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Gene Rearrangements (gene + rearrangement)
Kinds of Gene Rearrangements Terms modified by Gene Rearrangements Selected AbstractsA molecular analysis of biclonal follicular lymphoma: further evidence for bone marrow origin and clonal selectionEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Yuichi Nakamura Abstract We report a follicular lymphoma (FL) case presenting the coexistence of two tumor cell subpopulations in lymph node (LN) and bone marrow (BM), which exhibited an inverse pattern of immunoglobulin light (IgL) chain gene rearrangement and expression: Ig,,,+ in LN and Ig,+,, in BM. These tumor clones shared an identical BCL2-IgH recombination, accompanying t(14;18)(q32;q21) translocation, and an identical variable, diversity and joining segments joining with clone-specific VH somatic hypermutations on the untranslocated IgH allele. Our study provides further evidence that FL clones, originating from common progenitor cells, can be developed independently at different sites and with different IgL expression after immune selection. [source] PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements,GENES, CHROMOSOMES AND CANCER, Issue 2 2005Bruce Poppe We present an extensive characterization of 10 B-cell lymphomas with a t(9;14)(p13;q32). The presence of the PAX5/IGH gene rearrangement was demonstrated by fluorescence in situ hybridization (FISH) using a validated probe set, whereas complex karyotypic changes were reassessed by multiplex-FISH (M-FISH). Pathologic and clinical review revealed the presence of this rearrangement in 4 histiocyte-rich, T-cell-rich B-cell lymphomas (HRTR-BCLs) and 2 posttransplantation diffuse large B-cell lymphomas (PTLD-DLBCLs). In contrast to initial observations describing this translocation in lymphoplasmacytic lymphoma (LPL) and LPL-derived large B-cell lymphoma, our data showed a wide morphologic and clinical spectrum associated with the PAX5/IGH rearrangement, pointing to an association between this aberration and a subset of de novo DLBCLs presenting with advanced disease and adverse prognosis. In addition, the recurrent incidence of this rearrangement in both HRTR-BCL (4 cases) and PTLD-DLBCL (2 cases) was previously unrecognized and is intriguing. © 2005 Wiley-Liss, Inc. [source] Development and selection of ,, T cellsIMMUNOLOGICAL REVIEWS, Issue 1 2007Na Xiong Summary:, Two main lineages of T cells develop in the thymus: those that express the ,, T-cell receptor (TCR) and those that express the ,, TCR. Whereas the development, selection, and peripheral localization of newly differentiated ,, T cells are understood in some detail, these processes are less well characterized in ,, T cells. This review describes research carried out in this laboratory and others, which addresses several key aspects of ,, T-cell development, including the decision of precursor cells to differentiate into the ,, versus ,, lineage, the ordered differentiation over the course of ontogeny of functional ,, T-cell subsets expressing distinct TCR structures, programming of ordered V, gene rearrangement in the thymus, including a molecular switch that ensures appropriate V, rearrangements at the appropriate stage of development, positive selection in the thymus of ,, T cells destined for the epidermis, and the acquisition by developing ,, T cells of cues that determine their correct localization in the periphery. This research suggests a coordination of molecularly programmed events and cellular selection, which enables specialization of the thymus for production of distinct T-cell subsets at different stages of development. [source] Microenvironmental influences on human B-cell developmentIMMUNOLOGICAL REVIEWS, Issue 1 2000F. E. Bertrand Summary: Mammalian B-cell development can be viewed as a developmental performance with several acts. The acts are represented by checkpoints centered around commitment to the B-lineage and functional Ig gene rearrangement , culminating in expression of the pre-B-cell receptor (pre-BCR) and the BCR. Progression of cells through these checkpoints is profoundly influenced by the fetal liver and adult bone marrow (BM) stromal cell microenvironments. Our laboratory has developed a model of human B-cell development that utilizes freshly isolated/non-transformed human BM stromal cells as an in vitro microenvironment. Human CD34+ hematopoietic stem cells plated in this human BM stromal cell microenvironment commit to the B lineage and progress through the pre-BCR and BCR checkpoints. This human BM stromal cell microenvironment also provides survival signals that prevent apoptosis in human B-lineage cells. Human B-lineage cells exhibit differential expression of Notch receptors and human BM stromal cells express the Notch ligand Jagged-1. These results suggest a potential role for Notch in regulating B-lineage commitment and/or progression through the pre-BCR and BCR checkpoints. [source] Interleukin-6 is responsible for aberrant B-cell receptor-mediated regulation of RAG expression in systemic lupus erythematosusIMMUNOLOGY, Issue 3 2007Sophie Hillion Summary Defective regulation of secondary immunoglobulin V(D)J gene rearrangement promotes the production of autoantibodies in systemic lupus erythematosus (SLE). It remains unclear, however, whether the regulation of the recombination-activating genes RAG1 and RAG2 is effective in SLE. RAG1 and RAG2 messenger RNA expression was analysed before and after in vitro activation of sorted CD19+ CD5, B cells with anti-immunoglobulin M antibodies, in 20 SLE patients and 17 healthy controls. The expression of CDK2 and p27Kip1 regulators of the RAG2 protein, were examined. The levels of interleukin-6 (IL-6) and its influence on RAG regulation were also evaluated in vitro. SLE patients had increased frequency of RAG-positive B cells. B-cell receptor (BCR) engagement induced a shift in the frequency of ,- and ,-positive cells, associated with a persistence of RAG messenger RNA and the maintenance of RAG2 protein within the nucleus. While expression of the RAG2-negative regulator CDK2 was normal, the positive regulator p27Kip1 was up-regulated and enhanced by BCR engagement. This effect was the result of the aberrant production of IL-6 by SLE B cells. Furthermore, IL-6 receptor blockade led to a reduction in p27Kip1 expression, and allowed the translocation of RAG2 from the nucleus to the cytoplasm. Our study indicates that aberrant production of IL-6 contributes to the inability of SLE B cells to terminate RAG protein production. Therefore, we hypothesize that because of constitutive IL-6 signalling in association with BCR engagement, SLE B cells would become prone to secondary immunoglobulin gene rearrangements and autoantibody production. [source] Erythema multiforme-like lesions associated with lesional infiltration of tumor cells occurring with adult T-cell lymphoma/leukemiaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 4 2008Tomoyuki Ohtani MD A 66-year-old Japanese woman visited our hospital with a complaint of multiple papules on her trunk and extremities. She had a past medical history of appendicitis and blood transfusion 40 years earlier. For the last 10 years, she had noticed multiple, gradually enlarging papulonodular lesions with surrounding erythema on her trunk and extremities. ,Physical examination revealed multiple, violaceous papules or nodules, less than 10 mm in diameter, with surrounding erythema on her trunk and extremities (Fig. 1). The results of routine laboratory examinations, including blood count, liver function, renal function, serum calcium, and lactate dehydrogenase, were within the normal range. The peripheral blood picture showed a small population of atypical lymphocytes below 1% of the total white blood cells. Human T-cell lymphotropic virus type I (HTLV-I) serology was positive. A microscopic examination of a biopsy specimen from a nodule on the abdomen demonstrated diffuse infiltration of large pleomorphic T cells in the upper and middle dermis, although highly atypical lymphocytes, so-called flower cells, could not be recognized. Infiltrating lymphocytes were positive for CD2, CD3, CD4, CD5, CD7, and CD45, but negative for CD8 and CD20, immunohistologically. Bone marrow biopsy also demonstrated the infiltration of lymphocytes expressing CD2, CD3, CD4, CD5, and CD7, but not CD25. Southern blot analysis of the infiltrating cells in the skin revealed an integration of HTLV-I proviral DNA in T cells. Clonal T-cell receptor , gene rearrangement was detected in skin and bone marrow biopsies. No abnormal mass or bone defect was detected by chest or abdominal computed tomographic scanning, systemic gallium-67 citrate scintigraphy, or chest radiography. On the basis of these data, the patient was diagnosed with smouldering-type adult T-cell lymphoma/leukemia. Figure 1. Clinical features of adult T-cell lymphoma/leukemia (ATL) skin lesions. Crusted, target-like, dark-red plaques on the lower legs ,The patient was started on topical steroid and electron beam radiation therapy (27 Gy/14 days). Five days after the start of irradiation, she noticed multiple patches of edematous erythema appearing on the trunk and extremities (Fig. 2). As it was initially suspected that these newly emerging erythema multiforme or toxic eruptions were caused by irradiation, therapy was interrupted. Anti-herpes simplex virus antibody was not checked because no typical herpes simplex lesions were noticed. The patient was not taking any systemic drugs. A skin biopsy was taken from a representative lesion on the chest. The pathologic specimen showed epidermotropism, liquefaction degeneration in the basal layer, marked edema, and dense infiltration of mononuclear cells in the upper dermis. Infiltrating cells possessed abundant cytoplasm and large pleomorphic nuclei with distinct nucleoli (Fig. 3). These findings were consistent with the histopathologic findings of erythema multiforme, except for the atypical lymphoid cell infiltration. Immunohistochemical staining demonstrated that the phenotype of the skin-infiltrating cells was identical to that of the atypical cells in the initial lesions. As the eruptions did not disappear in spite of the interruption of radiation, total skin irradiation was restarted. After completion of therapy, both the erythema multiforme-like lesions and the initial adult T-cell lymphoma/leukemia nodules on the trunk and extremities had resolved, leaving brown pigmentation. The patient has been free of any recurrence of skin lesions or systemic symptoms for 6 years after the completion of total skin irradiation. Figure 2. Appearance of erythema multiforme (EM)-like lesions. Edematous red plaques involving the breast Figure 3. Microscopic examination of a biopsy specimen from (EM)-like lesions on the chest (hematoxylin and eosin staining). (a) Epidermotropism, liquefaction degeneration in the basal layer, and dense infiltration of mononuclear cells and severe edema in the upper dermis (×100). (b) High-power magnification revealed that the dermal infiltration included atypical lymphoid cells with abundant cytoplasm, convoluted large nuclei, and distinct nucleoli (×400) [source] Hydroa vacciniforme-like Epstein-Barr virus-associated monoclonal T-lymphoproliferative disorder in a childINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 10 2007Yu-Hung Wu MD Hydroa vacciniforme (HV) is a chronic photosensitivity disorder induced by ultraviolet radiation. Hydroa vacciniforme-like lymphoma is a rare cutaneous T-cell lymphoma occurring mainly in childhood. Recent studies have demonstrated an association between chronic latent Epstein-Barr virus (EBV) infection and both the benign skin disorder and the lymphoma. The authors report a 6-year-old boy with chronic EBV infection, HV-like skin eruptions, and chronic hepatitis. Histopathologic examination of a skin biopsy specimen demonstrated epidermal ballooning degeneration and dense superficial and deep perivascular and periappendageal lymphoid cell infiltrates extending to the fat lobules. Some blood vessels in the deep plexus were infiltrated by predominantly CD4+ and TIA-1+ cytotoxic T cells. The EBV genomes were found within tissue from three skin biopsies and peripheral blood cells. Monoclonal T-cell receptor gene rearrangement was present in skin biopsy specimens. Although no lymphoma has been found during 2 years of follow-up treatment, the possibility of lymphoma developing out of the current smoldering stage is of concern. The clinical manifestations of lymphoproliferative disorder and chronic active EBV infection are discussed. [source] A clonal cutaneous CD30+ lymphoproliferative eruption in a patient with evidence of past exposure to hepatitis EINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2000Freddye M. Lemons-Estes CDR, MC USN The patient was a 52-year-old white man who had worked in remote areas of the world during the past 2 years, including an extended period in rural areas of Central Africa and in Central and South America. He had no acute illnesses during the 2-year period except for rare, mild, upper respiratory tract infections. For approximately 1 year, however, he had developed recurrent, papular-vesicular, slightly painful lesions on the fingers and palms, that spontaneously healed over weeks to months ( Fig. 1). The patient had no other concurrent illnesses and no abnormal laboratory findings, except for positive enzyme-linked immunoabsorbent assay (ELISA) for immunoglobulin G (IgG) antibodies for hepatitis E virus (HEV) using a recombinant expressed HEV antigen (Genelabs Technologies, Inc., San Antonio). Prolonged treatment with minocycline did not appear to moderate the lesions. At approximately 2.5 years after the development of his first cutaneous lesion, however, the patient reported that he had had no new lesions for over 3 months. Figure 1. Vesicular ,lesion on the finger which regressed over a period of weeks A biopsy specimen showed an intraepidermal vesicle with prominent epidermal necrosis and reticular degeneration ( Fig. 2). Within the epidermis, there was a dense infiltrate of lymphoid cells. The majority of these cells were pleomorphic with prominent nucleoli and frequent mitotic figures ( Fig. 3). Sheets of atypical cells were found in the subjacent dermis. The infiltrate extended down into the reticular dermis. With extension into the dermis, the infiltrate became more polymorphous with more small lymphoid cells, large numbers of eosinophils, and some plasma cells located more deeply. Figure 2. Intraepidermal ,blister showing reticular degeneration and marked epidermotrophism of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (30×) Figure 3. Intraepidermal ,infiltrate of large atypical cells with extension into the dermis with a mixed infiltrate containing eosinophils and plasma cells (400×) Immunohistochemical stains for CD3 (DAKO), CD4 (Becton Dickinson), CD8 (Becton Dickinson), CD15 (LeuM1, Becton Dickinson), CD20 (L-26, DAKO), CD30 (Ber-H2, DAKO), CD45RO (UCHL1, DAKO), S-100 protein (DAKO), T-cell intracellular antigen (TIA) (Coulter), epithelial membrane antigen (EMA) (DAKO), KP-1 (CD68, DAKO), MAC-387 (DAKO), Epstein,Barr virus (EBV) latent membrane antigen-1 (LMP-1, DAKO), and EBV-encoded nuclear antigen 2 (EBNA2, DAKO) were performed on formalin-fixed tissue using the ABC method with DABA as the chromagen. CD3 showed diffuse membrane staining of the large atypical lymphoid cells, as well as the majority of the small lymphoid cells ( Fig. 4). CD4 showed positive membrane staining of the large atypical lymphoid cells and the majority of the small lymphoid cells. CD8 showed only scattered light membrane staining of small lymphoid cells. CD15 was negative, and CD20 showed foci of groups of small lymphoid cells mainly within the reticular dermis. CD30 showed positive membrane and paranuclear staining of the large atypical cells, most abundant within the epidermis and papillary dermis ( Fig. 5). CD45RO showed positive membrane staining of the large atypical cells and the majority of the small lymphoid cells. S-100 protein showed increased dendritic cells within the surrounding viable epidermis and the subjacent papillary dermis ( Fig. 6). TIA showed granular staining in the large atypical lymphoid cells and only rare staining in small lymphoid cells ( Fig. 7). EMA staining was essentially negative. KP-1 showed only scattered positive cells mainly in the lower papillary and the reticular dermis. MAC-387 showed membrane staining in the viable epidermis ( Fig. 8). LMP-1 and EBNA2 for EBV were negative within the lymphoid cells as well as within the overlying epidermis. Figure 4. Immunohistochemical ,staining for CD3 showing diffuse staining of lymphoid cells within the epidermis and dermis (150×) Figure 5. Immunohistochemical ,staining for CD30 showing membrane and paranuclear staining of large atypical lymphoid cells within the epidermis and papillary dermis (a, 150× b, 400×) Figure 6. Immunohistochemical ,staining for S-100 protein within the epidermis and in the papillary dermis (a, 150× b, 300×) Figure 7. Immunohistochemical ,granular staining of large atypical lymphoid cells for TIA (200×) Figure 8. Immunohistochemical ,staining for MAC-387 showing epidermal staining (100×) Gene rearrangement studies showed a ,-T-cell receptor gene rearrangement. The monoclonal band was detected with VJ1, VJ2, and D1J2 primer sets. The T-cell receptor , rearrangement assay has a sensitivity of 61% and a specificity of 94% for the detection of a monoclonal rearrangement in T-cell lymphomas for which amplifiable DNA can be recovered. Electron microscopy was performed on formalin-fixed material, positive-fixed with 2.5% phosphate-buffered glutaraldehyde and further with 1% osmium tetroxide by standard techniques. Intracellular, 50,60-nm, cytoplasmic, spherical, viral-like particles were identified ( Fig. 9). Figure 9. Electron ,microscopy showing 50,60-nm diameter, intracellular, viral-like particles (arrows) (70,000×) [source] Clear cell sarcoma of soft tissue: diagnostic utility of fluorescence in situ hybridization and reverse transcriptase polymerase chain reactionJOURNAL OF CUTANEOUS PATHOLOGY, Issue 4 2008Choladda V. Curry A 7-year-old girl presented with pain and progressive swelling on the left plantar surface. Biopsy of a 2.5 cm mass showed nests of large round to oval neoplastic cells with abundant amphophilic to clear cytoplasm, prominent nucleoli and high mitotic activity. Occasional cells showed spindled morphology. Infrequent melanin pigment was present. Melanocytic markers (HMB45, S-100) were diffusely positive. A diagnosis of clear cell sarcoma of soft tissue (CCSS) was made, and the mass was re-excised with negative margins. 28 months later, a 1.0 cm pulmonary nodule was identified and wedge excision showed metastatic CCSS. Cytogenetics showed a complex karyotype (unbalanced translocation der(12;14)(q10;q10), additional chromosome 22 material of unknown origin). Although the CCSS translocation t(12;22)(q13;q12) was not identified, EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH). Reverse transcription polymerase chain reaction (RT-PCR) showed an EWS-ATF1 fusion transcript, confirmed by direct sequencing. CCSS requires differentiation from malignant melanoma, because of overlapping clinical presentations, sites of involvement, histomorphology, immunocytochemical profiles and ultrastructure. In many circumstances, definitive diagnosis is only possible with confirmation of the CCSS-defining translocation. [source] Post-transplant EBV-negative anaplastic large-cell lymphoma with dual rearrangement: a propos of two cases and review of the literatureJOURNAL OF CUTANEOUS PATHOLOGY, Issue 2007Cynthia M. Magro Background:, Post-transplant lymphoproliferative disease (PTLD) is a recognized complication of the immunosuppressive regimens associated with solid organ transplantation. The vast majority of these lesions represent monomorphic B-cell lymphoproliferative disease. Rarely, however, T-cell malignancies may emerge, the commonest being anaplastic large-cell lymphoma (ALCL). Materials and methods:, We describe two patients who developed a post-transplant ALCL several years after transplantation. Comprehensive phenotypic and molecular studies were conducted. The technique of capillary gel electrophoresis was employed. Results:, One patient died of unrelated causes, while the other patient did achieve clinical remission. The neoplastic cell populace was composed of CD4-positive cytotoxic T cells exhibiting CD30 positivity. There were very few B cells. Striking and prominent clonally restricted infiltrates were identified whereby there was both a heavy chain and T-cell beta gene rearrangement. There was no evidence of lytic Epstein-Barr virus (EBV) infection. Conclusion:, T-cell-associated PTLD does not appear to be directly attributable to EBV infection. Iatrogenic immune dysregulation may result in excessive T-cell proliferation to various antigenic stimuli, hence resembling other drug-associated cell lymphoproliferative conditions such as angioimmunoblastic lymphadenopathy. The dual rearrangement may have some implications regarding the cell of origin. [source] Clear Cell Sarcoma of Soft Tissue with Cytogenetic and Molecular AnalysesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2006C. Vejabhuti A 7-year-old girl presented with pain and progressive swelling on the left plantar surface. Biopsy of a 2.5 cm mass demonstrated nests of large oval tumor cells with high nuclear-to-cytoplasm ratio, amphophilic to clear cytoplasm, prominent nucleoli, and brisk mitotic activity. Occasional cells showed spindled morphology. Infrequent melanin pigment was present. Melanocytic markers (HMB45, S-100) were diffusely positive. A diagnosis of clear cell sarcoma of soft tissue (CCSS) was made, and the tumor was re-excision with negative margins. 28 months later, a 1.0 cm pulmonary nodule was identified and showed CCSS. Cytogenetics demonstrated a complex karyotype (unbalanced translocation der(12;14)(p10;q10), additional chromosome 22 material of unknown origin). Although the CCSS translocation t(12;22)(q13;q12) was not identified, EWSR1 gene rearrangement was detected by fluorescence in situ hybridization (FISH). RT-PCR demonstrated an EWS-ATF1 fusion transcript, confirmed by direct sequencing. CCSS requires differentiation from malignant melanoma, due to overlapping clinical presentations, sites of involvement, histomorphology, immunocytochemical profiles, and ultrastructure. In many circumstances, definitive diagnosis is only possible with confirmation of the CCSS tumor-defining translocation. [source] Lupus erythematosus panniculitis (lupus profundus): Clinical, histopathological, and molecular analysis of nine casesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 6 2005Cesare Massone Background:, The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL). Methods:, We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20,71 years). Results:, Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of ,/,-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-, gene showed a polyclonal smear in all cases. Conclusions:, Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-, gene rearrangement. [source] Secondary Syphilis Presenting as Cutaneous T-Cell Lymphoma in an HIV-Positive PatientJOURNAL OF CUTANEOUS PATHOLOGY, Issue 1 2005A. Laungani We present the case of an HIV-positive 38-year-old Caucasian male with a history of fevers, chills, and disseminated nonpruritic erythematous papules that began on his abdomen. An initial skin biopsy revealed a lymphohistiocytic infiltrate at the dermoepidermal junction, exocytosis of atypical lymphocytes, and minimal spongiosis. Immunohistochemistry showed increased CD8-positive cells but only scattered CD30-positive cells. PCR analysis demonstrated T-cell receptor gamma gene rearrangement. RPR, blood and tissue cultures were all negative. The patient was thought to have a cytotoxic cutaneous T-cell lymphoma. Over time, the lesions progressed to the palms and soles and the patient remained febrile. Repeat biopsy demonstrated a lichenoid interface dermatitis with a superficial and deep perivascular, interstitial, and periadnexal lymphohistiocytic infiltrate and the formation of epithelioid granulomas throughout the dermis. The epidermis showed blurring of the dermoepidermal junction, spongiosis, and exocytosis of lymphocytes and neutrophils. Few spirochetes were demonstrated by Steiner stain. Repeat RPR and FTA-Abs serologies were positive. The patient was diagnosed with late secondary syphilis and was successfully treated with benzathine penicillin. This case demonstrates that atypical lymphoid infiltrates can simulate mycosis fungoides in an HIV-positive patient with secondary syphilis and also reiterates that syphilis is a great mimicker of other entities. [source] Combined histology and molecular biology for diagnosis of early stage gastric MALT lymphomaJOURNAL OF DIGESTIVE DISEASES, Issue 1 2006Zhi Hui YI OBJECTIVE: To establish a sequential diagnostic procedure of gastric mucosa-associated lymphoid tissue (MALT) lymphoma and provide evidence for selected optimal cases to be treated in the early stage. METHODS: Thirty-one cases of gastric lymphoid hyperplasia (GLH) were selected and multiple investigations including histology, protein level, DNA and chromosome levels, combined with clinical follow-up were performed. Histological grade was according to Isaacson's criteria of GLH; CD20, UCHL-1 (CD45RO), anti-kappa (,), anti-lambda (,) and Ki-67 were used for immunohistochemical staining; semi-nested polymerase chain reaction (PCR) was used to detect IgH gene rearrangement and reverse-transcription PCR (RT-PCR) was used to detect API2-MALT1 fusion of the chromosome translocation t(11;18)(q21;q21). Twenty-nine cases underwent eradication therapy for Helicobacter pylori. Changes in histological grade, endoscopic appearance, expression of Ki-67 and IgH gene rearrangement were compared after eradication treatment. RESULTS: Of the 31 cases of GLH with predominant chronic gastritis and gastric ulcer most were histological grade 2 and 3. Only one case had , light chain restriction and 10 cases had monoclonal IgH gene rearrangement. Expression of Ki-67 and monoclonal IgH gene rearrangement were significantly increased with increased lymphoid hyperplasia (P < 0.05). Two cases had API2-MALT1 fusion. Helicobacter pylori was eradicated in 25 cases and another course of treatment had to be given in 4 cases. All cases were followed up for 1.5,37 months. Of the 27 successful eradication cases, 18 showed complete regression both histologically and endoscopically, 4 had partial regression and 7 were unchanged. CONCLUSIONS: A sequential diagnostic procedure based on histology, expression of Ki-67 combined with clonality of IgH rearrangement and API2-MALT1 fusion helps to diagnosis of early stage gastric MALT lymphoma and choose the best treatment strategy. [source] Cutaneous extranasal NK/T-cell lymphomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2003R Ruiz Villaverde ABSTRACT Malignant neoplasm from natural killer (NK) cells are characterized by their positivty for CD56 and absence of monoclonal TCR gene rearrangement. We present the case of a 54-year-old man with a fungous mass in his left flank whose histological examination was consistent with cutaneous extranasal T/NK cell lymphoma. We review the literature and also discuss the prognose and treatment of this variety of lymphoma. [source] Immunohistochemical and gene rearrangement studies of central nervous system lymphomatoid granulomatosisNEUROPATHOLOGY, Issue 5 2007Hiroshi Nishihara Lymphomatoid granulomatosis (LYG) is a rare multisystem disorder with characteristic angiocentric lymphoproliferative features, most frequently involving the lung, skin, and rarely the CNS. LYG has been classified into three subtypes based on the relative proportions of atypical and inflammatory infiltrating cells. Most systemic LYGs have been shown to be EBV-associated, T-cell rich, B-cell proliferative disorders. Here, we present four cases of LYG arising from the CNS and have analyzed them by immunohistochemistry to assess the phenotype of the infiltrate, and by PCR-SSCP (single-strand conformation polymorphism) analysis for immunoglobulin heavy chain (IgH) and T-cell receptor (TcR) , gene rearrangements. Three cases revealed perivascular infiltration of T-cell dominant lymphoid cells, two cases showed monoclonal TcR, gene rearrangement, while the remaining case had a B-cell immunophenotype and monoclonal IgH gene rearrangement with EBV genome expression. This is the first report of a gene rearrangement study on CNS-LYG. We confirm that some cases of CNS-LYG are derived from T-cell monoclonal lymphoproliferative disease, although this disease should be classified as a borderline malignancy and should be separated from overt malignant lymphoma of CNS. [source] Diagnostic utility of EWS break-apart fluorescence in situ hybridization in distinguishing between non-cutaneous melanoma and clear cell sarcomaPATHOLOGY INTERNATIONAL, Issue 9 2010Joon Seon Song Clear cell sarcoma (CCS) is a rare soft tissue sarcoma with morphological similarities to malignant melanoma (MM), but with a distinct genetic background that includes the chromosomal translocation t(12;22)(q13;q12). Clear cell sarcoma is often misdiagnosed as MM because of similarities in target locations and immunophenotypes. Eighteen cases with MM in non-cutaneous sites were subjected to fluorescence in situ hybridization (FISH) to assess EWS gene breakage. Tissue microarrays were constructed using formalin-fixed, paraffin-embedded tissue and the EWSR1 (22q12) dual-color, break-apart rearrangement probe (Vysis) was used. Two patients were classified as CCS with EWS gene rearrangement, with a mean of 67.5% positive cells per sample according to break-apart FISH. The remaining 16 patients lacked break-apart signals of the EWS gene. The presence of type 1 (EWS exon 8-ATF1 exon 4) fusion transcripts was confirmed in FISH-positive patients by RT-PCR. Retrospective analysis revealed that the masses were located in the foot and buttock, respectively. Morphologically, tumor cells were not typical for those of CCS or MM. Break-apart FISH is an accurate and convenient method for differentiating between MM and CCS. Molecular detection of EWS gene rearrangement, either by break-apart FISH or RT-PCR, is mandatory in subjects with melanotic tumors of soft tissue. [source] Ocular adnexal IgG4-related disease has uniform clinicopathologyPATHOLOGY INTERNATIONAL, Issue 8 2008Yasuharu Sato IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39,86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation. [source] Prominent Dutcher body formation in a case of follicular lymphoma with BCL6 gene rearrangement and intact BCL2 gene,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Evan Kulbacki No abstract is available for this article. [source] Rearrangement of immunoglobulin heavy and light chains and VH family in thyroid and salivary gland lymphomasPATHOLOGY INTERNATIONAL, Issue 12 2002Kei Kato It is often difficult to differentiate extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) from non-neoplastic inflammatory conditions. Demonstration of clonal lymphoid proliferation by molecular procedures is important for accurate diagnosis. We examined the clonal population of B-cell lymphomas in nine cases of thyroid and two cases of salivary gland B-cell lymphoma using semi-nested polymerase chain reaction (PCR)-based assay for IgH gene arrangement and reverse transcription (RT)-PCR single-strand conformation polymorphism (SSCP) for the detection of IgL gene rearrangement. Clonality was evident in nine out of 11 cases of B-cell lymphomas examined by PCR, and in six of eight cases by RT-PCR SSCP. In addition, analysis of VH families was performed in eight cases. Although VH3 family was frequently used, each case demonstrated the VH4, VH5 or VH6 family. It is possible that the normal counterpart of thyroid or salivary gland lymphoma might be different from peripheral blood B lymphocytes, which usually use VH3 family. Our results indicate that although no clonality was noted in one case by both PCR and SSCP, these molecular methods are useful as supplementary diagnostic tests for both thyroid and salivary gland lymphomas. [source] Two Cases of Lymphomatoid Papulosis in ChildrenPEDIATRIC DERMATOLOGY, Issue 2 2003Eri Aoki Histologically there was an infiltration of small lymphocytic cells with scattered large atypical cells expressing CD30. Characterization of T-cell receptor gene rearrangement showed monoclonality of the infiltrating cells. The second patient, a 15-year-old Japanese girl, had a 2-week history of self-healing papulovesicular eruptions on her face and limbs. Large CD30+ atypical cells were also noted in the perivascular lymphocytic infiltration. Immunohistochemical studies revealed CD8 expression on almost all CD30+ cells in the second case. In the literature, there have been two reports of children with large CD30+ atypical cells expressing CD8 and two cases expressing CD4, whereas all adult cases reported have had cells expressing only CD4. [source] Pediatric ALK+ anaplastic large cell lymphoma with t(3;8)(q26.2;q24) translocation and c-myc rearrangement terminating in a leukemic phaseAMERICAN JOURNAL OF HEMATOLOGY, Issue 1 2007Sara Monaco Abstract Pediatric ALK-positive anaplastic large cell lymphoma (ALK+ ALCL) is usually associated with a favorable prognosis. ALK+ ALCL associated with a leukemic phase is uncommon, but has been associated with an aggressive clinical course and unfavorable prognosis. Overexpression of c-myc has been shown to be a consistent finding in ALK+, but not ALK-negative ALCL (ALK, ALCL), and the c-myc gene is considered a downstream target of deregulated ALK signaling. We describe a pediatric ALK+ ALCL with a leukemic phase at relapse. Similar to other rare cases described in the literature, it followed an aggressive clinical course despite multiple regimens of chemotherapy and bone marrow transplantation. Lymphoma cells showed aberrant ALK expression and c-myc overexpression. In addition to the characteristic t(2;5)(p23;q35) translocation, a t(3;8)(q26.2;q24) translocation was also present, and c-myc gene rearrangement was confirmed by FISH analysis. The findings in this case demonstrate the association of peripheral blood leukemic involvement and aggressive clinical course, and suggest that other factors, such as c-myc rearrangement, may be responsible for the aggressive clinical behavior in ALK+ ALCL. Am. J. Hematol., 2006. © 2006 Wiley-Liss, Inc. [source] Primary cutaneous follicle center lymphoma of the arm with a novel chromosomal translocation t(12;21)(q13;q22): A case reportAMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2006Tomislav M. Jelic Abstract We report a reciprocal translocation between the long arms of chromosomes 12 and 21, t(12;21)(q13;q22), in a patient with primary cutaneous follicle center lymphoma. Follicle center lymphoma of the skin and follicle center cell lymphoma of the lymph node are morphologically and immunophenotypically very similar. However, the clinical behavior and prognosis of these tumors are different due to the molecular basis of these malignancies. Follicle center cell lymphoma of the lymph node is determined by the presence of a unique translocation between chromosomes 14 and 18, t(14;18)(q32;q21), BCL-2-JH gene rearrangement, that is not present in primary cutaneous follicle center lymphomas. Chromosomal translocations in the primary skin lymphomas have not been previously reported. We hope that our discovery of a new translocation t(12:21)(q13q22) will encourage further investigation into the molecular basis of this translocation and other cytogenetic abnormalities in primary cutaneous B-cell lymphomas. Am. J. Hematol. 81:448,453, 2006. © 2006 Wiley-Liss, Inc. [source] ,, T-cell large granular lymphocyte (LGL) leukemia with spontaneous remissionAMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2004Tsutomu Shichishima Abstract T-cell large granular lymphocyte (LGL) leukemia is a clonal disorder with an indolent clinical course. In July 1995, a 46-year-old Japanese man was admitted to our hospital because his anemia had progressed. He had a white blood cell count of 3.9 × 109/L with 75% lymphocytes, which were intermediate to large and had almost round nuclei and azurophilic granules, and anemia with a red blood cell count (RBC) of 2.69 × 1012/L, hemoglobin (Hb) of 9.5 g/dL, and hematocrit (Hct) of 28.3%. Electron microscopic examination showed that most of the lymphocytes had a parallel tubular array and dense core granules in their cytoplasm. Flow cytometry and Southern blotting of the T-cell antigen receptor (TCR) genes using the peripheral blood species showed monoclonal proliferation of LGLs with a CD3+, TCR,,+, CD4,, CD8,, CD16+, CD56,, CD57,, HLA-DR+ phenotype, and a TCR , gene rearrangement, respectively, suggesting that the patient was diagnosed as having ,, T-cell LGL leukemia. He had no symptoms, organomegaly, or skin lesions. About 1.5 years after diagnosis, the anemia gradually improved with disappearance and appearance of a rearranged band in the TCR-, gene and TCR-, gene, respectively. About 7 years after diagnosis, the anemia improved completely with a RBC of 5.01 × 1012/L, Hb of 14.8 g/dL, and Hct of 44.3%, and he was in complete remission without TCR-, and -, gene rearrangements. He had received no therapy. This is the first report of spontaneous remission of ,, T-cell LGL leukemia. Am. J. Hematol. 75:168,172, 2004. © 2004 Wiley-Liss, Inc. [source] A method for the analysis of gene rearrangement in single immune cellsBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Article first published online: 16 APR 2010 No abstract is available for this article. [source] Mycosis fungoides and chronic lymphocytic leukaemia , composite T-cell and B-cell lymphomas presenting in the skinBRITISH JOURNAL OF DERMATOLOGY, Issue 2 2000P.R. Hull Composite lymphomas involving cutaneous B-cell and T-cell lymphomas are very uncommon. We report here the unique circumstance of a patient with mycosis fungoides (primary cutaneous T-cell lymphoma) who later developed chronic lymphocytic leukaemia (B-cell lymphoproliferation, B-CLL), which presented in the skin (leukaemia cutis) as a composite lymphoma affecting an earlobe. The presence of both lymphoproliferative disorders was confirmed with immunophenotyping and the finding of both immunoglobulin gene rearrangements and T-cell receptor gene rearrangements in the ear and the same T-cell receptor gene rearrangement in a plaque lesion of mycosis fungoides on the arm. [source] Age-associated difference in gene expression of paediatric acute myelomonocytic lineage leukaemia (FAB M4 and M5 subtypes) and its correlation with prognosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2009Aoi Jo Summary Acute myeloid leukaemia, French-American-British M4 and M5 subtypes (AML-M4/M5) is frequently associated with MLL gene rearrangement and its incidence is relatively high among infants. Clinically, paediatric AML-M4/M5 has been considered as an intermediate or undefined prognostic group. In this study, we analysed gene expression of 40 paediatric AML-M4/M5 patients excluding inv(16) and t(8;21) patients, and found striking differences among the patients in an age-associated manner. In particular, most of the infants displayed very distinct gene expression. On the basis of this difference, we divided paediatric patients into three subgroups (A, B and C) with the average age of 0·3, 3·1 and 6·6 years old respectively. All subgroups included patients with MLL gene rearrangement as well as normal and other karyotypes. Surprisingly, gene expression signatures of MLL gene rearrangement differed substantially among these subgroups. In addition, subgroup C presented extremely poor outcome (3-year event-free survival 28%) whilst eight patients with MLL gene rearrangement in subgroup C had all relapsed within 18 months. These results suggest that age is an important factor contributing to the biology of AML-M4/M5 and the sub-grouping procedures developed in this study could be a powerful tool to identify unfavourable risk patients within paediatric AML-M4/M5. [source] Clonality analysis of lymphoproliferative disorders in patients with Sjögren's syndromeCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2007L. Dong Summary The aim of this study was to clarify the nature of the clonal lymphocyte infiltration in Sjögren's syndrome (SS) patients associated with lymphoproliferative disorders. We examined B cell clonality in lymphoproliferative tissues from six primary SS patients associated with lymphoproliferative disorders or lymphoma by cloning and sequencing of the gene rearrangement of the immunoglobulin heavy chain complementarity determining region 3 (IgVH,CDR3). Three patients with sequential observation showed progressional clonal expansion with the presence of the same subclone in different tissues during the course of disease. Among them, one patient developed mucosa-associated lymphoid tissue (MALT) lymphoma in glandular parotid. The other three SS patients concomitant with malignant B cells lymphomas showed different clonal expansion of B cells between nodal sites and salivary glands. The cloanality analysis indicated that monoclonal B cell population could spread from one glandular site to another site during the course of SS, suggesting that the malignant clone may arise from the general abnormal microenvironment, not restricted to the glandular tissue, in some SS patients. [source] Aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumoursCLINICAL ENDOCRINOLOGY, Issue 5 2007Ana Banito Summary Objective, Follicular thyroid tumours present several genetic alterations such as aneuploidy, RAS mutations and PAX8/PPAR,rearrangements. The molecular basis of aneuploidy remains undefined in the majority of human cancers. It has been proposed that mutations in RAS oncogenes could be related to chromosomal instability, although this issue remains controversial. The aim of our study was to investigate the correlation between aneuploidy, RAS mutations and PAX8/PPAR, gene rearrangement in thyroid follicular tumours. Design, Ploidy status was determined by flow cytometry in 111 thyroid lesions (42 follicular thyroid adenomas, 27 follicular thyroid carcinomas, 19 follicular variants of papillary thyroid carcinoma, 20 poorly differentiated thyroid carcinomas and 3 anaplastic thyroid carcinomas). RAS mutations and PAX8/PPAR, fusion gene were investigated in 101 and 87 of these samples, respectively. Results, Altogether, 12 of 50 (24%) diploid tumours presented RAS mutation which contrasts with 3 of 51 (5·9%; P = 0·0124) RAS mutations in the group of aneuploid tumours. The aneuploid tumours harbouring RAS mutations were two poorly differentiated carcinomas and one follicular variant of papillary thyroid carcinoma with poorly differentiated areas. None of the tumours with RAS mutations expressed the PAX8/PPAR, fusion gene. Three of five (60%) follicular thyroid adenomas and 1 of 7 (14%) follicular thyroid carcinomas, with the PAX8/PPAR, fusion gene, were aneuploid. Conclusions, Our data suggest that aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours. [source] HPRT mutations, TCR gene rearrangements, and HTLV-1 integration sites define in vivo T-cell clonal lineages,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 2-3 2005Mark Allegretta Abstract HPRT mutations in vivo in human T-lymphocytes are useful probes for mechanistic investigations. Molecular analyses of isolated mutants reveal their underlying mutational changes as well as the T-cell receptor (TCR) gene rearrangements present in the cells in question. The latter provide temporal reference points for other perturbations in the in vivo clones as well as evidence of clonal relationships among mutant isolates. Immunological studies and investigations of genomic instability have benefited from such analyses. A method is presented describing a T-cell lineage analysis in a patient with HTLV-1 infection. Lineage reconstruction of an in vivo proliferating HPRT mutant clone allows timing of the integration event to a postthymic differentiated cell prior to the occurrence of HPRT mutations. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||