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Clonal Rearrangement (clonal + rearrangement)
Selected AbstractsCd8+/v,5.1+ large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.HEMATOLOGICAL ONCOLOGY, Issue 2 2002E. Granjo Abstract We report a case of CD8+/V,5.1+ T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3+/TCR,,+/CD8+bright/CD11c+/CD57,/CD56, large granular lymphocytes with expression of the TCR-V,5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR ,-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V, monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease. Copyright © 2002 John Wiley & Sons, Ltd. [source] Detection of clonal rearrangement of T-cell receptor genes in the diagnosis of primary cutaneous CD30+ lymphoproliferative disordersJOURNAL OF CUTANEOUS PATHOLOGY, Issue 11 2006Johannes Greisser Background:, Detection of clonality has been reported to be a helpful tool in the diagnosis of cutaneous lymphomas. Monoclonal rearrangement of T-cell receptor genes (TCR) was reported in fresh frozen tissue of lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large-cell lymphoma (ALCL), but the diagnostic value of T-cell clonality in formalin-fixed, paraffin-embedded biopsies has so far not been assessed. Methods:, Detection of clonal rearrangement of TCR, genes by highly sensitive polymerase chain reaction-based automated high-resolution fragment analysis (AHRFA) in archival LyP (n = 18) and ALCL (n = 17) tissue. Results:, Detection of clonality differed significantly among the histologic forms of LyP as well as between LyP and ALCL with clonality found in none of the 10 biopsies of LyP type A and B, in 4/8 (50%) of the LyP type C specimens, and in 11/17 (65%) of ALCL cases. Conclusions:, T-cell clonality can only be found in a minority (four of 18; 22%) of archival LyP specimens, even when employing a highly sensitive detection method and is thus of limited diagnostic value. Final diagnosis of LyP has to be based mainly on clinical, histologic, and immunohistochemical findings rather than on results of clonality studies. [source] Cutaneous pseudolymphoma in association with molluscum contagiosum in an elderly patientJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2003D. Moreno-Ramírez Background:, Molluscum contagiosum (MC) is a common cutaneous infection, which has been reported in association with cutaneous pseudolymphoma in few cases. Methods:, A 72-year-old woman with a nodule arising on the external canthus was reviewed. The lesion was surgically removed, and the histopathological study demonstrated an epidermal invagination filled by molluscum bodies and a diffuse infiltrate comprising atypical lymphocytes. Results:, Immunohistochemical stains disclosed predominance of T cells with positive CD30 labeling. Polymerase chain reaction failed to demonstrate clonal rearrangement of the T-cell receptor. Conclusion:, After ruling out systemic involvement, the patient was followed up for 2 years with no evidence of recurrence. We report this case to the best of our knowledge and discuss the literature about atypical clinical and histological presentations of MC. [source] The value of molecular analysis by PCR in the diagnosis of cutaneous lymphocytic infiltratesJOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2002Niels Holm The diagnosis and classification of cutaneous lymphomas remain a challenge for the clinician and dermatopathologist. This diagnostic dilemma is mainly encountered in the distinction between an early malignant lymphoma and a benign reactive lymphocytic infiltrate (pseudolymphoma). Until the beginning of the 1980s, our diagnostic tools were limited to the clinical presentation, course, and histopathology in diagnosis and classification of lymphocytic infiltrates. Advances in immunology and, in particular, in molecular genetics with the introduction of the Southern blot technique and the polymerase chain reaction (PCR) have revolutionized the diagnosis of lymphocytic infiltrates by determination of clonality. In some series, more than 90% of cutaneous T-cell lymphomas have a clonal rearrangement of the T-cell receptor ,-chain gene, as opposed to very low percentages of rearrangement in T-cell pseudolymphomas. However, the presence of clonality does not necessarily imply malignancy. Cases of pseudolymphomas, lichen planus and pityriasis lichenoides et varioliformis acuta were reported with clonal lymphocytic proliferations. Therefore, care should be exercised in the evaluation of the results of molecular analysis, and these should always be correlated with the clinical, histological and immunophenotypic picture to arrive at the correct diagnosis. It may be expected that the molecular methods for diagnosis of lymphocytic infiltrates will be improved and refined in future, and that sensitivity and specificity will increase. [source] CD19 negative precursor B acute lymphoblastic leukemia presenting with hypercalcemiaPEDIATRIC BLOOD & CANCER, Issue 1 2004Iyad Sultan MD Abstract A 9-month-old infant presented with hypercalcemia and lytic bone lesions. Suspicion for malignancy led to a bone marrow examination, which showed replacement of the marrow by a small round blue cell infiltrate. Flow cytometric analysis of these cells showed an unusual immunophenotype in that these cells were dim CD45, HLA-DR, and CD10 positive, but CD19, CD20, CD79a, and CD34 negative. Southern blotting showed clonal rearrangement of immunoglobulin heavy chain (IgH) which confirmed a diagnosis of precursor B acute lymphoblastic leukemia (ALL). He received supportive treatment with hydration and pamidronate, but had recurrent episodes of hypercalcemia. Once the correct diagnosis of ALL was established, the patient was treated with an infantile ALL chemotherapeutic regimen and the hypercalcemia resolved. This case highlights the usefulness of immunoglobulin gene rearrangement studies in atypical cases of ALL. © 2004 Wiley-Liss, Inc. [source] Epstein-Barr virus-related lymph node lesion resembling autoimmune disease-like clinicopathological findings in elderly patients Report of three casesAPMIS, Issue 12 2003MASARU KOJIMA Three cases of Epstein-Barr virus (EBV)-related lymphoproliferative disorders in elderly patients showing autoimmune disease-associated lymphadenopathy-like clinicopathological findings have been reported. Clinically, they were characterized by systemic lymphadenopathy, "B" symptoms, polyclonal hypergammaglobulinemia, elevated serum LDH and transient presence of various autoantibodies, and absence of atypical lymphocytosis in peripheral blood. One case was associated with idiopathic thrombocytopenic purpura. The clinical course was self-limiting. Histologically, they exhibited numerous lymphoid follicles with hyperplastic germinal centers and atypical interfollicular widening with prominent vascular proliferation. In the paracortical area, there was a mixed infiltrate comprising small to medium-sized lymphocytes and plasma cells, and variable numbers of eosinophils and T- and B-immunoblasts. In situ hybridization demonstrated a varying number of EBV-infected lymphocytes in the germinal center as well as in the interfollicular area. Polymerase chain reaction demonstrated that neither clonal rearrangement of T-cell receptor ,-gene nor immunoglobulin heavy-chain rearrangement was detected in two of the cases examined. Although acute EBV infection rarely occurs in older adults, EBV related to reactive lymphoproliferative disorder should be added to the differential diagnosis of autoimmune disease-associated lymphadenopathy and node-based peripheral T-cell lymphoma in elderly patients. [source] Application of combined immunofluorescence and fluorescence in situ hybridization on paraffin-embedded sections to characterize T-cell lymphoma with EBV-infected B-cell blastsGENES, CHROMOSOMES AND CANCER, Issue 4 2004Genevieve K. Temple Combined immunofluorescence (IF) and fluorescence in situ hybridization (FISH) on formalin-fixed, paraffin-embedded tissue sections were used to examine lymph node tissue from two patients diagnosed with T-cell lymphoma with Epstein,Barr virus (EBV),infected B-cell blasts. The majority of cells within the samples comprised T-cells staining positively for CD3. In addition, both patients had a population of large pleiomorphic cells that were positive for the B-cell marker CD20 and for EBV LMP-1. Standard PCR clonality testing of the nodes revealed both immunoglobulin heavy chain (IGH) and T-cell receptor (TCR) clonal rearrangements in one patient, although in the other case monoclonality was demonstrated only for TCRG. Cytogenetics of cultured lymphocytes from nodal tissue revealed two apparently unrelated abnormal clones in both patients. Combined IF and FISH revealed that these phenomena reflected two abnormal populations of B- and T-cells rather than reactive B-cell hyperplasia or biphenotypic evolution from a common ancestral lymphoma. True B-cell malignancy probably emerged within a preexisting but unrelated T-cell lymphoma. This is the first study to relate the phenotype of the abnormal cells in such cases to specific clonal populations of cells, and it demonstrates a method that may easily be introduced into a diagnostic cytogenetics laboratory with access to standard pathology laboratory resources. © 2004 Wiley-Liss, Inc. [source] Extranodal NK/T-cell lymphoma, nasal type, presenting after 5 years of remissionINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 3 2008Tomonobu Ito MD A 76-year-old woman with multiple edematous erythemas, erosions, and ulcers on the breast and abdomen was admitted to our hospital in June 2005. She had developed granulomatous bleeding lesions in the right nostril 6 years prior to her visit to our dermatology unit. She had been observed at the otorhinolaryngology department of our hospital, and a biopsy was taken from the nasal lesion. Computerized tomography and gallium scintigraphy (67Ga single-photon emission computed tomography) did not reveal any lesions corresponding to the diagnosis of malignant lymphoma. The histologic examination of the nasal specimen rendered a diagnosis of natural killer (NK)/T-cell lymphoma, nasal. Because imaging analysis indicated a small-sized tumor without metastases, oral prednisolone at 20 mg/day was administered for 1 month. The tumor decreased in size and disappeared after 19 months of low-dose steroid therapy. ,Five years after the initial treatment, the patient developed a fever of 38 °C with infiltrated erythemas and erosions on her breast. Erysipelas was initially suspected, but the antimicrobial agent did not show any effect and the multiple infiltrated erythemas and ulcers spread throughout her chest and abdomen (Fig. 1). The lymph nodes were not palpable. The right nasal cavity showed no granulomatous lesions or other signs of abnormality. The peripheral white blood cell count (3000/µL), red blood cell count (3.54 × 106/µL), and platelet count (112 × 103/µL) were reduced. Atypical lymphocytes were not observed. The serum lactic dehydrogenase (LDH; 1770 U/L; normal, 224,454 U/L), aspartate aminotransferase (AST; 140 U/L; normal, 10,30 U/L), and alanine aminotransferase (ALT; 57 U/L; normal, 3,29 U/L) levels were elevated. The soluble interleukin-2 (IL-2) receptor level was high (25,300 U/mL; normal, 167,497 U/mL). Epstein,Barr virus (EBV) serologic examination showed the immunoglobulin G (IgG) viral capsid antigen (VCA) at 1 : 320 and the EBV nuclear antigen (EBNA) at 1 : 40. IgM VCA and EBV early antigen-diffuse restricted antibody (EA) IgA and IgG were not detectable. Histologic findings from the left chest skin showed a distribution of atypical lymphocytes from the upper dermis to the subcutaneous tissue, and many foamy cells which had phagocytosed the hemocytes (Fig. 2a,b). Immunohistochemical analysis showed that the atypical lymphocytes were sCD3,, CD4,, CD8,, CD20,, CD56+, granzyme B+, and T-cell intracellular antigen (TIA-1) positive. Furthermore, EBV-encoded small RNAs (EBER), detected by in situ hybridization, exhibited a strong signal. The nasal lesions biopsied 6 years previously showed an identical staining pattern with the skin lesions immunohistochemically. Analysis of the T-cell receptor-, (TCR-,), TCR-,, and TCR-, gene did not reveal any clonal rearrangements, but the EBV gene was detected from the skin specimens by Southern blotting. Our patient's condition was diagnosed as a case of extranodal NK/T-cell lymphoma, nasal type, but the patient had concomitantly developed hemophagocytic syndrome (HPS). She was treated with a combination of steroid pulse therapy and chemotherapy (pirarubicin hydrochloride 30 mg/m2, cyclophosphamide 500 mg/m2, vincristine 1 mg/m2, prednisolone 30 mg/m2, etoposide 80 mg/m2). After the first session of chemotherapy, the lesions on the chest and abdomen diminished, but, 2 weeks later, the skin lesions recurred, and disseminated intravascular coagulation (DIC) induced by HPS supervened. The patient died as a result of multiple organ failure induced by HPS. Figure 1. Multiple infiltrated erythemas, erosions, and ulcers on the breast and abdomen Figure 2. Histologic findings of a skin biopsy specimen from the left chest (hematoxylin and eosin staining). (a) Dense infiltration of atypical lymphocytes from the upper dermis to the subcutaneous tissue (×40). (b) Many foamy cells had phagocytosed the hemocytes (×400) [source] | ||||||||||||||||||||||