Kiyoshi Ooya

Herpes virus type 8-negative primary effusion lymphoma associated with PAX-5 gene rearrangement and hepatitis C virus : A case report and review of the literature

At present, there is no case report of HHV8- primary effusion lymphoma (PEL) with t(9;14)(p13;q32) involving both PAX-5 and immunoglobulin heavy chain gene rearrangement, which is a rare translocation in B-cell non-Hodgkins lymphoma, in an HIV- patient. We examined an HIV-seronegative 63-year-old Japanese man with hepatitis C virus-associated liver cirrhosis and hepatocellular carcinoma manifesting peritoneal lymphomatous effusion without tumor mass at any body site. The lymphoma cells were examined twice by light microscopy, immunohistochemistry, three-color flow cytometry, cytogenetics, and molecular analyses. The nuclear morphology of lymphoma cells was similar to that of large noncleaved cells, although the lymphoma cell size was a little smaller that of the usual large-cell lymphoma. Immunophenotyping of lymphoma cells in the ascitic fluid revealed a mature peripheral B-cell phenotype (CD5- CD10- CD19+ CD20+ CD22+ Ig G+ lambda+). Cytogenetics showed a clonal population: 45,X,-Y, der(2) t(2;6)(q31;p21.3), t(4;8)(q21;q11.2), der(6) t(2;6)(q31;p21.3) add(6)(q15), t(9;14)(p13;q32.3) [10]/47, idem, +der(6) t(2;6), +16[10]. Southern blot analysis revealed rearranged fragments with a probe for immunoglobulin heavy chain, some of which were a size similar to those with a PAX-5 gene probe. Polymorphism, not rearrangement, of the c-MYC gene, was also found. HHV8 and the Epstein-Barr virus were not detected by polymerase chain reaction. This case is the first report of an HHV8- PEL with t(9;14) involving a PAX-5 gene rearrangement in an HIV-seronegative patient. This primary effusion lymphoma manifested spontaneous regression without any therapy. These findings suggest that there may be an additional subcategory of primary effusion lymphoma that is not associated with HHV8 nor c-MYC(R) but is pathogenetically associated with the PAX-5 gene or hepatitis C virus.

Autosomal recessive rough hypoplastic amelogenesis imperfecta. A case report with clinical, light microscopic, radiographic, and electron microscopic observations.

A case is presented of a 12-year-old Japanese girl with nearly complete lack of enamel in the deciduous and the permanent dentitions, coupled with a gross abnormality in the pattern of eruption. There was no family history of a similar condition. Deciduous molars were extracted, and hyperplastic gingival tissue was resected. On the basis of clinical, radiographic, and microscopic findings, a diagnosis of autosomal recessive rough hypoplastic amelogenesis imperfecta was made. The configuration of the abnormal enamel was examined with scanning and transmission electron microscopy as well as with light microscopy. Prismatic structure was virtually absent, and the scant enamel showed globular protrusions superficially. Two different surface structures were identified as covering parts of the enamel. At the ultrastructural level, calcified bodies located in the gingival tissue appeared to be composed, in part, of a dense enamel-like substance and, in part, of a tissue with features of afibrillar cementum.

Titanium lymph node pigmentation in the reconstruction plate system of a mandibular bone defect

A case of titanium pigmentation that involved a submandibular lymph node is reported. A 41-year old man had been treated for ameloblastoma by partial resection of the mandible followed by reconstruction with the use of a titanium plate to bridge the mandibular defect. Titanium pigmentation occurred in the surrounding soft tissue adjacent to the plate and within a submandibular lymph node 2 years after reconstruction.

Expression of survivin and X chromosome-linked inhibitor of apoptosis protein in ameloblastomas

To clarify the role of apoptosis in oncogenesis and cytodifferentiation of odontogenic epithelium, expression of survivin and X chromosome-linked inhibitor of apoptosis protein (XIAP), inhibitor of apoptosis protein (IAP) family proteins, was examined in tooth germs and in benign and malignant ameloblastomas by means of immunohistochemistry and reverse-transcription polymerase chain reaction. Immunoreactivity for survivin and XIAP was detected in developing and neoplastic odontogenic epithelium. In tooth germs, survivin expression was evident in inner enamel epithelium. Follicular, plexiform and metastasizing ameloblastomas showed survivin reactivity chiefly in neoplastic cells neighboring the basement membrane, and most neoplastic cells in basal cell and desmoplastic ameloblastomas and ameloblastic carcinomas were positive for survivin. Survivin mRNA levels were slightly higher in ameloblastomas than in tooth germs, suggesting that elevation of survivin expression might be involved in oncogenesis of odontogenic epithelium. Immunoreactivity for XIAP was detected in most odontogenic epithelial cells in tooth germs and in benign and malignant ameloblastomas, and XIAP mRNA levels were significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. The expression of survivin and XIAP in odontogenic tissues suggests that these IAP family proteins contribute to the biological properties of ameloblastomas, such as cell survival, proliferation, differentiation and tissue structuring, as well as to cellular regulation during tooth development.

Ph-negative non-Hodgkin's lymphoma occurring in chronic phase of Ph-positive chronic myelogenous leukemia is defined as a genetically different neoplasm from extramedullary localized blast crisis: report of two cases and review of the literature.

This report describes two cases of Philadelphia chromosome-negative (Ph(−)) non-Hodgkins lymphomas (NHLs) recognized in patients with chronic phase Ph-positive (Ph(+)) chronic myelogenous leukemia (CML). Lymph node biopsy of patient 1 was initially diagnosed as diffuse large B cell non-Hodgkins lymphoma (NHL, T cell rich variant), but at relapse showed immunoblastic features with a marked decrease of admixed lymphocyte components. Patient 2 presented with thickened parietal pleura which revealed a CD30-positive anaplastic large cell lymphoma showing null cell phenotype and genotype with abundant admixed neutrophils and lymphocytes. At the time of lymphoma diagnosis, the patients had CML for 33 and 10 months, respectively. DNA obtained from bone marrow cells at the time of lymphoma diagnosis showed BCR/ABL gene rearrangements by both Southern blot analysis and reverse transcription polymerase chain reaction (RT-PCR), but lacked both immunoglobulin and T cell receptor gene rearrangements. BCR gene rearrangement and BCR/ABL fusion gene were also identified in lymph node and pleural biopsies by Southern blot and RT-PCR analysis, respectively. However, both biopsy specimens also contained reactive lymphocytes and neutrophils, and no fusion signals between BCR and ABL genes were identified in the hyperdiploid lymphoma cells of either case by fluorescence in situ hybridization (FISH). These data suggest the lymphoma cells in both cases were not genetically associated with BCR/ABL. Therefore, these cases were not diagnosed as an extramedullary localized blast crisis in CML, but as Ph(−) NHLs. This represents the first definitive demonstration of peripheral B cell lymphoma occurring by a separate genetic pathway, lacking BCR/ABL, in patients with Ph(+) CML. A review of the literature identified two different subtypes of malignant lymphomas arising in patients with an antecedent or concurrent diagnosis of CML. The most common are T cell lymphomas displaying an immature thymic phenotype, while peripheral B cell lymphomas are more rare. Our study shows, however, that ‘Ph(+) NHL’ occurring in CML or acute lymphocytic leukemia (ALL) may represent an unrelated neoplasm, even if standard cytogenetic analysis reveals a Ph(+) chromosome, and that FISH is required to confirm whether a localized lymphoid neoplasm is either a true extramedullary localized blast crisis or genetically distinct neoplasm.

Simplified procedure for augmentation of the sinus floor using a haemostatic nasal balloon.

Perforation of the sinus membrane is the most common complication of sinus lift augmentation. A haemostatic nasal balloon can easily separate the sinus membrane without perforating it. The use of a haemostatic nasal balloon has three major advantages: a low risk of perforation of the sinus membrane even in anatomically complex conditions, a low incidence of infection and bleeding, and a shorter operating time.

A Recurrent Nonrandom Translocation (3;7)(q27;p12) Associated with Bcl-6 Gene Rearrangement in B-Cell Diffuse Large Cell Lymphoma

Two cases of B-cell diffuse large cell lymphoma associated with the t(3;7)(q27;p12) and BCL-6 rearrangement are described. Cytogenetic studies revealed [case 1] 47,XY,t(3;7)(q27;p12),+12 and [case 2] 45,X,-Y,t(3;7)(q27;p12),del(6)(q21q25),+16,-21. The translocation of each case had a non-random chromosomal change involving a 3q27 locus associated with BCL-6 gene rearrangement identified by Southern blot analysis. Both cases involved multiple lymph nodes and extranodal regions, such as stomach and peritoneal cavity in case 1, extranodal retroperitoneal space, subcutis, probable liver, and colon in case 2. Chemotherapy provided only short survival after onset: 17 and 16 months, respectively. Altered expression of adhesion molecules CD44, CD54 (case 1) and CD11a and CD18 (case 2) may help to explain the poor outcome of these patients.

Age-Related Morphological Changes in Squamous and Parietomastoid Sutures of Human Cranium

Age-related morphological changes in the inner and outer surfaces of the squamous and parietomastoid sutures were examined in 65 skulls (35 male, 30 female) obtained from Japanese subjects 5–90 years of age at the time of death. Dimensions were measured in both the horizontal and sagittal planes. Wavelength analysis was done by three-dimensional construction. Irregularities were evaluated by calculating fractal dimensions. The outer squamous suture showed no significant age-related changes in size, but wavelength increased because of the development of bony interdigitations with aging. The posterior part of the outer squamous suture showed significant age-related increases in both wavelength (p < 0.01, R2 = 0.164) and fractal dimension (p < 0.01, R2 = 0.101) in males. The parietomastoid suture showed significant age-related changes in size (p < 0.05), but not in wavelength or fractal dimension. These distinct morphological changes found on both the inner and outer surfaces of the squamous and parietomastoid sutures suggest that the age-related morphological characteristics of these sutures are affected by extrinsic mechanical forces.

Clear cell odontogenic tumor in the mandible : Report of a case with an immunohistochemical study of epithelial cell markers

A ram case of clear cell dontogenic tumor Is presented with an immunohistochemical study using epithelial cell markem. A 35‐year‐old Japanese man was admitted with a complaint of painless swelling In the anterior region of his mandible. Radiological examination showed a relatively well‐defined multilocular radloiucency with root resorption of the adjacent teeth. Despite a subtotal mandlbulectomy, the tumor recurred thm times. Histologically, the tumor was composed of proiiferating clear cells and Infiltrated through the cancellous bone. Histochemical and ultrastruc‐tural analyses detected cytoplasmic glycogen granules in the clear cells. They showed immunoreaetivities for cytokeratin 8,13 and 19, fllaggrin and anti‐ameloblastoma antibodb, suggesting an odontogenic epithelial origin.

Three-color flow cytometry in the diagnosis of malignant lymphoma based on the comparative cell morphology of lymphoma cells and reactive lymphocytes

This study examines the identification of unusual cell populations highly associated with lymphoma cells (UCP-L) in diagnostic biopsy specimens using three-color flow cytometry (3-FCM). Patterns of surface antigen expression were used to compare the morphology of distinct lymphoid cell populations present in biopsy specimens and determine the presence or absence of UCP-L. UCP-L were identified by their larger size as compared to admixed reactive lymphocytes, and the method is based on the concept that neoplastic lymphoma cells are larger than reactive lymphocytes. The comparison of relative cell sizes was determined by overlaying forward scatter histograms by multicolor gating using PAINT-A-GATE software. In order for separate gates to be set on UCP-L and reactive cell populations, UCP-L had to fulfill one or more immunophenotypic criteria. These included: (1) belonging to a subset of B cell antigen-positive cells showing restricted expression of kappa or lambda light chains; (2) belonging to a subset of CD4-positive cells having dim or absent expression of CD45RA; (3) showing alterations in antigen expression (loss, dimmer or brighter); or (4) expressing an immunophenotype that is present on only rare cell populations or is absent from reactive lymph nodes. The immunophenotypic profiles of the respective cell populations were demonstrated by cubic representations to assess more easily the co-expression of three antigens. The common morphology of UCP-L as defined by forward and side scatter grams was consistent with a ‘lymphoid appearance’ except in several cases of HTLV-I-positive T cell lymphoma and γδ T cell lymphoma. The immunophenotypic profiles of UCP-L were confirmed to correspond to the presumptive lymphoma cell population by use of a live gating procedure on the large cells, which eliminated interference by reactive cells or necrotic tissue fragments. Using this method, we identified UCP-L in 208 of 293 (71%) consecutive cases of non-Hodgkin’s lymphomas, while no UCP-L were seen in 72 cases of non-specific hyperplasia of lymph nodes. Twenty-seven cases could not properly be examined about the existence of UCP-L because of massive necrosis, extensive fibrosis or strong non-specific staining reactions of unknown cause. When those cases were eliminated from the analysis, 80% of non-Hodgkin’s lymphoma were found to contain UCP-L. In B cell lymphoma, the incidence of UCP-L in nodal lymphomas (80%) was much higher than in extranodal lymphomas (47%). Only one of 21 cases of Hodgkin’s lymphoma was found to have UCP-L. The 3-FCM procedure was validated by the combined use of immunohistochemistry, morphologic examination, cytogenetic and antigen receptor gene rearrangement analysis by Southern blot hybridization. Our findings indicate that detection of UCP-L by 3-FCM is a reliable method to distinguish non-Hodgkin lymphomas from reactive hyperplasias in the majority of cases, even when the reactive cell population predominates over the malignant cell population.