Kikuchi-Fujimoto Disease In the United States: Clinical and Laboratory Characteristics and Outcomes

Kikuchi-Fujimoto Disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a benign, idiopathic, self-limiting disease manifesting primarily as unilateral cervical lymphadenopathy in younger Asian women. In western countries this condition is very rare.

To compare clinical laboratory characteristics and delineate major differences between KFD and malignant lymphoproliferative disorders.

This is a retrospective review of two patients with KFD that were evaluated in our institution between 2008 and 2010.

Two previously healthy 26-year old Caucasian female patients initially presented with acute onset of B symptoms and cervical or mesenteric lymphadenopathy, respectively. Staging fusion PET/CT scans revealed non-bulky lymphadenopathy with the largest node measuring 2 cm and FDG avidity with SUV maximums ranging from 3.7 to 9.8. Contrast CT scan also noted mild splenomegaly in one patient. CBC and differential revealed mild thrombocytopenia and neutropenia in both patients. Comprehensive work-up for autoimmune and infectious etiologies was negative. Although, bone marrow biopsies were negative for the involvement with lymphoma, a diagnosis of aggressive lymphoma was presumed and chemotherapy was initially recommended. A review of histology of excisional lymph node biopsies revealed partial preservation of lymph node architecture with expansion of the paracortical areas, patchy areas of necrosis, consisting of brightly eosinophilic fibrinoid deposits, and associated karyorrhexis, surrounded by an expanded accumulation of pale-staining histiocytes. Neutrophils and eosinophils were consistently absent. Obliterated sinuses and proliferation of plasmacytoid monocytes and immunoblasts, found adjacent to areas of necrosis, can display atypical morphologic features that may mimic lymphoma. Flow cytometry analysis done on biopsied nodes did not identify clonal B-cell or T cell populations. In both patients B symptoms completely resolved without therapeutic intervention 6 month after diagnosis. Chronic fatigue and residual adenopathy persisted for more than 12 months.

Most patients with KFD are young Asian women, presenting with unilateral cervical lymphadenopathy. Presentation in axillary and inguinal lymph nodes and generalized lymphadenopathy is less common, and involvement of mesenteric lymph nodes is exceedingly rare. However, it is important to include it in the differential diagnosis of more frequent necrotizing lymphadenopathies associated with infections (i.e. tuberculosis, cat-scratch disease, histoplasmosis), autoimmune disorders (i.e. systemic lupus lymphadenitis), and lymphoma, because its course and treatment are entirely different. Although lymphomas can display extensive necrosis, neoplastic (lymphoma) cells are usually present in the periphery of the necrotic foci. SLE lymph node lesions usually contain prominent neutrophilic infiltrate, plasma cells, and lesions of vasculitis are also seen. In contrast, in KFD neutrophils and eosinophils are consistently absent, representing a distinctive feature of this lesion. Immuno-histochemical studies are useful, as histiocytes stain positively for lysozyme, myeloperoxidase, and CD68. SLE also expresses myeloperoxidase; however, CD68 staining is negative. Infectious agents that cause necrotizing granulomatous lesions can be identified by special stains for organisms. Although HHV-8, EBV, and parvovirus were suggested as possible causes, no correlations between these viruses and development of KFD have been shown so far. Rarely, patients with KFD develop secondary lymphoid malignancy or SLE.

Our cases suggested that excisional lymph node biopsy and a review by an experienced hematopathologist is essential for diagnosis of KFD. PET avid adenopathy and B symptoms might initially mimic a manifestation of aggressive lymphoma. However, characteristic histomorphology of the excised lymph node, and a lack of clonal lymphocyte population should be able to confirm diagnosis of KFD and prevent erroneous treatment with chemotherapy.

No relevant conflicts of interest to declare.