|Year : 2014 | Volume
| Issue : 2 | Page : 137-140
Kikuchi fujimoto disease: A clinical and cytohistopathological studies of four cases with brief review of literature
BR Vani, K Geethamala, V Srinivasa Murthy
Department of Pathology, Employees State Insurance Corporation Medical College and Post Graduates Institute of Medical Science and Research, Rajajinagar, Bangalore, Karnataka, India
|Date of Web Publication||19-May-2014|
B R Vani
Department of Pathology, Employees State Insurance Corporation Medical College and Post Graduates Institute of Medical Science and Research, Rajajinagar, Bangalore 560 010, Karnataka
Source of Support: None, Conflict of Interest: None
Background: Kikuchi Fujimoto Disease (KFD) is a benign, rare, and self-limiting disease occurring among young individuals. This is commonly encountered as cervical lymphadenitis and due to its long-term presentation, it often gets mistaken as malignant lymphomas. The authors highlighted this benign entity that occurred in wide range of age group, which needs just a symptomatic therapy and follow-up. Study Design: A total four cases of KFD diagnosed in Employees State Insurance Corporation (ESIC) Medical College and Post Graduates Institute of Medical Science and Research (PGIMSR), Rajajinagar, Bangalore over a period from June 2010 to June 2013. The clinical and cytohistological features in all four cases were evaluated. Results: In the present study, all the 4 cases were females with wide age range from 14 to 37 years and presented with painful cervical lymphadenopathy and fever. The predominant cytological features of KFD were karyhorrechtic debris and necrosis; however, all four cases needed biopsy for confirmed diagnosis. On histopathological study, 3 of 4 cases confirmed the diagnosis of KFD except a single case, which posed dilemma with lymphoma, which on immunohistochemistry proved it to be KFD. Conclusion: KFD being rare, awareness of this entity and referral of patients with persistent lymphadenopathy to rule out this rare entity is of at most importance and reduces the apprehension associated with mis-diagnosis with lymphomas. Also it further emphasizes the fact that histopathology is the confirmatory diagnostic tool for KFD.
Keywords: Cytology, fine needle aspiration cytology, histology, kikuchi fujimoto disease
|How to cite this article:|
Vani B R, Geethamala K, Murthy V S. Kikuchi fujimoto disease: A clinical and cytohistopathological studies of four cases with brief review of literature. Int J Health Allied Sci 2014;3:137-40
|How to cite this URL:|
Vani B R, Geethamala K, Murthy V S. Kikuchi fujimoto disease: A clinical and cytohistopathological studies of four cases with brief review of literature. Int J Health Allied Sci [serial online] 2014 [cited 2020 Feb 23];3:137-40. Available from: http://www.ijhas.in/text.asp?2014/3/2/137/132709
| Introduction|| |
Kikuchi Fujimoto's Disease (KFD) or histiocytic-necrotising lymphadenitis is a benign, rare, and self-limiting disease occurring among young individuals.  This is commonly encountered as cervical lymphadenitis; less commonly axillary, mesenteric and inguinal lymph nodes can be affected. Nevertheless, extranodal manifestations of splenomegaly and gastrointestinal and skin lesions do occur. ,, According to National Institute for Health and Care Excellence (NICE) referral guidelines, patients with persisting cervical lymphadenopathy for more than 3 weeks has been given important referral criterion to Head and Neck Clinics. , Due to its long-term presentation, it often mistaken for malignant lymphomas.  The authors highlighted this benign entity that occurred in wide range of age group, which needs just symptomatic therapy and follow-up. Confirmed diagnosis of KFD is only based on histological study. Hence patients presenting with persistent lymphadenopathy subsequent excision and histopathological examination (HPE) is a prerequisite.
| Case reports|| |
A young 14-year female presented to the surgical outpatient department (OPD) with right cervical swelling. Clinical examination revealed, swelling measuring 2 × 1 × 1 cm. No systemic complaints noted. Patient was referred for fine needle aspiration cytology (FNAC), which showed karyhorrechtic debris, histiocytes, lack of neutrophils in a background of necrosis hence the diagnosis of necrotising lymphadenopathy was made and biopsy confirmation was asked for [Figure 1]a-d]. Prior preoperative investigations were within normal limits. Day care surgery with excision of lymph node was done. Grossly structure of lymph node measuring 2 × 1 × 0.5 cm and on sectioning, cut surface was gray white, homogenous. The HPE showed an encapsulated lymph node with subcapsular aggregates of lymphoid follicles. Large areas of necrosis with karyhorrechtic debris and absence of neutrophils were noted. The necrotic areas were bordered by lymphocytes, histiocytes, plasma cells, foreign body type of giant cells and eosinophils. Endothelial cell proliferation and few of the vessels showed fibrin thrombi [Figure 2]a-d]. Considering the younger age, Ziehl Neelson (ZN) stain for acid-fast bacilli (AFB) was performed, which was negative. A confirmed diagnosis of KFD was offered. The patient was treated with symptomatic therapy and follow-up of the patient was done. also the patient remained stable till date.
|Figure 1: (a-c) H and E photomicrograph of fine needle aspiration cytology shows necrosis devoid of neutrophils and (d) karyhorrechtic debris|
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|Figure 2: (a, b) H and E photomicrograph of biopsy shows effaced architecture of lymph node with extensive areas of necrosis rimmed by histiocytes and karyhorrechtic debris (c) Arrow shows crescentric macrophages (d) karyhorrechtic debris|
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An 18-year female, herring from rural area with history of right-enlarged cervical since two months. The patient underwent FNAC and biopsy in her locality. Patient does not procure any of the reports, but produced the paraffin blocks. The blocks were sectioned and stained with hematoxylin and eosin (H and E). Histopathology revealed encapsulated lymph node with extensive areas of necrosis, karyhorrechtic debris devoid of neutrophils. Phagocytic histiocytes and plasma cells were seen. ZN stain for AFB was negative and also polymerase chain reaction (PCR). A confirmed prescription for the diagnosis of KFD was given. The patient was given a course of steroids and she is stable in carrying her activities till date.
A 31-year female, homemaker presented to surgical OPD with left-sided neck swelling. On examination, two swellings in the left cervical region, larger measuring 1.5 × 1 × 1 cm and smaller measuring 0.5 × 0.5 cm. Patient was subjected to FNAC, which gave the diagnosis of necrotising lymphadenopathy and biopsy confirmation was asked for patient was subjected for excision and received two gray white lymph node structures, larger measuring 1.5 × 1 × 1 cm and smaller measuring 0.5 × 0.5 cm. Immediate imprints were taken and rapid staining revealed only acellular amorphous eosinophilic necrotic material. The HPE showed encapsulated lymph node with areas of necrosis, karyhorrechtic debris lacking neutrophils. AFB stain was negative. Further microbiological examination was negative for tubercle bacilli. Confirmed diagnosis of KFD was offered. Patient was subjected to symptomatic therapy and is doing fine.
A 37-year female, tailor by occupation presented to surgical department with swelling on left-side neck. Clinical examination revealed multiple-matted lymphnodes, larger measuring 2 × 2 × 0.5 cm, smaller measuring 0.5 × 0.5 cm. Patient was subjected to FNAC and a diagnosis of reactive lymphadenitis was made. There were no evidences of granulomas, atypical or immature cells. Patient was given a course of antibiotics and repeat FNAC was done, but retained reactive lymphadenitis cytomorphology and was suggested for biopsy confirmation. Excised tissue showed multiple lymphnodes, larger measuring 2 × 2 × 1 cm, and smaller measuring 0.5 × 0.5 cm. The HPE revealed preserved lymph node architecture with central areas of coagulative necrosis and karyhorrechtic debris. Fibrin deposits, occasional monocytoid and plasmacytoid cells were noted. Considering the age, long duration of presentation and in view of mono-plasmacytoid cells, immunohistochemistry (IHC) was carried out to rule out lymphoma. Lymphoma panel marker results revealed negativity for lymphoma. Hence, the diagnosis of KFD was given and patient was treated with steroids. Patient remained symptomatically well during the follow-ups.
| Discussion|| |
Kikuchi Fujimoto disease being a rarer entity was discovered in 1972 by Dr Masahiro Kikuchi and Dr Fujimoto from Japan, who presented individually a case of lymphadenitis with extensive nuclear debris and histiocytic proliferation in a Japanese Journal of Haematological Society. ,, Hence this distinct disease entity came into existence. It is also known by various names like histiocytic- necrotising lymphadenitis, lymphadenitis without granulocytic infiltration, necrotising lymphadenitis and Kikuchis disease. ,,
Kikuchi Fujimoto's disease are frequently diagnosed in oriental races, Caucasians, Hispanics, Middle Eastern and Japanese population. ,, Very few cases have been reported from Indian population. The documented literature shows equal distribution among males and females, but few case series having female preponderance and mean age of presentation being 30 years. ,, In the present study, all four cases were females with wide age range of distribution from 14 to 37 years. In 36 months study, conducted in our institute, 80 lymph node specimens were reviewed of which 30% were malignant; rest were benign among, which 5.7% were diagnosed cases of KFD.
The most common clinical presentations are cervical painful lymphadenopathy and flu-like symptoms. Less commonly non-specific symptoms like headache, arthralgia, cutaneos rash, axillary/mesenteric lymphadenopathy, splenomegaly and parotid enlargements. ,, Very few cases of aseptic meningitis, bone marrow hemophagocytosis and interstitial lung disease have been documented. , In the present case, series all patients presented with painful cervical lymphadenopathy and fever.
The etiology of KFD remains obscure, but several infectious agents and autoimmune association have been encrypted. The infectious agents include Epstein-Barr virus (EBV), parvovirus, herpesviridae HHV-6, Yersinia More Details, Brucellosis More Details, barteonella, entamoeba, toxoplasma, human immunodeficiency virus (HIV), cytomegalovirus (CMV) have been implicated; and however, no particular viruses have been isolated in the reported cases. ,, Imamura et al.,  found histopathological similarities between KFD and systemic lupus erythematosis (SLE). Tanaka et al.,  found occurrence of certain human leukocyte antigen (HLA) class 11genes in KFD. However, association of Kikuchi with SLE is unclear. In the present case, series screening for HIV, HBsAg and VDRL were negative in all cases. Despite this negativity the possible viral etiology could not be established; however, multifactorial process of environmental, biological and genetic influence may promote KFD.
The diagnosis of KFD poses a diagnostic dilemma due to its rarity, non-specific symptoms and other disease mimickers. Currently the confirmed diagnosis is based on HPE. , FNAC though being easy outpatient procedure; sampling error and cytodiagnostic dilemmas make it, a not so sensitive diagnostic modality. , However, cytomorphology of necrotic debris, phagocytic histiocytes, non-phagocytizing histiocytes, plasmacytoid monocytes and paucity of neutrophils clinches the diagnosis.  In the present article, two of four cases gave FNAC diagnosis of necrotising lymphadenitis, among which one case is of reactive lymphadenitis and other case had no available reports. All four cases needed excision biopsy for confirmed diagnosis. KFD being a chronic disorder, blood investigations may not give any diagnostic clues except for commoner raised C-reactive protein and erythrocyte sedimentation rate (ESR), which may be seen in any chronic diseases. , Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI)/ultrasonography also falls short to enable a precise diagnosis. , Histopathology being the confirmed diagnosis, the features which are seen are partial effacement of architecture of lymph node with residual follicles having reactive germinal centers, patchy irregular or confluent and cortical wedge shaped areas of necrosis. These necrotic areas consist of eosinophilic fibrinoid deposits, nuclear fragments or karyhorrechtic debris and histiocytes of varied subtypes like lymphohistiocytic, phagocytic, reactive and foamy cell type. At the periphery of the necrotic areas thrombosed vessels, nests of plasmacytoid monocytes and immunoblast seen. , On histopathology, a varied differentials mimicking similar picture have been tabulated [Table 1]. ,,,,,
In the present study, the above points were considered to rule out mimickers and helped us to arrive at a confirmed diagnosis of KFD. The KFD being self-limiting, supportive therapy, includes analgesics and anti-inflammatory medications that will suffice. However, improved therapy with corticosteroids is found to be beneficial in some of the patients. , In this study, patients were given supportive as well as steroid therapy.
| Conclusion|| |
Kikuchi Fujimoto disease being rare, awareness of this entity and referral of patients with persistent lymphadenopathy to rule out this rare entity is of importance. Patients present with fever and lymphadenopathy frequently at outpatient clinics; prompt and relevant investigations of these people help to arrive at early diagnosis and appropriate therapy. Hence, it also helps to reduce the apprehension associated with misdiagnosis of this entity with lymphomas.
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[Figure 1], [Figure 2]