CHOP (cyclophosphamide, adriamycin, vincristine, and prednisolone) therapy achieves a response in more than 60% patients with diffuse large B-cell lymphomas (DLBCLs). However, DLBCL shows a heterogeneous response to chemotherapy, and some patients are refractory to CHOP therapy. This difference in response to therapy is most likely due to differences in biological characteristics. We used cDNA microarray analysis to identify genes differentially expressed in anthracycline containing chemotherapy-resistant DLBCLs (7 patients) compared with anthracycline containing chemotherapy-sensitive DLBCLs (6 patients). Nine genes on the cDNA chip showed increased expression in anthracycline containing chemotherapy-resistant patients. We chose the preferentially expressed antigen of melanoma (PRAME) gene because it showed the highest expression in anthracycline containing chemotherapy-resistant DLBCLs on the cDNA chip, and it has been linked to prognosis of hematological malignancies. We also examined the relationship between PRAME gene expression and progression-free survival (PFS) in 45 patients with DLBCL. The progression-free survival of PRAME-positive patients (n=12) was significantly worse than that of PRAME-negative patients (n=33) (p=0.0373). Our results therefore indicate that PRAME expression in DLBCL correlates with response to anthracycline containing chemotherapy. [J Clin Exp Hematopathol 49(1) : 1-7, 2009]

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To assess the humoral response to the influenza vaccine in patients undergoing R-CHOP therapy (rituximab combined with cyclophosphamide, doxorubicin, vincristine, and predonisolone) for non-Hodgkin lymphoma (NHL), the anti-hemagglutinin (HA) titer in 7 NHL patients undergoing therapy was compared with those in 10 control group subjects in the 2005/2006 season. Four weeks after vaccination, the HA titers against the influenza type A H1N1 and type B antigens, the same antigens that had been used in the previous seasons, were elevated in all patients treated with R-CHOP. In contrast, there was no increase in the geometric mean titer for type A H3N2 antigen, which was newly included in 2005/2006 season, in the patients treated with R-CHOP, while there was a significant increase in the 10 control subjects (p = 0.014). This study showed that vaccination against influenza virus generated an appreciable humoral response to recall antigens in NHL patients treated with R-CHOP therapy, but not to the primary antigen. [J Clin Exp Hematopathol 49(1) : 9-13, 2009]

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Previous reports emphasized that localized lymphoid hyperplasia (LLH) of the large intestine is usually histologically characterized by large lymphoid follicles with striking enlarged germinal centers, and a narrow surrounding mantle zone and marginal zone (MZ). To clarify the histological varieties of LLH of the large intestine, 16 such cases have been studied. The present study demonstrated histological diversity of the LLH of the large intestine including (i) reactive follicular hyperplasia (RFH) (n=8), (ii) RFH with progressive transformation of the germinal center (PTGC) (n=3), (iii) RFH with MZ hyperplasia (n=3) and (iv) RFH with PTGC and MZ hyperplasia (n=2). Overall histomorphological findings of the present series appear quite different from previous descriptions of LLH of the large intestine. The present study showed histological variety of the LLH of the large intestine. Moreover, LLH of the large intestine should be differentiated from extranodal marginal zone B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma as well as follicular lymphoma. Immunohistological studies demonstrated the reactive nature of all 16 lesions. However, three cases showing RFH demonstrated immunoglobulin heavy chain gene rearrangement by polymerase chain reaction study in 12 cases examined. It remains unclear whether these three cases showing RFH could be a sign of the prelymphomatous stage (incipient follicular lymphoma) or representing merely an exaggeration of normal B-cell clonal response in the germinal centers. [J Clin Exp Hematopathol 49(1) : 15-21, 2009]

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Until now, no method has been available to discriminate mature plasmacytoid DC (pDC) from myeloid DC (mDC) immunohistochemically. In this study, we report that these DC-subsets can be distinguished in routine pathological sections. Immature and mature monocyte-derived DCs (MoDCs) were S100 calcium binding protein B (S100B)⁺, while pDCs generated from pDC-precursors were S100B^-. In contrast, both mature MoDC and pDC were fascin⁺. Epidermal Langerhans cells (LCs) were S100B⁺/fascin^-. Although the majority of DCs were S100B⁺/fascin⁺ in the dermis with nonspecific inflammation, dermal DCs were mostly S100B^-/fascin⁺ in psoriasis vulgaris, in which type I interferon secreted by pDC-precursors is thought to play a major role. S100B⁺/fascin⁺ DCs were accumulated in the superficial lymph node (LN), while they were scarce in the deep LN. In the superficial LN with dermatopathic lymphadenitis, a large number of S100B⁺/fascin⁺ DCs were accumulated in the T-zones, where numerous LC-derived DCs are accumulated. In contrast, almost all DCs were S100B^-/fascin⁺ in the superficial LN with Kikuchi's lymphadenitis, in which numerous pDC-precursors are known to be present. In contrast to the superficial LN, the deep LN contained numerous S100B^-/fascin⁺ DCs and a few S100B⁺ DCs. Thus, the distributions of S100B⁺ DC or S100B^-/fascin⁺ DC correspond to the putative distribution of mDC or mature pDC, respectively. [J Clin Exp Hematopathol 49(1) : 23-31, 2009]

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We describe a rare case of secondary malignant fibrous histiocytoma (MFH) following Langerhans cell histiocytosis (LCH). A 23-year-old Japanese male exhibited systemic lymphadenopathy, multiple lung tumors, and osteolytic changes in bilateral iliac bones in 1989. A biopsy specimen from the left iliac bone revealed an infiltration of S-100 protein-positive histiocyte-like cells intermingled with eosinophils, which confirmed the diagnosis of eosinophilic granuloma, a type of LCH. Although the patient was treated with prednisolone initially, the disease did not respond well and progressed gradually over time. The patient subsequently received multiple courses of chemotherapy and immunosuppressive therapy with many kinds of anticancer agents for 6 years. He also received radiotherapy totaling 136.8 Gy for lung tumors and osteolytic lesions of the pelvis. In 1997, because of the LCH refractoriness, biopsy was performed again from the right inguinal lymph node. Microscopic examinations demonstrated a mixture of spindle-shaped cells and histiocyte-like cells, which appeared to be in a storiform pattern. The tumor cells were immunohistologically positive for CD68 and vimentin, but negative for CD1a and S-100 protein. Therefore, the patient was diagnosed with MFH. Although chemotherapy was continued, the patient died of pneumonia during the neutropenic period following chemotherapy. Autopsy revealed systemic invasion of MFH and dissemination of mucormycosis. LCH was not detected histologically in any tissues. [J Clin Exp Hematopathol 49(1) : 33-37, 2009]

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There are several reports describing [¹⁸F] fluorodeoxyglucose positron emission tomography (FDG-PET) findings in patients with lymphomatoid granulomatosis (LYG). We report a case of grade I LYG that showed increased uptake of FDG. The patient was a 63-year-old Japanese male who underwent an FDG-PET/computed tomography (CT) scan in screening for a malignant lesion. Increased uptake of FDG [maximum standard uptake value (SUV_max), 3.7] was observed in the right hilar region in FDG-PET and enhanced CT revealed a round, abnormal mass that also showed increased FDG uptake. The patient had no previous symptoms. A tumor biopsy was performed and the histological diagnosis was grade I LYG. Therefore, increased SUV_max in FDG-PET might be useful for diagnosing of LYG. [J Clin Exp Hematopathol 49(1) : 39-44, 2009]

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Post-transplant lymphoproliferative disorder (PTLD) is one of the most important complications of solid organ transplantation or hematopoietic stem cell transplantation. Most PTLDs are associated with Epstein-Barr virus (EBV) infection. Although post-transplant Hodgkin lymphoma (HL) is included in PTLD, there have been no studies in the literature on adult cases of post-transplant HL after cord blood stem cell transplantation (CBSCT). This is due to the fact that EBV infection of cord blood cells usually does not occur, and EBV-infected lymphocytes of the recipient should be eradicated by preconditioning therapy. We report a 26-year-old woman case of post-transplant HL, which occurred after CBSCT for relapsed acute lymphoblastic leukemia. Three years and eight months after CBSCT, the enlarged cervical lymph node was histologically diagnosed as EBV associated post-transplant HL, which showed immunophenotypes of classical HL and latency type II EBV infection. She underwent chemotherapy, and has survived 4 years and 6 months after CBSCT. Differential diagnosis of post-transplant HL with good prognosis and HL-like PTLD with aggressive behavior is important, and immunohistochemical methods were useful and essential for it. The source of EBV associated HL in this case will be discussed. [J Clin Exp Hematopathol 49(1) : 45-51, 2009]

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