Ossifying fibromyxoid tumor of soft parts. Cytogenetic findings

Ossifying fibromyxoid tumor (OFMT) of soft parts is a recently described, rare but morphologically distinctive soft tissue tumor. The histogenesis of this lesion remains uncertain, although several immunohistochemical and ultrastructural features suggest that it is an unusual neural tumor, possibly of Schwann cell origin. We report here a case of a malignant variant of OFMT that occurred in the foot of a 52-year-old man. The karyotype of a pulmonary metastasis exhibited the following complex numeric and structural aberrations:72 approximately 74,XXY,-5,+6,+del(8)(p21),del(9)(p22),+10,der(11)t(3;11)(p21;p15),del(12) (q13),der(13)t(5;13)(q13;q34),+18,+19,+20,-22 [cp10]. A kidney metastasis exhibited the following karyotypic abnormalities: 46,XY,add(3)(p11),+der(3)t(3;?;11)(3qter-->3p11::?::11q13-->11qter), -5,del(8)(p21),add(9)(q22),del(9)(p22),der(11)t(3;11)(p21;p15),del(12)(q13),+der(13)t(5;13) (q13;q34),-22. To our knowledge, this is the first reported case of OFMT in which clonal chromosomal aberrations have been shown.     

Pulmonary metastases from a low-grade endometrial stromal sarcoma confirmed by chromosome aberration and fluorescence in-situ hybridization approaches: a case of recurrence 13 years after hysterectomy

Pulmonary metastasis from low-grade endometrial stromal sarcomas (ESSs) occasionally are found after long, disease-free periods, mostly as incidental histological or radiological discoveries. We describe a case of low-grade ESS presenting as nodular pulmonary metastases finally diagnosed by estrogen-receptor staining, cytogenetic and fluorescence in situ hybridization (FISH) analyses, and perusal of the histology of hysterectomy material. An abnormal nodule in the lung field was discovered by means of chest X-ray of a 47-year-old woman. She had been disease free for 13 years after hysterectomy for an alleged leiomyoma. A computed tomographic scan revealed nodules, with fluctuation in size over the 2-year period, in both lungs. Finally the lesion in the left lung was resected, and pulmonary endometriosis was suspected because of the lack of stromal cell nuclear atypia and positive immunohistochemical reactions for estrogen and progesterone receptors. However, a characteristic karyotype was identified cytogenetically: 46, XX, t(7;17)(p15;q11), the translocation of which, specific to ESS, was confirmed by FISH analysis. A final diagnosis of pulmonary metastases from an ESS could be made by reviewing the histology of the previous uterine tumor. In this case, metastatic lesions from an ESS showed a decrease as well as an increase in size, despite the malignant potential. Immunostaining for estrogen and progesterone receptors and cytogenetic and FISH analyses, together with clinical information on the past gynecological history, are valuable diagnostic keys.     

Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses

Bath application of the inhibitors of phospholipases, nordihydroguaiaretic acid (NDGA) and p-bromophenacyl bromide (BPB), to the rat hippocampal slices suppressed long-term potentiation (LTP) in Schaffer/commissural-CA1 pyramidal synapses. On the other hand, neither of the two inhibitors suppressed LTP in mossy fiber-CA3 pyramidal cell synapses. BPB did not suppress phosphatidylinositol-specific phospholipase C (PI-PLC) activity of the slices. These results suggested that the mechanisms of LTP were quite different in the CA1 and CA3 subfields of rat hippocampus: in CA1, the involvement of an arachidonate metabolism was strongly suggested, whereas in CA3, an arachidonic acid cascade may not be necessary for LTP.     

HEPATITIS-ASSOCIATED APLASTIC ANEMIA WITH SYSTEMIC PLASMACYTOSIS

An autopsy case of hepatitis associated aplastic anemia was presented. A 58-year-old Japanese female with non-A, non-B hepatitis was admitted on August 2, 1983. Moderate grade of fever and hemorrhagic diathesis appeared on September 16, when hepatitis was evaluated as being under resolving. The peripheral blood and bone marrow findings were consistent with aplastic anemia. Since infection was suggested by increased levels of serum gamma-globulin and CRP, treatment with antibiotics as well as prednisolone and blood transfusion was initiated. Since September 21, gradual tenderness and edema on the right lower abdominal wall appeared. She died on October 3.
On postmortem examination, systemic plasmacytosis with lymphadenopathy and septic monilial infection was revealed. Numerous plasma cells were atypical, but were immunohistochemically proved to be polyclonal. The bone marrow showed a massive and diffuse plasma cell proliferation with extremely scarce myeloid cells and megakaryocytes. There was a large granulomatous lesion with monilial infection in the wall of the ileocecum. By these findings, systemic plasmacytosis was suspected to be due to chronic monilial infection.
The pathogenesis of systemic plasmacytosis in aplastic anemias and in other diseases were discussed with relation to the present case.     

Transforming growth factor J3 type II receptor (TGFpRII) mutation in gastric lymphoma without mutator phenotype

A new mutation in the serine-threonine klnase domain of the transforming growth factor β type II receptor (TGFpRII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A mfssense mutation (ACA to GCA, Thr to Ala) was detected In exon 5, and a wild type allele was also present. This Is the first naturally occurring mutation in the klnase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach Is an addition to an expanding catalogue of tumors with TGFβRII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.     

Primrose syndrome associated with unclassified immunodeficiency and a novel ZBTB20 mutation

Primrose syndrome is a congenital malformation syndrome characterized by intellectual disability, developmental delay, progressive muscle wasting, and ear lobe calcification. Mutations in the ZBTB20 gene have been established as being accountable for this syndrome. In this study, a novel de novo ZBTB20 mutation, NM_001164342.2:c.1945C>T (p.Leu649Phe), has been identified through whole exome sequencing (WES) in a female patient presenting a typical Primrose phenotype. Because the present patient exhibited recurrent otitis media, detailed immunological examinations were performed in this study and subnormal immunoglobulin levels were firstly identified in a Primrose patient. Anatomical anomaly of the inner ear has never been reported in this patient and WES data did not include any relevant variants causally linked with the immunologic defect. Thus, there is a possibility of a relation between an unclassified immunodeficiency with selective IgG2 deficiency and Primrose syndrome and this may be the reason of recurrent otitis media frequently observed in Primrose patients. Because subnormal levels of IgG2 in this patient might be caused by an unrelated and still uncharacterized genetic cause, further studies are required to prove the causal link between aberrant ZBTB20 function and immunodeficiency.     

Clostridium sordellii phospholipase C: gene cloning and comparison of enzymatic and biological activities with those of Clostridium perfringens and Clostridium bifermentans phospholipase C

The gene encoding Clostridium sordellii phospholipase C (Csp) was cloned and expressed as a histidine-tagged (His-tag) protein, and the protein was purified to compare its enzymatic and biological activities with those of Clostridium perfringens phospholipase C (Cpa) and Clostridium bifermentans phospholipase C (Cbp). Csp was found to consist of 371 amino acid residues in the mature form and to be more homologous to Cbp than to Cpa. The egg yolk phospholipid hydrolysis activity of the His-tag Csp was about one-third of that of His-tag Cpa, but the hemolytic activity was less than 1% of that of His-tag Cpa. His-tag Csp was nontoxic to mice. Immunization of mice with His-tag Cbp or His-tag Csp did not provide effective protection against the lethal activity of His-tag Cpa. These results indicate that Csp possesses similar molecular properties to Cbp and suggest that comparative analysis of toxic and nontoxic clostridial phospholipases is helpful for characterization of the toxic properties of clostridial phospholipases.     

Hyperglycemia potentiates H(2)O(2) production in adipocytes and enhances insulin signal transduction: potential role for oxidative inhibition of thiol-sensitive protein-tyrosine phosphatases

Insulin signal transduction in adipocytes is accompanied by a burst of cellular hydrogen peroxide (H(2)O(2)) that facilitates insulin signaling by inhibiting thiol-dependent protein-tyrosine phosphatases (PTPs) that are negative regulators of insulin action. As hyperglycemia is associated with increased cellular reactive oxygen species, we postulated that high glucose conditions might potentiate the H(2)O(2) generated by insulin and modulate insulin-stimulated protein phosphorylation. Basal H(2)O(2) generation was increased threefold in differentiated 3T3-L1 adipocytes by growth in 25 mM glucose versus 5 mM glucose. High glucose increased the sensitivity of the insulin-stimulated H(2)O(2) signal to lower concentrations of insulin. Basal endogenous total PTP activity and the activity of PTP1B, a PTP implicated in the negative regulation of insulin signaling, were reduced in high glucose conditions, and their further reduction by insulin stimulation was more enhanced in high versus low glucose medium. Phosphorylation of the insulin receptor, IRS-1, and Akt in response to insulin was also significantly enhanced in high glucose conditions, especially at submaximal insulin concentrations. In primary rat adipocytes, high glucose increased insulin-stimulated H(2)O(2) production and potentiated the oxidative inhibition of total PTP and PTP1B activity; however, insulin signaling was not enhanced in the primary cells in high glucose apparently due to cross-regulation of insulin-stimulated protein phosphorylation by activation of protein kinase C (PKC). These studies indicate that high glucose can enhance insulin stimulated H(2)O(2) generation and augment oxidative PTP inhibition in cultured and primary adipocytes, but the overall balance of insulin signal transduction is determined by additional signal effects in high glucose, including the activation of PKC.     

Undifferentiated (embryonal) sarcoma of the liver in middle-aged adults: smooth muscle differentiation determined by immunohistochemistry and electron microscopy

Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation.     

Comparison of an immunochromatography test with multiplex reverse transcription-PCR for rapid diagnosis of respiratory syncytial virus infections

A new commercial rapid 10-min one-step immunochromatography (IC) test, SAS RSV test, was compared to another IC test, Directigen EZ RSV, employing RT-PCR as the "gold standard" for detecting respiratory syncytial virus. Of 102 clinical samples, 79 were positive by RT-PCR, 66 (82.5%) were positive with the SAS RSV test, and 55 (69.6%) were positive with Directigen EZ RSV. The specificity of the new test was 91.3% (21 of 23), similar to that of Directigen EZ RSV (100% [23 of 23]). This test performs well enough to be used for patient care.