and rabbit anti-human CD3 epsilon in sinonasal 'T'-cell lymphoma. Int J Hematol. 1993 Dec;59(1):25–30. [PubMed] [Google Scholar]
  41. Young J. D., Hengartner H., Podack E. R., Cohn Z. A. Purification and characterization of a cytolytic pore-forming protein from granules of cloned lymphocytes with natural killer activity. Cell. 1986 Mar 28;44(6):849–859. doi: 10.1016/0092-8674(86)90007-3. [DOI] [PubMed] [Google Scholar]

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