Search PubMed⌕ Search

Biomedical subjects

Adnan Mansoor

Publications and source records attributed to Adnan Mansoor.

7 recordsLinked to original sources

Immunoglobulin VH somatic hypermutation in mantle cell lymphoma: mutated genotype correlates with better clinical outcome.

Mantle cell lymphoma is an aggressive B-cell lymphoma for which the biology is incompletely understood. Previous studies have reported that somatic hypermutation of the variable region of the immunoglobulin heavy chain gene (V(H)), as commonly defined as <98% homology, can be detected in approximately one-third of mantle cell lymphoma, although the V(H) mutation status has not been found to significantly correlate with patient survival. In this study, we assessed V(H) mutation in 55 mantle cell lymphomas using a method slightly different from those used in the previous studies, and we came to different conclusions. Using DNA extracted from formalin-fixed/paraffin-embedded tumors in all cases, we identified monoclonal IGH bands in 54 of 55 cases with the FR1c/J(H) primer; a monoclonal IGH band was amplified using another IGH primer set, FR256/J(H), in the remaining case. Cloning was performed in all cases, and an average of six clones were sequenced and analyzed for each case. Intraclonal heterogeneity was detected in 45 (82%) cases. Further analysis was performed in 53 cases, in which a predominant IGH species was identified. Most (32 of 53 cases, 60%) cases were 'mutated', with <98% homology. V(H)1-69, V(H)4-59 and V(H)3-74 were utilized in 29 (55%) cases. Intraclonal evolution and non-productive V(H) rearrangements were more frequent in the mutated group. Patients with the 'mutated' genotype had longer overall survival (P=0.017, Log rank) that is independent of the international prognostic index. To conclude, our data suggest that the V(H) mutation frequency in mantle cell lymphoma may be higher than previously believed. Importantly, using our methodology, we found that the V(H) mutation status may be a useful prognostic marker for these patients.

Adult↗

Ring chromosome 7 with amplification of 7q sequences in a pediatric case of hepatosplenic T-cell lymphoma.

Hepatosplenic T-cell lymphoma is rare, and most cases that have been reported with cytogenetic abnormalities have an isochromosome 7q with or without trisomy 8. A 7-year-old boy who had hepatomegaly and splenomegaly was diagnosed with hepatosplenic T-cell lymphoma on the basis of a bone marrow biopsy. The karyotype of the lymphoma cells at diagnosis included a ring chromosome 7 and trisomy 8. Fluorescence in situ hybridization analysis with chromosome 7 probes demonstrated amplification of a 7q31 sequence in the ring chromosome. While isochromosome 7q is a common abnormality in hepatosplenic T-cell lymphoma, and other structurally abnormal chromosomes 7 have been reported in a small number of cases, this is the first reported case of ring chromosome in hepatosplenic T-cell lymphoma.

Bone Marrow↗

Waldenstrom macroglobulinemia involving extramedullary sites: morphologic and immunophenotypic findings in 44 patients.

Waldenstrom macroglobulinemia (WM) is a clinicopathologic syndrome in which a B-cell neoplasm involving the bone marrow, usually lymphoplasmacytic lymphoma (LPL), is associated with immunoglobulin M paraprotein in the serum. Extramedullary involvement occurs in a subset of patients and is infrequently examined histologically. The files of M.D. Anderson Cancer Center were searched for patients with WM who underwent biopsy of one or more extramedullary sites during the course of disease. Each biopsy specimen was classified using the criteria of the World Health Organization classification. The study group consisted of 44 patients (26 men and 18 women), with a total of 51 specimens obtained from lymph nodes (n = 36), soft tissue (n = 4), spleen (n = 3), skin (n = 2), lung (n = 2), tonsils (n = 1), colon (n = 1), liver (n = 1), and gallbladder (n = 1). Lymphoplasmacytic lymphoma was the most common histologic type, in 40 (78%) samples. This category was morphologically heterogeneous and was further subclassified as lymphoplasmacytic (n = 21), lymphoplasmacytoid (n = 18), and polymorphous (n = 1). Four of these LPL cases morphologically resembled marginal zone B-cell lymphoma. Four additional samples were involved by diffuse large B-cell lymphoma, probably transformed from LPL. Three more samples were involved by LPL with unusual features: two were CD5-positive and one was a composite tumor with classical Hodgkin's disease. Other categories of lymphoma in this group of patients with WM included small lymphocytic lymphoma/chronic lymphocytic leukemia (n = 2), mantle cell lymphoma (n = 1), and follicular lymphoma (n = 1). Waldenstrom macroglobulinemia is most commonly associated with LPL but can rarely occur with other types of B-cell lymphoma. Lymphoplasmacytic lymphoma in patients with WM is morphologically heterogeneous and can be indistinguishable from marginal zone B-cell lymphoma. CD5+ B-cell lymphomas with features otherwise typical of LPL are rare, and we think these tumors are part of the spectrum of LPL.

Adult↗

Diffuse large B-cell lymphoma occurring in patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Clinicopathologic features of 12 cases.

Of 92 patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM) treated at our institution, diffuse large B-cell lymphoma (DLBCL) also developed in 12 (13%). In 10 patients, DLBCL developed 12 to 128 months (median, 44 months) after the diagnosis of LPL/WM. Two patients had LPL/WM and DLBCL simultaneously. Clinicopathologic features at diagnosis of LPL/WM did not predict the risk of DLBCL. Onset of DLBCL was characterized by worsening constitutional symptoms, profound cytopenias, extramedullary disease, and organomegaly. Immunoglobulin light chain expression was identical in both LPL/WM and DLBCL. In situ hybridization for Epstein-Barr virus (EBV) in 8 cases of DLBCL was negative. Of 11 patients with clinical follow-up information available, 8 (73%) died within 10 months of diagnosis of DLBCL. DLBCL, most likely as a result of histologic transformation, occurs in a subset of patients with LPL/WM and is associated with aggressive clinical course and poor outcome. EBV is unlikely to be involved in transformation.

Adult↗

The stromal composition of malignant lymphoid aggregates in bone marrow: variations in architecture and phenotype in different B-cell tumours.

We present evidence that different B-cell tumours, in bone marrow, have different relationships to stroma. Marrow core biopsies from 46 patients with B-cell tumours were immunostained with antibodies for distinct stromal cells. Cases included follicular lymphoma (FL), chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), lymphoplasmacytic lymphoma (LPL), and nodal, extranodal and splenic marginal zone lymphoma (NMZL, MALT, SMZL). In normal marrow, low-affinity nerve growth factor receptor (LNGFR) highlighted a fine network of adventitial reticular cells (ARC). The nodular aggregates of CLL/SLL, NMZL, MALT and SMZL were characterized by distortion of the ARC network and downregulation of LNGFR. In contrast, the aggregates of FL, LPL and MCL were composed of linear arrays of ARC in tight association with individual tumour cells. LNFGR+ was upregulated in ARC associated with the aggregates in FL, LPL and focally in MCL. Upregulation of CD35, vascular cell adhesion molecule (VCAM-1) and CD40 on ARC was noted exclusively in FL. Marrow lymphoid aggregates in CLL/SLL, NMZL, MALT and SMZL probably grow by displacing the pre-existing marrow stroma, while FL and LPL maintain a close association with the ARC network. In FL, expression of follicular dendritic cell-associated markers is modulated in pre-existing marrow stromal cells.

Bone Marrow↗