Kikuchi-Fujimoto Disease



Kikuchi-Fujimoto Disease


Carlos E. Bueso-Ramos, MD, PhD





Key Facts


Clinical Issues



  • Self-limited clinical course in most patients


  • Might represent phenotype of diverse disease entities


  • Prognosis is different according to underlying cause


  • Young patients


  • Acute tender cervical lymphadenopathy


  • Low-grade fever; systemic symptoms


  • Systemic survey and follow-up is recommended to rule out systemic lupus erythematosus


Microscopic Pathology



  • Multiple, pale circumscribed foci are found in paracortical area of lymph node


  • Lack of extension of process into perinodal tissue


  • 3 phases: Proliferative, necrotizing, xanthomatous


  • Lesions are composed of mononuclear cells with round to irregular nuclei


  • Abundant karyorrhectic debris


  • Plasmacytoid dendritic cells are present


  • Paracortical areas of coagulative necrosis are seen


  • Large numbers of histiocytes, including crescentic histiocytes and activated lymphoid cells


  • Absence of neutrophils


Ancillary Tests



  • Predominance of CD3(+), CD8(+) T cells


  • Histiocytes express myeloperoxidase, lysozyme and CD68


  • ↑ plasmacytoid dendritic cells expressing CD68, CD123, CD303


  • No evidence of monoclonal Ig or TCR rearrangements







Cervical lymph node involved by Kikuchi-Fujimoto disease. The paracortex shows a circumscribed, wedgeshaped area of necrosis that extends to the capsule.






MIP FDG-PET scan of Kikuchi-Fujimoto disease. This image reveals an area of FDG uptake in the right cervical region that was interpreted as suspicious for lymphoma image.


TERMINOLOGY


Abbreviations



  • Kikuchi-Fujimoto disease (KFD)


Synonyms



  • Necrotizing lymphadenitis without granulocytic infiltration


  • Histiocytic necrotizing lymphadenitis


  • Kikuchi-Fujimoto lymphadenopathy


Definitions



  • Self-limited, benign form of lymphadenopathy characterized by



    • Proliferation of histiocytes and plasmacytoid monocytes


    • Apoptosis with abundant karyorrhectic debris


    • Systemic symptoms and low-grade fever in subset of patients


ETIOLOGY/PATHOGENESIS


Unknown



  • Viral, infectious, or autoimmune cause has been suggested


  • Exuberant T-cell-mediated response to variety of stimuli in genetically susceptible people


  • Cytokine-mediated mechanisms



    • ↑ interleukin-6, interferon-α, FAS ligand


  • Viruses suggested to be involved in KFD include



    • Epstein-Barr virus (EBV) and human herpes virus 6 (HHV6)


    • Identified in small subset of cases; unlikely to be cause


CLINICAL ISSUES


Epidemiology



  • Age



    • Usually < 30 years (range: 2-75 years)


  • Gender



    • Women are affected more often



      • Female to male ratio is 4:1


  • Ethnicity



    • KFD has been described in a variety of ethnic backgrounds



      • Asian descent most common


Site



  • Lymphadenopathy



    • Cervical lymph nodes most often involved


Presentation



  • Fever typically lasts for 1 week



    • Can persist for up to 1 month


  • Upper respiratory symptoms


  • Most common initial manifestations are



    • Tender and painful lymphadenopathy


    • Lymphadenopathy with fever


  • Uncommon manifestations



    • Weight loss, night sweats, nausea, vomiting


    • Generalized lymphadenopathy


    • Joint pain


    • Extranodal involvement by KFD


    • Splenomegaly, hepatomegaly


Laboratory Tests



  • Rule out other causes of necrotizing lymphadenopathy


  • No specific tests are available for detecting KFD


  • Anemia


  • Elevated lactate dehydrogenase levels


  • Granulocytopenia and atypical lymphocytosis in peripheral blood (50%)


  • Elevated erythrocyte sedimentation rates


  • Polyclonal hypergammaglobulinemia



  • Negative serologic studies for



    • EBV, Cytomegalovirus, influenza, adenovirus


    • Toxoplasmosis, Mycoplasma, Q fever


  • Usually negative autoimmune laboratory studies



    • Antinuclear antibodies, rheumatoid factor, antidouble-strand DNA antibodies


    • Rare patients with KFD are subsequently diagnosed to have systemic lupus erythematosus


Natural History



  • Diagnosis is usually established by lymph node biopsy



    • Excisional biopsy is often required because KFD can be patchy



      • Assessment of lymph node architecture is very helpful in establishing diagnosis


  • Spontaneous resolution occurs, usually within 1-4 months


  • Small (˜ 3%) subset of patients develop relapse


Treatment



  • No specific therapy required


  • Anti-inflammatory agents


Prognosis



  • Excellent


IMAGE FINDINGS


CT Findings



  • Computed tomography (CT) is preferred modality


  • Cervical lymph nodes in KFD tend to be located in posterior triangle


  • Lymph nodes appear as clusters



    • < 4 cm in greatest dimension


    • Nonenhancing necrosis


  • Any lymph node group can be involved in KFD


MACROSCOPIC FEATURES


General Features



  • Size: 0.5-4.0 cm


MICROSCOPIC PATHOLOGY


Histologic Features



  • Lymph node



    • Architecture: Partial or extensive involvement



      • Often patchy in early stages


    • KFD begins in paracortex and near capsule



      • Degree of apoptosis/necrosis varies from one case to another


      • No granulocytes identified in necrotic areas


      • Plasma cells usually absent or rare


      • Process does not extend into perinodal tissues


      • Immunoblasts are numerous in viable paracortex contiguous with necrosis


      • No hematoxylin bodies identified


    • Sinuses are patent or compressed



      • Can be filled by histiocytes or monocytoid B cells


    • Hyperplastic lymphoid follicles in uninvolved areas


    • ± thrombosed blood vessels


    • 3 histologic subtypes of KFD have been described



      • Lymphohistiocytic/proliferative; thought to be early stage


      • Necrotic


      • Phagocytic/foamy cell; thought to be late stage


    • > 1 stage of KFD can be present within lymph node


    • Lymphohistiocytic/proliferative type



      • Proliferation of histiocytes (including C-shaped forms)


      • Increased plasmacytoid dendritic cells


      • Small lymphocytes and immunoblasts are present


      • Relatively little apoptosis or necrotic debris


    • Necrotic type



      • Abundant apoptosis within distinct foci of necrosis associated with eosinophilic debris


      • Histiocytes and plasmacytoid dendritic cells undergo apoptosis


      • Fibrin thrombi may be present in blood vessels


    • Phagocytic/foamy cell type



      • Numerous histiocytes containing phagocytosed debris (foamy cytoplasm)



      • Histiocytes often form rim surrounding necrotic areas


Cytologic Features



  • Diagnosis can be suggested in touch imprints of lymph node



    • Highlights cytologic characteristics of plasmacytoid dendritic cells (pDC)


    • Touch imprint often better than fine needle aspiration (FNA) smears


  • Frequency of CD123(+) pDC is high in KFD



    • Valuable indicator for diagnosis of KFD


    • Useful for distinguishing KFD from reactive lymphadenopathy and neoplasms


Skin



  • Most frequently located on face or upper body


  • KFD in skin can grossly present as



    • Erythematous papules


    • Indurated lesions or plaques


    • Ulcers


  • Histologic findings in skin include



    • Dermal lymphohistiocytic infiltrate; most common


    • Epidermal changes



      • Necrotic keratinocytes


      • Nonneutrophilic karyorrhectic debris


      • Basal vacuolar change


    • Edema of papillary dermis


ANCILLARY TESTS


Immunohistochemistry



  • Histiocytes are CD4(+), CD68(+), lysozyme(+), myeloperoxidase(+, dim)


  • Plasmacytoid dendritic cells are



    • CD68(+), CD123(+), CD303(+)


    • Myeloperoxidase(-), fascin(-)


  • T cells are predominantly CD8(+)


  • Immunoblasts are CD30(+) and of CD8(+) T-cell lineage


  • B cells are rare or absent in areas of necrosis


Flow Cytometry



  • Predominance of CD8(+) T cells without aberrancies


  • Rare polytypic B cells


  • Insufficient to establish diagnosis of KFD



    • Helpful to exclude non-Hodgkin lymphoma

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Jul 8, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Kikuchi-Fujimoto Disease

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