Presumptive complicating Clostridium paraputrificum bacteremia as a presenting manifestation in a patient with undiagnosed ulcerative colitis followed by acute colonic pseudo-obstruction.

Clostridium paraputrificum is a member of the commensal flora of the gastrointestinal tract and skin. Despite being linked with cases of severe invasive infection, this organism is an uncommon pathogen in humans. Here, we report a case of undiagnosed ulcerative colitis in which the presentation was one of presumptive complicating C. paraputrificum bacteremia and, later, acute colonic pseudo-obstruction. The patient was an elderly male with prostate cancer who was admitted in a state of shock secondary to suspected septicemia from an abdominal source. Only one of two sets of anaerobic blood cultures were positive for C. paraputrificum. Endoscopic and pathological investigations revealed proctitis consistent with ulcerative colitis. The patient's abdominal manifestations worsened, and abdominal imaging demonstrated de novo massive colonic dilatation without any apparent mechanical obstruction. We speculated that C. paraputrificum bacteremia caused by undiagnosed ulcerative colitis had created ideal conditions for acute colonic pseudo-obstruction. This case demonstrates that C. paraputrificum bacteremia can be associated with latent severe gastrointestinal pathologies, indicating the need to investigate any abdominal source of infection, even if only a single blood culture is positive.

Vanishing Cardiac Tumor by Chemotherapy in a Patient With Diffuse Large B-Cell Lymphoma.

A 70-year-old Japanese man presented with a massive cardiac tumor associated with diffuse large B-cell lymphoma. Standard chemotherapy resulted in complete remission and the cardiac tumor disappeared. (Level of Difficulty: Intermediate.).

Monitoring of MYD88 L265P mutation by droplet digital polymerase chain reaction for prediction of early relapse in a patient with Bing-Neel syndrome.

Bing-Neel syndrome (BNS) is a rare neurologic complication of lymphoplasmacytic lymphoma (LPL) characterized by direct infiltration of lymphoplasmacytic cells (LPCs). Although no standard treatment has yet been established, patients with BNS harboring the MYD88 L265P mutation have been reported to respond favorably to ibrutinib, which can cross the blood-brain barrier and trigger apoptosis of MYD88 L265P-positive LPCs. However, it is still unclear whether monitoring of MYD88 L265P mutation status would be useful for predicting relapse/progression or for assisting diagnosis and evaluating response to chemotherapy. Here, we report the case of a patient with BNS receiving ibrutinib in whom we detected relapse early by monitoring for molecular residual disease (MRD) based on the presence of the MYD88 L265P mutation in cerebrospinal fluid (CSF) on droplet digital polymerase chain reaction assay. Persistent MRD increased 2 weeks before the onset of relapse symptoms without any abnormal imaging findings or evidence of clonal LPCs on CSF cytology, flow cytometry analysis, or immunofixation electrophoresis. Our findings suggest that an increase in MRD levels is correlated with relapse in patients with BNS.

Comparison of Epstein-Barr virus-positive mucocutaneous ulcer associated with treated lymphoma or methotrexate in Japan.

AIMS: The aim of the present study was to compare treated lymphoma-associated Epstein-Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) and methotrexate (MTX)-associated EBVMCU. METHODS AND RESULTS: Of a series of 15 Japanese patients (11 women, four men; median age 74 years, range 35-84 years), seven received MTX for the treatment of autoimmune disease and eight developed EBVMCU after treatment of malignant lymphoma [diffuse large B-cell lymphoma (n = 4) without EBV association, adult T-cell leukaemia/lymphoma (n = 2), angioimmunoblastic T-cell lymphoma (n = 1), and follicular lymphoma (n = 1)]. Ulcers were observed in the oral cavity (n = 11), gastrointestinal tract (n = 2), and skin (n = 2). All were histologically characterised by a mixture of EBV-positive large B-cell proliferation and Hodgkin/Reed-Sternberg-like cells on a polymorphous background. A total of 46% (6/13) had monoclonal immunoglobulin heavy chain gene rearrangement, but none had clonal T-cell receptor gene rearrangement. Spontaneous regression occurred in 13 of 15 cases (87%); the other two cases (13%) achieved complete remission after treatment. Of two patients in the treated lymphoma-associated subgroup, one developed multiple new ulcerative lesions on previously unaffected skin, and the other had a relapse of EBVMCU in the oral cavity. No significant clinicopathological differences were found between the subgroups. Notably, none of the patients died from EBVMCU. However, the treated lymphoma-associated subgroup had lower overall survival (P = 0.004) and a shorter follow-up period (P = 0.003) than the MTX-associated subgroup, owing to death from non-associated causes. CONCLUSIONS: Treated lymphoma-associated EBVMCU, which is an indolent and self-limited condition, must be recognised to avoid misdiagnosing it as a relapse of malignant lymphoma during treatment.

A patient with severe fever with thrombocytopenia syndrome and hemophagocytic lymphohistiocytosis-associated involvement of the central nervous system.

Severe fever with thrombocytopenia syndrome (SFTS), a severe infectious disease caused by novel bunyavirus, SFTS virus (SFTSV), is endemic to China, Korea, and Japan. Most SFTS patients show abnormalities in consciousness. Pathological findings in the central nervous system (CNS) of SFTS patients are not reported. A 53-year-old Japanese man was admitted to Uwajima City Hospital with an 8-day history of fever and diarrhea. Laboratory tests revealed leukopenia, thrombocytopenia, and liver enzyme elevation. He was diagnosed as having severe fever with thrombocytopenia syndrome (SFTS) following detection of the SFTSV genome in his blood. Bone marrow aspiration revealed hemophagocytic lymphohistiocytosis. He suffered progressive CNS disturbance and died on day 13 from onset of first symptoms. The SFTSV genome load in blood and levels of certain cytokines increased over the disease course. Necrotizing lymphadenitis with systemic lymphoid tissues positive for nucleocapsid protein (NP) of SFTSV was revealed by immunohistochemical (IHC) analysis. SFTSV-NP-positive immunoblasts were detected in all organs examined, including the CNS, and in the vascular lumina of each organ. Parenchymal cells of all organs examined were negative for SFTSV-NP on IHC analysis. Microscopic examination of the pons showed focal neuronal cell degeneration with hemosiderin-laden macrophages around extended microvessels with perivascular inflammatory cell infiltration and intravascular fibrin deposition. Autopsy confirmed this patient with SFTS was positive for systemic hemophagocytic lymphohistiocytosis including in the CNS. This patient's neurological abnormalities may have been caused by both functional and organic abnormalities. These novel findings provide important insights into the pathophysiology of SFTS.

Visual assessment of Ki67 using a 5-grade scale (Eye-5) is easy and practical to classify breast cancer subtypes with high reproducibility.

AIMS: Personalised breast cancer therapy requires pathological characterisation of tumours. The proliferative index, based on Ki67, is pivotal, but a standard method has not been established. Here we look for an easy and practical way to evaluate Ki67. METHODS: Immunohistochemical staining of estrogen receptors, progesterone receptors, HER2 and Ki67 (MIB-1) was performed on resected specimens from 406 primary invasive ductal carcinomas. Ki67 labelling index (LI) from manual counting was compared with visual assessment using a 5-grade scale (Eye-5). Next, 10 pathologists evaluated 100 samples with marked hot spots by using Eye-5. Another 100 samples without marking were also assessed by eight pathologists. One year later, two pathologists reviewed 222 cases with Eye-5. Prognosis was analysed among estrogen receptor-positive cases with postoperative endocrine therapy. RESULTS: Eye-5 showed good correlation to LI. All 136 cases of score 4-5 had LI >20% and all 56 cases of score 1 had LI<20%, which means that manual counting was not necessary for about half of the cases. Interobserver and intraobserver variability was low even when a hot spot was not fixed. Eye-5 also correlated with histological grade and lymph node metastasis. Combining Eye-5 and histological grade created a new algorism to predict LI, which allows 80% of all cases (74% of luminal cases) without manual counting. Cases of Eye-5 score 1-2 had significantly better survival than score 3-5. CONCLUSIONS: Visual assessment of Ki67 by a 5-grade scale (Eye-5) is fast, easy, and reliable with acceptably low interobserver and intraobserver variability. Eye-5 can replace LI in many luminal tumours, and is a strong candidate as a standard method of evaluating Ki67.

[Calcified amorphous tumor of the right atrium after open heart surgery; report of a case].

A 37-year-old woman, who had undergone surgery of atrial septal defect (ASD) at 12-year-old, developed bradycardia and referred to our hospital. Transthoracic echocardiography revealed high echoic tumor in the right atrium. The image of the tumor was of low intensity by T2 weighted magnetic resonance imaging (MRI) and floating mass with a stalk to the right atrium in cine MRI. She underwent tumor resection under cardiopulmonary bypass. Histopathologilal examination of the tumor was calcified amorphous tumor. The postoperative course was uneventful.

An autopsy case of acute cor pulmonale and paradoxical systemic embolism due to tumour cell microemboli in a patient with breast cancer.

A 62-year-old woman was admitted to our hospital because of severe respiratory distress. Diagnostic imaging studies suggested the existence of inexplicable cor pulmonale. Although we immediately sought the aetiology of her severe condition, she died suddenly on the fourth day after admission. Postmortem autopsy revealed tumour cell microemboli in the small pulmonary arteries. In addition, tumour cell embolisation identical to that in primary breast cancer cells was also observed in microvessels in systemic multiple organs, such as the liver, brain, kidneys, spleen, uterus, bone marrow and adrenal glands-with simultaneous findings of peripheral infarction. Systemic tumour cell embolism mediated through the patent foramen ovale superimposed on pulmonary tumour cell emboli (PTCE) is considered to be the mechanism underlying inexplicable cor pulmonale. The rapid aggravation of her condition terminated in death.

Mouse embryonic stem cells are not susceptible to cytomegalovirus but acquire susceptibility during differentiation.

BACKGROUND: Cytomegalovirus (CMV) is the most significant infectious cause of congenital anomalies of the central nervous system caused by intrauterine infection in humans. The timing of infection and the susceptibility of cells in early gestational stages are not well understood. In this study we investigated the susceptibility of embryonic stem (ES) cells to CMV infection during differentiation. METHODS: ES cell lines were established from transgenic mice integrated with the murine CMV (MCMV) immediate-early (IE) promoter connected with a reporter lacZ gene. The susceptibility of the ES cells was analyzed in terms of viral gene expression and viral replication after induction of differentiation. RESULTS: ES cells were nonpermissive to MCMV infection in the undifferentiated state. Upon differentiation, permissive cells appeared approximately 2 weeks after the leukemia inhibitory factor was removed. Upon neural differentiation by retinoic acid (RA), glial cells showed specific susceptibility in terms of expression of the viral antigen. The MCMV IE promoter was not activated in ES cells from the transgenic mice. Activation of the IE promoter was detected approximately 2 weeks after induction of differentiation and observed predominantly in glial cells. Upon MCMV infection of the ES cells, viral infection was correlated with the activation of the IE promoter. CONCLUSIONS: ES cells are nonpermissive to MCMV infection and acquire permissiveness about 2 weeks after induction of differentiation, especially in glial cells. Acquisition of permissiveness in differentiated ES cells may be associated with activation of the IE promoter.