Clinical characteristics and incidence of toxoplasmosis after autologous hematopoietic stem cell transplantation: A retrospective study and literature review.

BACKGROUND: Toxoplasmosis is a rare but life-threatening infection occurring in immunocompromised hosts, including allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. However, thus far, the clinical features and incidence of toxoplasmosis in autologous HSCT (auto-HSCT) recipients remain unknown. This retrospective survey aimed to analyze 152 patients who received auto-HSCT between 1998 and 2017. METHODS: Serological tests for Toxoplasma gondii-specific IgG were performed on 109 (71.7%) recipients, and 12 pre-HSCT recipients (11%) were Toxoplasma seropositive. Among the 12 recipients, three who did not receive trimethoprim-sulfamethoxazole (TMP/SMX) prophylaxis developed cerebral, pulmonary or disseminated toxoplasmosis due to reactivation after auto-HSCT and died despite treatment. RESULTS: The incidences of toxoplasmosis were 2% and 25% among 152 auto-HSCT recipients (five recipients received auto-HSCT two times) and 12 pre-HSCT Toxoplasma seropositive recipients, respectively. Further, we conducted a literature review and identified 21 cases of toxoplasmosis following auto-HSCT. In these previous cases, the mortality rate was high, especially for pulmonary and disseminated toxoplasmosis. Our findings suggest that, similar to toxoplasmosis after allo-HSCT, toxoplasmosis after auto-HSCT is a fatal complication. CONCLUSIONS: Serial screening of T. gondii-specific IgG before HSCT could contribute to the detection of Toxoplasma reactivation and allow for prompt diagnosis and treatment. The present study is the first to reveal the incidence of toxoplasmosis after auto-HSCT among seropositive patients in Japan.

Anaplastic transformation of thyroid cancer in mesentery metastases presenting as intestinal perforation: a case report.

BACKGROUND: Anaplastic thyroid carcinoma is a highly aggressive form of thyroid cancer associated with a very poor prognosis. Anaplastic transformation most commonly occurs in the thyroid itself or within regional lymph nodes. Here we report the case of a patient with papillary thyroid cancer, presenting with colon perforation as a result of anaplastic transformation of metastases in the mesentery tissue. There have been no previous reports of this form of anaplastic transformation. CASE PRESENTATION: A 74-year-old man was admitted to our hospital, presenting with abdominal pain that he had been experiencing for 1 week prior to admission. The patient had a history of papillary thyroid carcinoma, for which he underwent a total thyroidectomy and mediastinal lymph node dissection 6 years earlier, and subsequently received radioactive iodine therapy for postoperative recurrence in the lung 2 years later. During the present reported admission, a computed tomography scan revealed a large intra-abdominal mass infiltrating into the colon and retroperitoneum and also highlighted the pneumoperitoneum. The patient was diagnosed with generalized peritonitis as a result of colon perforation, as such, we conducted an emergency laparotomy. Intraoperative findings showed a mass affecting the ascending colon and kidney, following which, an ileostomy and biopsy were completed. Poorly differentiated spindle cells were identified in the biopsy specimens, and histopathological and immunohistochemical findings revealed the absence of thyroid carcinoma cells. The tumor was therefore believed to be a primary sarcoma. Following surgery, the patient recovered from sepsis that had arisen as a result of colon perforation, however, rapidly developed systemic metastases and died 1 month post-operation. An autopsy was performed, and the patient was diagnosed with anaplastic papillary thyroid cancer at the mesentery site of metastasis. This conclusion was reached owing to the presence of the squamous differentiation of lymph node cells, and because tumor cells were positive results for paired-box gene 8 expressions. CONCLUSIONS: Anaplastic transformation of papillary thyroid carcinoma should be considered in the diagnosis of a large mesentery mass in patients with a history of papillary carcinoma. An appropriate biopsy and paired-box gene 8 immunostaining can be useful in confirming such a diagnosis.

[Successful Treatment of Squamous Cell Lung Cancer without PD-L1 Expression Using Fourth-Line Nivolumab].

A 71-year-old woman was diagnosed with stage ⅢB locally advanced lung squamous cell cancer(cT0N3M0).Programmed death-ligand 1(PD-L1)immunostaining was negative.First -line nedaplatin plus docetaxel and second-line carboplatin plus nab-paclitaxel were followed by sequential thoracic radiation therapy(60 Gy).The patient developed radiation pneumonitis, but her condition improved with corticosteroids.However, chest computed tomography(CT)revealed multiple nodules in both lungs.Third -line carboplatin plus tegafur/gimeracil/oteracil potassium(S-1)was not successful, and fourth- line nivolumab(3mg/kg every 2weeks)was adopted.On day 9 after first administration, she developed fever and radiation recall pneumonitis.Multiple nodules rapidly formed, but they later gradually decreased in number.After 13 courses of nivolumab, the nodules had disappeared completely.Mediastinal lymph nodes decreased in size, but an abdominal lymph node remained enlarged.Nivolumab was continued, and after 24 courses, the abdominal lymph node began to shrink, and the multiple lung metastases continued to disappear.Currently, the best overall response is good partial response to nivolumab.

[Miliary tuberculosis with markedly elevated soluble interleukin-2 receptor levels mimicking intravascular large B-cell lymphoma].

An 81-year-old woman with type 2 diabetes mellitus presented to our hospital due to anorexia, leg edema, and respiratory distress. Laboratory results revealed anemia, thrombocytopenia, elevated lactate dehydrogenase, and markedly elevated soluble interleukin-2 receptor levels. Computed tomography showed ground-glass opacities and consolidation in both lung fields, but no lymphadenopathy was noted. Intravascular large B-cell lymphoma (IVLBCL) was considered as a differential diagnosis; therefore, bone marrow and random skin biopsy were performed. Her respiratory condition deteriorated, with the occurrence of acute respiratory distress syndrome, disseminated intravascular coagulation, hemophagocytic syndrome, and further alveolar hemorrhage. Methylprednisolone pulse therapy was performed, but did not improve the patient's condition. On hospital day 6, the acid-fast bacterial smear of the sputum using the Gaffky scale was 2, and on the next day, tuberculosis DNA was detected in the polymerase chain reaction. In the bone marrow biopsy, multiple epithelioid cell granulomas were found; thus, the patient was diagnosed with miliary tuberculosis. Although anti-tuberculosis therapy was started immediately, she died on hospital day 22. The soluble interleukin-2 receptor level increased up to 19,400 U/ml. The differential diagnosis should be cautiously made because miliary tuberculosis can mimic IVLBCL.

Clival Metastasis of Hepatocellular Carcinoma with an Initial Histopathological Diagnosis of Atypical Pituitary Adenoma.

Histologically, hepatocellular carcinoma (HCC) and atypical pituitary adenoma are similar, posing a potential clinical problem. A 76-year-old woman, whose past medical history was significant for hepatitis C virus (HCV), positivity without liver cirrhosis was presented with abducens nerve (CN VI) palsy. Contrast-enhanced magnetic resonance imaging (MRI) showed a clival tumor with infiltration of the right cavernous sinus. Subtotal resection was performed using a right anterior petrosal approach. Histological diagnosis was pituitary adenoma. Thirty-four days after the operation, MRI imaging showed residual tumor growth without any liver masses on computed tomography (CT). The patient underwent a second operation using an endoscopic transnasal transsphenoidal approach. Histological examination of the specimen gave a positive reaction for α -fetoprotein. Repeat whole-body CT showed an enhanced liver mass. Based on these findings, the lesion was diagnosed as metastatic HCC. The patient died of liver failure 6 months later. In this case, tumor diagnosis was difficult because of the histological similarity of HCC and pituitary adenoma, and the fact that the clival tumor grew prior to presentation of the liver mass on CT. This case emphasizes the importance of comparing the pathological diagnosis with the patient's clinical course.

[Direct Carotid Puncture for Endovascular Thrombectomy in a 96-Year-Old Patient with Acute Cerebral Infarction:A Case Report].

We report a case of direct carotid puncture for endovascular thrombectomy in a 96-year-old patient with acute cerebral infarction. Anatomical difficulties of carotid artery access, including an unfavorable aortic arch type and the tortuosity of carotids, could have resulted in a recanalization delay or failure in patients with acute ischemic stroke. A 96-year-old woman developed sudden right hemiparesis. By initiating thrombectomy, we could not access the common carotid artery;therefore, we performed a direct carotid puncture on the neck and achieved successful recanalization with improvement of hemiparesis. We discuss the limitations and technical aspects of this technique. We conclude that in case of stroke, a direct carotid artery puncture is a feasible alternative to an anatomically difficult transfemoral access.

[Neurolymphomatosis due to enteropathy-associated T-cell lymphoma clinically diagnosed by FDG-PET/CT and subsequently confirmed by autopsy].

A 59-year-old man who complained of abdominal pain was referred to our hospital. Computed tomography (CT) revealed mesenteric lymph node swelling and intestinal perforation. Histopathological study of the resected ileum and lymph node demonstrated diffuse proliferation of medium-sized atypical lymphocytes. Immunohistochemistry results were positive for cluster of differentiation (CD) 3, CD8, and CD56 cells, negative for CD5 and CD4 cells, and negative for Epstein-Barr virus-encoded RNA-fluorescent in situ hybridization (EBER-FISH). It also revealed the expression of γδ T-cell receptors. On the basis of these findings, enteropathy-associated T-cell lymphoma (EATL) was diagnosed. Although the patient received two courses of cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone (CHOP) and dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) therapy, facial nerve and lower limb paralysis manifested. Magnetic resonance imaging (MRI) and lumbar puncture revealed central nervous system invasion of the EATL. Despite intrathecal chemotherapy and high-dose cytarabine therapy, the patient's neurological symptoms deteriorated. Fluorodeoxyglucose positron emission tomography (FDG-PET) /CT scan showed the accumulation of FDG along both median and sciatic nerves, and he was diagnosed with neurolymphomatosis (NL). He died on day 120 after admission. Autopsy specimens exhibited infiltration of lymphoma cells in the median and sciatic nerves. Although only one case of suspected NL in a patient with type 2 EATL has been previously reported, we clinically diagnosed NL using FDG-PET/CT and confirmed the diagnosis by autopsy. This case is valuable in terms of the pathological diagnosis of NL.

Multicentric Castleman's disease with multiple hepatic mass lesions mimicking malignant liver tumors.

Multicentric Castleman's disease (MCD) is a rare, non-malignant lymphoproliferative disorder. We report a case of MCD with multiple liver masses. A 26-year-old woman presented with asymptomatic anemia and hypoalbuminemia. Laboratory tests detected high CRP levels and findings indicative of polyclonal gammopathy. Abdominal CT revealed multiple hepatic large masses (≤10 cm) and partial calcification in the right lobe. Multiple enlarged lymph nodes were also identified in the cardiophrenic angle and porta hepatis. We suspected hepatic malignancy, but pathological examinations of the liver and lymph nodes demonstrated polyclonal plasma cell infiltration and fibrosis. IL-6 staining was positive for plasma cell infiltration of lymph nodes. A few plasma cells were positive for IgG4, and tests for HIV and HHV-8 were negative. Serum IL-6 and plasma VEGF levels were both elevated (45 and 536 pg/ml, respectively). The patient was diagnosed with plasma cell type MCD. We started treatment with PSL 1 mg/kg/day, which led to improvement of anemia, hypoalbuminemia, and high CRP levels. Marginal regression of liver masses was also observed. At the last follow-up, the patient had been progression-free for 18 months. To our knowledge, this is the first report of a plasma cell type MCD with liver masses.

Clinical characteristics and computed tomography findings of pulmonary toxoplasmosis after hematopoietic stem cell transplantation.

The prognosis of pulmonary toxoplasmosis, including disseminated toxoplasmosis involving the lungs, following hematopoietic stem cell transplantation (HSCT) is extremely poor due to the difficulties associated with early diagnosis and the rapidly progressive deterioration of multiorgan function. In our institution, we identified nine cases of toxoplasmosis, representing incidences of 2.2 and 19.6 % among all HSCT recipients and seropositive HSCT recipients, respectively. Of the patients with toxoplasmosis, six had pulmonary toxoplasmosis. Chest computed tomography (CT) findings revealed centrilobular, patchy ground-glass opacities (n = 3), diffuse ground-glass opacities (n = 2), ground-glass opacities with septal thickening (n = 1), and marked pleural effusion (n = 1). All cases died, except for one with suspected pulmonary toxoplasmosis who was diagnosed by a polymerase chain reaction assay 2 days after the onset of symptoms. In pulmonary toxoplasmosis, CT findings are non-specific and may mimic pulmonary congestion, atypical pneumonia, viral pneumonitis, and bronchopneumonia. Early diagnosis and treatment is crucial for overcoming this serious infectious complication. Pulmonary toxoplasmosis should be considered during differential diagnosis in a recipient with otherwise unexplained signs of infection and CT findings with ground-glass opacities, regardless of the distribution.

Cerebral amyloid angiopathy in posttransplant patients with hereditary ATTR amyloidosis.

OBJECTIVE: To investigate the prevalence and clinical features of posttransplant CNS symptoms in patients with hereditary ATTR amyloidosis and their Pittsburgh compound B (PiB)-PET imaging correlates. METHODS: We monitored prevalence and type of CNS symptoms in 53 consecutive posttransplant patients with hereditary ATTR amyloidosis. (11)C-PiB-PET was performed in 15 patients with various disease durations. We also analyzed pathologic and biochemical characteristics of ATTR amyloid deposition in the brain of a posttransplant patient. RESULTS: Transient focal neurologic episodes (TFNEs) attributed to ATTR-type cerebral amyloid angiopathy (CAA) were found in 11.3% of posttransplant hereditary ATTR amyloidosis patients. TFNE occurred on average 16.8 years after onset of the disease. Patients with longer duration of illness (≥10 years) showed increased (11)C-PiB retention in the brain. The (11)C-PiB accumulation pattern in hereditary ATTR amyloidosis was unique and different from those in Alzheimer disease or Aß-type CAA. In the autopsy case, ATTR amyloid deposition was mainly localized to leptomeningeal vessels and leptomeninges of the brain. Amyloid fibrils in the brain were almost completely composed of variant transthyretin (TTR). CONCLUSIONS: TFNE due to ATTR-type CAA occurred frequently in posttransplant patients with long disease durations. (11)C-PiB-PET is a useful diagnostic tool for ATTR-type CAA. ATTR amyloid deposition in the CNS, as measured by PiB-PET, was detected approximately 10 years before onset of TFNE.

[Discordant lymphoma of duodenal EBV-positive peripheral T-cell lymphoma not otherwise specified and ileal diffuse large B-cell lymphoma].

A 79-year-old woman was admitted with a 5-kg weight loss and anorexia. Computed tomography showed diffuse lymphadenopathy, and thickening of the duodenal and ileal walls. The patient then underwent biopsy of these sites. Pathological examination revealed duodenal Epstein-Barr virus (EBV)-positive peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) and EBV-negative ileal diffuse large B-cell lymphoma (DLBCL) to be present simultaneously. Combination chemotherapy including rituximab produced a reduction of the duodenal EBV-positive PTCL-NOS lesion, but had no effect on the EBV-negative ileal DLBCL lesion. Thereafter, new lymphadenopathy, high fever, and lactate dehydrogenase (LD) elevation developed, complicated by pneumonia. The patient died due to rapid deterioration of the lymphoma and pneumonia on day 108 after initiation of treatment. EBV-positive PTCL-NOS is reportedly rare and the prognosis is poor. Moreover, EBV-negative ileal DLBCL was diagnosed simultaneously. This case is considered to have had an extremely rare discordant lymphoma, although the exact etiology of its development remains unknown. We speculate that age-related disorders of the immune system and HCV infection may have been associated with the pathogenic mechanism of lymphomagenesis in this case.

Gastrointestinal post-transplant lymphoproliferative disorder with rapidly forming characteristic lesions after cord blood transplantation: a report of two cases.

Epstein-Barr virus (EBV)-related post-transplant lymphoproliferative disorder (PTLD) frequently involves the gastrointestinal tract, but the endoscopic characteristics of this condition have not been discussed in detail. We report two cases of EBV-related PTLD involving rapidly forming characteristic lesions. Case 1 was a 60-year-old man with acute myeloid leukemia who underwent cord blood transplantation (CBT) after which he initially achieved complete remission (CR). He developed nausea and vomiting on day 99. Gastrointestinal endoscopy showed no tumor-like lesions in his stomach. However, a second endoscopic evaluation, which was performed 7 days after the first, revealed multiple raised lesions in his stomach, and a histopathological examination of the biopsy specimen resulted in a diagnosis of EBV-related PTLD. Case 2 was a 36-year-old man with acute myeloid leukemia who underwent CBT after achieving his second CR. He suffered nausea and pharyngalgia on day 309. Although the initial gastrointestinal endoscopic examination showed only multiple erosive or small ulcerative lesions, a second endoscopic evaluation, which was performed 10 days after the first, revealed a raised lesion with a central ulcer in the duodenum. Histopathological examination of the biopsy specimen yielded a diagnosis of EBV-related PTLD. Both patients were successfully treated by reducing the dose of immunosuppressive agents and administering rituximab.

Intrasellar Symptomatic Salivary Gland Rest with Inflammations.

BACKGROUND: Instances of ectopic salivary gland tissue within the pituitary gland are rare, they are mostly asymptomatic, and the underlying pathophysiology of symptomatic cases is unclear. We report a case of intrasellar salivary gland rest that presented clinical symptoms and clearly related to inflammatory changes. CASE DESCRIPTION: In the present case, headache, bitemporal hemianopia, and hormone abnormality led to the detection of ectopic salivary gland tissue within the pituitary gland of a 24-year-old man. Imaging revealed a well-circumscribed intrasellar cystic lesion having a diameter of major axis of 16 mm, for which tumorectomy was performed using the nasal approach. The tumor was cystic with stringy content. Pathologic findings revealed that the lesion was composed principally of secretions lacking cell components, whereas the salivary gland tissue was found in the cyst wall. Dilated ducts due to the leakage of secretions were also observed. Acute and chronic inflammation was present around the salivary gland. CONCLUSIONS: Not only are instances of symptomatic ectopic salivary glands rare, but this was also the first case detected to be caused by the pathophysiology involving the leakage of secretions from an ectopic salivary gland and associated inflammation. We report this case to help elucidate the pathophysiology of the condition.

Bone marrow metastasis of rhabdomyosarcoma mimicking acute leukemia: a case report and review of the literature.

Bone marrow metastasis of rhabdomyosarcoma has been reported to be difficult to distinguish from acute leukemia. We herein describe a case of rhabdomyosarcoma with bone marrow metastasis mimicking acute lymphoblastic leukemia. A 29-year-old woman was admitted with thrombocytopenia, blast-like cells in the peripheral blood and a coagulation disorder. Bone marrow aspirates showed 94.8% blast-like cell infiltration (CD45(-), myeloperoxidase(-), and CD56(+)), and CT scan revealed the presence of an infiltrating mass in the nasal cavity. Based on a biopsy of the nasal cavity, the patient was diagnosed with rhabdomyosarcoma exhibiting bone marrow metastasis. She received chemotherapy, followed by radiation therapy, and has since remained alive for 26 months, as of the last follow-up.

[Successful long-term control of recurrent primary central nervous system anaplastic large cell lymphoma after autologous hematopoietic stem cell transplantation with concurrent whole brain and spinal cord radiotherapy].

A 24-year-old woman was hospitalized with seizures in 2002. Magnetic resonance imaging demonstrated an intraspinal mass and inhomogeneous gadolinium enhancement along the cerebrospinal meninges. Cerebrospinal fluid (CSF) cytology showed large atypical cells expressing CD2, cytoplasmic CD3, CD7, CD13 and CD30. The patient was finally diagnosed with primary central nervous system anaplastic large cell lymphoma (ALCL). She completed 5 courses of methotrexate (MTX)/ procarbazine (PCZ)/ vincristine (VCR) (MPV) chemotherapy, followed by 2 courses of high dose cytarabine (AraC) and achieved a complete remission. In 2003, she suffered from headache. CSF analysis showed atypical lymphoid cells expressing CD 30. First CNS relapse was diagnosed. She then underwent autologous peripheral blood stem cell transplantation (auto-PBSCT) after administration of thiotepa, buslfan, and cyclophosphamide. However, second CNS relapse occurred in 2004. She received 5 courses of MPV chemotherapy followed by 36 Gy of craniospinal irradiation. Although there was no recurrence of the CNS disease, a third relapse was detected in the right breast in 2009. Pathological and immunohistochemistry analysis revealed ALK-1 positive ALCL. She was treated with 6 courses of cyclophosphamide/adriamycin/vincristine/predonine (CHOP) chemotherapy and 30.6 Gy of local radiation therapy. She has remained in remission for 6 years, to date, since the last therapy and has an excellent quality of life.

[Fatal bone marrow necrosis and fat embolism following sepsis in a patient with acute lymphoblastic leukemia after consolidation chemotherapy].

We report a 58-year-old Japanese man with acute lymphoblastic leukemia. On the seventh day of his second course of consolidation therapy, he developed herpes zoster, and on the 17th day, he developed a high fever, dyspnea, and lapsed into a coma. Streptococcus constellatus was isolated from blood culture. Despite intensive therapy, multiple organ failure progressed rapidly, and he died on the 19th day. Pathological examination of autopsy specimens revealed bone marrow necrosis and fat embolism in multiple organs. In this patient, sepsis led to bone marrow necrosis and, subsequently, to fat embolism.

Acute exacerbation of Toxoplasma gondii infection after hematopoietic stem cell transplantation: five case reports among 279 recipients.

Toxoplasmosis is a rare and possibly underestimated complication following hematopoietic stem cell transplantation (HSCT) associated with a high mortality rate, although the incidence of toxoplasmosis after HSCT in Japan has not been established. We retrospectively studied patients with toxoplasmosis after HSCT, and identified five patients who had been diagnosed with an acute exacerbation of toxoplasmosis among 279 HSCT recipients at our institution between 1998 and 2011, representing an incidence of 1.8 %. Among 87 autologous HSCT recipients, one definite case was diagnosed. The serological test for Toxoplasma gondii before HSCT was positive in 18 of 192 allogeneic HSCT recipients. Of the 18 seropositive patients, three had definite infections, and one had possible infection. All four definite cases were diagnosed at autopsy. In the definite cases, three allogeneic HSCT recipients had disseminated or pulmonary toxoplasmosis and one autologous HSCT recipient had toxoplasmic encephalitis, although toxoplasmosis was not suspected at the premortem examination due to non-specific clinical and radiological manifestations. Thus, acute exacerbation of toxoplasmosis should be suspected in recipients after HSCT. Early diagnosis and treatment for toxoplasmosis would certainly contribute to a decrease in mortality after HSCT.

[Long-term remission of Langerhans cell sarcoma by AIM regimen combined with involved-field irradiation].

A 67-year-old woman presented with a right inguinal mass in May 2006. CT scan showed lymph node involvement from the right inguinal to the common iliac and (18)F-FDG-PET revealed uptake in those areas. Biopsy results indicated Langerhans cell sarcoma (LCS). Interestingly, tumor cells expressed a high MIB1 index of 30%. We administered doxorubicin, ifosfamide, and mesna (AIM) chemotherapy, which were reported to effectively treat soft tissue sarcoma. After 5 courses of AIM therapy and involved-field radiation for residual diseases and a relapsed lesion on her right cervical node, she has remained in complete remission for more than 4 years. LCS is an intractable malignant disease and the optimal therapeutic strategy remains unclear. The AIM regimen combined with radiation therapy may be an effective treatment option for this disease.

Epstein-Barr virus-associated lymphoproliferative disorder developed after anti-thymocyte globulin therapy in a patient with bone marrow failure associated with T-cell large granular lymphocytic leukemia.

A 75-year-old man was referred to our hospital for marked neutropenia and anemia. Bone marrow examination showed marked hypoplasia with 45.2% infiltration of CD3+, CD8+, CD16+ and CD57+ granular lymphocytes. Monoclonal rearrangement of T-cell receptor gene was observed by Southern blot analysis. Taking these findings together, T-cell large granular lymphocyte leukemia (T-LGL) with bone marrow failure was diagnosed. The patient was treated with immunosuppressive therapy (IST) consisting of anti-thymocyte globulin and cyclosporine. Although pancytopenia subsided after IST, fever and lymphoadenopathy developed on the 29th day after IST. The presence of Epstein-Barr virus (EBV) in peripheral blood was confirmed using real time PCR (3.5×10(6) copies/10(6)WBC). Although gancyclovir and foscarnet were started, rapidly progressive hepatomegaly and liver dysfunction developed. The patient died on the 42nd day after IST. Autopsy specimen showed infiltration of abnormal CD20-positive large lymphocytes in the portal area of the liver, white pulp of the spleen, kidneys and adrenal glands. The nuclear EBV-encoded RNA (EBER) stain was positive in the abnormal large lymphocytes and a diagnosis of EBV-associated B-cell lymphoproliferative disorder (EBV-LPD) was made. We should regard the potential risk of EBV-LPD after immunosuppressive therapy for patients with bone marrow failure caused by T-LGL.

The first autopsy case of pandemic influenza (A/H1N1pdm) virus infection in Japan: detection of a high copy number of the virus in type II alveolar epithelial cells by pathological and virological examination.

We report the pathological and virological findings of the first autopsy case of the 2009 pandemic influenza (A/H1N1pdm) virus infection in Japan. A man aged 33 years with chronic heart failure due to dilated cardiomyopathy, mild diabetes mellitus, atopic dermatitis, bronchial asthma, and obesity died of respiratory failure and multiple organ dysfunction syndrome. Macroscopic examination showed severe pulmonary edema and microscopically the lung sections showed very early exudative-stage diffuse alveolar damage (DAD). Immunohistochemistry revealed proliferation of the influenza (A/H1N1pdm) virus in alveolar epithelial cells, some of which expressed SAalpha2-3Gal on the cell surface. Influenza (A/H1N1pdm) virus genomic RNA and mRNA were also detected in alveolar epithelial cells. Real-time PCR revealed 723 copies/cell in the left lower lung section from which the influenza (A/H1N1pdm) virus was isolated. Electron microscopic analysis revealed filamentous viral particles in the lung tissue. The concentrations of various cytokines/chemokines in the serum and the autopsied lung tissue were measured. IL-2R, IL-6, IL-8, IL-10, IFN-alpha, MCP-1, and MIG levels were elevated in both. These findings indicated a case of viral pneumonia caused by influenza (A/H1N1pdm) virus infection, showing characteristic pathological findings of the early stage of DAD.