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The optimal treatment strategy for primary mediastinal large B-cell lymphoma (PMBL) remains unknown. We retrospectively analyzed 345 patients with newly diagnosed PMBL to identify prognostic factors and optimal treatments. Focusing on patients treated with cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (R-CHOP) (N=187), a higher International Prognostic Index (IPI) and the presence of pleural or pericardial effusion were identified as adverse prognostic factors for overall survival (OS) in patients treated with R-CHOP without consolidative radiation therapy (RT) [IPI: hazard ratio (HR), 4.23; 95% confidence interval (CI), 1.48-12.13; P=0.007; effusion: HR, 4.93; 95% CI, 1.37-17.69; P=0.015]. Combined with IPI and the presence of pleural or pericardial effusion for the stratification of patients treated with R-CHOP without RT, those with lower IPI and the absence of effusion comprised approximately onehalf of these patients and could be identified as curable [OS and progression free survival (PFS) at 4 years, 95% and 87%, respectively)] Taken together, our simple indicators of IPI and the presence of effusion could stratify patients with PMBL and thereby facilitate treatment selection.

We report the case of a 62-year-old man who presented with malignant lymphoma as recurrent multiple cranial nerve palsy after spontaneous regression of oculomotor nerve palsy. He developed ptosis and diplopia due to right oculomotor nerve palsy. Brain MRI/MRA showed no abnormality, and he recovered with conservative medical management. Three months later, he showed diplopia due to right abducens nerve palsy and facial pain and trigeminal sensory loss. Neurological examination revealed multiple cranial nerve palsy involved cranial nerve III, V, IX, and X of the right side. Serum soluble interleukin-2 receptor levels were normal, and cerebrospinal fluid examination was unremarkable. Steroid and subsequent intravenous immunoglobulin therapy didn't improve his symptoms. Six weeks after his admission, he showed rapid enlargement of the cervical lymph node and the right tonsil, and post-contrast T1-weighted MRI showed enlargement and enhancement of the left infraorbital nerve, the bilateral cavernous sinus, the bilateral facial nerves, and the left trigeminal nerve. The histopathologic examination of the tonsil biopsy revealed diffuse large B cell lymphoma. The cause of these symptoms was thought to be infiltrating the cavernous sinus, and adjacent nerves. Spontaneous regression of malignant lymphoma is an exceptional event, but this possibility should be considered so as to the correct diagnosis and proper treatment.

An 80-year-old man, presenting with gait disturbance and memory loss, had findings of normal pressure hydrocephalus. Primary leptomeningeal lymphoma (PLML) was diagnosed based on cytology and flow cytometry of cerebrospinal fluid obtained by examination. Gadolinium-enhanced MRI showed enhancement of the brain and spinal cord but FDG-PET/CT revealed no lymph node swelling. With intrathecal chemotherapy, meningeal lesions disappeared and the gait disturbance and memory loss improved. However, the disease recurred three months later, manifesting as left facial nerve palsy, but the symptoms disappeared in response to intrathecal chemotherapy and systemic rituximab administration. Although a tumor lesion in the spinal canal was suggested by MRI examination, the patient has maintained a good clinical course for four years with intrathecal chemotherapy every three months. PLML is a very rare disease and its diagnosis is difficult. Repeated intrathecal chemotherapy appeared to be effective against PLML in this case.

We report a case of testicular malignant lymphoma in a hemodialysis patient. A 65-year-old man who had been undergoing hemodialysis for 8 years and 10 months consulted our hospital with right testicular enlargement in August 2012. Under a diagnosis of testicular cancer from manipulation test and ultrasonography, high orchiectomy was performed. Computed tomography showed swelling of the retroperitoneal lymph nodes. Histopathological examination revealed diffuse, non-Hodgkin B-cell lymphoma, CD20＋. R-CHOP chemotherapy was initiated and retroperitoneal lymph node swelling completely disappeared after 1 cycle of chemotherapy. After completing 2 cycles of chemotherapy, the patient developed interstitial pneumonia, and thus radiotherapy to the retroperitoneal space including the left testis was performed. As of July 2014, the patient remains alive without recurrence.

An 87-year-old woman was diagnosed with primary diffuse large B-cell lymphoma of the pancreas by endoscopic ultrasonography-guided fine needle aspiration. Complete remission was achieved after treatment with six courses of R-CHOP chemotherapy. However, two and a half years later, she was readmitted because of weakness during walking. At this time, laboratory tests revealed hypercalcemia associated with high plasma levels of parathyroid hormone-related protein (PTHrP), but bone lesions were not detected. Although computed tomography only revealed splenomegaly, we suspected a recurrence of her malignant lymphoma because she also had marked elevation of soluble interleukin-2 receptor and lactate dehydrogenase levels. Bone marrow examination revealed the involvement of Burkitt's lymphoma cells with malignant transformation. Immunohistochemical analysis confirmed that hypercalcemia was caused by a paraneoplastic syndrome related to PTHrP-producing B-cell lymphoma cells. Unfortunately, the patient's general condition rapidly deteriorated, and she died soon after admission. Our case is unusual because of the presentation of bone marrow relapse of malignant lymphoma.

The patient was a 73-year-old woman. At 63 years of age, she had developed follicular lymphoma that showed a complete response to R-CHOP therapy. Over the subsequent 8 years, she experienced 4 relapses and was administered rituximab monotherapy once, combined rituximab-fludarabine therapy twice, and CHASE-R therapy once, achieving a complete response each time. Before her first therapy, hepatitis B virus (HBV) surface antigen was negative, while hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody were not measured. Later, before her second salvage therapy, anti-HBs was negative, but then changed to positive before her third salvage therapy. HBV-DNA was negative before CHASE-R therapy. At 16 months after completing the CHASE-R therapy, she developed hepatitis and HBV-DNA had changed to positive. Hepatitis did not become fulminant and entecavir administration was effective. It was surmised that HBV had resolved, but she became negative for anti-HBs following the rituximab-containing chemotherapy. Therefore, this is a rare case in which de novo hepatitis developed after the final chemotherapy. The prognosis of patients with de novo hepatitis accompanying treatment of B-cell lymphoma is poor. In those who undergo lymphoma salvage therapy, the risk for and clinical course of HBV reactivation might differ from those of treatment-naïve patients.

Primary hepatosplenic CD5-positive diffuse large B cell lymphoma (CD5⁺ DLBCL) has recently been characterized as showing hepatosplenomegaly without lymphadenopathy, a portal and intrasinusoidal pattern of infiltration in the liver, and bone marrow invasion by lymphoma cells, without intravascular involvement. A 45-year-old man presented with fever and malaise in June 2013. Computed tomography showed hepatosplenomegaly and multiple liver tumors without lymphadenopathy. An ultrasonography-guided needle biopsy of the liver mass revealed portal and intrasinusoidal infiltration of CD5⁺CD20⁺ lymphoma cells and large numbers of destroyed hepatocytes. These findings were diagnostic of primary hepatosplenic CD5⁺ DLBCL. Upon admission, lymphoma cells also appeared in the peripheral blood and serum hepatocyte growth factor (HGF) was markedly elevated. A bone marrow biopsy revealed extensive invasion by lymphoma cells. Seven days after admission, his laboratory data showed elevated aminotransferase and serum creatinine levels. Therefore, dose-reduced CH(O)P, with rituximab (R-CHOP) therapy, plasma exchange, and continuous hemodiafiltration, was initiated. The patient achieved complete remission after 4 courses of R-CHOP therapy. HGF is useful for predicting acute liver damage. If the HGF level is high, remission induction therapy, with plasma exchange, is necessary at an early stage.

Bendamustine is one of the new key drugs for patients with indolent lymphoma. Bendamustine, together with rituximab, significantly improves the treatment outcomes of these patients. In addition, previous clinical studies have shown the complication rate of severe infection in bendamustine-containing regimens to be relatively low as compared to those of conventional chemotherapeutic regimens such as CHOP. However, some clinical case reports have raised the possibility that bendamustine may abrogate the immune responses of patients and trigger opportunistic infections including cytomegalovirus reactivation. Herein, we report three indolent lymphoma cases becoming positive on cytomegalovirus antigenemia assay during bendamustine monotherapy. All events occurred after more than three courses of treatment with bendamustine. One patient showed decreased CD4 positive T lymphocytes before the development of cytomegalovirus antigenemia. All three patients were successfully treated with valganciclovir. Although the precise risk is unknown, it should be noted that bendamustine can potentially cause reactivation of/infection with cytomegalovirus and physicians should pay attention to the possibility of this infection during treatment with bendamustine-containing regimens.

A 60-year-old man was admitted to our hospital complaining of fever, headache and vertigo. Neurological examination on admission showed mild ataxic gait. Brain magnetic resonance imaging showed linear high intensity in the left parietal lobe on diffusion-weighted imaging (DWI) and laboratory data revealed elevated serum lactate dehydrogenase and soluble interleukin-2 receptor. Although intravascular lymphoma was suspected from these findings, bone marrow and skin biopsies were negative. Two months later, he presented with sensory disturbance of the left upper limb, and new lesions in the right frontal and bilateral parietal lobes were detected on DWI. A systemic evaluation showed multiple low-density lesions in the bilateral kidneys on computed tomography. Based on the results of a renal biopsy, we made a histological diagnosis of intravascular large B-cell lymphoma (IVLBCL). As IVLBCL is quite rare and often has a poor prognosis, a systemic evaluation to determine the proper biopsy site is needed for early diagnosis.

An 87-year-old man presented with appetite loss and abdominal distension. Routine blood tests revealed hypoproteinemia. Abdominal computed tomography revealed ascites, which was subsequently drained. Biochemical analysis of the ascitic fluid detected chyle. Esophagogastroduodenoscopy revealed nodular swelling of the mucosa, swelling folds, and widespread erosions in the stomach. Stage I diffuse large B-cell gastric malignant lymphoma was diagnosed on the basis of the Lugano International Conference classification system. Six courses of R-CHOP [rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine (Oncovin(®)), and prednisolone] therapy were administered, following which complete remission was achieved and the chylous ascites mostly disappeared.

A 57-year-old woman presented with motor and cognitive impairments under treatment for cryptogenic organizing pneumonia with immunosuppressive agents. Magnetic resonance imaging showed widespread signal abnormalities in the cerebral white matter. Susceptibility-weighted imaging showed attenuated contrast of the cerebral medullary vein in the lesions, and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) revealed decreased uptake at the same site and increased uptake in multifocal lung involvements. Lung biopsy findings were consistent with diffuse large B-cell lymphoma. Polymerase chain reaction for JC Virus DNA in cerebrospinal fluid yielded positive results. Based on these findings, the present case was given a diagnosis of progressive multifocal leukoencephalopathy (PML). The patient was treated with oral mefloquine, but her respiratory condition deteriorated and chemotherapy was required to prevent further deterioration. As a result, chemotherapy to treat lymphoma could not result in beneficial immune reconstitution, PML continued to progress despite mefloquine treatment, and the patient developed decorticate posture. The efficacy of mefloquine in patients with non-HIV-associated PML warrants further investigation.

A 68-year-old man developed a rapidly-growing right cervical tumor, a biopsy of which allowed for the diagnosis of diffuse large B-cell lymphoma, not otherwise specified. Magnetic resonance imaging demonstrated a right cervical mass lesion of 80 mm in diameter that extended from the medial region of the parotid gland to the posterior region of the neck. While undergoing a chest X-ray in an upright position, he lost consciousness and briefly fell. A transient loss of consciousness recurred while changing his position on the bed, and an electrocardiogram at that time revealed sinus arrest of a seven second duration. This syncope was considered to be a carotid sinus syncope (CSS) induced by the compression of the carotid sinus by his cervical bulky lymphoma. Temporary cardiac pacing was immediately started and rituximab was administered. Three days later, CHOP therapy was started. As his cervical tumor rapidly shrank, the frequency of sensed sinus arrests decreased to zero per day by day 9 of CHOP therapy, resulting into the removal of the pacemaker. In certain cases with CSS due to cervical lymphoma, cardiac pacing, if needed at the onset, is considered to become removable early after chemotherapy in association with tumor shrinkage.

A 49-year-old man was diagnosed with pure red cell aplasia (PRCA) based on low reticulocyte count (0.1%) and near absence of erythroblasts in the bone marrow (BM). While a small number of CD20-positive large abnormal cells was observed in the BM, Multiplex PCR confirmed B cell monoclonality. Gallium scintigraphy showed abnormality only in the BM, and we made a diagnosis of PRCA secondary to BM-derived B-cell malignant lymphoma. He was treated with rituximab-combined CHOP therapy with subsequent resolution of both disorders. He was further treated with high dose chemotherapy with auto-PBSCT, sustaining complete remission of the PRCA and lymphoma.

A 63-year-old woman was admitted to our hospital with high-grade fever, liver dysfunction, and pancytopenia. Computed tomography of the whole body revealed hepatosplenomegaly but no lymphoadenopaties. Bone marrow aspiration showed infiltrations of CD20-positive large atypical B-lymphocytes with severe hemophagocytosis. Although she was a human T-cell leukemia virus type 1 carrier, the atypical lymphocyte in bone marrow had IgH rearrangement but not TCR rearrangement. From these clinical and laboratory data, the patient was diagnosed as having B-cell lymphoma-associated hemophagocytic syndrome (B-LAHS) and treated with R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). After 4 cycles of R-CHOP, she had achieved complete remission. However, increased numbers of CD4+CD25+ flower cells were observed in peripheral blood and HTLV-1 provirus DNA was detected after 5 cycle of R-CHOP. The patient was diagnosed as adult T-cell leukemia-lymphoma (ATL) complicated by B-LAHS. Our observations suggest that continuous immunosuppressive statement for B-cell lymphoma or the chemotherapy against B-LAHS may induce the development of ATL in an HTLV-1 carrier.

We present a 68-year-old man suffering from transverse myelopathy since May 2010. The spinal cord MRI showed a T2- hyperintense lesion invading the Th5 level spinal cord. Although the patient transiently responded to steroid-pulse therapy, his neurological symptoms degenerated three months after wards. On admission, he had an apparent hepatosplenomegaly, but no lymphadenopathy. A laboratory examination revealed bicytopenia and increased levels ofLDH and soluble IL-2 receptors. Histological analysis ofa skin biopsy specimen demonstrated proliferation of large atypical lymphoid cells positive for CD20 and CD79a in the small capillaries, leading to our diagnosis of intravascular large B-cell lymphoma(IVLBCL). Thus, the patient's progressive myelopathy was probably caused by IVLBCL invasion. The patient responded well to Rituximab-combined CHOP therapy(R-CHOP), and his neurological symptoms improved immediately. A spinal cord MRI showed the disappearance of the abnormal signal after two courses of R -CHOP. IVLBCL often presents with neurological manifestations, including transverse myelopathy.

There is evidence of a slight increase in malignant lymphoma among rheumatoid arthritis(RA)patients receiving methotrexate( MTX). Increased rates of lymphoma have been attributed to reactivation of the Epstein-Barr virus(EBV). A 72-yearold woman was admitted to our hospital for generalized lymph adenopathy. She suffered from RA and has been treated with MTX for 7 years; the total amount of MTX received was around 2, 700 mg. The cervical lymph node revealed a diffuse proliferation of large atypical lymphocytes. An immunophenotype revealed CD10+, CD19+, CD20+, and k+. The chromosome analysis showed a complex abnormality containing t(14;18)(q32;q21). The tumor cells were positive for EBV sequences by in situ hybridization(ISH). A rituximab containing regimen was effective, but a systemic relapse occurred 4 years later. The biopsied sample was diagnosed as diffuse large B-cell lymphoma. FISH analysis revealed positive for t(14;18)(q32;q21), however, EBV was negative using ISH. In general, the concurrence of t(14;18)(q32;q21)and EBV in the B-cell lymphoma is rare. In addition, the negative change in EBV in the relapsed lymphoma cells revealed a quite rare phenomenon.

We report a resected case of malignant lymphoma with hypersensitivity pneumonitis. A 62-year-old woman, who presented with fever, wheeze and dry cough was referred to our department under the diagnosis of malignant B cell lymphoma in lower lobe of the left lung and hypersensitivity pneumonitis. She underwent left lower lobectomy as a therapy for malignant lymphoma. Pathological findings showed multiple small nodules macroscopically, which was observed as bronchiolocentric interstitial pneumonitis with lymphocytes microscopically. Post operative course was uneventful and no sign of acute exacerbation was seen. It is rare that lung with hypersensitivity pneumonitis is observed as a macroscopical specimen. Hypersensitivity pneumonitis differs from idiopathic pulmonary fibrosis, but we have to take care of post operative course because post operative acute exacerbation was reported.

A 76-year-old man was admitted to our hospital with dyspnea. Chest CT revealed bronchial stenosis caused by mediastinal lymphadenopathy. An FDG-PET scan showed increased FDG uptake in the mediastinal lymph nodes, lumbar vertebrae and left ilium. Neither the first biopsy specimen from the left ilium nor the endobronchial lesion showed malignant cells, but both were positive on acid-fast bacillus staining. Genetic testing found the Mycobacterium avium (MAC) gene. Therefore, we diagnosed disseminated MAC infection, and started antibiotic therapy. However, he did not respond to the therapy, and his bronchial stenosis worsened. We performed a biopsy of the newly-appearing supraclavicular lymph node, and of the left ilium again, and confirmed a new diagnosis; diffuse large B cell lymphoma, coexistent with disseminated MAC infection. This case suggests not only the simultaneous occurrence of disseminated MAC infection and diffuse large B cell lymphoma, but also the coexistence of both diseases within the same organs, and that there may be some relationship between the two diseases.

We report a 62-year-old woman with intravascular lymphomatosis (IVL) which presented as subacute encephalopathy. She was admitted to our hospital because of loss of consciousness in the middle of February, 2006. Laboratory tests indicated elevated serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed multiple infarct-like lesions mainly in the white matter. After admission, her consciousness was soon improved, but the inflammatory response did not disappear with any antibiotics or virucides. Her consciousness was not exacerbated, and she was discharged in the middle of March, although the reason for loss of consciousness remained unknown. After discharge she developed an abnormal behavior and mental deterioration, and therefore she was readmitted late in March. On second admission, her consciousness was drowsy. Neurological examinations revealed conjugate deviation of her eyes to the left, left hemiparesis, and generalized hyporeflexia. Laboratory tests showed more elevated CRP than that of the last time, and raised soluble IL-2 receptor (sIL-2R). The repeated MRI of the brain disclosed that initial lesions of the white matter progressively enlarged and increased in number. To make an appropriate diagnosis of the lesions on the brain MRI, the open brain biopsy was performed. Microscopic examination showed that many small vessels were occluded by lymphoma cells (B-lymphocytes) with hemorrhage, and IVL was diagnosed. She was treated with regimens of combined chemotherapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone). After chemotherapy her consciousness and left hemiparesis were gradually improved and the levels of CRP were normalized. The infarcts-like lesions detected on the brain MRI became reduced and decreased. IVL is a rare disease, and the prognosis is generally poor, with a rapidly fatal outcome, leading to a postmortem diagnosis. In the present report, we successfully treated the patient by rituximab in addition to standard CHOP therapy. Rituximab may play an important role in the treatment of IVL.

We present a case of a 62-year-old female was admitted with complaints of slowly developing paraplegia ascending from the distal portions, and a 7-month history of recto-urinary dysfunction. T2-weighted magnetic resonanse imaging (MRI) of the spinal cord showed hyperintense lesions in the thoracic and sacral cord. Multiple sclerosis was assumed, and steroid pulse therapy was therefore administered: this temporarily improved the symptoms and imaging findings. However, the symptoms recurred in 2 months. The patient died after ineffective steroid therapy. Large B-cell lymphoma cells were identified on bone marrow biopsy. Macroscopic neuropathology revealed neoplastic cells in the blood vessels of the cauda equina. Paraplegia appeared to have developed slowly and in a non-stepwise manner, since the cauda equina has been gradually invaded by intravascular malignant lymphomatosis.

A 75-year-old woman was admitted for general fatigue. Diagnostic investigations showed no lymphadenopathy or hepatosplenomegaly. Laboratory examinations revealed severe anemia and an undetectable level of haptoglobin in the peripheral blood. A direct Coombs test was positive. Bone marrow examination showed abnormal, large, CD20-positive lymphocytes and erythroid hypoplasia. Accordingly, a diagnosis of primary diffuse large B-cell lymphoma (DLBCL) of the bone marrow with autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia was made. The patient was treated with prednisolone and 3 courses of rituximab, followed by 6 courses of R-CHOP. AIHA and erythroid hypoplasia subsided after prednisolone and 3 courses of rituximab. Treatment with 6 courses of R-CHOP resulted in complete remission. Isolated bone marrow disease as a presenting feature of DLBCL is very rare. Although malignant lymphomas are often associated with immunologic disorders, this is the first report of diffuse large B-cell lymphoma with isolated bone marrow disease and simultaneous autoimmune hemolytic anemia and erythroid hypoplasia. This case provides valuable information concerning the pathophysiology of an immunologic anomaly with malignant lymphoma.

A 38-year-old man with non-Hodgkin's lymphoma presented with hypesthesia and muscle weakness in the left upper limb. A lack of F-waves in left median and ulnar nerve conduction studies suggested a lesion at the proximal segments of the peripheral nerves, such as the left brachial plexus or nerve roots. Cervical magnetic resonance imaging revealed no lesions compressing nerve roots or peripheral nerves. Small and obscure uptake on the left side of the cervical nerve roots on 67Ga-scintigraphy was indistinguishable from artifact. Positron emission tomography-computed tomography (PET/CT) revealed a region of high glucose uptake in a left cervical intervertebral foramen, leading to a diagnosis of neurolymphomatosis. Neurological symptoms improved following additional chemotherapy, and the high glucose-uptake lesion disappeared. FDG-PET/CT is useful for rapid and non-invasive evaluation of neurolymphomatosis.

A 76-year-old woman was admitted to our hospital because of exertional dyspnea and leg edema during the previous month. Her systolic blood pressure on admission was 80 mmHg with 12 mmHg of pulsus paradoxous, and her pulse rate was 110 beats/min. Chest radiography revealed marked cardiomegaly and echocardiography showed massive pericardial effusion mainly behind the left ventricle and collapse of the right ventricle. The initial diagnosis was pericardial tamponade. Pericardiocentesis and pericardial drainage revealed bloody pericardial effusion. After drainage, her vital signs improved and her symptoms immediately disappeared. The cytological analysis of the pericardial effusion revealed numerous lymphoma cells. Computed tomography of the neck, chest and abdomen showed no evidence of tumor masses, lymph node enlargement, or hepatosplenomegaly. Infectious disease, collagen disease and aortic dissection were excluded. The final diagnosis was primary effusion lymphoma. The prognosis of primary effusion lymphoma is generally unfavorable because it is frequently accompanied by immunodeficiency disease. However, there was no human immunodeficiency virus infection in this patient. Fortunately, the effect of chemotherapy was excellent and the patient is doing well 1 year after the diagnosis.

A 49-year-old man was admitted with high-grade fever, night sweating and cervical lymphadenopathy in September 2005. On examination, both neutrophilia and thrombocytosis were noted in the peripheral blood, a bone marrow examination revealed marked both myeloid and megakaryocytic hyperplasia. The sera obtained at initial presentation showed an elevated levels of granulocyte-colony stimulating factor (G-CSF) and interleukin-6 (IL-6). A pathologic diagnosis of T-cell rich B-cell lymphoma was made based on an inguinal lymph node biopsy. Following treatment with CHOP accompanied by rituximab (R-CHOP), both the neutrophilia and thrombocytosis subsided after 3 courses of R-CHOP, resulting in a complete remission after 4 courses of chemotherapy. Neutrophilia, thrombocytosis and T-cell rich B-cell lymphoma in this patient were considerably ameliorated with chemotherapy. We report here a patient with T-cell rich B-cell lymphoma associated with both neutrophilia and thrombocytosis, suggesting that the lymphoma triggered both myeloid and megakaryocytic hyperplasia.

Malignant lymphoma is often accompanied by an autoimmune disorder. Here, we describe a 82-year-old woman with pure red cell aplasia (PRCA) complicated with relapsed diffuse large B-cell lymphoma. Primary treatment involving chemotherapy, continuous oral administration of prednisolone and a single infusion of rituximab was unsuccessful for both diseases, but the following treatments with 3 courses of rituximab alone for once a week dramatically improved the PRCA as well as the lymphoma. As PRCA complicated with lymphoma is rare, the ideal therapeutic strategy has not yet been established for it. Rituximab may be a good alternative for treating such cases.

A 54-year-old woman was admitted due to high-grade fever, cervical lymphadenopathy and general malaise in May 2003. On examination, severe anemia was noted, direct Coombs and cold hemagglutinin tests were positive and the haptoglobin level was low in the peripheral blood. However, a bone marrow examination revealed marked erythroid hypoplasia. A diagnosis was made of co-existing combined type autoimmune hemolytic anemia (AIHA) and erythroid hypoplasia. A pathologic diagnosis of de novo CD5-positive diffuse large B-cell lymphoma (de novo CD5+ DLBCL) was made based on a cervical lymph node biopsy. The patient was treated with CHOP accompanied by rituximab (R-CHOP), resulting in complete remission after 3 courses of chemotherapy. The AIHA and erythroid hypoplasia subsided after 2 courses of R-CHOP. The sera obtained during erythroid hypoplasia significantly inhibited the growth of erythroid progenitor cells (erythroid colony-forming units, CFU-E) from her bone marrow collected after recovery. We report here a patient with de novo CD5+ DLBCL associated with both AIHA and erythroid hypoplasia, suggesting that the lymphoma triggered an abnormal immunity which generated some humoral inhibitors against erythropoiesis.

A 77-year-old man was admitted to our hospital with complaints of abdominal pain and body weight loss. Esophagogastroduodenoscopy on admission revealed large ulcerative tumor in the entire region from upper to lower body of the stomach. We diagnosed gastric malignant lymphoma, diffuse large B-cell type and determined stage IV according to the Lugano International Conference classification. Due to gastric perforation occurred on day 4 of chemotherapy, total gastrectomy and partial resection of the transverse colon were performed. Complete remission was achieved by 2 cycles of postoperative chemotherapy together with rituximab.

Bronchoesophageal fistulae associated with lymphomas are generally associated with chemo-radiotherapy. We report here an unusual case of lymphoma with a therapy-unrelated bronchoesophageal fistula. Previously, only 10 similar cases have been reported. A 70-year-old male was diagnosed as having gastric diffuse large B-cell lymphoma in May 1998. In January 1999, he noted a cough after eating and drinking. Because of the presence of a febrile temperature, productive cough and dyspnea, he was referred to our hospital and diagnosed as having aspiration pneumonia. Antibiotics did not improve his symptoms. When tracheal intubation was performed with bronchoscopy, a bronchoesophageal fistula was revealed. Malignant lymphoma cells were found around the fistula in the biopsy specimen. The patient died of pneumonia after treatment with airway stenting and chemotherapy. Induction of necrosis by chemotherapy or low blood flow with stenting and dopamine probably caused enlargement of the fistula.

Background: It is relatively rare to encounter a case of neovascular glaucoma induced by malignant lymphoma metastasized into the eyeball., Case: A 79-year-old woman initially visited our ophthalmology clinic with the chief complaint of blurring of vision in the left eye which was affected by neovascular glaucoma. She had a history of systemic malignant lymphoma, first diagnosed from skin biopsy and treated to complete remission 3 years previously. A metastatic brain lesion, detected 2 months before her initial visit to our clinic, was cured by radiotherapy., Findings: By ultrasound biomicroscopy (UBM) we detected abnormal thickening of the temporal half of the ciliary body of her left eye. Cytological examination of the aqueous humor revealed invasion by malignant cells of presumed lymphocyte origin. Radiation therapy to the left eye normalized the intraocular pressure in a week, followed by a reduction in the neovascularization of the iris and the thickening of the ciliary body., Conclusion: This case showed that metastatic malignant lymphoma in the eye could result in neovascular glaucoma and that UBM is useful to detect and to observe lesions in the iris and ciliary body.

A 76-year-old woman was admitted to the University of Tokyo Hospital in June 2002 because of fever of unexplained origin. She had suffered a high grade fever (above 39 degrees C) for 2 weeks. Initial evaluation revealed elevated CRP and pancytopenia. Bone marrow aspiration (BMA) was performed, and a diagnosis of pure red cell aplasia (PRCA) was made. One month later, she complained right hypochondrial pain, and aspiration from her enlarged gall bladder was performed. Her fever and PRCA ameliorated, and she was discharged in August, 2002. In April 2003, she was readmitted to our hospital because of the recurrence of high grade fever, elevation of CRP, and pancytopenia. BMA was performed and revealed diffuse large B cell lymphoma. In the case of extranodal lymphoma which only presents pyrexia, differentiation with other diseases is very difficult especially in the elderly. It is necessary to bear in mind the possibility that a hematological malignancy, especially malignant lymphoma, can be latent in elderly patient with fever of unknown origin.

We report a 47-year-old woman with progressive multifocal leukoencephalopathy (PML). She was a carrier of HTLV-I virus, and developed subacute right hemiparesis and marked motor aphasia. She had a malignant lymphoma in the left neck and basal cell carcinoma in the right inguinal region. Three months after the onset, she became unable to walk because of the right leg weakness or to speak because of motor aphasia. Magnetic resonance imaging (MRI) revealed multifocal T2-high lesions in the white matter of the left frontal lobe, and a brain biopsy revealed demyelinating pathology. A biopsy of the left parotid gland revealed a diffuse pleomorphic type large B cell lymphoma. Although anti-HTLV-I antibody was positive in the serum and cerebrospinal fluid (CSF), no adult T-cell leukemia (ATL) cells were found in the blood or CSF. The patient was then admitted to our hospital. Neurological examinations revealed severe motor aphasia, mild sensory aphasia/cognitive impairment, right hemiplegia, mild right hemihypesthesia, limb-kinetic apraxia in the left hand, idiomotor apraxia, agraphia, perseveration, marked spasticity and brisk tendon reflex in four extremities, and positive bilateral pathological reflexes. MRI showed multifocal T2-high lesions mainly in the cerebral white matter, predominantly in the left hemisphere, and partly in the cerebral cortex. No gadolinium enhancement was found. In addition, 99mTcECD-SPECT showed a broad decrease in cerebral blood flow (CBF) in the cortex. Anti-HTLV-I antibody was positive but anti-HIV antibody was negative in serum. ATL cells were found in 1-3% of the peripheral white blood cells after admission. CSF examination revealed that the cell count (1/microl), protein level (24 mg/dl), and IgG index (0.4) were all normal. However, the myelin basic protein level (321 pg/ml; normal < 102) was increased, JC virus DNA was detected by PCR, and anti-HTLV-I antibody (x 8) was detected in CSF. The regulatory region of the JC virus DNA in the CSF was partly deleted; immunostaining with anti-JC virus protein antibodies revealed the existence of JC virus in biopsied brain specimens, and these findings were consistent with PML. Her symptoms such as motor aphasia, cognitive dysfunction and left hemiparesis were subacutely progressive, and she developed akinetic mutism two weeks after admission. Since the efficacy of cytosine arabinoside for PML has been reported, she was administered 80 mg/day of the drug for five days. After treatment, her communication function was mildly improved but the efficacy was transient. Since it has been reported that HTLV-I, as well as HIV, activates the JC virus promoter and its proliferation, the latent infection of HTLV-I in the central nervous system (CNS) in this case might have stimulated the JC virus proliferation, promoting lesion extension over the cerebral cortex. There have been only a few reports of broad decreases in CBF by SPECT in PML patients. Further MRI and SPECT studies on PML patients are therefore necessary to evaluate the significance of HTLV-I in promoting the JC virus infiltration into the CNS.

We report a rare case of malignant lymphoma arising from the posterior mediastinum with bilateral pleural effusion. A 71-year-old man was admitted to our hospital for evaluation of a posterior mediastinal tumor and bilateral pleural effusion revealed on a chest CT scan. Because no tumor tissue could be obtained by fiberbronchoscopy, video-assisted thoracoscopic surgery was performed. The tumor sample was composed of large, atypical lymphocytes positive for CD20 on immunohistochemical analysis. A diagnosis of diffuse large B cell lymphoma was made from the typical histological features. The patient was treated with combination chemotherapy (CHOP) and rituximab and improved dramatically.

A 29-year-old man with diffuse large B-cell lymphoma treated by radiotherapy for his relapsed lesion followed by 4 doses of weekly rituximab was admitted to our hospital with interstitial pneumonia. After steroid pulse therapy, he had contraction of the left visual field. He was diagnosed as having progressive outer retinal necrosis due to a varicella-zoster virus that was detected from the left vitreous sample. Systemic antiviral treatment failed to prevent rapid development of whole layer necrosis of the left retina. Vitrectomy with silicone oil tamponade saved his final visual acuity. This unusual event might be related to rituximab causing deterioration of humoral immunity.

A 77 year-old woman who had been treated for Evans' syndrome was admitted to our hospital because of the development of bilaterally-enlarging abnormal lung shadows. She had been diagnosed as having Evans' syndrome since she was 64 years old, and had been treated with corticosteroids. She had also been found positive for hepatitis C virus, and was suffering from chronic hepatitis. The pathological examination of a transbronchial biopsy specimen revealed B-cell malignant lymphoma of the diffuse large-cell type. A computed tomography (CT) scan showed lung tumors, hilar lymph node swelling, but no other definite tumors. Gallium scintigraphy showed positive accumulation only in the lungs, and so a diagnosis of primary pulmonary lymphoma was made. She received several courses of standard CHOP therapy and achieved a partial remission. She died 8 months later, however, of bleeding from esophageal varices associated with liver cirrhosis. To our knowledge, primary pulmonary lymphoma associated with Evans' syndrome is extremely rare. Although the underlying mechanism remains to be clarified, it is likely that immunological disorders complicating Evans' syndrome lead to the development of malignant lymphoma in some cases.

Malignant lymphomas cause various neurological complications by several ways. They include 1) infiltration and compression due to lymphoma itself, 2) ischemia due to intravascular proliferation of lymphoma cells, 3) paraneoplastic syndrome, 4) immunodeficiency due to lymphomas, 5) organ dysfunction due to lymphomatous infiltration, and 6) complication related to therapies against lymphomas. We presented 4 patients with neurological complications caused by B cell lymphomas as follows. Our first patient was a 67-year-old woman with primary intracranial lymphoma whose onset simulated that of a cerebral infarct. The second patient was a 52-year-old man with lymphoma, who developed myelopathy caused by an intradural extramedullary spinal cord tumor. He received chemotherapy and radiation therapy, followed by complete remission. The third was a 80-year-old man with left cavernous sinus syndrome, which did not respond to therapies against lymphoma. The fourth was a 55-year-old man who presented with numb chin syndrome on both sides, followed by multifocal lymphomatous involvement of the cranial nerves, spinal roots and leptomeninges. Malignant lymphomas may affect any regions of the central and peripheral nervous systems by various ways. Early diagnosis and treatment are essential for the better outcome of neurological complications due to lymphomas.

A 56-year-old woman was admitted because of anemia in April 2001. A diagnosis of malignant lymphoma (ML) (diffuse mixed, B-cell type) had been made in March 2000 whereafter she had been treated with CHOP chemotherapy and had achieved complete remission (CR). On examination, it was found she had concurrently developed pure red cell aplasia (PRCA) and warm type autoimmune hemolytic anemia (AIHA) without relapse of the ML. The PRCA and AIHA were successfully treated with prednisolone. To our knowledge, only 4 cases of PRCA and AIHA associated with ML have been reported. Moreover, this is the first report of the coexistence of PRCA and AIHA occurring during the CR of ML.

We report a case of pleural malignant lymphoma associated with chronic tuberculous pyothorax. A 67-year-old male was hospitalized because of left lateral chest swelling and pain. He had suffered from pulmonary tuberculosis at the age of six and tuberculous pleurisy at the age of 24. We made a histologic diagnosis of malignant lymphoma diffuse large B-cell type. He was medicated THP-COP (THP, CY, VCR, PSL) therapy and his chest pain and swelling has improved gradually. From the view point of molecular biology, we detected Epstein-Barr virus (EBV) infection in the pyothorax wall. In conclusion, we should be more careful about medical examination in patients with EBV positive tuberculous pyothorax considering the complication of malignant lymphoma.

We report a 71-year-old man with intravascular malignant lymphomatosis who showed high serum LDH and urinary disturbance for one year before manifesting dementia. High serum LDH was found at a health check at age 70. Two months later, he had an onset of backache and urinary retention. MRI of the spinal cord was unremarkable. One year later, he showed decline of mental activities and was admitted to our hospital. He was agitated and confused. However cranial nerve palsy or limb weakness was not noted. The MRI of the brain showed T2-high signal in bilateral occipital, right temporal lobe and the left insular cortices. The abdominal CT scan showed swelling of the adrenals on both sides. Adrenal biopsy revealed diffuse large B cell lymphoma. He developed respiratory distress and he died two months after the admission. Post mortem examination revealed intravascular and extravascular proliferation of lymphoma cells in most of the internal organs including adrenals, spleen, liver and the kidneys. In the brain, the laminar necrosis was seen in the left occipital cortex and hemorrhagic infarctions were noted in the insular and temporal cortices and the medial temporal cortex. Sacral spinal cord showed necrosis of the gray matters and loss of myelinated fibers in the white matter. Intravascular proliferation of the lymphoma cells were also seen in the vessels of the brain and the spinal cord. This patient suggests the importance of survey for intravascular malignant lymphomatosis, when high serum LDH and myelopathy of lumbosacral area are seen.

A 47-year-old woman was admitted for examination of massive right pleural effusion on chest radiography, together with chief complaints of dry cough and body weight loss. Exudative effusion was aspirated by thoracentesis, revealing many lymphocytes and a high level of adenosine deaminase. Thoracoscopy with local anesthesia was performed. Elevated white lesions and miliary nodules were observed, and these lesions were examined by thoracoscopic biopsy, leading to a diagnosis of malignant lymphoma. Treatment with chemotherapy (THP-COP) resulted in partial remission. Thoracoscopy with local anesthesia in cases of pleural effusion with malignant lymphoma can be a safe and useful procedure for diagnosis.

Two cases of pyothorax-associated malignant lymphoma were reported. The presence of chronic tuberculous pyothorax after thoracoplasty and the development of non-Hodgkin's lymphoma on the chest wall are closely related. Both patients had suffered from tuberculous pyothorax for more than thirty years, and developed new painful chest wall tumors. CT and MRI delineated both malignant lymphoma and pyothorax. Gallium-67 accumulated strongly in malignant lymphoma, however did not in pyothorax. Gallium-67 scintigraphy was useful for detection of malignant lymphoma in both cases; therefore it could be a useful test for diagnosing of pyothorax-associated lymphoma.

The authors report the case of a 54-year-old male with extraaxial primary malignant lymphoma associated with calcified chronic subdural hematoma. He slowly developed progressive headache accompanied by a bulge in the left forehead. Skull radiogram showed a large biconvex calcification in the left frontoparietal region, with concave change in the overlying bone. Computed tomograms and magnetic resonance images revealed a left frontoparietal chronic subdural hematoma surrounded by a calcified rim, with marginal enhancement in the frontal portion extending upward to the subcutaneous tissue through the underlying bone. The lesion was suspected to be an infectious calcified hematoma. The patient underwent a craniotomy for the removal of the hematoma. It was observed that the tumor was located mainly in the epidural and subdural space. The extent of the tumor corresponded with the enhanced area of the lesion in the preoperative neuroimages. The histological diagnosis was malignant lymphoma of B cell origin. General examination, which included bone marrow study and Ga scintigraphy, failed to prove systemic lymphoma. Extraaxial primary malignant lymphoma is extremely rare, and this is the first report of a lymphoma associated with calcified chronic subdural hematoma. The authors review the literature and discuss the clinical features and the pathogenesis of the lesion.

We report a 73-year-old woman with intravascular malignant lymphomatosis (IML) who showed generalized telangiectasia as well as various neurological symptoms. In July 1998, she developed fever, dizziness, and confusion followed by left hemiparesis, and was admitted to our hospital on August 11, 1998. Laboratory tests indicated a normochromic normocytic anemia, thrombocytopenia, elevated serum lactic dehydrogenase (LDH), C-reactive protein (CRP), and cerebrospinal fluid protein. Magnetic resonance imaging (MRI) of the brain revealed an infarct-like lesion in the left frontal lobe and multiple white matter lesions. After admission, her neurological status deteriorated and lapsed into coma and quadriplegia. At the end of September 1998, generalized telangiectasia appeared, and she was diagnosed as IML on skin biopsy. Although combination chemotherapy failed to improve her neurological symptoms, telangiectasia disappeared in a few days, and the infarct-like lesion on MRI decreased in size. Serum LDH, CRP, and thrombocyte counts were normalized. Autopsy findings revealed perivascular clustering of B cell type lymphoma cells in the left frontal lobe where abnormal signal intensity was found on MRI, as well as the spleen and the bone marrow. This case emphasizes the importance of early diagnosis and treatment in IML.

B cell lymphoma-associated hemophagocytic syndrome (B-LAHS) is clinically characterized by hepatosplenomegaly and bone marrow invasion without lymphadenopathy and skin lesions. Several cases of B-LAHS have been reported to demonstrate histopathologic findings of intravascular lymphomatosis (IVL), which in Western countries is characterized by a high rate of skin involvement and, rarely, bone marrow involvement and hemophagocytosis. Here we describe two interesting cases of B-LAHS. One patient was a 52-year-old woman whose bone marrow showed proliferation of large CD20-positive cells and hemophagocytosis at presentation. Combination chemotherapy was not effective, and the patient died of progressive disease. At autopsy, the lymphoma cells showed extravascular proliferation in many organs such as the bone marrow and liver, whereas in the adrenal glands, the lymphoma cells showed intravascular proliferation. The other patient was a 50-year-old man who had swellings of the bilateral kidneys and adrenal glands at presentation. Skin involvement by large lymphoma cells, a rare complication of B-LAHS, was observed. At autopsy, there was no evidence of IVL. Both of these patients showed high fever and cytopenia, and the disease took an aggressive clinical course, as in other reported cases of B-LAHS.

A case with systemic non-Hodgkin lymphoma involving the sella turcica and kidney is reported. A 69-year-old man presented with a progressive two month history of visual disturbance and headache. Neurological examination revealed bilateral visual disturbance and right optic atrophy. MRI showed a contrast-enhancing mass in the sella turcica. The tumor extended to the right optic nerve. Without extensive studies for systemic disease, the patient immediately underwent transsphenoidal surgery. The slightly firm, fibrous and vascular-rich tumor was subtotally removed. The histopathological examination revealed a malignant lymphoma, diffuse-large-cell type with B-cell phenotype. The postoperative course was uneventful and the patient's symptoms subsided gradually. The patient received radiation therapy and the tumor disappeared. Postoperative CT examinations of the abdomen and pelvis revealed a large mass at the upper portion of the left kidney. Ga-scan also suggested the mass to be consistent with the abdominal CT. However, the patient suddenly died of acute heart failure with unknown cause just before starting chemotherapy for systemic lymphoma. Patients presenting primary central nervous system lymphoma (PCNSL) may have systemic non-Hodgkin lymphoma. To exclude systemic non-Hodgkin lymphoma, systemic investigation is essential for the initial management of patients presenting PCNSL.

A case of intravascular malignant lymphomatosis (IML) presenting as progressive cerebral infarction is reported. A 62-year-old previously healthy male developed progressive dementia. MRI of the brain at the nearest hospital revealed multiple infarcts with unknown etiology. His level of consciousness deteriorated rapidly, and then he was transferred to our hospital for further evaluation. High grade fever, raised serum C reactive protein (CRP), and raised lymphoma markers (serum LDH and soluble IL-2 receptor (sIL-2R)) were observed. Repeated brain MRI disclosed progression of multifocal cerebral infarctions. We considered IML most likely, and we performed muscle biopsy. However muscle biopsy didn't demonstrate any proliferation of neoplastic cells of lymphoid origin within small vessels. Thereafter IML was diagnosed by brain biopsy. The patient underwent chemotherapy, but died of pneumonia due to severe myelosuppression. IML is a rare disease but most commonly shows neurological symptomatology as its clinical manifestation. Dementia is the most common neurological symptom, and progressive multiple infarction is the most common of the MRI findings. Rapidly progressive dementia associated with multiple infarction, when elevated CRP, LDH and sIL-2R are observed in the laboratory data, is suggestive of IML.