Necrotizing Lymphadenitis

Synonyms: Kikuchi's Lymphadenitis, Kikuchi- Fujimoto Disease

Definition

A benign and self-limiting lymphadenopathy of unknown etiology characterized by large areas of necrosis and karyorrhectic debris.

Clinical Features

Most common in:
- Japan
- other Asian countries1,2
Usually:
- young women
- cervical lymphadenopathy:
  - persistent
  - painless
  - modest dimensions
May be fever
Generally benign and self-limited
Sometimes:
- accompanying skin lesions 3,4
Isolated fatal cases 5
Rare associations:
- following diffuse large B-cell lymphoma6
- stroma-rich Castleman's disease7
- lupus erythematosus

Pathogenesis

Necrosis due to cytoxic lymphocyte-mediated apoptotic cell death8,9
Etiology unknown
Early suggestion that Toxoplasma may be involved not substantiated
Epstein–Barr virus (EBV), human herpesvirus (HHV)-6, HHV-8, and other viruses implicated:
- evidence not conclusive 10–13

Histopathology

Paracortical necrotizing lesions (Fig. 1
Fig. 1: Necrotizing lymphadenitis. Low-power view showing necrotizing change centered in the subcapsular region.
):
- focal
- well circumscribed
Abundant karyorrhectic debris (Fig. 2
Fig. 2: Necrotizing lymphadenitis. High-power view showing the boundary between an area of karyorrhexis/pyknosis and an area of karyolysis.
)
Scattered fibrin deposits
Collections of large mononuclear cells14
Very scanty:
- plasma cells
- neutrophils15,16
Plasmacytoid monocytes:
- often numerous 17,18
- if diffuse growth may simulate malignant lymphoma 19–21
Occasionally:
- prominent secondary xanthomatous reaction 22
Electron microscopy:
- tubuloreticular structures and intracytoplasmic rodlets:
  - similar to those in lupus erythematosus23

Diagnosis

Important diagnostic features:
- very scanty plasma cells and neutrophils15,16
- in material from fine needle aspiration:
  - medium-sized cells with eccentrically placed nuclei consistent with plasmacytoid monocytes 24

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Necrotizing Lymphadenitis

Malignant lymphoma with secondary necrosis

References

1 Chan JKC, Saw D. Histiocytic necrotizing lymphadenitis (Kikuchi's disease). A clinicopathologic study of 9 cases. Pathology. 1986;18:22–28.

2 Lin HC, Su CY, Huang CC, Hwang CF, Chien CY. Kikuchi's disease: a review and analysis of 61 cases. Otolaryngol Head Neck Surg. 2003;128:650–653.

3 Kuo TT. Cutaneous manifestation of Kikuchi's histiocytic necrotizing lymphadenitis. Am J Surg Pathol. 1990;14:872–876.

4 Spies J, Foucar K, Thompson CT, LeBoit PE. The Histopathology of cutaneous lesions of Kikuchi's disease (necrotizing lymphadenitis): a report of five cases. Am J Surg Pathol. 1999;23:1040–1047.

5 Chan JK, Wong KC, Ng CS. A fatal case of multicentric Kikuchi's histiocytic necrotizing lymphadenitis. Cancer. 1989;63:1856–1862.

6 Yoshino T, Mannami T, Ichimura K, Takenata K, Nose S, Yamadori I, et al. Two cases of histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto's disease) following diffuse large B-cell lymphoma. Hum Pathol. 2000;31:1328–1331.

7 Chan JK, Luk SC, Ho PL. Stroma-rich Castleman's disease with superimposed Kikuchi's lymphadenitis-like changes. Int J Surg Pathol. 1996-97;4:197–202.

8 Felgar RE, Furth EE, Wasik MA, Gluckman SJ, Salhany KE. Histiocytic necrotizing lymphadenitis (Kikuchi's disease): in situ end-labeling, immunohistochemical, and serologic evidence supporting cytotoxic lymphocyte-mediated apoptotic cell death. Mod Pathol. 1997;10:231–241.

9 Takakuwa T, Ohnuma S, Koike J, Hoshikawa M, Koizumi H. Involvement of cell-mediated killing in apoptosis in histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease). Histopathology. 1996;28:41–48.

10 Chiu CF, Chow KC, Lin TY, Tsai MH, Shih CM, Chen LM. Virus infection in patients with histiocytic necrotizing lymphadenitis in Taiwan, detection of Epstein virus, type 1 human T-cell lymphotropic virus, and parvovirus B19. Am J Clin Pathol. 2000;113:774–781.

11 Hollingsworth HC, Peiper SC, Weiss LM, Raffeld M, Jaffe ES. An investigation of the viral pathogenesis of Kikuchi-Fujimoto disease. Lack of evidence for Epstein–Barr virus or human herpesvirus type 6 as the causative agents. Arch Pathol Lab Med. 1994;118:134–140.

12 Huh J, Kang GH, Gong G, Kim SS, Ro JY, Kim CW. Kaposi's sarcoma-associated herpesvirus in Kikuchi's disease. Hum Pathol. 1998;29:1091–1096.

13 Sumiyoshi Y, Kikuchi M, Ohshima K, Yoneda S, Kobari S, Takeshita M, et al. Human herpesvirus-6 genomes in histiocytic necrotizing lymphadenitis (Kikuchi's disease) and other forms of lymphadenitis. Am J Clin Pathol. 1993;99:609–614.

14 Dorfman RF, Berry GJ. Kikuchi's histiocytic necrotizing lymphadenitis. An analysis of 108 cases with emphasis on differential diagnosis. Semin Diagn Pathol. 1988;5:329–345.

15 Pileri S, Kikuchi M, Lennert K. Histiocytic necrotizing lymphadenitis without granulocytic infiltration. Virchows Arch [A]. 1982;395:257–271.

16 Turner RR, Martin J, Dorfman RF. Necrotizing lymphadenitis. A study of 30 cases. Am J Surg Pathol. 1983;7:115–123.

17 Facchetti F, de Wolf-Peeters C, van den Oord JJ, de Vos R, Desmet VJ. Plasmacytoid monocytes (so-called plasmacytoid T-cells) in Kikuchi's lymphadenitis. An immunohistologic study. Am J Clin Pathol. 1989;92:42–50.

18 Sumiyoshi Y, Kikuchi M, Takeshita M, Ohshima K, Masuda Y, Parwaresch MR. Immunohistologic studies of Kikuchi's disease. Hum Pathol. 1993;24:1114–1119.

19 Chamulak GA, Brynes RK, Nathwani BN. Kikuchi-Fujimoto disease mimicking malignant lymphoma. Am J Surg Pathol. 1990;14:514–523.

20 Menasce LP, Banerjee SS, Edmondson D, Harris M. Histiocytic necrotizing lymphadenitis (Kikuchi–Fujimoto disease): continuing diagnostic difficulties. Histopathology. 1998;33:248–254.

21 Tsang WY, Chan JK, Ng CS. Kikuchi's lymphadenitis. A morphologic analysis of 75 cases with special reference to unusual features. Am J Surg Pathol. 1994;18:219–231.

22 Kuo TT. Kikuchi's disease (histiocytic necrotizing lymphadenitis). A clinicopathologic study of 79 cases with an analysis of histologic subtypes, immunohistology, and DNA ploidy. Am J Surg Pathol. 1995;19:798–809.

23 Eimoto T, Kikuchi M, Mitsui T. Histiocytic necrotizing lymphadenitis. An ultrastructural study in comparison with other types of lymphadenitis. Acta Pathol Jpn. 1983;33:863–879.

24 Tsang WY, Chan JK. Fine needle aspiration cytologic diagnosis of Kikuchi's lymphadenitis. A report of 27 cases. Am J Clin Pathol. 1994;102:454–458.

Last updated: 29 Jul 2006