This inflammatory process of the lymph nodes was first described as subacute necrotizing lymphadenitis. It is most common in Asia but has been described worldwide. It is most common in women with a mean age of 30 years. It presents with cervical lymphadenopathy usually with fever, sore throate, weight loss, chills, myalgias, arthralgias, splenomegaly, and skin rash. The disease usually resolves within 1-3 months. Recurrence is rare and death is rare.
These atypical mononuclear cells are probably transformed monocytes. The pathologist is faced with the task of differentiating these histologic changes from infectious causes as well as a lymphoma. Infectious simulators include Toxoplasmosis, Yersinia enterocolitica, Bartonella henselae, HIV-1, and Epstein-Barr virus. Special stains for microorganisms including Gram, Giemsa, Ziehl-Neelson, and Warthin-Starry stain should be performed and are characteristically negative. Features that are helpful in distinguishing this disease from lymphoma include partial effacement of the lymph node with patent sinuses, reactive histiocytes lacking a starry-sky pattern, and a low mitotic rate.
The cause has long been speculated to be of an infectious or autoimmune origin because of the symptoms. Various organisms including Human Herpes virus 6 and 8, parvovirus B19, and Epstein-Barr virus (EBV). A recent study using three independent techniques found 9 out of 10 cases positive for EBV. The techniques were by in-situ hybridization, DNA polymerase chain reaction, and immunohistochemistry.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION SYNONYMS Subacute necrotizing lymphadenitis
AGE RANGE-MEDIAN 30-50 years SEX (M:F) Females NEPAL
Kikuchi-Fujimoto disease in Nepal: a study of 6 cases.
Adhikari RC, Sayami G, Lee MC, Basnet RB, Shrestha PK, Shrestha HG.
Department of Pathology, Tribhuvan University Teaching Hospital, Kathmandu, Nepal.
Arch Pathol Lab Med. 2003 Oct;127(10):1345-8. Abstract quote
CONTEXT: Kikuchi-Fujimoto disease is a benign disorder, predominantly affecting young women with a predilection for cervical lymphadenopathy. Although the disease has been recognized worldwide, to our knowledge no cases have been reported previously from Nepal.
OBJECTIVES: To determine the prevalence of Kikuchi-Fujimoto disease in Nepal and to analyze clinicopathologic features.
METHODS: We reviewed 6 cases of Kikuchi-Fujimoto disease recorded at 3 different hospitals in Nepal during a period from June 1998 to June 2002. Clinical data and histopathology are presented.
RESULTS: This study included 5 females and 1 boy, aged 13 to 32 years. These patients presented with prolonged fever and lymphadenopathy. The 5 female patients had cervical lymphadenopathy, and the boy had axillary lymphadenopathy. Complete blood counts revealed raised erythrocyte sedimentation rates in all patients and anemia in 2 patients. The size of excised lymph nodes (in greatest dimension) ranged from 1.5 to 5 cm. Typical histologic features were seen, namely, architectural effacement due to presence of pale nodular lymphohistiocytic foci with karyorrhectic debris, coagulation necrosis, eosinophilic debris, and absence of granulocytic infiltration. In a follow-up of the cases, disease recurrence was not found.
CONCLUSION: Our study emphasizes that Kikuchi-Fujimoto disease should be considered as one of the differential diagnoses in patients with prolonged fever and cervical lymphadenopathy and that it should be differentiated from tuberculous lymphadenitis in regions where tuberculosis is prevalent.
DISEASE ASSOCIATIONS CHARACTERIZATION BREAST IMPLANT
Kikuchi's histiocytic necrotizing lymphadenitis associated with ruptured silicone breast implant.
Sever CE, Leith CP, Appenzeller J, Foucar K.
Pathology Associates, Presbyterian Hospital, Albuquerque, NM, USA.
Arch Pathol Lab Med 1996 Apr;120(4):380-5 Abstract quote
OBJECTIVE--In this report we explore the relationship between Kikuchi's necrotizing lymphadenitis (Kikuchi-Fujimoto disease, KD) and a leaky silicone breast implant. P
ATIENT--The simultaneous occurrence of KD and silicone lymphadenopathy in an axillary lymph node of a patient with a leaking silicone breast implant is reported. Since both KD and silicone implants have been implicated in autoimmune diseases, including systemic lupus erythematosus, serologic tests for antinuclear antibodies and rheumatoid factor were performed.
RESULTS--Axillary lymph nodes showed both silicone lymphadenopathy, as well as classic morphologic and immunophenotypic features of KD. Screening tests for systemic autoimmune disorders were within normal range, suggesting that the unusual Kikuchi's-like immune reaction in one axillary lymph node was localized. The patient has no evidence of progressive immunologic disorders 3 years later. Subsequent lymph node biopsies showed silicone adenopathy with no evidence of KD.
CONCLUSIONS--Our findings indicate that silicone compounds may be associated with transient abnormal immune reactions and lend further support to the hypothesis that KD represents an exuberant T-cell-mediated immune response to a variety of nonspecific stimuli.
Two cases of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto's disease) following diffuse large B-cell lymphoma.
Yoshino T, Mannami T, Ichimura K, Takenaka K, Nose S, Yamadori I, Akagi T.
Department of Pathology, Internal Medicine Okayama University Medical School, Okayama, Japan.
Hum Pathol 2000 Oct;31(10):1328-31 Abstract quote
Histiocytic necrotizing lymphadenitis (HNL) is often mistaken for malignant lymphoma clinically and is also sometimes difficult to differentiate from lymphoma even histopathologically.
In this report, we describe the first 2 reported cases of HNL following non-Hodgkin's lymphomas. The patients were 27- and 30-year-old women who developed cervical and axillary lymph node swellings, respectively, in the course of remission of diffuse large B-cell lymphoma. The affected lymph nodes showed the typical histology of HNL: irregular-shaped "necrotic" foci with histiocytes engulfing apoptotic bodies intermingled with large-sized blastic lymphocytes.
These findings mimicked the partial involvement of large-cell lymphoma. However, the blastic cells were almost exclusively T cells, and numerous apoptotic bodies were present, which excluded the possibility of recurrence of diffuse large B-cell lymphoma.
Spontaneous clearance of psoriasis during the course of Kikuchi-Fujimoto disease.
Kato A, Kono T, Ishii M, Wakasa K, Taniguchi S.
Department of Dermatology, Osaka City University Medical School, Japan.
J Am Acad Dermatol 2002 Nov;47(5 Suppl):S287-8 Abstract quote
A 23-year-old woman had psoriasis vulgaris since childhood. She noted painless enlargement of several lymph nodes in the cervical region accompanied by fever and malaise.
A biopsy specimen from a cervical lymph node revealed histiocytic necrotizing lymphadenitis without granulocyte infiltration (Kikuchi-Fujimoto disease), a rare and benign lymphadenopathy of unknown cause.
During the course of the Kikuchi-Fujimoto disease, the patient's recalcitrant psoriatic lesions spontaneously subsided. Complete clearance of psoriatic lesions continued until remission of Kikuchi-Fujimoto disease.
SYSTEMIC LUPUS ERYTHEMATOSUS
- Lupus. 2006;15(6):384-7. Abstract quote
Kikuchi-Fujimoto's disease (KFD), or histiocytic necrotizing lymphadenitis, is a benign and self-limited lymphadenitis commonly found in young women. It often shares clinical features with systemic lupus erythematosus (SLE), such as arthralgias, fever and leukopenia. The etiology of KFD remains unknown and controversial. Clinical course is favorable, with spontaneous remission in less than four months in almost all cases.
Herein, we present two cases. The former is a 53-year old woman presenting with cervical lymphadenopathy, arthralgia, pancytopenia and positive antinuclear antibody (ANA). Lymph node biopsy revealed histopathological features compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The latter patient was a 20-year old woman presenting with left cervical lympadenopathy, a butterfly rash that was reminiscent of SLE, and a positive antinuclear antibody.
Based upon clinical, histological and laboratory findings, the diagnosis of SLE was excluded. Careful attention should be paid to differentiating between KFD and SLE, because of their similar presentations, yet different clinical courses and therapeutic requirements.
- Kikuchi-Fujimoto's disease associated with systemic lupus erythematosus: case report and review of the literature.
Hospital Santa Izabel, Nucleo de Reumatologia da Bahia/Escola Bahiana de Medicina e Saude Publica (EBMSP), Praca Almeida Couto, 500, CEP 40.000-000 Nazare, Salvador, Bahia, Brazil.
- Clin Rheumatol. 2005 Feb;24(1):60-3. Epub 2004 Oct 27. Abstract quote
Kikuchi-Fujimoto's disease (KFD) or histiocytic necrotising lymphadenitis is a benign and self-limited disease, of unknown aetiology, which affects mainly young women. It presents with localised lymphadenopathy, predominantly in the cervical region, accompanied by fever and leukopenia in up to 50% of the cases. KFD has been rarely described in association with systemic lupus erythematosus (SLE), and its diagnosis can precede, postdate or coincide with the diagnosis of SLE.
We present a patient with the diagnosis of SLE characterised by arthritis, leukopenia, malar rash, photosensitivity and positive ANA, besides cervical lymphadenopathy whose biopsy was compatible with KFD, which improved after using prednisone. Although the presence of lymphadenopathy is not uncommon in SLE patients, particularly in the phases of disease activity, the concomitance with KFD has rarely been reported in the literature.
Its recognition is necessary because one can avoid laborious investigation for infectious and lymphoproliferative diseases.
- Ann Hematol. 2003 Mar;82(3):186-8. Epub 2003 Feb 22. Abstract quote
Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotizing lymphadenitis found mainly in young women. Patients typically present with cervical lymphadenopathy and fever and follow almost always a benign course with excellent outcomes. The etiology of KFD remains unknown and controversial although several viruses have been associated with this disease. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. Despite its usually benign course, several cases with fatal outcomes have been reported.
We report here a case of clinically aggressive KFD, which featured several autoimmune-related events and resulted in a fatal outcome. Autopsy studies showed characteristic findings of SLE, which suggests a remarkable link between SLE and KFD. Early and intensive immunosuppressive treatment may be the only option for patients who develop very aggressive forms of KFD in order to avoid a fatal outcome.
Kikuchi-Fujimoto necrotizing lymphadenitis associated with cutaneous lupus erythematosus: a case report.
Lopez C, Oliver M, Olavarria R, Sarabia MA, Chopite M.
Department of Dermatopathology, Instituto de Biomedicina, Hospital Vargas, Universidad Central de Venezuela, Caracas.
Am J Dermatopathol 2000 Aug;22(4):328-33 Abstract quote
Histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a rare entity, and even more rarely, it is associated with other diseases. In a few cases, the condition is associated with cutaneous lupus erythematosus (CLE). Histiocytic necrotizing lymphadenitis predominantly affects young women, who present with solitary or multiple cervical lymphadenopathy accompanied by symptoms such as fever, weight loss, sweating, or, in exceptional cases, hepatosplenomegaly. Laboratory examinations show normal or nonspecific results. The disease is of unknown origin, although a viral origin has been suggested, with the suspected agents including Epstein-Barr virus, herpesvirus type 6, and cytomegalovirus (CMV). Although the first and most of the more recent cases have been reported in Oriental patients, the disease has a wide geographic distribution. The clinical evolution is favorable, with spontaneous remission in less than 4 months in almost all cases.
We present a case of a 37-year-old woman from Peru who presented with cervical adenopathies on two occasions. Biopsy of a lymph node revealed a histopathologic picture compatible with Kikuchi-Fujimoto histiocytic necrotizing lymphadenitis. The adenopathy disappeared in a few months. A year later, she presented with a maculopapular rash in the nasal and malar regions. The results of the skin biopsy and immunofluorescence examination were compatible with chronic CLE. The results of the serology testing for CMV were positive. Treatment with chloroquine was initiated, with almost complete recovery by 5 months. No manifestations of systemic lupus erythematosus have occurred since. The epidemiologic, clinical, and anatomopathologic aspects as well as the differential diagnosis of this entity are reviewed.
Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's disease, associated with systemic lupus erythemotosus.
Martinez-Vazquez C, Hughes G, Bordon J, Alonso-Alonso J, Anibarro-Garcia A, Redondo-Martinez E, Touza-Rey F.
Infectious Diseases Unit, Hospital Xeral of Vigo, Santiago de Compostela Medical School, Spain..
QJM 1997 Aug;90(8):531-3 Abstract quote
Histiocytic necrotizing lymphadenitis, Kikuchi-Fujimoto's Disease (KFD), is a condition rarely associated with systemic lupus erythematosus (SLE). The diagnosis of KFD can precede, postdate or coincide with the diagnosis of SLE. Lymphadenopathy is a common clinical presentation of KFD and SLE, and is histologically indistinguishable in both conditions.
We describe two cases of KFD associated with SLE. The diagnosis of KFD in one case was made several years before the diagnosis of SLE, and the other was simultaneous. Both showed large lymphadenopathy, but neither fever nor neutropenia. Lymph-node biopsy showed necrosis, with proliferation of histiocytes and immunoblasts, paucity of neutrophils and absence of hemathoxilin bodies. Both patients responded favourably to steroid treatment.
Patients with KFD should be assessed for SLE and have long-term follow-up checking for development of SLE. KFD should be ruled out in SLE flare-up accompanied by lymphadenopathy.
PATHOGENESIS CHARACTERIZATION GENERAL
Spontaneous regression of Kikuchi lymphadenopathy with oligoclonal T-cell populations favors a benign immune reaction over a T-cell lymphoma.
Lin CW, Chang CL, Li CC, Chen YH, Lee WH, Hsu SM.
Department of Pathology, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei.
Am J Clin Pathol 2002 Apr;117(4):627-35 Abstract quote
To aid in the initial diagnosis of Kikuchi lymphadenitis and to assess whether the composition of the T cells might shed light on the pathogenesis, we used nested polymerase chain reaction tests followed by high-resolution gel electrophoresis to determine the pattern of T-cell antigen receptor rearrangement in 56 consecutive cases.
Except for 1 unusual case with recurrent lymphadenopathy, none had a monoclonal beta or gamma rearrangement. Eight cases had a polyclonal pattern at both beta and gamma loci, 20 cases had a mixed polyclonal beta and oligoclonal gamma pattern, and 27 cases had an oligoclonal pattern at both loci. The high frequency of oligoclonality did not indicate an early-stage T-cell lymphoma in evolution, as confirmed by spontaneous resolution of the lymphadenopathy in all cases within 6 months. Rather, it is consistent with reports of oligoclonal T cells in a variety of immune reactions.
We conclude that, in the vast majority of cases, absence of a monoclonal T-cell receptor rearrangement excludes the possibility of T-cell lymphoma, and the presence of an oligoclonal pattern implies a benign immune reaction.
Involvement of cell-mediated killing in apoptosis in histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease).
Takakuwa T, Ohnuma S, Koike J, Hoshikawa M, Koizumi H.
Department of Pathology, St Marianna University School of Medicine, Kawasaki, Japan.
Histopathology 1996 Jan;28(1):41-8 Abstract quote
Histiocytic necrotizing lymphadenitis, also called Kikuchi-Fujimoto (KF) disease, is a benign disorder characterized histologically by paracortical necrotic foci surrounded by histiocytic aggregates.
We analysed affected lymph node tissues from 34 patients with the disease in an attempt to elucidate its histogenesis. The 'necrotizing' cells showed typical apoptotic changes, including cell shrinkage and condensed and fragmented nuclei. Apoptotic bodies with a peculiar ultrastructure were demonstrated, and DNA fragmentation was detected in these cells by in situ end labelling. Immunostaining for the apoptosis-regulating proteins bcl-2, bax, c-myc and p53 failed to show their involvement in KF disease. However, perforin, a killer cell-specific cytolytic protein essential for provoking apoptosis in target cells, was found to be expressed abundantly by the infiltrating cells, which were thought to be cytotoxic T-lymphocytes. Perforin-expressing cells were present in the apoptotic foci of 28 of the 34 patients (82.4%). Virtually no cells containing perforin granules were present in non-pathological regions, lymph node tissues from control subjects with reactive or tuberculous lymphadenitis or those from patients with KF disease with negligible apoptosis.
Therefore, the 'necrosis' associated with KF disease appears to be attributable to trans apoptotic death of the killer cell target in the affected nodes. We propose that KF disease should be called apoptotic lymphadenitis.
Lack of human herpesvirus 8 and Epstein-Barr virus in Kikuchi's histiocytic necrotizing lymphadenitis.
George TI, Jones CD, Zehnder JL, Warnke RA, Dorfman RF.
Department of Pathology, Stanford University Medical Center, Stanford, CA.
Hum Pathol 2003 Feb;34(2):130-5 Abstract quote
Kikuchi's histiocytic necrotizing lymphadenitis is a self-limited disorder that typically involves the cervical lymph nodes of young women. Although a viral etiology has been postulated, a definitive viral agent has not been identified. Recent reports have suggested that human herpesvirus 8 (HHV 8) or Epstein-Barr virus (EBV) may play an etiologic role.
We investigated the presence of HHV 8 and EBV in archival tissue from 34 cases of Kikuchi's histiocytic necrotizing lymphadenitis. We examined 29 cases for HHV 8 using a nested polymerase chain reaction (PCR) on paraffin-embedded or frozen tissue, and 24 cases for EBV RNA using in situ hybridization (ISH) for EBER1. Controls included reactive lymph nodes from 8 adult women presenting with cervical or axillary lymphadenopathy. The study patients included 7 men and 27 women with a mean age of 28 years. All patients were previously healthy without evidence of immunocompromise and presented with cervical, axillary, or inguinal lymphadenopathy. Two cases exhibited EBV RNA by ISH; this was confirmed by PCR for EBV DNA. HHV 8 DNA was not amplified by nested PCR in any of the cases of Kikuchi's histiocytic necrotizing lymphadenitis or reactive lymph nodes; control PCR demonstrated the presence of amplifiable DNA in all cases.
These findings suggest that HHV 8 and EBV do not play causative roles in Kikuchi's histiocytic necrotizing lymphadenitis.
Human herpesviruses HHV-4 (EBV) and HHV-6 in Hodgkin's and Kikuchi's diseases and their relation to proliferation and apoptosis.
Krueger GR, Huetter ML, Rojo J, Romero M, Cruz-Ortiz H.
Department of Pathology and Laboratory Medicine, UT Houston Medical School, TX 77030, USA.
Anticancer Res 2001 May-Jun;21(3C):2155-61 Abstract quote
BACKGROUND: Human herpesviruses types 4 and 6 (EBV, HHV-6) are frequently found in Hodgkin 's disease (HD) and--to a certain extent--in Kikuchi-Fujimoto's disease (KFD). Both viruses are apparently related to proliferative and/or apoptotic processes as represented by HD or KFD respectively. OBJECTIVE: To correlate frequency and location of antigen- and DNA expression of both viruses in HD and KFD tissue sections in relation to markers for cell proliferation and apoptosis.
STUDY DESIGN: Archival lymph node biopsies from 103 patients with HD and 14 KFD patients were investigated immunohistologically for viral antigen expression (EBV LMP- 1: HHV-6 pl 10/60), Ki67/PCNR, marker for proliferation (MIB1)/p53 and WAF1 for apoptosis. Viral DNA was shown by in situ hybridization. Apoptosis was determined by ISEL and TUNEL techniques. RESULTS: HD is frequently infected by both EBV and HHV-6 while KFD tends to be infected only by HHV-6. EBV in HD is present in HD cells and in Reed-Sternberg cells (HD/RS cells), HHV-6 preferentially in lymphocytes and in histiocytes in both HD and in KFD. Proliferation marker Ki67 is found in lymphocytes and histiocytes of both diseases and in HD and RS cells in HD. Apoptosis is demonstrated in lymphocytes and histiocytes preferentially in KFD and to a lesser extent also in HD.
CONCLUSION: Although EBVand HHV-6 may not be openly oncogenic in HD and KFD, they may well influence the course of the disease. Dual infection in HD appears to support proliferative processes, i.e. a predominance of EBV effects. Single infection with HHV-6 in KFD instead appears to favor an apoptotic course. These effects are--according to the literature--possibly cytokine-mediated.
Histiocytic necrotizing lymphadenitis. A clinico-pathologic study of 45 cases with in situ hybridization for Epstein-Barr virus and hepatitis B virus.
Cho KJ, Lee SS, Khang SK.
Department of Anatomic Pathology, Korea Cancer Center Hospital, Seoul, Korea.
J Korean Med Sci 1996 Oct;11(5):409-14 Abstract quote
Forty-five cases of histiocytic necrotizing lymphadenitis (HNL) or Kikuchi-Fujimoto disease were reviewed clinico-pathologically and studied for Epstein-Barr virus (EBV) and hepatitis B virus (HBV) by in situ hybridization to assess their causative role.
Histologically, the lymph nodes typically showed relatively well defined paracortical lesions composed of large atypical mononuclear cells, histiocytes, and karyorrhectic nuclear debris. Mild to moderate degree of coagulation type necrosis was present in 24 cases. Clinical features did not vary greatly from previously described female preponderance, young age onset, subacute cervical lymphadenopathy, and frequent leukopenia, except for a few cases with recurrent disease over 8-9 years.
Serologic tests revealed EBV IgG antibody in one case, HBV surface antibody in 11 cases and HBV surface antigen in 2 cases. In situ hybridization was performed on 41 cases using internal repeat 1 fragment DNA and EBV-coded small RNA (EBER-1) for EBV, and pan-HBV DNA probe for HBV detection, and showed that all cases were negative for EBV or HBV genome.
Our results suggest EBV or HBV may not have causative role in the pathogenesis of HNL.
GROSS DISEASE/CLINICAL VARIANTS CHARACTERIZATION GENERAL
- Conn Med. 2006 Sep;70(8):491-4. Abstract quote
Kikuchi-Fujimoto disease (KFD) is a benign and self-limiting disease. The entity was first described in 1972 by Kikuchi and Fujimoto in Japan independently. KFD is prevalent in Asia, although it may be seen in a wide geographic distribution. It commonly affects young women.
Cervical lymphadenopathy is the most prominent sign and should be differentiated from lymphoproliferative, autoimmune, and infectious diseases.
We report a female patient with KFD presenting with enlarged tender cervical lymph nodes and provide a brief review of the literature. The diagnosis is established on the basis of histology of lymph node excisional biopsy.
Enigmatic Kikuchi-Fujimoto DiseaseA Comprehensive Review
Xavier Bosch, MD, etal.
Am J Clin Pathol 2004;122:141-152 Abstract quote
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.
- Joint Bone Spine. 2006 May;73(3):311-3. Epub 2006 Jan 4. Abstract quote
Subacute necrotizing lymphadenitis or Kikuchi-Fujimoto disease is a benign pathological entity diagnosed chiefly in young adults.
We report a case in a 20-year-old woman who presented with swollen lymph nodes and a fever. Disseminated lymphadenopathy with nodes measuring up to 6 cm in diameter was found upon physical examination. The erythrocyte sedimentation rate was elevated to 40 mm/h and the lactic dehydrogenase level to 593 IU/l. Findings were negative from serological tests for rubella, hepatitis B, hepatitis C, HIV, and toxoplasmosis, as well as from tests for tuberculosis.
A biopsy of a cervical lymph node showed nonsuppurative necrosis, karyorrhexis, and a marked histiocytic reaction consistent with Kikuchi-Fujimoto disease. No treatment was given, and a full recovery was achieved within 3 months.
In this patient, the disseminated lymphadenopathy and constitutional symptoms strongly suggested a hematological malignancy and more specifically a lymphoproliferative disease.
Kikuchi-Fujimoto's disease: report of familial occurrence in two human leucocyte antigen-identical non-twin sisters.
Amir AR, Amr SS, Sheikh SS.
Dhahran Health Center, Dhahran, Saudi Arabia.
J Intern Med 2002 Jul;252(1):79-83 Abstract quote
Kikuchi-Fujimoto's disease (KFD) is a self-limiting condition usually presenting as cervical lymphadenopathy, with fever and leukopenia, in young adult females. No specific aetiology has been identified yet, although some authors believe that KFD is a 'forme fruste' of systemic lupus erythematosus. Certain human leucocyte antigen (HLA) types have also been associated with KFD.
We herein report KFD in two non-twin sisters with HLA-identical phenotype, who presented 10 years apart. Neither patient had evidence of recent infection or connective tissue disease.
The familial occurrence emphasizes the possibility of genetic predisposition and calls for a more extensive search for a specific cause of KFD.
HISTOLOGICAL TYPES CHARACTERIZATION LYMPH NODE Classic Case Paracortical patchy zones of eosinophilic fibrinoid necrosis with nuclear dust surrounded by a mixed lymphohistiocytic infiltrate with debris-laden macrophages, foamy histiocytes, immunoblasts, and aytpical mononuclear cells
No granulomas, granulocytes, multinucleated giant cells, and only rare plasma cells
Early proliferative phase Lymphohistiocytic cells with atypical mononuclear cells Prenecrotizing phase Numerous histiocytes and single cell necrosis Postnecrotic phase Numerous xanthomatous foamy cells
Histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease): continuing diagnostic difficulties.
Menasce LP, Banerjee SS, Edmondson D, Harris M.
Department of Histopathology, Christie Hospital, Manchester, UK.
Histopathology 1998 Sep;33(3):248-54 Abstract quote
AIMS: To describe the clinicopathological and immunophenotypic features of 25 cases of Kikuchi-Fujimoto disease (K-F), which remains a poorly recognized entity and is still frequently confused with malignant lymphoma, and to discuss the main diagnostic problems experienced by the referring pathologist.
METHODS AND RESULTS: Haematoxylin and eosin sections of 27 lymph node biopsies were re-examined. Immunostains for B-lymphocytes, T-lymphocytes and macrophages were performed. Clinical and follow-up data were obtained through a questionnaire to the referring pathologist or from the patients' notes where available. The suggested initial diagnoses are discussed. The lymph nodes showed a necrotizing process characterized by patchy or confluent areas of necrosis associated with karyorrhexis and absence or paucity of granulocytes. This was associated with a proliferation of large blastic cells consisting of a mixture of T-lymphocytes and histiocytes. Fragmentation of the biopsy was a frequent feature. The diagnosis of K-F was suggested by the referring pathologist in three cases only. The most common suggested diagnosis was that of a non-Hodgkin's lymphoma.
CONCLUSION: This series documents continuing difficulties in the diagnosis of Kikuchi-Fujimoto disease in the UK and emphasizes that cases are still being mistakenly diagnosed as malignant lymphomas. The diagnosis of Kikuchi-Fujimoto disease merits active consideration in any nodal biopsy showing fragmentation, necrosis and karyorrhexis, especially in young women presenting with cervical lymphadenopathy.
VARIANTS Skin Skin changes occur in 30% of cases and include a perivascular and nodular collection of lymphocytes and histiocytes. Atypical mononuclear cells are present. The histiocytes often contain nuclear debris.
- Eur J Pediatr. 2004 Apr;163(4-5):210-3. Epub 2004 Feb 20. Abstract quote
Kikuchi-Fujimoto disease (KFD) is a histiocytic necrotising lymphadenitis, which is a benign disease of unknown aetiology. Misdiagnosing KFD as lymphoma or systemic lupus erythematosus is not uncommon due to the similarity of clinical and histopathological features of these diseases.
A 12-year-old female suffered from cervical lymphadenopathy, leukocytopenia, fever and especially skin rash. The biopsy of the lymph node was compatible with KFD. The skin biopsy showed interface alterations with vacuolar degeneration of the basal cells suggesting lupus erythematosus; however, the patient did not fulfill the diagnostic criteria for systemic lupus erythematosus.
After treatment with acetaminophen, fever subsided and the skin rashes disappeared without relapse during a 10-month follow-up period.
CONCLUSION: The histopathological findings of cutaneous lesions in KFD are usually similar to those observed in the involved lymph nodes. This report suggests that interface change might be one of the pathological features of the cutaneous manifestations of KFD.
Kikuchi-Fujimoto lymphadenitis with cutaneous involvement.
Rakic L, Arrese JE, Thiry A, Pierard GE.
Department of Dermatopathology, CHU Sart Tilman, University of Liege, Belgium.
J Eur Acad Dermatol Venereol 1999 Sep;13(2):118-22 Abstract quote
We report a case of Kikuchi-Fujimoto disease with cutaneous involvement in a European man. In contrast, the disease is most prevalent in women of Asian descent. The condition is probably under-recognized when histology is not used to identify lymphadenitis of protracted course. Skin lesions may mimic clinically other unrelated disorders including lymphomas and immune or infectious dermatoses.
Histology of skin lesions may bring a clue to the diagnosis when apoptotic plasmacytoid monocytes are recognized. The relationship between Kikuchi-Fujimoto disease and lupus erythematous remains a matter of debate.
Immunohistochemical monitoring of plasmacytoid cells in lymph node sections of Kikuchi-Fujimoto disease by a new pan-macrophage antibody Ki-M1P.
Hansmann ML, Kikuchi M, Wacker HH, Radzun HJ, Nathwani BN, Hesse K, Parwaresch MR.
Department of Pathology, University of Kiel, Germany.
Hum Pathol 1992 Jun;23(6):676-80 Abstract quote
The new monoclonal antibody Ki-M1P, which detects a formalin-resistant epitope on conventional paraffin sections, was applied in 20 cases of different stages of Kikuchi-Fujimoto disease.
This new pan-macrophage immunoreagent detects plasmacytoid T cells, referred to as plasmacytoid cells, and renders a reliable delineation of these cells against other similar cell types, such as blasts of high-grade B- and T-cell lymphoma. Histiocytes as well as macrophages were strongly positive, and plasmacytoid cells showed a somewhat weaker and primarily granular, intracytoplasmic immunoreactivity. Plasmacytoid cells, being a diagnostic feature of the Kikuchi-Fujimoto disease, facilitate a clear distinction of this disease entity from large cell or high-grade lymphomas.
These results may represent an additional argument favoring the histiocytic origin of plasmacytoid cells. Additionally, they may point to an immunohistochemical tool that facilitates the differential diagnosis between Kikuchi-Fujimoto disease, especially in early stages of the disease, and malignant lymphoma.
Apoptotic cell death in Kikuchi's disease: a TEM study.
Iguchi H, Sunami K, Yamane H, Konishi K, Takayama M, Nakai Y, Nakagawa T, Shibata S, Nishimura K.
Department of Otolaryngology, Osaka City University Medical School, Japan.
Acta Otolaryngol Suppl 1998;538:250-3 Abstract quote
The pathogenesis of Kikuchi's disease (Kikuchi-Fujimoto disease, histiocytic necrotizing lymphadenitis) remains unclear. However, some previous studies have suggested that a disorder in cellular immunity is responsible for this disease, and apoptotic cell death appears to be the principal finding in the histogenesis of this disease.
In the present study, a lymph node from a female patient with Kikuchi's disease was examined by transmission electron microscopy (TEM). TEM revealed specific morphological features of apoptotic cells, such as nuclear chromatin condensation and fragmentation along the nuclear membrane with intact organelles, and the presence of histiocytes phagocytosing karyorrhectic debris (apoptotic bodies) in areas affected by Kikuchi's disease.
Although neither the role nor the trigger of apoptosis in Kikuchi's disease has been clearly determined, our findings show that apoptotic cell death clearly plays a role in the pathogenesis of Kikuchi's disease.
DIFFERENTIAL DIAGNOSIS CHARACTERIZATION ANTIBIOTIC-ASSOCIATED REACTIONS IN SKIN
- Adverse Antibiotic-Induced Eruptions Associated With Epstein Barr Virus Infection and Showing Kikuchi-Fujimoto Disease-Like Histology.
Carlson JA, Perlmutter A, Tobin E, Richardson D, Rohwedder A.
From the *Divisions of Dermatology and Dermatopathology, Department of Pathology, Albany Medical College, Albany, New York; daggerUpstate Infectious Disease, Albany, New York; double daggerFour Irongate Center, Glens Falls, New York; and section signBio-Med-Mol-Service, Kalkar, Germany.
Am J Dermatopathol. 2006 Feb;28(1):48-55. Abstract quote
The antibiotic-induced eruption of infectious mononucleosis is a well-known clinical phenomenon. Latent viral infection with herpesviridae (eg, human herpes virus 6 (HHV-6) and Epstein-Barr virus (EBV)) is suspected to play a role in the drug hypersensitivity syndrome. The cutaneous pathologic findings have not been reported in the former, and are infrequently reported in the latter entity.
Herein, we describe the biopsy findings of a cefprozil-induced rash in infectious mononucleosis and a minocycline-associated drug hypersensitivity syndrome. Biopsy of these exanthematous eruptions revealed an acute vacuolar interface superficial and deep perivascular and interstitial lymphocytic dermatitis. CD8+ lymphocytes predominated and were associated with non-neutrophilic nuclear (karyorrhectic) debris and numerous small CD68+ and CD123+ monocytes.
These aforementioned features have been described in cutaneous lesions of Kikuchi-Fujimoto disease, an entity whose clinicopathologic findings overlap with both infectious mononucleosis and lupus erythematosus. Serologic evidence of active and chronic active EBV infection was found in both patients, respectively. No evidence of EBV or HHV6 was found in the cutaneous lesions. Plasmacytoid monocytes (CD68+/CD123+ cells), which produce type I interferon, are believed to play a role in viral immunity by protecting other cells from viral infections and promoting survival of antigen-activated T cells.
Their presence in these two putative examples of viral-drug immune dysregulation could be a clue to pathogenesis and represent a common cellular component of some adverse cutaneous drug eruptions
Kikuchi-Fujimoto disease mimicking malignant lymphoma.
Chamulak GA, Brynes RK, Nathwani BN.
Department of Pathology, Los Angeles County, University of Southern California Medical Center.
Am J Surg Pathol 1990 Jun;14(6):514-23 Abstract quote
Histiocytic necrotizing lymphadenitis is a rare, benign entity described independently both by Kikuchi and Fujimoto et al. This disease, which has a broad morphologic spectrum, can readily be mistaken for malignant lymphoma.
Our report on the morphologic features in 10 selected cases of this disease highlights those features that mimicked lymphoma and those that helped us to make an accurate diagnosis.
The distinctive features were (a) pathologic areas, which are pale and do not occupy the entire lymph node; (b) preserved sinuses in the uninvolved areas; (c) prominent mottling by histiocytes or transformed lymphoid cells in the nonpathologic areas; (d) frequent absence of overt necrosis; (e) presence of benign histiocytes with moderate to marked nuclear irregularities and scanty to moderate cytoplasm that resembled cleaved cells; (f) variable amounts of nuclear debris, usually extracellular; (g) presence of so-called plasmacytoid T cells at the periphery of or immediately outside the pathologic areas; (h) moderate numbers of mitotic figures and transformed lymphoid cells of medium and large size (immunoblasts); and (i) absence of inflammatory and granulomatous reaction.
Because overt necrosis is often absent and histiocytes resemble cleaved cells, we support the suggestion that this entity should be called "Kikuchi-Fujimoto disease" rather than "histiocytic necrotizing lymphadenitis."
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS
Child fatality associated with pathological features of histiocytic necrotizing lymphadenitis (Kikuchi-Fujimoto disease).
O'Neill D, O'Grady J, Variend S.
Department of Histopathology, Sheffield Children's Hospital, United Kingdom.
Pediatr Pathol Lab Med 1998 Jan-Feb;18(1):79-88 Abstract quote
We report a case of histiocytic necrotizing lymphadenitis without granulocytic infiltration (Kikuchi-Fujimoto disease), diagnosed at necropsy in a 19-month-old child dying unexpectedly after a febrile illness.
This is the youngest case with this disease that has been thus far reported. It is one of only two reported cases in which the patient died during the acute phase of the illness.
Histological findings not unlike those seen in the lymph nodes were present at extranodal sites; this is the first case in which this feature has been described. In keeping with many other reported cases, it was not possible to identify an underlying etiology that might explain the morphologic changes.
Am J Clin Pathol 2000;113:774.
J Am Acad Dermatol 1994;30:504.
Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
Starry sky-Low power microscopic description of a lymph node with an increase in macrophages creating a mottled appearance resembling a starry sky.
Basic Principles of Disease
Learn the basic disease classifications of cancers, infections, and inflammation
Commonly Used Terms
This is a glossary of terms often found in a pathology report.
Learn how a pathologist makes a diagnosis using a microscope
Surgical Pathology Report
Examine an actual biopsy report to understand what each section means
Understand the tools the pathologist utilizes to aid in the diagnosis
How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate
Recent teaching cases and lectures presented in conferences
Last Updated February 22, 2007
mail to The Doctor's Doctor with
questions or comments about this web site.
Read the Medical Disclaimer.
Copyright © The Doctor's Doctor