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) 

In This Article

Histologic Features

KFD can be diagnosed with confidence if careful attention is given to the architectural features and the characteristic cytologic composition of lymph node biopsy specimens. The characteristic histopathologic findings of KFD include irregular paracortical areas of coagulative necrosis with abundant karyorrhectic debris, which can distort the nodal architecture, and large numbers of different types of histiocytes at the margin of the necrotic areas. The degree of necrosis varies considerably from one case to another (Figure 1). Thrombosed vessels usually are seen around the areas of necrosis. The karyorrhectic foci are formed by different cellular types, predominantly histiocytes and plasmacytoid monocytes, but also immunoblasts, some of which may be atypical, and small and large lymphocytes. The number of plasmacytoid monocytes, small and large lymphocytes, and immunoblasts is variable (Figure 2). Atypia in the reactive immunoblastic component is not uncommon and can be mistaken for lymphoma when a proliferation of plasmacytoid monocytes, immunoblasts, and small lymphocytes is seen without necrosis. Various types of histiocytes can be observed, including nonphagocytic histiocytes, the so-called crescentic histiocytes (Figure 3), tingible body macrophages, and foamy histiocytes. There usually are areas of paracortical hyperplasia with small and large lymphoid cells and, occasionally, large, pale, interdigitating dendritic cells. Neutrophils characteristically are absent, and plasma cells are absent or scarce.[16,17,18]

Figure 1.

Kikuchi-Fujimoto disease. Extensive paracortical area of coagulative necrosis (H&E, original magnification x40).

Figure 2.

Kikuchi-Fujimoto disease. Large lymphoid cells and immunoblasts, some of which have wide cytoplasm with an eccentric nucleus (arrow) (H&E, original magnification x600).

Figure 3.

Kikuchi-Fujimoto disease. Karyorrhectic foci with large numbers of histiocytes, including crescentic histiocytes (arrow), and some lymphoid cells (H&E, original magnification x400).

Histiocytes and plasmacytoid monocytes make the most distinctive cell types found within the karyorrhectic foci. In fact, it has been considered that the earliest recognizable foci and minimum diagnostic criterion of KFD are paracortical clusters of plasmacytoid monocytes with interspersed karyorrhexis and crescentic histiocytes.[16]

Reactive lymphoid follicles are present in 50% to 60% of cases, and follicular hyperplasia has been found in approximately 10% of cases.[16,17,18] It has been reported that the karyorrhectic process can extend beyond the confines of the nodal capsule.[16] Chamulack and colleagues[102] reported the occurrence of karyorrhexis in the perinodal tissue in 2 of 10 cases of KFD. Tsang and coworkers[16] confirmed this finding in 15 of 75 cases. The process might even obliterate the peri-nodal lymphatics. Biopsies of skin lesions from patients with KFD with cutaneous involvement have revealed dermal infiltration by apoptotic plasmacytoid monocytes[60] and other cell infiltrates that essentially are composed of the same components as affected lymph nodes, including histiocytic aggregates, atypical lymphoid cells, karyorrhectic debris, and patchy necrosis.[19,61] The same features, along with lupus dermatitis-like histologic findings, were reported by Spies et al[63] in 1999 in a series of 5 patients affected by necrotizing lymphadenitis consistent with KFD and unspecific skin rashes. The authors suggested that this histologic pattern might be highly specific of KFD cutaneous involvement. Yet only 1 of the patients was reportedly followed up during 4 months without showing clinical features suggestive of SLE.[63]

Kuo[17] proposed classification of the histopathologic features of KFD into 3 evolving histologic stages: proliferative, necrotizing, and xanthomatous. The proliferative stage consists basically of various histiocytes, plasmacytoid monocytes, and a variable number of lymphoid cells with karyorrhectic nuclear fragments and eosinophilic apoptosis debris. If cellular aggregates in a given lymph node showed any degree of coagulative necrosis, the case was classified as necrotizing. If foamy histiocytes predominated in the KFD lesions, the case was classified as xanthomatous regardless of the presence or absence of necrosis. The most common type was the necrotizing type, accounting for slightly more than half of the cases. As Kuo[17] pointed out, the 3 histologic types might represent different stages of the disease or might reflect differences in cause or host reaction. Judging from the histologic changes, KFD perhaps begins as proliferative, progresses to necrotizing, and finally resolves into xanthomatous. However, sequential biopsy specimens were not available in the study by Kuo[17] to verify this postulated concept. Also, data on the duration of the disease did not correlate with the progression of the 3 histologic types.


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