[Primary diffuse large B-cell lymphoma of the breast in a male patient with Sjögren's syndrome].

When a 74-year-old male patient visited our hospital for the treatment of herpes zoster, his computed tomography (CT) revealed a mass in his right breast, axillary lymph node enlargement, and multiple lung nodules. A histological examination of the breast and lymph node biopsies revealed diffuse large B-cell lymphoma (DLBCL) while the bronchial and salivary gland biopsies showed secondary amyloidosis and Sjögren's syndrome (SjS). According to the Ann Arbor staging, the clinical stage of the lymphoma was evaluated as IIE. The patient achieved a complete remission after six cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP-COP) combined with intrathecal chemotherapy to prevent meningeal infiltration and irradiation after chemotherapy. Primary breast lymphoma was diagnosed within 2% of the breast tumor. Only sixteen male cases of breast lymphoma have been previously reported. In those reports, gynecomastia and hormonal therapy accounted for nine cases, but none of the cases coexisted with SjS. The present case is suggestive of the need to investigate possible autoimmune involvement in the development of lymphoma.

[Primary biliary cholangitis complicated by primary hepatic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue].

An 89-year-old woman was admitted to our hospital owing to liver dysfunction and ascites. Enhanced computed tomography (CT) revealed hepatomegaly and heterogeneous density in the liver. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) /CT revealed diffuse accumulation of FDG throughout the liver. Histopathology of a biopsy specimen revealed hepatic mucosa-associated lymphoid tissue (MALT) lymphoma. Complete remission (CR) was achieved with two cycles of rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone. Because a second CT demonstrated liver cirrhosis and a test for anti-mitochondrial antibody was positive, liver biopsy was repeated, and pathological examination confirmed primary biliary cholangitis (PBC). The lymphoma recurred after 18 months and was treated with rituximab, which again resulted in CR. Over the subsequent 7 years, the patient had no liver dysfunction or recurrent lymphoma. Interestingly, despite the underlying PBC, liver dysfunction in this case appeared only with the MALT lymphoma.

Positive Pattern Recognition System Using Alanine Aminotransferase, Type IV Collagen 7s, and E Value (Liver Stiffness) for the Diagnosis of Nonalcoholic Steatohepatitis Based on Natural History.

Introduction: The use of a simple diagnostic system for nonalcoholic fatty liver disease (NAFLD) instead of a biopsy is expected. We investigated a positive pattern recognition system for the evaluation of nonalcoholic fatty liver (NAFL) and the stages of nonalcoholic steatohepatitis (NASH). Methods: A total of 68 Japanese patients with biopsy-confirmed NAFLD were enrolled. Serological biomarkers and medical imaging markers were investigated to determine candidate markers. The markers were statistically evaluated, and the patients were distributed to pattern combinations. Results: We selected three markers based on natural history and set the critical values: alanine aminotransferase/ALT (persistent ≧ 44 IU/L) as a marker for hepatitis, type IV collagen 7S (≧5.1 ng/mL) for fibrosis, and E value (≧5.5 kPa) for stiffness. After evaluation of statistical accuracies, every patient was classified into their combination patterns. Comparing the relationships between histological classifications and positive patterns, the patients with NAFL were mainly distributed in pattern (ALT, type IV collagen, E value: -, -, -), those with NASH stage 0-1 in (+, -, +), those with NASH stage 2-3 in (+, +, +), and those with NASH stage 4 in (-, +, +). Conclusions: The positive patters changed with the NAFL and NASH conditions. Our results indicated a correlation between the positive patterns using three markers and the histological results. The positive pattern recognition system based on natural history is useful for the differential diagnosis of NAFLD and for the evaluation of the severity of fibrosis in patients with NASH.

Association of the Low-density Lipoprotein Cholesterol/High-density Lipoprotein Cholesterol Ratio with Glecaprevir-pibrentasvir Treatment.

Objective The change in serum lipid levels by direct-acting antiviral (DAA) treatment for chronic hepatitis C varies depending on the type of DAA. How the lipid level changes induced by glecaprevir-pibrentasvir (G/P) treatment contribute to the clinical outcome remains unclear. We conducted a prospective observational study to evaluate the effectiveness of G/P treatment and the lipid level changes. Methods The primary endpoint was a sustained virologic response at 12 weeks (SVR12). The total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and LDL-C/HDL-C (L/H) ratio were measured every two weeks. Patients This study included 101 patients. Seventeen cases of liver cirrhosis and nine cases of DAA retreatment were registered. The G/P treatment period was 8 weeks in 74 cases and 12 weeks in 27 cases. Results SVR12 was evaluated in 96 patients. The rate of achievement of SVR12 in the evaluable cases was 100%. We found significantly elevated TC and LDL-C levels over the observation period compared to baseline. The serum levels of HDL-C did not change during treatment but were significantly increased after treatment compared to baseline. The L/H ratio was significantly increased two weeks after the start of treatment but returned to the baseline after treatment. Conclusion The primary endpoint of the SVR12 achievement rate was 100%. G/P treatment changed the serum lipid levels. Specifically, the TC and LDL-C levels increased during and after treatment, and the HDL-C levels increased after treatment. G/P treatment may be associated with a reduced thrombotic risk. Therefore, validation in large trials is recommended.

Near Tetraploidy Acute Myeloid Leukemia in Long-term Remission with Persistent Clonal Hematopoiesis with del(20)(q12q13).

Patients with near tetraploidy/tetraploidy (NT/T)-acute myeloid leukemia (AML) are rare and generally show poor survival. A 62-year-old man was referred to our hospital with pancytopenia. A bone marrow examination revealed the proliferation of extremely large blasts, and led to the diagnosis of AML M0. A cytogenetic analysis showed an NT-karyotype of 91, XXYY, -5, add(18)(p21),del(20)(q12q13) ×2. Complete remission was achieved with single remission induction chemotherapy. Although consolidation chemotherapies were not available because of his critical condition, he remained in remission and survived for more than 40 months without cytopenia. However, repeated bone marrow examinations showed persistent clonal hematopoiesis with del(20)(q12q13) without apparent myelodysplasia.

Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura.

A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved.

Fatal Epstein-Barr Virus Reactivation in an Acquired Aplastic Anemia Patient Treated with Rabbit Antithymocyte Globulin and Cyclosporine A.

Epstein-Barr virus (EBV) associated lymphoproliferative disorder (LPD) after immunosuppressive therapy for aplastic anemia (AA) is extremely rare in a nontransplant setting and has not been well described. This report describes a severe AA patient in whom fatal EBV-LPD developed after being treated with rabbit antithymocyte globulins (ATG) and cyclosporine A (CsA). An 81-year-old man was diagnosed as having severe AA. He was started on CsA followed by administration of ATG for five consecutive days. One month after the start of ATG, persistent fever which was not responsive to antibiotics or antifungal agents developed and atypical lymphocytes emerged in peripheral blood. Repeated blood cultures were negative. An extremely high level of EBV virus in his peripheral blood plasma was detected by means of a quantitative real-time PCR assay. Even after the cessation of CsA, the fever persisted and the peripheral atypical lymphocytes proliferated rapidly. The patient suffered from respiratory failure, liver dysfunction, and metabolic acidosis. Rituximab was administered without success and he died.

[Leukemic meningitis in B-cell prolymphocytic leukemia].

An 84-year-old woman was admitted because of anemia and marked leukocytosis. The white cell count was 237,660/microliter, with 93% abnormal lymphoid cells. The cells had abundant cytoplasm and prominent nucleoli. They were positive for CD 5, 19, 20, 22, 23, HLA-DR, IgM, IgD and kappa chain. Thus, a diagnosis of B-cell PLL was made. Chromosome analysis disclosed a complex karyotypic abnormality. Massive splenomegaly was detected by abdominal computed tomography. No external or internal lymphadenopathy was found. The patient was intermittently treated with etoposide. Although the white cell counts had been suppressed, she refused to take the drug because of side effects. When the white cell count exceeded more than 200,000/microliter again, she developed severe headache, diplopia, nausea, and vomiting. A lumber puncture disclosed infiltration of the prolymphocytes in the cerebrospinal fluid. Though intrathecal chemotherapy alleviated the symptoms and the leukemic cells disappeared, the effects were transient. When the therapy was withheld because of bone marrow suppression, the meningitis recurred and the symptoms progressed. The patient died six months after the initial presentation.

Two cases of nonsecretory multiple myeloma presenting as primary plasma cell leukemia.

Plasma cell leukemia (PCL) is a rare variant of multiple myeloma (MM) with a poor prognosis. Nonsecretory myeloma is also a rare form of MM characterized by the absence of detectable M-protein in the serum and urine. This report describes two cases of nonsecretory PCL. The first patient was an 85-year-old man in whom the lack of monoclonal immunoglobulins made it difficult to make a diagnosis because the malignant cells showed an atypical morphology. He died of rapid disease progression before starting chemotherapy. The second patient was a 78-year-old woman whose tumor cells displayed a typical plasma cell morphology. She was successfully treated with bortezomib-containing chemotherapy.

An atypical familial Mediterranean fever patient who developed ulcers in the terminal ileum and recurrent abscess-like lesions in multiple organs.

We herein describe the case of a 25-year-old woman who suffered from atypical familial Mediterranean fever for more than a decade. She presented with a periodic fever, abdominal pain and persistent ulcers in the terminal ileum. Colchicine was effective, and familial Mediterranean fever was diagnosed. A genetic study showed a heterozygous E148Q mutation in the MEFV gene. Multiple, recurrent, abscess-like lesions developed asynchronously in the spleen, liver, and a lung. Infliximab was administered when colchicine treatment became ineffective. However, infliximab treatment soon became ineffective, probably because antibodies were generated against it. Therefore, etanercept treatment was started, and the patient showed an immediate response.

Primary and isolated adult T-cell leukemia/lymphoma of the bone marrow.

The distribution of adult T-cell leukemia/lymphoma (ATLL) is typically systemic. In addition to peripheral blood (PB) and lymph nodes, extranodal sites such as the skin, lung, liver, gastrointestinal tract, and central nervous system are frequently involved. We report a unique case of ATLL in which the patient presented with prolonged fever. A 65-year-old man had high-grade fever lasting for 2 weeks. He showed no lymphadenopathy, hepatosplenomegaly, skin lesions, or PB involvement. Bone marrow examination showed widespread infiltration of ATLL cells. (18)F-fluorodeoxy glucose positron emission tomography (FDG-PET) revealed that the disease was confined to the bone marrow.

Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans.

Brown adipose tissue (BAT) can be identified by (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) combined with X-ray computed tomography (CT) in adult humans. The objective of this study was to clarify the relationship between BAT and adiposity in healthy adult humans, particularly to test the idea that decreased BAT activity may be associated with body fat accumulation with age. One hundred and sixty-two healthy volunteers aged 20-73 years (103 males and 59 females) underwent FDG-PET/CT after 2-h cold exposure at 19 °C with light clothing. Cold-activated BAT was detected in 41% of the subjects (BAT-positive). Compared with the BAT-negative group, the BAT-positive group was younger (P < 0.01) and showed a lower BMI (P < 0.01), body fat content (P < 0.01), and abdominal fat (P < 0.01). The incidence of cold-activated BAT decreased with age (P < 0.01), being more than 50% in the twenties, but less than 10% in the fifties and sixties. The adiposity-related parameters showed some sex differences, but increased with age in the BAT-negative group (P < 0.01), while they remained unchanged from the twenties to forties in the BAT-positive group, in both sexes. These results suggest that decreased BAT activity may be associated with accumulation of body fat with age.

Interferon-α/ß and anti-fibroblast growth factor receptor 1 monoclonal antibody suppress hepatic cancer cells in vitro and in vivo.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most commonly occurring primary liver cancer and ranks as the fifth most frequently occurring cancer, overall, and the third leading cause of cancer deaths, worldwide. At present, effective therapeutic options available for HCC are limited; consequently, the prognosis for these patients is poor. Our aim in the present study was to identify a novel target for antibody therapy against HCC. METHODOLOGY/PRINCIPAL FINDINGS: We used Western blot and flow cytometric and immunocytochemical analyses to investigate the regulation of FGFR1 expression by interferon-α/ß in several human hepatic cancer cell lines. In addition, we tested the efficacy of combined treatment with anti-FGFR1 monoclonal antibody and interferon-α/ß in a murine xenograft model of human HCC. We found that interferon-α/ß induces expression of FGFR1 in human HCC cell lines, and that an anti-FGFR1 monoclonal antibody (mAb) targeting of the induced FGFR1 can effectively inhibit growth and survival of HCC cells in vitro and in vivo. Moreover, the combination of interferon-α, anti-FGFR1 mAb and peripheral blood mononuclear cells (PBMCs) exerted a significant antitumor effect in vitro. CONCLUSIONS: Our results suggest that the combined use of an anti-FGFR1 antibody and interferon-α/ß is a promising approach to the treatment of HCC.

Extramedullary relapse of AML with t(9;11)(p22;q23) associated with clonal evolution from trisomy 8 into tetrasomy 8.

This report describes a patient with extramedullary relapse of acute myeloid leukemia (AML) without involving bone marrow. A 57-year-old man was diagnosed as having acute monoblastic leukemia with t(9;11)(p22;q23) and trisomy 8. Ten months after achieving complete response (CR) with chemotherapy, masses developed in his left forearm and in the back of his thigh, preceded by enigmatic peripheral neurological symptoms. Aspiration from the forearm showed leukemic relapse, and fluorescence in situ hybridization (FISH) revealed that the majority of the cells had 11q23 anomaly and tetrasomy 8. Bone marrow or meningeal relapse was not observed. To our knowledge, this is the first case report of clonal evolution associated with the development of myeloid sarcoma as a relapse in AML.