Low serum alkaline phosphatase activity in Kikuchi-Fujimoto disease.

Various laboratory findings are helpful in making a diagnosis of Kikuchi-Fujimoto disease (KFD); however, they are not specific. We found decreased serum alkaline phosphatase (SAP) activity in children with KFD. The levels of SAP fell in the acute phase and recovered during convalescence. We conclude that low SAP activity is a characteristic of KFD and may be an auxiliary diagnostic marker for the disease.

Cutting needle biopsy combined with immunohistochemical study of myeloperoxidase for the diagnosis of histiocytic necrotizing lymphadenitis.

CONCLUSION: Cutting needle biopsy (CNB) combined with immunohistochemical study of myeloperoxidase (MPO) is a useful minimally invasive diagnostic procedure for histiocytic necrotizing lymphadenitis (HNL). OBJECTIVES: HNL is mainly diagnosed by pathological findings of open surgical biopsy (OSB) specimens. Recently the appearance of anti-MPO positive histiocytes has been reported as a highly specific pathological diagnosis for HNL. Considering the cosmetic impact and burden on the patients, we performed CNB combined with immunohistochemical study of MPO for the diagnosis of HNL. Few studies have reported the utility of this method in the diagnosis of HNL. METHODS: A retrospective study was conducted using clinical data from 20 HNL patients. RESULTS: CNB was performed in 8 patients and OSB in 13 (OSB after CNB in 1). MPO-positive histiocytes were observed in all of the 20 cases. The accuracy of the diagnoses was finally confirmed by the clinical courses in all cases.

Expression of Epstein-Barr virus and granzyme B in cytologic smears of histiocytic necrotizing lymphadenitis.

Histiocytic necrotizing lymphadenitis (HNL) is a non-neoplastic disease of the lymph nodes that is self-limiting in its clinical course. In this study, the expression of Epstein-Barr virus (EBV), granzyme B, and other phenotypic markers of HNL was investigated in fine needle-aspirated (FNA) cytologic smears obtained from 38 patients with HNL. The smear were subjected to immunohistochemical staining for granzyme B, CD3, CD4, CD8, CD20, and CD68 in addition to in-situ hybridization for EBV to determine whether marker expression could be correlated with disease pathogenesis. The mean age of 28 female and 10 male patients was 22.8 years. CD8-positive cytotoxic T cells were noted in 65.0% of the smears (13/20 cases), whereas CD4 and CD68 were rarely observed. Granzyme B reactivity was seen in lymphocytes, especially in apoptotic areas, and in histiocytes, with positive rates of 25.0% (9/36) and 11.1% (4/36), respectively. Most FNA smears showed immunoreactivity to both CD3 and CD20, with a predominance of CD3-positive cells. In-situ hybridization for EBV was positive in 22.9% (8/35) of the cases. The immunohistochemical staining and EBV in-situ hybridization results obtained in bleached FNA smears were similar to those in histologic sections. Overall, our results implicate that even though EBV positivity and granzyme B immunoreactivity are noted in HNL, they do not appear to have any apoptosis-associated role.

Involvement of DNase gamma in apoptotic DNA fragmentation in histiocytic necrotizing lymphadenitis.

DNA fragmentation induced by endonucleases is a hallmark of apoptotic process. One of the endonucleases responsible for apoptotic DNA fragmentation has been identified as DNase gamma. It has been suggested that massive nuclear debris observed in histiocytic necrotizing lymphadenitis (HNL, Kikuchi disease) results mainly from apoptosis of T-lymphocytes rather than necrosis. To identify the role of DNase gamma in apoptotic foci of HNL paraffin embedded tissue sections of HNL and lymphadenopathy with hyperplastic germinal centers and paracortex in the neck lymph nodes were immunohistochemically stained for DNase gamma and the results compared with the reactivity of TdT-mediated dUTP nick end labeling (TUNEL). Immunoreactivity for DNase gamma was detected in fragmented and condensed nuclei found abundantly in HNL as well as TUNEL reactivity. Moreover, the ratio of DNase gamma immunoreactivity to TUNEL reactivity, which represents probability of apoptosis relevant to DNase gamma, was higher in foci of nuclear debris in HNL than in the hyperplastic paracortex in lymphadenopathy including T-cell apoptosis. Our findings suggest that apoptosis detected in HNL depends more specifically upon DNase gamma than apoptosis in the hyperplastic paracortex of lymphadenopathy, and that the dysregulation of DNase gamma activation is involved in apoptosis in HNL.

Myeloperoxidase expression by histiocytes in Kikuchi's and Kikuchi-like lymphadenopathy.

Forty-five examples of Kikuchi's lymphadenitis (KL), 5 Kikuchi-like lupus erythematosus lymphadenopathies, 25 nonnecrotizing lymphadenitidies (5 toxoplasmic, 5 sarcoid-like, 6 dermatopathic, 4 suppurative, 3 tubercular, 2 with sinus histiocytosis), 4 examples of hyaline-vascular Castleman disease (CD), 2 plasmacytoid monocyte tumors (PM-Ts), and 61 accessory cell neoplasms were studied by a panel of antibodies, including the PG-M1 (against a macrophage-restricted CD68 epitope) and a polyclonal anti-myeloperoxidase (MPO). In KL and Kikuchi-like lupus erythematosus lymphadenopathies, 25 to 75% of CD68(+) histiocytes co-expressed MPO. This did not occur in nonnecrotizing lymphadenitidies and accessory cell neoplasms. MPO(+)/CD68(+) elements corresponded to nonphagocytosing mononuclear cells and some crescentic macrophages and phagocytosing histiocytes. Typical PMs were MPO(-)/CD68(+) in all cases, including CD and PM-T. Our observations suggest that in KL and KL-like lymphadenopathies: 1) MPO(+)/CD68(+) blood monocytes might be attracted into tissues because of the lack or paucity of granulocytes and the need of MPO for oxidative processes; 2) PMs are more likely to be involved in the cytotoxic immune reaction than in phagocytic phenomena; 3) the peculiar phenotype of the histiocytic component can be usefully used for the differentiation from malignant lymphoma and PM-T.

Expression of inducible nitric oxide synthase in human granulomas and histiocytic reactions.

Inducible nitric oxide synthase (iNOS) is required in immune response against infections and is involved in granuloma formation in animals; in murine macrophages, iNOS is induced by lipopolysaccharide and interferon-gamma. In contrast, the role of iNOS in human immune response against infections is still questioned, and its expression in granulomas is poorly investigated. Using Western blotting and immunohistochemistry, we investigated iNOS expression in human lymph nodes with nonspecific reactions and in tissues containing granulomas caused by mycobacteria, Toxoplasma, Cryptococcus neoformans, Leishmania, Bartonella, noninfectious granulomas (sarcoidosis, foreign body), and other hystiocitic reactions (Kikuchi's disease, Omenn syndrome). iNOS was undetectable in nonspecific reactive lymphadenitis, foreign-body granulomas, and Omenn syndrome, whereas it was strongly expressed in infectious granulomas, sarcoidosis, and Kikuchi's diseases. Immunohistochemistry demonstrated that iNOS was selectively expressed by the epithelioid and multinucleated giant cells within the granulomas. Use of an anti-nitrotyrosine antibody, recognizing nitrosilated amino acid residues derived from nitric oxide production, revealed a consistent positivity within the cells expressing iNOS, thus suggesting that iNOS is functionally active. Detection of cytokines by reverse transcriptase-polymerase chain reaction demonstrated that tissues that were positive for iNOS, also expressed the Thl-type cytokine interferon-gamma mRNA, but not the Th2-type cytokine interleukin-4. Taken together, these results indicate that iNOS is involved in different human immune reactions characterized by histiocytic/granulomatous inflammation and associated with Th1-type cytokine secretion.