MRI in predicting curative resection of rectal cancer: new dilemma in multidisciplinary team management.
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Humans↗
Biomedical subjects
Andrew C Wotherspoon
Publications and source records attributed to Andrew C Wotherspoon.
Neuron-specific enolase expression in multiple myeloma.
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Adenocarcinoma↗
Potential of surface-coil MRI for staging of esophageal cancer.
OBJECTIVE: The aim of this pilot study was to assess the feasibility of external surface-coil MRI as a new method of imaging the esophagus and esophageal cancer. CONCLUSION: The results for the 10 patients investigated indicate that by using a high-resolution axial T2-weighted sequence (small field of view, thin section images), MRI provides detailed imaging of the anatomic layers of the esophageal wall and tumor. Three independent radiologists found good correlation in the morphologic appearance and extent of tumor between MRI and matched histology sections. This study illustrates the potential of the technique as an alternative form of local staging for esophageal cancer.
Adenocarcinoma↗
The efficacy of alemtuzumab for refractory chronic lymphocytic leukemia in relation to cytogenetic abnormalities of p53.
We reviewed the efficacy of alemtuzumab in the treatment of 28 patients with refractory chronic lymphocytic leukemia (CLL) in whom p53 status was known. Overall responses of 53.6% (complete responses 17.9%) were attained with no significant difference between patients with (50%) or without (55%) p53 deletion (p=0.214). We confirm the efficacy of alemtuzumab in refractory CLL irrespective of p53 deletions, and advocate its introduction earlier in disease course.
Adult↗
Isolated bone marrow involvement in diffuse large B cell lymphoma: a report of three cases with review of morphological, immunophenotypic and cytogenetic findings.
Diffuse large B cell lymphoma (DLBL) comprises a heterogenous entity characterized by the presence of large cells, exhibiting a mature B cell phenotype. The high proliferation rate and aggressive disease remain a therapeutic challenge, but the apparent biological diversity permits a risk-stratification model for prognostic grouping through the International Prognostic Index (IPI). Empirical to this approach is the consideration of cytogenetic data, offering an insight into the pathogenetic events which may underlie neoplastic clonal evolution and disease progression. We describe three cases of DLBL presenting with isolated marrow disease, a rare primary finding in this lymphoma. All three cases showed involvement of blood and bone marrow without evidence of splenic or lymph node involvement on imaging studies. Histological and immunophenotypic findings were similar in all three cases, outlining the phenotypic maturity of this disease. Cytogenetic analysis revealed complex karyotypes in the two cases examined. M-FISH (multicolour fluorescent in situ hybridization) performed on bone marrow from case 1 showed several cryptic translocations not evident on G-banding, including a novel translocation between 2p and 9p, and an unbalanced translocation between 14q and 11q. Cytogenetic analysis in case 2 showed abnormalities involving 7q, 9p at the site of the INK4a gene, and the bcl-2 locus, findings confirmed by M-FISH. These cases serve to highlight the biological and cytogenetic heterogenity of DLBL and emphasize the need for complementary investigations in the characterization of this entity.
Adult↗
B-prolymphocytic leukaemia with t(11;14) revisited: a splenomegalic form of mantle cell lymphoma evolving with leukaemia.
We reviewed eight cases that were diagnosed before 1995 with B-prolymphocytic leukaemia (B-PLL) harbouring t(11;14)(q13;q32) and/or cyclin D1 staining. Thirteen B-PLL patients without t(11;14) were selected as controls. Peripheral blood, bone marrow and histological sections were re-examined without cytogenetic information. Final diagnosis was made using morphology, cytogenetics, immunophenotype and immunohistochemistry. Clinical characteristics were similar for both groups except for younger age, male predominance and extranodal involvement in cases with t(11;14). CD5 was more frequently positive in the t(11;14)+ group (80%) than in the t(11;14)- group (31%). Surface membrane immunoglobulin was strongly expressed by all t(11;14)+ cases, but only 45% of t(11;14)- cases. Histopathological and cytological review of cases with t(11;14) showed an infiltrate with a mixture of cells, some resembling prolymphocytes and others with mantle cell lymphoma (MCL) morphology. Blood films of cases with t(11;14) showed features suggestive of B-PLL in three, and in others, a mixture of cells resembling MCL and nucleolated ones; none corresponded to the blastoid form of MCL. We suggest that 'B-PLL' with t(11;14) may represent a splenomegalic form of MCL evolving with leukaemia. These cases illustrate the importance of tissue diagnosis with cyclin D1 staining and fluorescence in situ hybridization analysis in B-cell leukaemia with prolymphocytic features.
Aged↗
Variable frequencies of t(11;18)(q21;q21) in MALT lymphomas of different sites: significant association with CagA strains of H pylori in gastric MALT lymphoma.
t(11;18)(q21;q21) is a specific chromosomal translocation associated with mucosa-associated lymphoid tissue (MALT) lymphoma. It fuses the amino terminal of the API2 gene to the carboxyl terminal of the MALT1 gene and generates a chimeric fusion product. Although the translocation is frequently detected in gastric and pulmonary MALT lymphoma, its incidence in MALT lymphomas from other sites is largely unknown. It also remains unknown whether the occurrence of the translocation is influenced by the nature of preceding diseases associated with MALT lymphomas. We screened for t(11; 18)(q21;q21) in 417 cases of MALT lymphoma from 8 major sites by reverse transcription-polymerase chain reaction. t(11;18)(q21;q21) was found at highest frequencies in MALT lymphomas from the lung (38%) and stomach (24%), and at moderate frequencies in those from the conjunctiva (19%) and orbit (14%). However, the translocation was found only rarely in MALT lymphomas from the salivary gland (1%) and was absent in those from the thyroid, skin, liver, and other rare sites, and in immunoproliferative small intestinal disease (IPSID). In gastric MALT lymphoma, t(11;18)(q21;q21) was significantly associated with infection by CagA-positive strains of Helicobacter pylori. As CagA-positive strains of H pylori are much more potent in induction of host inflammatory responses, including activation of neutrophils, which release highly genotoxic oxygen reactive species, we therefore examined neutrophil infiltration in recognized precursors of MALT lymphoma including H pylori-associated gastritis, lymphoepithelial sialadenitis, and Hashimoto thyroiditis. Neutrophil infiltration was prominent in H pylori-associated gastritis but not in lymphoepithelial sialadenitis and Hashimoto thyroiditis. Our results demonstrate that t(11;18)(q21; q21) occurs at markedly variable frequencies in MALT lymphoma of different sites and suggest that the occurrence of the translocation is influenced by the nature of premalignant diseases associated with MALT lymphoma. Oxidative damage might play a role in development of t(11;18)(q21; q21).
Adaptor Proteins, Signal Transducing↗
Prognostic features of splenic lymphoma with villous lymphocytes: a report on 129 patients.
Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade B-cell lymphoma defined in the World Health Organization classification as the leukaemic form of splenic marginal zone lymphoma. Presenting features and response to therapy have been described, but information on prognostic factors is scanty. Clinical, laboratory and follow-up data were collected on 129 patients with SLVL to determine features predicting disease behaviour and survival. Diagnosis was made on clinical, morphological and immunophenotypic features and, where available, bone marrow and spleen histology. Median age was 69 years (range 39-90 years) and male:female ratio, 0.9. The majority had splenomegaly, but lymphadenopathy and hepatomegaly were rare. Median Hb was 11.8 g/dl, white blood cell count was 16 x 10(9)/l and platelet count was 145 x 10(9)/l; 27% of patients had monoclonal protein in serum and/or urine. While 27% of patients remained untreated, 10% transformed to high-grade lymphoma. Median follow-up was 61 months and median survival was 13 years, with 72% of patients alive at 5 years. Cox regression analysis showed that increasing age, anaemia, thrombocytopenia and lymphocytosis > 16 x 10(9)/l were independent adverse predictors of overall survival. However, only anaemia and lymphocytosis > 16 x 10(9)/l remained highly significant independent prognostic factors when only deaths due to lymphoma were analysed. Splenectomized patients fared better than those receiving chemotherapy only (P = 0.001 for SLVL deaths). We conclude that SLVL is mainly a disease of the elderly with a relatively benign course but, when treatment is required, splenectomy is beneficial.
Adult↗
Granulomatous slack skin disease--disease features and response to pentostatin.
Granulomatous slack skin disease (GSSD) is a rare condition characterized clinically by redundant skin folds, which show a predilection towards flexural areas, and histologically by a granulomatous T-cell infiltrate and loss of elastic fibres. The disease is often indolent, although rapid progression and transformation have been described. There is much debate as to whether this condition is a subset of mycosis fungoides or a separate disease entity in itself. We describe a case of GSSD with unique manifestations including granulomatous bone marrow involvement and hypercalcaemia. The patient has twice achieved a good response to pentostatin after failure of combination chemotherapy. This is the first report of the successful use of the purine analogue pentostatin in the management of GSSD.
Adult↗
Micronodular T-cell/histiocyte-rich large B-cell lymphoma of the spleen: histology, immunophenotype, and differential diagnosis.
Occasionally, primary large B-cell lymphomas (LBLs) arising in the spleen present with a micronodular pattern involving the splenic white pulp but sparing the red pulp. Histologically, the nodules contain scattered large B cells in a background of numerous T cells and histiocytes. They can cause substantial difficulty in histologic diagnosis as the morphology can mimic reactive and inflammatory lesions as well as other lymphoid neoplasms. In this study, we examined the histology and immunophenotype of the micronodular T-cell/histiocyte-rich LBL (MTLBL) of the spleen with a view to establish the characteristics that may be helpful in diagnosis. Paraffin-embedded material from 17 cases of MTLBL was studied. Clinical features and histology were reviewed and immunohistochemistry was performed for immunoglobulins, CD20, CD79a, CD3, CD68, CD10, BCL6, BCL2, OCT-2, epithelial membrane antigen, CD30, CD138, and EBV markers. The median age of presentation was 56 years, and the most frequent presenting features were anemia and B symptoms. All cases showed a micronodular pattern of involvement. The tumor nodules comprised a mixture of numerous CD3+ T cells and CD68+ histiocytes and scattered large CD20+ B cells with immunoglobulin light chain restriction. They were positive for BCL6 and OCT2 but negative for CD10, CD138, and EBV markers. There was variable expression of epithelial membrane antigen, Bcl-2, and CD30. No follicle dendritic cell meshwork infrastructure underlying the nodules could be demonstrated by staining for CD21 or CD35 antigens. The prognosis was poor; seven of the 12 cases with follow-up were dead within 2 years. MTLBL is unique variant of T-cell/histiocyte-rich diffuse LBL, characterized by primary splenic presentation and a micronodular architecture. The main differential diagnoses include granulomatous inflammation, Hodgkin's lymphoma, follicular lymphoma, and peripheral T-cell lymphomas.
Adult↗
Unusual case of leukemic mantle cell lymphoma with amplified CCND1/IGH fusion gene.
We describe a case of leukemic mantle cell lymphoma (MCL) with complex karyotype and amplification of the CCND1/IGH fusion gene. Testing for the presence of t(11;14), the hallmark of MCL, revealed multiple copies of the fusion signals. We therefore conducted extensive molecular cytogenetic studies to delineate the nature and consequences of such an abnormality. We localized the amplification to the der(14)t(11;14) and to a der(2) chromosome in a form of interspersed chromosome 11 and 14 material. This resulted in high expression of cyclin D1 mRNA and the protein expressed independently of the cell cycle phase. CGH analysis revealed that the overrepresentation on chromosome 11 included chromosomal band 11q23 in addition to the CCND1 locus at 11q13. The band 11q23 harbors the ataxia telangiectasia mutated (ATM) gene recently proposed to be involved in the pathogenesis of MCL with high incidence of deletions in this locus. Using YAC 801e11, containing the ATM gene, we demonstrated several hybridization signals, suggesting that this region also formed part of the amplicon. This case also showed TP53 gene abnormalities: protein expression, monoallelic deletion, and a mutation in exon 5. The clinical course was aggressive, and the patient died within 6 months of presentation. This is to our knowledge the first description of amplification of the CCND1/IGH fusion gene in a human neoplasm, which may have played a role in the fulminating course of the disease in this patient.
Cyclin D1↗
Splenectomy in mantle cell lymphoma with leukaemia: a comparison with chronic lymphocytic leukaemia.
We reviewed data on 63 patients with mantle cell lymphoma (MCL) with leukaemia (n = 16) and chronic lymphocytic leukaemia (CLL, n = 47), splenectomized over a 10-year period. Primary indications for surgery were cytopenia(s) or autoimmune phenomena and progressive or refractory disease with splenomegaly. The spleens removed were on average larger in MCL (median 2.6 kg) than in CLL (1.0 kg). Splenectomy improved the blood counts in 62% of patients with MCL and 47% with stage C CLL, both with cytopenias. The MCL patients showed a decrease in the leucocytosis (medians 60.3-29.1 x 10(9)/l before and after splenectomy), whereas there was an increase in the leucocytosis in CLL (medians 24.2-44 x 10(9)/l). With a median follow up post splenectomy of 10 months (range: < 1-128), 18 patients (four MCL and 14 CLL) have not required further therapy for up to 66 months. We conclude that splenectomy is a useful treatment in MCL and advanced CLL for the correction of cytopenias, reducing the leucocyte count and allowing prolonged periods of clinical remission without therapy. Differences seen between MCL and CLL in spleen size, and in response of the leucocytosis suggest a central role for the spleen in the evolution of MCL with leukaemia.
Adult↗
Translocation t(2;7)(p12;q21-22) with dysregulation of the CDK6 gene mapping to 7q21-22 in a non-Hodgkin's lymphoma with leukemia.
BACKGROUND AND OBJECTIVES: A female patient presented with splenomegaly and lymphocytosis with atypical lymphoid cell morphology. We identified t(2;7)(p12;q21) prompting studies of the translocation breakpoint and its consequences on protein expression to confirm or otherwise the recently reported involvement of CDK6 and IG k genes in the t(2;7) leading to over-expression of CDK6 protein. DESIGN AND METHODS: A variety of clinical and laboratory techniques including cell marker, cytogenetic and histologic studies were applied in order to establish the diagnosis. Fluorescence in situ hybridization (FISH) and Southern blotting were used for mapping the translocation breakpoint and Western blotting for assessing protein expression. RESULTS: Immunophenotyping showed the presence of a B-cell population with strong expression of FMC7, CD22, CD79b, CD5 and k restricted surface immunoglobulins. Based on morphology and immunophenotypic markers the diagnosis of B-cell non-Hodgkin's lymphoma was made. Karyotyping revealed a clone with t(2;7)(p12;q21-22). Evidence for clonal evolution with additional abnormalities including a deletion of the TP53 was present. We established by FISH and Southern blotting that the breakpoint on 7q21-22 fell in a region 66kb telomeric to the previously reported breakpoint for the t(2;7) and was the same as that observed in a t(7;21). CDK6 protein was over-expressed. The patient received alkylating agents and splenectomy and is alive but the lymphocytosis persists with evidence of disease progression. INTERPRETATIONS AND CONCLUSIONS: We have demonstrated that CDK6 expression is dysregulated even when the breakpoint on 7q21-22 is located 66kb upstream from the coding region. Interestingly, the precise assignment of the lymphoma type in our case was not possible even when the splenic histology was analyzed.
Aged↗