Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

Xavier Bosch, MD; Antonio Guilabert, MD; Rosa Miquel, MD; Elias Campo, MD

Am J Clin Pathol. 2004;122(1)

Abstract and Introduction

Abstract

To determine the clinicopathologic significance of Kikuchi-Fujimoto disease (KFD) and review the literature on this condition, we conducted a MEDLINE search of English-language articles published between 1972 and December 2003.

KFD has a worldwide distribution, and Asiatic people have a higher prevalence. Its pathogenesis remains controversial. Patients are young and seek care because of acute tender, cervical lymphadenopathy and low-grade fever. Histologic findings include paracortical areas of coagulative necrosis with abundant karyorrhectic debris. Karyorrhectic foci consist of various types of histiocytes, plasmacytoid monocytes, immunoblasts, and small and large lymphocytes. There is an abundance of T cells with predominance of CD8+ over CD4+ T cells. Differential diagnosis includes lymphoma, lymphadenitis associated with systemic lupus erythematosus, and even adenocarcinoma. KFD is an uncommon, self-limited, and perhaps underdiagnosed process with an excellent prognosis. Accurate clinicopathologic recognition is crucial, particularly because KFD can be mistaken for malignant lymphoma.

Introduction

Kikuchi-Fujimoto disease (KFD; so-called histiocytic necrotizing lymphadenitis) is an enigmatic, benign, and self-limited syndrome characterized by regional lymphadenopathy with tenderness, usually accompanied by mild fever and night sweats. Initially described in Japan, KFD was first reported almost simultaneously by Kikuchi and by Fujimoto and associates in 1972 as a lymphadenitis with focal proliferation of reticular cells accompanied by numerous histiocytes and extensive nuclear debris.^[1] Clinicians and pathologists are unfamiliar with this entity. We provide a comprehensive review of KFD with special emphasis on the clinicopathologic significance of this condition.

1 2 3 4 5 6 7 8 9 10 11

Next Section

Cite this: Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review - Medscape - Jul 01, 2004.

Table 1. Microorganisms More Frequently Reported to Have a Causative Role in KFD
Microorganism	Supportive Data	Contrary Data
Yersinia enterocolitica	Positive IIF assay applied to lymphatic tissue in 1 case^[24]; positive serologic results reported^[23]	Histologic features of mesenteric lymphadenitis differ from those of KFD
Toxoplasma gondii	Positive serologic results reported^[25]	Histologic features of toxoplasmic lymphadenitis differ from those of KFD
Epstein-Barr virus	Detected by ISH^[19,26] and PCR^[19,27]	Not detected by ISH,^[27,28,29] SB,^[30] or PCR^[31]; 50% positive detection in KFD but also 50% positive detection in control samples by PCR^[30]
HHV-6	Detected by PCR^[32]	Not detected by PCR^[27] or SB^[32]; 100% positive detection in KFD but also 50% positive detection in control samples by ISH^[32]
HHV-8	23% incidence rate by PCR^[33]	Not detected in KFD, but 100% detection in control samples by PCR^[29]
HTLV-1	Positive serologic results reported^[34,35]	Not detected by ISH or PCR^[26]
Hepatitis B virus	None	Not detected by ISH^[28]
Parvovirus B19	Detected by immunohistochemical analysis in 1 case^[36]	Not detected by immunohistochemical analysis^[26]
Herpes simplex, CMV, varicella zoster	None	Not detected by PCR^[30,31]

CMV, cytomegalovirus; HHV, human herpesvirus; HTLV-1, human T-lymphotropic virus type 1; IIF, indirect immunofluorescence; ISH, in situ hybridization; KFD, Kikuchi-Fujimoto disease; PCR, polymerase chain reaction; SB, Southern blotting.

Table 2. Clues to the Differential Diagnosis of Kikuchi-Fujimoto Disease
Condition	Clinical Features	Histologic Features	Immunohistochemical and Genetic Features
SLE-associated lymphadenopathy	Elevation of ANA titers; SLE features in the follow-up	Hematoxylin bodies; Azzopardi phenomenon; sparse CD8 T cells; abundance of plasma cells
Herpes simplex-associated lymphadenopathy	Skin and mucous membranes have ulcerative lesions near sites of lymphadenopathy	Presence of neutrophils; viral inclusions; no striking polymorphous histiocytic infiltrate	Histiocytes MPO
Non-Hodgkin lymphoma		No striking polymorphous histiocytic infiltrate; most T-cell lymphomas CD4+	Histiocytes MPO-; T-cell arrangement gene-positive
Plasmacytoid T-cell leukemia	Elderly men who have or will develop MML	Proliferation of PC-like cells; no striking polymorphous histiocytic infiltrate	PC-like cells MPO
Kawasaki disease	Mostly children younger than 5 y; typical skin involvement	Geographic necrosis; fibrinoid thrombosis; no striking polymorphous histiocytic infiltrate; presence of neutrophils; PC absent or not prominent
Nodal colonization by AML		No striking polymorphous histiocytic infiltrate; lacking CD8 T cells	CD34+; neutrophilic elastase-positive; HLA-DR+
Metastatic adenocarcinoma		Signet-ring cells containing mucin rather than nuclear debris	Presence of cytokeratin; absence of histiocyte-associated antigens
Infectious lymphadenitis		Occasional presence of granulomas; usual presence of polymorphonuclear leukocytes	Histiocytes MPO

AML, acute myeloid leukemia; ANA, antinuclear antibodies; MML, myelomonocytic leukemia; MPO, myeloperoxidase; PC, plasmacytoid cells; SLE, systemic lupus erythematosus.

Comments

Commenting is limited to medical professionals. To comment please Log-in.

Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.

processing....

Enigmatic Kikuchi-Fujimoto Disease: A Comprehensive Review

Abstract and Introduction

Abstract

Introduction

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Comments

Email This

Feedback