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Background Undernutrition is a negative predictor of adverse outcomes in patients with heart failure (HF). Despite the survival advantage of elevated body mass index (BMI) in patients with HF, BMI does not necessarily reflect a favorable nutritional status. In the present study, we investigated the clinical impact of nutritional screening in patients with HF and overweight/obesity. Methods We examined the data from 170 patients with overweight or obesity status (defined as BMI ≥ 25 kg/m2) who admitted for acute HF. Their controlling nutritional status (CONUT) score was calculated on admission. The CONUT score is regarded as an index of the nutritional status. Results The median duration of follow-up was 1096 days (interquartile range, 805–1096 days). Undernutrition was identified in 66.5% of the patients. Kaplan–Meier survival analysis demonstrated that patients with undernutrition had a higher incidence of all-cause death and readmission due to HF than those without undernutrition. Multivariate Cox regression analysis revealed that the CONUT score, but not BMI and the geriatric nutritional risk index, was independently correlated with poor prognosis. Conclusions Undernutrition is highly prevalent and independently predicts poor outcomes in patients with overweight/obesity and acute HF.

Chromosome translocations involving the immunoglobulin heavy chain (IGH) gene locus at chromosome region 14q32 are often observed in B-cell lymphoid neoplasms. Of these, t(14;18)(q32;q21) results in juxtaposition of the IGH gene on chromosome 14 and the BCL2 gene on chromosome 18, leading to the overexpression of BCL2 anti-apoptotic protein, which plays a critical role in the development of follicular lymphoma (FL). However, BCL2 overexpression is not observed in approximately 10 % of FL, and the molecular pathogenesis of BCL2-negative FL has not been elucidated. Here, we identify the SRY-related high-morbidity-group (HMG) box 5 (SOX5) gene on chromosome 12p12 as a novel IGH-involved translocation partner in the case of BCL2-negative follicular lymphoma (FL) with a complex karyotype including t(12;14)(p12.2;q32) by long-distance inverse PCR. As a result of this translocation, the SOX5 gene is juxtaposed to the enhancer of the IGH gene; SOX5 overexpression in neoplastic cells was demonstrated by immunohistochemistry. The results of the present study suggest a role for SOX5 in the molecular pathogenesis of FL.

The preferentially expressed antigen of melanoma (PRAME), a tumor-associated antigen, is considered a prognostic marker for various human malignancies. The prognostic significance of PRAME expression for diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab-containing chemotherapy has not been evaluated to date, and the ability of immunohistochemistry (IHC) to detect PRAME expression in these patients has not yet been studied, although IHC is simple to perform in clinical practice. We evaluated the prognostic significance of PRAME expression based on IHC analysis in 160 DLBCL patients treated with R-CHOP therapy. There was a significant association between higher PRAME expression and shorter progression-free survival (PFS), and a trend toward shorter overall survival (OS) in patients with higher PRAME expression than that in patients with lower PRAME expression (5-year PFS, 48.1 vs. 61.1 %; 5-year OS, 65.6 vs. 79.1 %). Patients with high PRAME expression tended to have lower chemotherapeutic responses. Thus, IHC is useful for detecting and assessing PRAME expression in DLBCL. Further, we found a positive correlation between IHC and quantitative real-time RT-PCR measurements of PRAME expression. Our findings indicate that IHC results of PRAME expression can be a novel prognostic maker in DLBCL patients treated with R-CHOP therapy.

Isolated primary granulocytic sarcoma is a rare disease that presents as an extramedullary tumor of myeloid lineage cells. Most patients subsequently develop acute myelogenous leukemia (AML) within a short period, and their prognosis is poor. Herein, we report the case of a 33-year-old woman with a primary isolated granulocytic sarcoma which originated in the small intestine. After she recovered from surgery, she received intensive chemotherapy equivalent to that for AML, followed by allogeneic bone marrow transplantation from an HLA-matched, unrelated donor. Four years after the transplantation, she remains in complete remission without graft-versus-host disease or any other symptoms. This case illustrates the effectiveness of our therapeutic strategy for isolated granulocytic sarcoma, not only with surgical resection of the tumor and intensive chemotherapy equivalent to that for AML, but also with allogeneic bone marrow transplantation, performed while no sign of AML is observed.

The distribution of dendritic cells (DCs) expressing DC-specific ICAM-3-grabbing non-integrin (DC-SIGN, CD209) and the morphological interaction of DC-SIGN⁺ DCs with other cells, especially B cells, in tonsillar and other lymphoid tissues were investigated by multiple immunohistochemistry (IHC) using the graphics editing program Photoshop, which enabled staining with 4 or more antibodies in formalin-fixed paraffin sections. Images obtained by repetition of conventional IHC using diaminobenzidine color development in a tissue section were processed on Photoshop for multiple staining. DC-SIGN⁺ DCs were present in the area around the lymphoid follicles and formed a DC-SIGN⁺ DC-rich area, and these cells contacted not only T cells, fascin⁺ DCs, and blood vessels but also several subsets of B cells simultaneously, including naïve and memory B cells. DC-SIGN⁺ DCs may play an important role in the regulation of the immune response mediated by not only T cells but also B cells. The multiple IHC method introduced in the present study is a simple and useful method for analyzing details of complex structures. Because this method can be applied to routinely processed paraffin sections with conventional IHC with diaminobenzidine, it can be applied to a wide variety of archival specimens.

Dendritic cells (DCs) take up tumour-specific antigen and migrate to regional lymph nodes to generate anti-tumour immunity. Although DC infiltration within human tumour tissue has been reported, the subset distribution has not been fully investigated. This study used immunohistochemistry to investigate DC subset distribution in colorectal adenocarcinoma. DCs expressing CD83, which are considered to be mature DCs, were present mainly in the invasive margin of cancer stroma. CD83(+) DCs in the invasive margin formed clusters with lymphocytes, the majority of which were CD45RO(+) T cells. The number of CD4(+) T cells was greater than that of CD8(+) T cells in these DC-lymphocyte clusters. The elongated cytoplasmic processes of CD83(+) DCs engulfed CD4(+) T cells. DCs that express CD1a were located throughout tumour tissue. Although the number of CD1a(+) DCs was almost the same as that of CD83(+) DCs in the invasive margin of cancer stroma, CD1a(+) DCs were mostly scattered and rarely formed clusters with lymphocytes. DCs that expressed both CD1a and CD83 were rare. Moreover, about 20% of lymphocytes in DC-lymphocyte clusters were positive for Ki-67, and CD83(+) DCs were attached to Ki-67(+) cells. CD83(+) DCs were also present in T-cell areas that had a distinctive structure involving the presence of B-cell lymphoid follicles. These results suggest that in the invasive margin of the colorectal cancer stroma, mature CD83(+) DCs form clusters with T cells to promote T-cell activation for the generation of tumour-specific immunity.

Follicular dendritic cells (FDC) are found in the follicles of virtually all secondary lymphoid tissues. In health, these cells trap and retain antigens (Ag) in the form of immune complexes and preserve them for months in their native conformation. FDC thus serve as a long-term repository of extracellular Ag important for induction and maintenance of memory responses. In retroviral infection, FDC trap and retain large numbers of retroviral particles with profound effects on FDC. FDC-trapped retrovirus induces follicular hyperplasia, and conventional Ag trapped prior to infection are lost and new Ag cannot be trapped. Concomitantly, antibody-forming cells (AFC) specific for Ag lost from FDC decrease followed by loss of specific serum antibody (Ab). Eventually, FDC die and follicular lysis occurs. From the pathogen perspective, binding to FDC is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection. Furthermore, FDC permit HIV to infect surrounding cells even in the presence of a vast excess of neutralizing Ab. Preliminary data suggest that FDC maintain virus infectivity-even when the virus cannot replicate. Thus retrovirus infection monopolizes FDC networks, thereby transforming the FDC Ag repository into a highly infectious retroviral reservoir.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a very rare type of cutaneous lymphoma that localizes primarily in the subcutaneous adipose tissue without palpable involvement of the lymph nodes. Most often, it presents as multiple, painless, subcutaneous nodules on the extremities and trunk. In this study, we describe an unusual case of SPTCL that mimicked phlegmonous inflammation; PET/CT revealed massive diffuse involvement of the lower legs, low-grade nodal active disease, and occult involvement of the intra-abdominal visceral fat. A repeat PET/CT study after CHOP chemotherapy revealed complete resolution of abnormal FDG uptake in the initially involved sites.

A 70-year-old man was admitted to our hospital with fever, generalized lymphadenopathy and hypoxia in October 2009. Blood examination demonstrated leukocytosis, anemia, thrombocytopenia and hyper γ-globulinemia. Peripheral blood and bone marrow smear showed marked plasma cell proliferation mimicking plasma cell leukemia. However, flow cytometric analysis showed that plasma cells were of polyclonal origin and M-protein was not detected by immunofixation of serum protein. Elevations of soluble interleukin 2 receptor and serum IL-6 were observed. A heavy Epstein-Barr viral load was detected in serum by real-time PCR. Biopsy was obtained from the right inguinal lymph node. The pathological diagnosis was angioimmunoblastic T-cell lymphoma (AITL) and rearrangement of the T-cell receptor Cβ1 gene was detected. The patient was treated with CHOP therapy, and all clinical manifestations, including fever, lymphadenopathy, anemia, thrombocytopenia, hyper γ-globulinemia, plasmacytosis and hypoxia, were improved. Only a few reported cases have demonstrated AITL with marked polyclonal plasmacytosis. Although pathological mechanisms of plasmacytosis in AITL patients have not been fully elucidated, it is suggested that IL-6 and IL-10 were involved in its pathogenesis in the present case.

An autopsy case of intrahepatic cholangiocarcinoma (ICC) with a peculiar form of extensive portal invasion is reported here. A 76-year-old woman presented with anorexia and abdominal discomfort. A high level of serum carbohydrate antigen 19-9 and endoscopically detected esophageal varices were found. Obvious mass lesion was not identified on CT scan and no portal blood flow was found. The patient died 6 months after admission. At autopsy multiple irregular shaped tumors in the liver were found. The size of the largest one was 3 x 2 cm. These tumors were well-differentiated adenocarcinomas with partial mucinous carcinoma morphology. Surprisingly, portal veins contained mucinous fluid and the inner surface was lined with a single layer of tumor cells but not endothelial cells. Invasion of carcinoma into the tissue outside the blood vessels was hardly observed in organs other than the liver. This form of extensive invasion of the tumor, termed intimal carcinoma spreading, caused complete obstruction of the portal system. To our knowledge there has been no report on this type of portal invasion of ICC.

Intravascular lymphoma (IVL) of the uterus, a rare manifestation of malignant lymphoma, was diagnosed in a 71-year-old woman, who had fever, edema, and genital bleeding. Only 4 cases of uterine IVL have been reported in detail in the literature in English, to the author’s knowledge. The patient was treated with total hysterectomy with bilateral salpingo-oophorectomy, accompanied by subsequent chemotherapy in combination with rituximab. Preoperative endometrial cytology and biopsy showed atypical lymphocytes intermingled with nonneoplastic epithelial cells. Intravascular proliferation of atypical lymphocytes was detected by histological examination of the resected materials, in which almost the entire uterine structure, including a large endometrial polyp, ovaries, and uterine tubes were involved. Immunohistochemically, tumor cells were positive for CD20 and CD79a and negative for CD5 and CD10. In situ hybridization for Epstein-Barr virus was negative. IVL generally has a poor prognosis. However, in the present case, the patient has been disease free for at least 51 months, and a favorable outcome can be expected.

A 69-year-old man with blastic natural killer cell lymphoma (BNKL) was treated mainly with methotrexate (MTX). He presented with skin and bone marrow involvement at onset. Neoplastic cells were blastic in appearance with CD3−, CD4−, CD8−, CD7−, CD16−, CD56+ and HLA-DR+ phenotype. Molecular studies showed germline configuration of both immunoglobulin H and T cell receptor genes, and negative results for Epstein–Barr virus-encoded small RNA (EBER). He was treated with standard acute lymphoblastic leukemia (ALL) induction therapy, followed by 1 cycle of high-dose MTX (HD-MTX) as consolidation therapy. However, BNKL relapsed during standard ALL maintenance therapy. Three cycles of HD-MTX were effective in achieving a second complete remission and then he received low dose MTX as maintenance therapy. BNKL remained well controlled for 4 years. Chemotherapeutic toxicity was mild and manageable. Since BNKL reportedly has a poor prognosis, this encouraging result warrants further investigation of MTX as either a single agent or in a combination regimen as a first-line treatment for patients with BNKL.

Pyothorax-associated lymphoma was found in a man who had a history of collapse therapy for pulmonary tuberculosis about 50 years ago. An autopsy specimen revealed histology of diffuse large B-cell lymphoma with latency III Epstein-Barr virus (EBV) infection. However, an open biopsy 2 years and 7 months before death showed a polymorphic appearance with abundant T-lymphocytes. Most of the EBV-infected atypical lymphocytes did not express either B- or T-cell markers as far as examined in the paraffin-embedded biopsy specimen, and rearrangements of immunoglobulin and T-cell receptors were not found. It seemed difficult to diagnose a B-cell lymphoma at the time of biopsy. However, retrospectively considered, if a phenotype of EBV-infected atypical lymphocytes is uncertain in cases showing polymorphic appearance, it might be better to consider the future evolution to overt B-cell lymphoma. Since pyothorax-associated lymphoma shows latency III infection of EBV, at least the immunohistochemistry of EBNA-2 and LMP-1 seems helpful for the diagnosis to prove which cells are infected by EBV.

Host defense againstMycobacterium lepraeinfection is chiefly mediated by gamma interferon (IFN-γ)-secreting cytotoxic T cells. Since which antigen-presenting cell populations act to stimulate these T cells is not fully understood, we addressed the role of monocyte-derived dendritic cells (DCs). The DCs phagocytosedM. lepraeand expressed bacterially derived antigens (Ags), such as phenolic glycolipid 1 (PGL-1), in the cytoplasm, as well as on the cell surface. The expression of HLA-ABC and -DR Ags on DCs was down-regulated byM. lepraeinfection, and that of CD86 was up-regulated, but not as fully as byMycobacterium bovisBCG infection. Induction of CD83 expression required a large number ofM. lepraecells. When a multiplicity of infection of >40 was used, the DCs induced a significant proliferative and IFN-γ-producing response in autologous T cells. However, these responses were significantly lower than those induced by BCG- orMycobacterium avium-infected DCs. A CD40-mediated signaling inM. leprae-infected DCs up-regulated the expression of HLA Ags, CD86, and CD83 but did not enhance T-cell-stimulating ability. Therefore,M. leprae-infected DCs are less efficient at inducing T-cell responses. However, when the surface PGL-1 onM. leprae-infected DCs was masked by a monoclonal antibody, the DCs induced enhanced responses in both CD4+- and CD8+-T-cell subsets.M. lepraeis a unique pathogen which remains resistant to DC-mediated T-cell immunity, at least in the early stages of infection.

Follicular lesions include germinal center (GC) hyperplasia, regressive transformation of GCs, and follicle lysis. The present histologic, electron microscopic, and immunohistochemical study of six autopsy cases after organ transplantation accompanied by the administration of immunosuppressive drugs revealed a peculiar regression of lymph node GCs in two cases, which has not been noted previously. The histologic findings of the regressive GCs were classified into three patterns. In pattern A, the GCs had few or no lymphocytes and were surrounded by a poorly developed mantle zone-like structure. Apoptotic cell death of GC lymphocytes was found in a few GCs, but most GCs lacked tingible body macrophages. In pattern B, the GC lymphocytes and tingible body macrophages were absent, showing crowded follicular dendritic cells (FDCs) in a corpuscular shape. In pattern C, the lymphocytic mantle was absent. The GCs were smaller than those in the other patterns, and the shape was irregular because of disintegration of FDCs. The immunostaining for FDC markers revealed dispersed growth of FDCs. On electron microscopy, the lesions were composed of a dense mass of elliptical and oval cells without prominent cytoplasmic processes, a labyrinthlike structure, and emperipolesis of lymphocytes. The distinct desmosomelike adhesive junctions, specific electron microscopic features of FDCs, were evident. We propose to call these follicular lesions "FDC-only lymphoid follicles." It is speculated that this follicle may be evoked after preceding follicular hyperplasia with a complicated mechanism including increased apoptosis of GC lymphocytes and decreased lymphocyte migration to lymph node GCs caused by immunosuppressive drugs.

The following are the clinical and autopsy findings in a 63-year-old woman with myelopathy associated with the human T-cell lymphotropic virus Type I (HTLV-I). HTLV-I antibody was positive in both the serum and cerebrospinal fluid (CSF). In the lower thoracic region, demyelination and the loss of axons were accompanied by a proliferation of astrocytes, and gliosis was found in the lateral columns. Perivascular and parenchymal infiltrations of macrophages, lymphocytes, and plasma cells were also observed, but neither viral inclusion bodies nor atypical lymphocytes were found.

The distribution of lysozyme in normal gastric and duodenal mucosa was studied by light- and electron-microscopic immunocytochemical techniques (direct enzyme-labeled antibody method). In the duodenal mucosa, lysozyme was found in the Paneth cells and the epithelial cells of Brunner's glands. Electron-microscopically, lysozyme was found in rough endoplasmic reticulum and perinuclear spaces, which were assumed to be protein-synthesizing organelles, and also in the secretory granules of Paneth cells. Additionally, lysozyme was detected in the stomach in mucinous granules and in some parts of the rough endoplasmic reticulum within the epithelial cells of the pyloric glands, the mucous neck cells of the fundic glands, and in several surface epithelial cells of the plyoric and fundic regions. This suggests that some quantity of lysozyme in gastrointestinal secretion originates from the gastric and duodenal glands, and that it acts as a defense mechanism in the gastrointestinal tract.

The distribution of low affinity IgE Fc receptors (FcϵR2, FceRII) in reactive and neoplastic follicles was studied by an indirect immunoperoxidase method with monoclonal antibody specifically reacting to FceRII (H107). The tissues examined in this study included lymph nodes, extranodal tissues of divergent diseases, and follicular lymphomas. In the germinal centers (GCs) of the lymph follicles, FceRII showed a lace-like pattern irrespective of the distribution of IgE. In general, FceRII was positive only in the light zone and not in the dark zone of GCs. The distribution of FceRII was different from that of DRC1 which was always present in the entire portion of GC. There were two types of DRC1(+) FDC which were FceRII(+) and FceRII(−). FceRII was seen by immunoelectron microscopy on the cell surface of follicular dendritic cells (FDCs). IgE-positive GCs in Kimura's disease and Warthin's tumor were intensely positive for FceRII in their entire portion. In IgE-positive GCs, an increased number of FceRII-positive lymphoid GC cells was recognized by immunoelectron microscopic observation. In follicular lymphoma, there were also two types of FDC which were FceRII(+) and FceRII(−). These findings indicated that FceRII on FDCs was closely related to the IgE immune response and also was a marker for functional phase or differentiation of FDCs.

The purpose of this investigation was to clarify the mechanisms of amyloid fibril formation in human lymph nodes. In our present study, amyloid deposition was observed diffusely in all compartments of the lymph nodes. The deposition form showed extremely characteristic findings in its morphological features. Namely, amyloid deposits mainly consisted of clusters of round or oval nodules. Each amyloid nodule was frequently enclosed with long-stretched cytoplasmic processes of abutting reticulum cells and/or macrophages. Amyloid fibrils often formed parallel amyloid bundles radiating to outlying sections of the nodule from the center. The amyloid bundles closely adhered to the cytoplasmic membrane of not only the abutting reticulum cells, macrophages and sinus endothelium but also to the lymphocytes and plasma cells. In the central portion of the amyloid nodules, a concentric core was also observed. The most interesting finding was the intracellular formation of amyloid fibrils in all cells, such as macrophages, reticulum cells, foreign body giant cells and lymphocytes in the process of degeneration. Some fibrils localized in the limited area of the cytoplasm and others appeared in all parts of the cells, including the nucleus. Their cell membranes were missing in several areas and the cell organella had gradually dissolved. Finally the cell residuums were completely replaced by amyloid fibrils and transformed into a nodular structure with radiating bundles of amyloid fibrils.