Biomedical subjects

Henry Y Dong

Publications and source records attributed to Henry Y Dong.

10 recordsLinked to original sources

PubMed2006

Heterogeneous CD52 expression among hematologic neoplasms: implications for the use of alemtuzumab (CAMPATH-1H).

PURPOSE: CD52 is a GPI-linked glycoprotein expressed by B cells, T cells, monocytes, and macrophages. The humanized monoclonal antibody alemtuzumab (CAMPATH-1H) is specific for CD52 and is Food and Drug Administration - approved for the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). The utility of CAMPATH in the treatment of other hematologic neoplasms has been explored; however, a comprehensive survey of CD52 expression among a broad spectrum of WHO-defined tumor types has not been completed. EXPERIMENTAL DESIGN: We evaluated 294 hematologic neoplasms for the presence of CD52 using standard immunohistochemical techniques on paraffin-embedded biopsy specimens fixed with formalin, B-Plus, Zenker's acetic acid, or B5-formalin. RESULTS: The vast majority of low-grade B cell lymphoproliferative disorders (CLL/small lymphocytic leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, hairy cell leukemia, and mucosa-associated lymphoid tissue lymphomas) express CD52. In addition, we found that the majority of precursor B cell acute lymphoblastic leukemia/lymphomas express this antigen. In contrast, there is surprising heterogeneity in CD52 expression among more aggressive B cell lymphomas, with 25% of cases of diffuse large B cell lymphoma and Burkitt lymphoma demonstrating no detectable CD52. In addition, the majority of neoplasms of the T cell lineage are negative for the antigen, including most cases of precursor T cell acute lymphoblastic leukemia/lymphoma, anaplastic large cell lymphoma, and peripheral T cell lymphoma, not otherwise specified. Finally, the vast majority of cases of acute myeloid leukemia, Hodgkin lymphoma, and multiple myeloma are negative for CD52 expression. CONCLUSION: In contrast with CLL, the variable expression of CD52 among other hematologic malignancies suggests that target validation on a case-by-case basis will likely be necessary to guide the rational analysis of CAMPATH therapy.

Acute Disease↗

PubMed2006

Expression of the B cell-associated transcription factors PAX5, OCT-2, and BOB.1 in acute myeloid leukemia: associations with B-cell antigen expression and myelomonocytic maturation.

The aberrant expression of the B-cell transcription factor PAX5 has been described in a subset of acute myeloid leukemia (AML) with t(8;21)(q22;q22) in association with B-cell antigen expression. However, the expression of other B cell-associated transcription factors, particularly OCT-2 and its B cell-specific coactivator BOB.1, has not been described in AML. In this study, expression of PAX5, OCT-2 and BOB.1 was evaluated by immunohistochemical staining of bone marrow samples from 83 cases of AML. The expression patterns were correlated with t(8;21)(q22;q22), B cell-associated antigen expression, and AML subtype. We confirmed the expression of PAX5 in AML with t(8;21)(q22;q22), but also demonstrated its expression in cases that express B-cell antigens but lack this translocation. Although OCT-2 and BOB.1 were not associated with PAX5 expression, we report expression of OCT-2 in AML with myelomonocytic/monocytic maturation and BOB.1 in normal hematopoietic elements.

Acute Disease↗

PubMed2006

Detection of the t(11;18) API2/MALT1 translocation associated with gastric MALT lymphoma in routine formalin-fixed, paraffin-embedded small endoscopic biopsy specimens by robust real-time RT-PCR.

The t(11;18)(q21;q21) API2/MALT1 translocation is a specific chromosomal abnormality in extranodal marginal B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type, particularly in those occurring in the stomach and lungs. Identification of t(11;18) may aid in the diagnosis of MALT lymphoma and strongly predicts resistance of gastric MALT lymphoma to Helicobacter pylori eradication therapy. We developed a robust real-time reverse transcription-polymerase chain reaction (RT-PCR) procedure to efficiently detect t(11;18) in virtually all types of specimens used in routine diagnostic workups. We blindly tested 40 samples from 38 patients with gastric MALT lymphoma; 10 (25%) of 40 samples, or 8 (21%) of 38 patients were positive for t(11;18). In contrast, t(11;18) was not detected in 8 cases of gastric large B-cell lymphoma, 11 cases of chronic active gastritis, and 16 samples unrelated to lymphoma. Our findings suggest that real-time RT-PCR for t(11;18) may be a valuable tool with much relevance in the current clinical management scheme.

Biopsy↗

PubMed2005

B-cell specific activation protein encoded by the PAX-5 gene is commonly expressed in merkel cell carcinoma and small cell carcinomas.

PAX-5 is a B cell specific transcription factor crucial for B cell ontogeny and has been detected in most of human B-cell lymphomas. In mouse, PAX-5 is also highly expressed in the central nervous system under tight temporal and spatial controls during embryogenesis. In humans, however, detection of PAX-5 in cells other than B lymphocytes has rarely been reported. We have encountered cases of Merkel cell carcinoma expressing PAX-5 during our routine evaluation of lymphoma. Because Merkel cell carcinoma is a small blue round cell tumor constantly in the differential diagnosis of lymphoma, we expanded our study in an effort to determine if PAX-5 is significantly expressed in neuroendocrine tumors. Based on our immunohistochemistry results using a monoclonal anti-PAX5 antibody with paraffin-embedded tissue sections, we report herein that PAX-5 was detected in 29 of 31 (93.5%) of Merkel cell carcinoma and 22 of 30 (73.3%) of small cell carcinoma, but in none of 17 cases of carcinoid tumor. Furthermore, the staining intensity of PAX-5 in Merkel cell carcinoma was frequently comparable with that in most B-cell lymphomas. We conclude that expression of PAX-5 is not confined to the B cell lineage and is frequently associated with neuroendocrine carcinomas.

B-Lymphocytes↗

PubMed2005

Plasmablastic lymphoma in HIV-positive patients: an aggressive Epstein-Barr virus-associated extramedullary plasmacytic neoplasm.

AIDS-associated aggressive B-cell lymphomas often have plasmacytoid features. Plasma cell neoplasms in HIV patients were commonly described to have atypical morphology and an aggressive clinical course in the literature. We reviewed 14 cases of neoplasms with marked plasmacytic differentiation in HIV-positive patients to determine their clinicopathologic features. Of these, 13 of 14 had homogeneous morphology and were generally CD45(+), CD20-, PAX-5-, and CD138(+). All were positive for Epstein-Barr virus-encoded RNA (EBER) but lacked EBV late membrane proteins (LMP). Human herpes virus 8 (HHV8) DNA was detected in 6 of 10 cases by nested PCR, but HHV8 latent nuclear antigen (LNA) was absent. The 13 patients ranged in age from 28 to 44 years (median, 41 years) (11 male patients; 2 female patients). All patients had extramedullary and 11 of 13 had extranodal tumor at the initial presentation; 2 had distant marrow involvement. The most commonly involved location was the oral cavity (6 of 13 cases), followed by bone and soft tissue (4 of 13), and the gastrointestinal tract (3 of 13). All 11 patients with follow-up died within 34 months (median, 7 months). The 14th patient who had a nodal disease with more undifferentiated morphology and expression of the HHV8 LNA protein was alive without disease at last follow-up (>72 months), probably representing a novel HHV8(+) lymphoma. We conclude that most plasmacytic tumors in HIV-positive individuals are extramedullary, clinically aggressive EBV(+) tumors identical to plasmablastic lymphoma that does not have the clinical features of plasma cell myeloma.

Adult↗

PubMed2003

B-cell lymphomas with coexpression of CD5 and CD10.

Coexpression of CD5 and CD10 is highly unusual in B-cell lymphomas and may pose a diagnostic challenge. We report 42 cases of B-cell lymphoma with simultaneous expression of CD5 and CD10. They made up approximately 0.4% of all B-cell lymphomas seen during the study period and included the following cases: large B-cell lymphoma (LBCL), 14 (33%); follicular lymphoma (FL), 10 (24%); mantle cell lymphoma (MCL), 9 (21%); chronic lymphocytic leukemia, 4 (10%); acute precursor B-cell lymphoblastic leukemia/lymphoma, 2 (5%); and other low-grade B-cell lymphomas, 3 (7%). All MCLs had overexpression of bcl-1 or the t(11;14) and were CD43+. All FLs had typical histomorphologic features and were bcl-2+ and bcl-6+ but CD43-. Of 14 LBCLs, 5 were histologically high-grade. Six (43%) of 14 patients with LBCL died within 10 months of diagnosis of CD5+CD10+ lymphoma (median survival, 4 months), including all 3 patients with stage IV disease and 2 of 5 with histologically high-grade lymphoma. Our findings indicate that coexpression of CD5 and CD10 is rare but occurs in diverse subtypes of B-cell lymphoma. Investigation of bcl-1, bcl-6, and CD43 and morphologic evaluation may resolve the potential confusion in diagnosis and lead to the recognition of the correct lymphoma subtype.

Adult↗

PubMed2003

CD30-positive T-cell lymphomas co-expressing CD15: an immunohistochemical analysis.

The characteristic histologic features and immunophenotype are usually diagnostic and allow distinguishing CD30 positive T-cell lymphoma (including anaplastic large cell lymphoma) from classical Hodgkin's lymphoma. The latter differs by expression of CD15 and lack of CD45, pan-T antigens and ALK expression. We report nine cases of large cell hematopoietic neoplasms in which the neoplastic cells co-expressed CD30 and CD15, and had immunophenotypic and morphologic features of T-cell lymphoproliferative process. The average age of the CD15-positive group was 61.9 years; 6 cases occurred in men and 3 in women. The tumors were located in lymph nodes in 8 cases, and in liver in 1 case. Two cases expressed ALK protein. There were no statistically significant differences in phenotypic parameters between the CD15-positive and CD15-negative neoplasms (p>0.05). However, the CD15-positive group appeared to show a minor trend toward less positivity for EMA (44% versus 72%), ALK protein (22% versus 51%), and CD45RO (33.3% versus 83.3%, p=0.07), when compared to the typical CD15-negative neoplasms. In summary, although the co-expression of CD30 and CD15 is typical for classical HL, it may be also present in a subset of peripheral T-cell neoplasms including ALK-positive anaplastic large cell lymphoma. Combined and sensible use of morphology and a broad immunophenotypic panel in cases with limited material and/or those with overlapping histologic patterns will best discriminate between HL and ALCL. It is incumbent upon the pathologist to distinguish between these two clinicopathologic entities, since treatment options and clinical outcomes differ.

Adolescent↗

PubMed2002

KSHV- and EBV-associated germinotropic lymphoproliferative disorder.

Kaposi sarcoma-associated herpesvirus (KSHV) is known to be associated with 3 distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), and MCD-associated plasmablastic lymphoma. We report 3 cases of a previously undescribed KSHV-associated lymphoproliferative disorder. The disease presented as localized lymphadenopathy and showed a favorable response to chemotherapy or radiotherapy. Histologically, the lymphoproliferation is characterized by plasmablasts that preferentially involved germinal centers of the lymphoid follicles, forming confluent aggregates. They were negative for CD20, CD27, CD79a, CD138, BCL6, and CD10 but showed monotypic kappa or lambda light chain. Clusters of CD10(+)CD20(+) residual follicle center cells were identified in some of the follicles. The plasmablasts were positive for both KSHV and EBV, and most of them also expressed viral interleukin-6 (vIL-6). Unexpectedly, molecular analysis of whole tissue sections or microdissected KSHV-positive aggregates demonstrated a polyclonal or oligoclonal pattern of immunoglobulin (Ig) gene rearrangement. The plasmablasts showed somatic mutation and intraclonal variation in the rearranged Ig genes, and one case expressed switched Ig heavy chain (IgA), suggesting that they originated from germinal center B cells. We propose calling this distinctive entity "KSHV-associated germinotropic lymphoproliferative disorder."

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

CD148 and CD27 are expressed in B cell lymphomas derived from both memory and naïve B cells.

CD148 and CD27 are activation antigens involved in B cell and T cell activation and development. They have been recently proposed as markers of normal human memory B cells corresponding to the presence of somatically hypermutated IgV genes. We undertook an immunohistochemical study of CD148 and CD27 expression on neoplastic B cells in 116 cases of B cell non-Hodgkin's lymphoma. All cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma, Burkitt's lymphoma, and the vast majority of cases of marginal zone B cell lymphoma and most cases of plasmacytoma/myeloma expressed CD148 and CD27. Follicular lymphoma and diffuse large B cell lymphoma were also immunoreactive for CD148 and CD27 with some variation and discordance in expression. Cases of precursor B-lymphoblastic lymphoma/leukemia did not express CD148 or CD27. Our findings demonstrate that CD148 and CD27 are expressed in a wide range of B cell non-Hodgkin's lymphomas, and, therefore, do not serve to distinguish between neoplastic cells of naïve and memory B cell derivation.

B-Lymphocytes↗

PubMed2002

CD5- mantle cell lymphoma.

Mantle cell lymphoma (MCL) typically expresses B-cell antigens and CD5 and overexpresses bcl-1 protein. However, unusual cases of bcl-1+ and CD5-MCL have been observed, posing a practical challenge for correct diagnosis and management. We identified 25 cases (48 samples) of bcl-1+ and CD5- lymphoma. CD5 expression was assessed by flow cytometric analysis alone (1 case), immunohistochemical analysis alone (17 cases), or dual flow cytometric/immunohistochemical methods (7 cases). The morphologic features were consistent with MCL with centrocytic cytomorphology in 20 cases and blastic variant in 5 cases. The t(11;14) was confirmed in 8 of 11 cases by fluorescence in situ hybridization of paraffin-embedded tissue. Cytogenetic analysis revealed the t(11;14) within a complex karyotype in 2 additional cases. These data show that MCL may lack CD5 expression. Evaluation of bcl-1 expression by immunohistochemical analysis or molecular genetics may be indicated if MCL is suspected clinically or morphologically despite a lack of CD5 expression.

Aged↗