Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience

AM Kovrigina

National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

For correspondence: Prof. Alla Mikhailovna Kovrigina, PhD in Biology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail:

For citation: Kovrigina AM. Comparative Pathomorphology of Lymph Node Changes in Kikuchi-Fujimoto and Autoimmune Diseases with Lymphadenopathy: Own Experience. Clinical oncohematology. 2021;14(1):80–90. (In Russ).

DOI: 10.21320/2500-2139-2021-14-1-80-90


Background. Pathomorphological analysis of lymph node tissues in immune-mediated lymphadenopathies commonly presupposes differential diagnosis with tumors of lymphoid and myeloid tissues with partial lesions in lymph nodes. Besides, further study is required on pathogenetic relationship between autoimmune diseases with lymphadenopathy and Kikuchi-Fujimoto disease (KFD) with morphological substrate characterized by histiocytic necrotizing lymphadenitis.

Aim. To compare, based on biopsy material, morpho-immunohistochemical characteristics of changes in lymph node tissues in patients with pathomorphological diagnosis of KFD and in patients with autoimmune diseases with lymphadenopathy, i.e. systemic lupus erythematosus (SLE) and adult Still’s disease (ASD).

Materials & Methods. Morphological and immunohistochemical analyses were carried out on lymph node biopsies of 20 patients, 16 out of them with KFD (men/women 15:1, median age 26.5 years, range 18–47 years; in 44 % of cases lesions were only in cervical lymph nodes). In 2 female patients (aged 19 and 33 years) SLE was diagnosed based on clinical and laboratory data, and 2 patients (a woman aged 43 years and a man aged 25 years) were diagnosed with ASD.

Results. Morphological and immunohistochemical analyses detected three major cell populations similar in KFD and SLE and probably reflecting pathogenetic relationship of these diseases: histiocytes expressing myeloperoxidase (MPO+), CD123+ plasmacytoid dendritic cells, cytotoxic CD8+ T-cells, and granzyme B+. In 55 % of KFD cases and 2 SLE cases there were many activated CD30+ lymphoid cells clustered and scattered in the areas of cytotoxic T-cells.

Conclusion. To exclude SLE during subsequent additional examination of patients with morphological substrate characterized by histiocytic necrotizing lymphadenitis it is reasonable to use the term “Kikuchi-like changes” instead of KFD. When the data of immunohistochemical analysis in KFD, SLE, and ASD patients are compared, MPO+ histiocytes in lymph node tissue can serve as diagnostic immunohistochemical marker of immunoinflammatory process. If they are detected, differential diagnosis with myeloid sarcoma is required. CD30 expression by activated cytotoxic lymphoid cells was identified in SLE and in 55 % of KFD cases, which is another important common diagnostic characteristic of the substrate of two diseases (KFD and SLE) and requires differential diagnosis with anaplastic large-cell lymphoma and Hodgkin’s lymphoma. Within the analyzed group of 20 patients morphological substrate of lymph nodes in 2 ASD patients differed in its morphological and immunohistochemical parameters from that in KFD and SLE patients and was characterized by expanded paracortex and morpho-immunohistochemical characteristics of extrafollicular B-cell activation.

Keywords: morphology, immunohistochemistry, Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis, systemic lupus erythematosus, adult Still’s disease, CD30, myeloperoxidase.

Received: July 30, 2020

Accepted: December 2, 2020

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  1. Jeon YK, Paik JH, Park SS, et al. Spectrum of lymph node pathology in adult onset Still’s disease; analysis of 12 patients with one follow up biopsy. J Clin Pathol. 2004;57(10):1052–6. doi: 10.1136/jcp.2004.018010.
  2. Cush JJ, Medsger TA, Christy WC, et al. Adult-onset Still’s disease. Arthrit Rheum. 1987;30(2):186–94. doi: 10.1002/art.1780300209.
  3. Kojima M, Nakamura S, Itoh H, et al Systemic Lupus Erythematosus (SLE) Lymphadenopathy Presenting with Histopathologic Features of Castleman’ Disease: A Pathologic Study of Five Cases. Pathol Res Pract. 1997;193(8):565–71 doi: 10.1016/S0344-0338(97)80015-5.
  4. Graef E, Magliulo D, Hollie N, et al. Clinical Characteristics of Lymphadenopathy in Systemic Lupus Erythematous: A Case Control Study from a Tertiary Care Center. Arthrit Rheumatol. 2019;71(Suppl 10): Abstract.
  5. Kikuchi M. Lymphadenitis showing focal reticulum cell hyperplasia with nuclear debris and phagocytosis. Nippon Ketsueki Gakkai Zasshi. 1972;35:379–80.
  6. Fujimoto Y, Kozima Y, Yamaguchi K. Cervical subacute necrotizing lymphadenitis. A new clinicopathological entity. Naika. 1972;20:920–7.
  7. Pileri S, Kikuchi M, Helbron D, Lennert K. Histiocytic necrotizing lymphadenitis without granulocytic infiltration. Virch Arch Pathol Anat. 1982;395(3):257–71. doi: 10.1007/bf00429352.
  8. Turner RR, Martin J, Dorfman RF. Necrotizing lymphadenitis. A study of 30 cases. Am J Surg Pathol. 1983;7(2):115–23.
  9. Feller AC, Lennert K, Stein H, et al. Immunohistology and etiology of histiocytic necrotizing lymphadenitis: report of three instructive cases. Histopathology. 1983;7(6):825–39. doi: 1111/j.1365–2559.1983.tb02299.x.
  10. Dorfman RF. Histiocytic necrotizing lymphadenitis of Kikuchi and Fujimoto. Arch Pathol Lab Med. 1987;111(11):1026–9.
  11. Sumiyoshi Y, Kikuchi M, Ohshima K, et al Human herpesvirus-6 genomes in histiocytic necrotizing lymphadenitis (Kikuchi’s disease) and other forms of lymphadenitis. Am J Clin Pathol. 1993;99(5):609–14. doi: 10.1093/ajcp/99.5.609.
  12. Huh J, Kang GH, Gong G, et al. Kaposi’s sarcoma associated herpesvirus in Kikuchi’s disease. Hum Pathol. 1998;29(10):1091–6. doi: 10.1016/S0046-8177(98)90419-1.
  13. Chiu CF, Chow KC, Lin TY, et al. Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan. Detection of Epstein-Barr virus, type 1 human T-cell lymphotropic virus, and parvovirus B19. Am J Clin Pathol. 2000;113(6):774–81. doi: 10.1309/1A6Y-YCKP-5AVF-QTYR.
  14. Adoue D, Rauzy O, Rigal-Huguet F. Syndrome de Kikuchi, infection a Cytomegalovirus et maladie lupique. Rev Med Intern. 1997;18(4):338–42. doi: 10.1016/s0248-8663(97)84023-4.
  15. Imamura M, Ueno H, Matsuura A, et al. An ultrastructural study of subacute necrotizing lymphadenitis. Am J Pathol. 1982;107(3):292–9.
  16. Meyer O, Kahn MF, Grossin M, et al. Parvovirus B19 infection can induce histiocytic necrotizing lymphadenitis (Kikuchi’s disease) associated with systemic lupus erythematosus. Lupus. 1991;1(1):37–41. doi: 10.1177/096120339100100107.
  17. Lamzaf L, Harmouche H, Maamar M, et al. Kikuchi-Fujimoto disease: Report of 4 cases and review of the literature. Eur Ann Otorhinolaryngol Head Neck Dis. 2014;131(6):329–32. doi: 10.1016/j.anorl.2013.01.007.
  18. Ferrao E, Grade M, Arez L, et al. Kikuchi-Fujimoto’s disease associated to a systemic erythematosus lupus: a clinical case. Eur J Intern Med. 2003;14:S76. doi: 10.1016/S0953-6205(03)91417-8.
  19. Merwald-Fraenk H, Wiesent F, Dorfler R, et al. Lymphadenitis und systemischer Lupus erythematodes. Z Rheumatol. 2016,75(10):1028–31. doi: 10.1007/s00393-016-0170-7.
  20. Dumas G, Prendki V, Haroche J, et al. Kikuchi-Fujimoto disease: retrospective study of 91 cases and review of the literature. Medicine (Baltimore). 2014;93(24):372–82. doi: 10.1097/0000000000000220.
  21. Kishimoto K, Tate G, Kitamura T, et al. Cytologic features and frequency of plasmacytoid dendritic cells in the lymph nodes of patients with histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease). Diagn Cytopathol. 2010;38(7):521–6. doi: 10.1002/dc.21265.
  22. Lennert K, Remmele W. Karyometric research on lymph node cells in man. I. Germinoblasts, lymphoblasts & lymphocytes. Acta Haematol. 1958;19(2):99–113. doi: 10.1159/000205419.
  23. Ronnblom L, Alm GV. A pivotal role for the natural interferon alpha-producing cells (plasmacytoid dendritic cells) in the pathogenesis of lupus. J Exp Med. 2001;194(12):F59–F64. doi: 10.1084/jem.194.12.f59.
  24. Pabon-Porras MA, Molina-Rios S, Florez-Suarez JB. Rheumatoid arthritis and systemic lupus erythematosus: Pathophysiological mechanisms related to innate immune system. SAGE Open Med. 2019;7:1–24. doi: 10.1177/2050312119876146.
  25. Barrat FJ, Su LJ. A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection. Exp Med. 2019;216(9):1974–85. doi: 10.1084/jem.20181359.
  26. Rollins-Raval MA, Marafioti T, Swerdlow SH, Roth CG. The number and growth pattern of plasmacytoid dendritic cells vary in different types of reactive lymph nodes: an immunohistochemical study. Hum Pathol. 2013;44(6):1003–10. doi: 10.1016/j.humpath.2012.08.020.
  27. Katsiari CG, Liossis S-NC, Sfikakis PP. The Pathophysiologic Role of Monocytes and Macrophages in Systemic Lupus Erythematosus: A Reappraisal. Semin Arthrit Rheum. 2010;39(6):491–503. doi: 10.1016/j.semarthrit.2008.11.002.
  28. Ma W-T, Gao F, Gu K, et al. The Role of Monocytes and Macrophages in Autoimmune Diseases: A Comprehensive Review. Front Immunol. 2019;10:1140. doi: 10.3389/fimmu.2019.01140.
  29. Pileri SA, Facchetti F, Ascani S, et al. Myeloperoxidase expression by histiocytes in Kikuchi’s and Kikuchi-like lymphadenopathy. Am J Pathol. 2001;159(3):915–24. doi: 10.1016/S0002-9440(10)61767-1.
  30. Strzepa A, Pritchard KA, Dittel BN. Myeloperoxidase: A new player in autoimmunity. Cell Immunol. 2017;317:1–8. doi: 10.1016/j.cellimm.2017.05.002.
  31. Pilichowska ME, Pinkus JL, Pinkus GS. Histiocytic Necrotizing Lymphadenitis (Kikuchi-Fujimoto Disease). Am J Clin Pathol. 2009;131(2):174–82. doi: 10.1309/AJCP7V1QHJLOTKKJ.
  32. Jang SJ, Min JH, Kim D, Yang WI. Myeloperoxidase positive histiocytes in subacute necrotizing lymphadenitis express both CD11c and CD163. Basic Appl Pathol. 2011;4(4):110–5. doi: 10.1111/j.1755-9294.2011.01114.x.
  33. Andersen MH, Schrama D, Straten PT, et al. Cytotoxic T cells. J Invest Dermatol. 2006;126(1):32–41. doi: 10.1038/sj.jid.5700001.
  34. Suarez-Fueyo A, Bradley SJ, Tsokos GC. T cells in Systemic Lupus Erythematosus. Curr Opin Immunol. 2016;43:32–8. doi: 10.1016/j.coi.2016.09.001.
  35. Tabata T, Takata K, Miyata-Takata T, et al. Characteristic Distribution Pattern of CD30-positive Cytotoxic T Cells Aids Diagnosis of Kikuchi-Fujimoto Disease. Appl Immunohistochem Mol Morphol. 2018;26(4):274–82. doi: 10.1097/pai.0000000000000411.
  36. Salman-Monte TC, Ruiz JP, Almirall M, et al. Lymphadenopathy syndrome in systemic lupus erythematosus: Is it Kikuchi-Fujimoto disease? Reumatol Clin. 2017;13(1):55–6. doi: 10.1016/j.reumae.2016.04.004.
  37. Sukswai N, Jung HR, Amr SS. Immunopathology of Kikuchi-Fujimoto Disease: A reappraisal using novel immunohistochemistry markers. Histopathology. 2020;77(2):262–74. doi: 10.1111/his.14050.