Clinicopathologic analysis of 6 lymphomatoid gastropathy cases: expanding the disease spectrum to CD4-CD8+ cases.

Lymphomatoid gastropathy, which was first reported in 2010, is a rare NK-cell proliferation of cyCD3, CD4, CD5, CD8, CD56 phenotypes with unknown etiology. The diagnosis is challenging, as there is histopathologic similarity to malignant lymphoma. In the 2010 report on 10 cases, all lesions were located in the stomach, and all regressed without any therapy. In the present study, we analyzed 6 cases of lymphomatoid gastropathy by investigating the clinicopathologic, immunohistochemical, and molecular findings. Endoscopic and morphologic appearances of all cases were consistent with previous reports, but 2 cases showed previously unreported unique immunophenotypes of CD4CD8. Three of 6 patients underwent lower gastrointestinal examination (1 case underwent double-balloon endoscopic examination), but no patient had lesions in the lower gastrointestinal tract. No obvious difference of histology was found between the cases of CD4-CD8-typical phenotype and ones of CD4CD8 phenotype. Both cases had similar clinical behavior as the other 4 cases, implying that the spectrum of the disease is broader than initially thought. Careful clinical and endoscopic follow-up is required for the diagnosis of lymphomatoid gastropathy, and additional case studies and molecular studies are warranted to further investigate the pathophysiology of this peculiar benign mimic of lymphoma.

Multicentric Castleman's disease with abundant IgG4-positive cells: a clinical and pathological analysis of six cases.

BACKGROUND: Differentiation between multicentric Castleman's disease and systemic immunoglobulin (Ig) G4-related lymphadenopathy is sometimes difficult. It has been suggested that measurement of the IgG4-/IgG-positive cell ratio is useful for the differential diagnosis of the two diseases. However, the authors present a detailed report of six patients with multicentric Castleman's disease with abundant IgG4-positive cells (IgG4-/IgG-positive cell ratio, >40%). RESULTS: In the present series, the patients showed systemic lymphadenopathy, polyclonal hypergammaglobulinaemia and elevated serum interleukin-6 (IL-6) and C-reactive protein levels. Further, anaemia, hypoalbuminaemia, hypocholesterolaemia and thrombocytosis were observed. These findings were consistent with those of multicentric Castleman's disease. Although five patients showed elevated serum IgG4 levels, only two patients showed an increased serum IgG4/IgG ratio. However, the two patients showed highly elevated serum IgG4 levels, but the serum IgG4/IgG ratios were, although increased, not very high. Also, a patient with increased serum IgG4/IgG ratio showed a good response to antihuman IL-6 receptor monoclonal antibody (tocilizumab). Histologically, the germinal centres were mostly small and regressive, and frequently penetrated by hyalinised blood vessels, and there was no eosinophil infiltration. These findings were different from those of IgG4-related lymphadenopathy. CONCLUSIONS: The authors conclude that multicentric Castleman's disease sometimes occurs with abundant IgG4-positive cells and elevated serum IgG4 levels. Therefore, the two diseases cannot be differentially diagnosed by immunohistochemical staining alone. Laboratory findings, especially IL-6 level, C-reactive protein level and platelet count, are important for the differential diagnosis of the two diseases.

Systemic IgG4-related lymphadenopathy: a clinical and pathologic comparison to multicentric Castleman's disease.

IgG4-related disease sometimes involves regional and/or systemic lymph nodes, and often clinically and/or histologically mimics multicentric Castleman's disease or malignant lymphoma. In this study, we examined clinical and pathologic findings of nine patients with systemic IgG4-related lymphadenopathy. None of these cases were associated with human herpes virus-8 or human immunodeficiency virus infection, and there was no T-cell receptor or immunoglobulin gene rearrangement. Histologically, systemic IgG4-related lymphadenopathy was classified into two types by the infiltration pattern of IgG4-positive cells: interfollicular plasmacytosis type and intra-germinal center plasmacytosis type. The interfollicular plasmacytosis type showed either Castleman's disease-like features or atypical lymphoplasmacytic and immunoblastic proliferation-like features. By contrast, the intra-germinal center plasmacytosis type showed marked follicular hyperplasia, and infiltration of IgG4-positive cells mainly into the germinal centers, and some cases exhibited features of progressively transformed germinal centers. Interestingly, eight of our nine (89%) cases showed eosinophil infiltration in the affected lymph nodes, and examined patients showed high elevation of serum IgE. Laboratory examinations revealed elevation of serum IgG4 and soluble interleukin-2 receptors. However, the levels of interleukin-6, C-reactive protein, and lactate dehydrogenase were within normal limits or only slightly elevated in almost all patients. One patient showed a high interleukin-6 level whereas C-reactive protein was within the normal limit. Autoantibodies were examined in five patients and detected in four. Compared with the previously reported cases of multicentric Castleman's disease, our patients with systemic IgG4-related lymphadenopathy were significantly older and had significantly lower C-reactive protein and interleukin-6 levels. In conclusion, in our systemic IgG4-related lymphadenopathy showed pathologic features only partially overlapping those of multicentric Castleman's disease, and serum data (especially C-reactive protein and interleukin-6) are useful for differentiating the two. Our findings of eosinophil infiltration in the affected tissue and elevation of serum IgE may suggest an allergic mechanism in the pathogenesis of systemic IgG4-related lymphadenopathy.

Patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma exhibit favorable prognosis despite a non-germinal center B-cell-like phenotype.

Diffuse large B-cell lymphomas are detected frequently in the oral cavity. Although tonsillar lymphomas have been rather well characterized, lymphomas originating from non-tonsillar regions, such as the gingiva, palate, and tongue, have not been well studied. We examined the pathology of clinical samples obtained from 21 patients with localized primary non-tonsillar oral diffuse large B-cell lymphoma. Immunohistological examination of CD10, Bcl-6, and MUM1 determined that 17 of 21 (81%) samples exhibited non-germinal center B-cell type, an increased proportion of non-germinal center B-cell type compared with previous reports in samples of tonsillar origin (P<0.05). The four remaining samples exhibited germinal center B-cell type, although one sample expressed MUM1. Follow-up clinical survival data were obtained from the 17 patients over a range from 4 to 173 months (mean 52 months). All patients were treated with chemotherapies, irradiation, or surgical resection. Sixteen patients achieved complete remission and two patients relapsed, but no patient has died of disease. Extranodal diffuse large B-cell lymphomas of non-germinal center B-cell type are generally characterized by poor prognosis, regardless of localized disease. Interestingly, our results indicate that, unlike similar lymphomas of tonsillar origin, localized primary non-tonsillar oral diffuse large B-cell lymphomas exhibit favorable prognosis, suggesting that these lymphomas may be clinicopathologically distinct.