PubMed Health⌕ Search

Biomedical subjects

Shih-Sung Chuang

Publications and source records attributed to Shih-Sung Chuang.

At least 19 recordsLinked to original sources

Massive expansion of EBV+ monoclonal T cells with CD5 down regulation in EBV-associated haemophagocytic lymphohistiocytosis.

Haemophagocytic lymphohistiocytosis (HLH) comprises primary and secondary forms; the secondary form is most commonly triggered by the Epstein-Barr virus (EBV; EBV-HLH). Patients with EBV-HLH usually exhibit oligoclonal or monoclonal T cell proliferation, which may mimic T cell lymphoproliferative disorder (T-LPD). This article reports on EBV-HLH in a 17-month-old girl with an extreme surge of reactive T lymphocytosis (absolute count 167x10(9)/l) with CD5 down regulation. Bone marrow aspirate and trephine contained florid haemophagocytosis and massive infiltration of CD3+ Epstein-Barr virus-encoded RNA+ lymphocytes, as seen by double labelling. These lymphocytes were monoclonal for EBV and T cell receptor gamma chain gene rearrangement. The patient responded dramatically to intravenous immunoglobulin, interferon alpha2b, ganciclovir and prednisolone, suggesting restoration of her immune system and eradication of the clonal T cells through these immunoregulatory agents. Thus, careful clinicopathological correlation is warranted in the interpretation of immunophenotyping and clonality data in T cell proliferation in association with EBV-HLH to avoid erroneous diagnosis of T-LPD.

CD5 Antigens↗

Tissue microarray analysis of interleukin-20 expression.

Knowledge about the biological functions and clinical implications of interleukin (IL)-20, a recently discovered cytokine in the IL-10 family, is still incomplete. Our aim was to determine the distribution of IL-20 expression and to delineate the cell types that express IL-20 in healthy and neoplastic tissue, because this information will significantly affect the exploration of its pathophysiological roles. We used tissue microarray technology and an immunohistochemical survey using an anti-IL-20 monoclonal antibody to examine IL-20 expression in 36 non-neoplastic and 14 neoplastic tissues. IL-20 protein was positively stained in 30 non-neoplastic tissue types and five major cell types: epithelial cells, myoepithelial cells, endothelial cells, macrophages, and skeletal muscle cells. We also found that several types of tumor cells stained positive for IL-20, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung. Our data provide valuable references for further investigation of the biological functions and clinical implications of IL-20 in humans.

Gene Expression Profiling↗

Comparison of the expression and prognostic significance of differentiation markers between diffuse large B-cell lymphoma of central nervous system origin and peripheral nodal origin.

PURPOSE: Whether diffuse large B-cell lymphoma (DLBCL) of primary central nervous system origin (PCNSL) is biologically different from DLBCL of peripheral nodal origin (NL) remains unclear. The purpose of this study was to compare the expression frequencies and prognostic significance of a panel of cell differentiation markers between these two disease entities. EXPERIMENTAL DESIGN: This study included HIV-unrelated patients with PCNSL (n = 51) and NL (n = 72) treated at four hospitals in Taiwan for whom archival tumor tissue was available. Immunohistochemistry for CD10, BCL-6, MUM-1, vs38c, CD138, and BCL-2 was done. CD10, BCL-6, and MUM-1 expression results were used to classify all cases into the germinal center B-cell (GCB) or the non-GCB subgroup. The prognostic significances of clinical and immunophenotypic markers were evaluated. RESULTS: Nuclear MUM-1 expression was significantly higher in PCNSL than in NL (P < 0.001; 84% versus 53%). PCNSL tumors were more frequently classified into the non-GCB subgroup than NL tumors (P = 0.020; 78% versus 62%). For patients with PCNSL, univariate analysis showed that patients with BCL-6 expression had a trend towards longer survival (P = 0.073; median survival, 25.3 versus 7.3 months), and multivariate analysis showed BCL-6 was an independent prognostic factor (P = 0.026). For patients with NL, both of univariate (P = 0.003) and multivariate analyses (P = 0.002) showed that GCB was significantly associated with favorable survival. CONCLUSION: The higher frequency of non-GCB subclassification, which was mainly contributed by nuclear MUM-1 expression in PCNSL implies that it has a more differentiated cellular origin than NL. BCL-6 expression in patients with PCNSL and GCB subgroup in patients with NL were favorable prognostic factors.

Antibodies, Monoclonal↗

Search for the tumor-related proteins of transition cell carcinoma in Taiwan by proteomic analysis.

To better understand the carcinogenesis of bladder cancer in Taiwan, we utilized the proteomic approach to search for potential biomarkers of transitional cell carcinoma (TCC). Analysis by 2-DE and MS/MS indicated that seven proteins are down-regulated and three proteins up-regulated in grade III samples as compared with those of grade II. Of these deregulated proteins, fatty acid binding proteins, annexin V, heat-shock protein 27, and lactate dehydrogenase have been shown to be associated with bladder cancer. Our studies also found altered expression of a group of proteins that have not been documented previously in bladder cancer, including annexin I, 15-hydroxyprostaglandin dehydrogenase, galectin-1, lysophospholipase and mitochondrial short-chain enoyl-coenzyme A hydratase 1 precursor. These results illustrate a pattern of differential protein expression between low- and high-grade tumors and it may be utilized as the molecular fingerprinting of a subset of bladder cancers. In addition, the present study provides a valuable resource in the study of pathological mechanisms in cancers of urothelial origin. The immunohistochemical staining of grade II and III TCC samples with antiserum to annexin I protein was utilized to confirm that the annexin I protein is up-regulated in grade III TCC.

Adult↗

Primary non-Hodgkin's lymphoma of bone: a rare disorder with high frequency of T-cell phenotype in southern Taiwan.

Primary non-Hodgkin's lymphoma of bone (PLB) is a rare disorder representing less than 1% of all non-Hodgkin's lymphomas and has rarely been reported in Taiwan. A retrospective clinicopathological study was performed according to the 2002 World Health Organization criteria and identified 14 cases during a 13-year period in 2 medical centers in southern Taiwan. There was male predominance (M:F = 6:1) with a median age of 42 and bone pain (6 patients, 43%) as the most common symptom. Half of the patients had monostotic and the other half polyostotic lesions. Axial skeletons (10 cases, 71%) were the most frequent sites of involvement. The staging results were stage I (9 patients, 64%), stage II (2, 14%) and stage IV (3, 21%). Eight cases (57%) were of B-cell phenotype and the remaining 6 (43%), T-cell. Histologically, 7 (50%) were diffuse large B-cell lymphomas (DLBCLs) and 5 (36%) anaplastic large cell lymphomas. Seven patients received chemotherapy and radiotherapy; 4 chemotherapy and 3 radiotherapy alone. Of the 11 patients with follow-up information, 6 (55%) died of disease within 1 year including 5 with T-cell lymphomas, while all the 5 patients surviving over 1 year were of B-cell phenotype. The overall 1-year survival rate was 45%. The survival of B-cell lymphomas was significantly better than T-cell tumors (p = 0.016, log-rank test). In summary, this study reported the largest series of PBL in Taiwan and confirmed that the majority was DLBCL and B-cell tumors had more favorable prognosis. As compared to the Western series, the cases showed a striking male predominance, higher percentage of axial skeleton involvement, higher relative frequency of T-lineage tumors and poorer prognosis.

Adult↗

Fatal HHV-8-associated hemophagocytic syndrome in an HIV-negative immunocompetent patient with plasmablastic variant of multicentric Castleman disease (plasmablastic microlymphoma).

Virus-associated hemophagocytic syndrome (VAHS) triggered by HHV-8 is extremely rare and has been reported only in 9 immunocompromised patients. We report the first case of HHV-8-associated VAHS in an HIV-negative, immunocompetent patient with plasmablastic variant (plasmablastic microlymphoma) of multicentric Castleman disease (MCD). This 61-year-old man presented with fever, cough, and bilateral inguinal lymphadenopathy. Biopsy of the right inguinal lymph node revealed plasmablastic MCD with nodular aggregates of plasmablasts expressing IgM, MUM1, HHV-8 latency-associated nuclear antigen, and viral interleukin-6. These plasmablasts were monotypic for Iglambda light chain expression but not Igkappa. All the B-cell clonality assays, including IgH-FR2, IgH-FR3, DH-JH, Igkappa, and Iglambda PCR, showed a polyclonal pattern. His serum human interleukin-6 level was markedly elevated and was negative for EBV acute infection/reactivation. The marrow aspirate showed florid hemophagocytosis. His disease progressed rapidly to multisystemic illness, and he died of acute respiratory failure in 1 month. Our case showed that HHV-8 might trigger VAHS in an immunocompetent patient with plasmablastic MCD. We speculated that our patient developed VAHS under the cytokine storm associated with the proliferating HHV-8-infected plasmablasts, similar to the EBV-triggered VAHS in patients with EBV-associated T-cell lymphoma.

Antigens, Viral↗

Mantle cell lymphoma in Taiwan: clinicopathological and molecular study of 21 cases including one cyclin D1-negative tumor expressing cyclin D2.

Mantle cell lymphoma (MCL) is a rare B-cell lymphoma that has never been characterized in Taiwan. The purpose of the present paper was to retrospectively identify 21 cases in male patients, with a median age of 61, involving lymph node (91%), marrow (71%), and peripheral blood (23%). Eighteen (86%) were in stages III/IV with 1 and 5 year survival rates of 78% and 17%, respectively. Mixed nodular and diffuse pattern (45%) was most common while interstitial pattern (92%) predominated in marrow. Eighteen (86%) were of classical morphology, two were pleomorphic and one was blastic. The tumors expressed IgM and bcl-2 (100%), cyclin D1 (95%), CD5 (86%), CD43 and IgD (62%), CD52 (60%), and bcl-6 (5%). Ki-67 index>or=30% (P=0.1834) was associated with a trend toward poorer survival while p21, p27, or p53 expression was not statistically significant for survival. Real-time polymerase chain reaction for cyclin D1 (CCND1) gene mRNA expression showed high levels in nine cyclin D1-positive patients and a low level in the single cyclin D1-negative patient. The latter patient was cyclin D2 positive and negative for immunoglubuin heavy chain gene and CCND1 gene translocation by locus-specific interphase fluorescent in situ hybridization. In conclusion, it is confirmed that the usual morphological variants and aberrant immunophenotype of MCL in the West occur in Taiwan and that this disease carries a poor prognosis.

Adult↗

A clinicopathologic and molecular study of follicular lymphoma in Taiwan.

BACKGROUND: The clinicopathologic and molecular features of follicular lymphoma (FL) in Taiwan have not been well defined. We conducted a retrospective study including history review, immunohistochemistry, and molecular study for the major breakpoint region (MBR) of t(14;18) and correlated these findings with survival. PATIENTS AND METHODS: Sixty-five FLs were identified, with a male to female ratio of 1.9:1 and a median age of 63 years (mean, 60 years). Sixty cases (92%) were nodal, 4 (6%) were extranodal, and 1 (2%) was indeterminate. The median ages of the nodal and extranodal cases were 63 years and 44 years, respectively. Disease staging in 59 patients included 15 patients (25%) with stage I disease, 14 (24%) with stage II, 20 (34%) with stage III, and 10 (17%) with stage IV. Forty-four patients received chemotherapy, 2 patients received chemotherapy with palliative radiation therapy, and 13 patients received supportive treatment/observation. RESULTS: The 5-year survival rate was 52.6%. The cases were classified as grades 1 (n = 27; 42%), 2 (n = 22; 34%), 3A (n = 13; 20%), and 3B (n = 3; 5%). Twenty cases (31%) were positive for MBR, including 19 of 57 (33%) nodal cases and 1 of 4 (25%) primary extanodal FLs. Patients with low-stage disease (stages I/II) had a better survival rate than patients with high-stage disease (III/IV; log-rank test, P = 0.012). CONCLUSION: This is the largest series of Taiwanese FLs with immunophenotypes and MBR detection rates similar to those of the West. Disease stage was statistically significant with regard to survival. Although the number of extranodal FLs cases was small, the patients were younger, their tumors had lower CD10 expression, and they had more favorable survival rates than patients with nodal disease.

Adult↗

Gastrointestinal stromal tumor (GIST) in southern Taiwan: a clinicopathologic study of 93 resected cases.

The purpose of this study was to determine the clinicopathologic features of gastrointestinal stromal tumor (GIST) in southern Taiwan. The pathology files from a medical center in southern Taiwan (1993 to 2003) were searched for primary mesenchymal tumors of the gastrointestinal tract. Hematoxylin/eosin sections and history were reviewed, and immunohistochemistry was performed using anti-CD 117, CD34, smooth muscle actin (SMA), and S-100 protein. Only primary resected GISTs were included in this study. Univariate and multivariate analyses were carried out using the T-test to evaluate the significance of primary tumor size and mitotic activity for the prediction of recurrence and metastasis. A total of 121 surgically resected primary mesenchymal tumors were identified, and 93 of these were GISTs. These 93 patients showed a slight female predominance (male: female = 1:1.2). The clinical presentations were variable and site-dependent. The most common tumor locations were the stomach (57%) and the small intestine (39%). Microscopically, 88 tumors (95%) were composed of spindle cells, the remaining five (5%) consisted of mixed epithelioid and spindle cells. No pure epithelioid type GIST was found. In addition to CD117, 66 cases (71%) were positive for CD34, 23 cases (25%) were positive for SMA, and 19 cases (21%) were positive for S-100. In a mean follow-up time of 27.3 months (median: 26 months), 19 cases (20.6%) were clinically malignant and mainly manifested as liver metastases (seven cases, 37% of malignant GISTs). Univariate analysis revealed that both primary tumor size and mitotic activity were significantly increased in the group affected by recurrence and/or metastasis (p = 0.001 and 0.035, respectively). Compared to GISTs in the western countries, those in southern Taiwan are characterized by a slight female predominance, a relatively higher frequency of small intestinal localization, a higher rate of S-100 protein expression, and a less aggressive behavior. Tumor size and mitotic activity were useful predictors of malignancy.

Adult↗

Synchronous CIN 3 and cervical lymphoma: a case report and review of the literature.

Primary cervical lymphoma is rare, with less than 60 cases reported in the English literature, including a few cases of synchronous cervical intraepithelial neoplasia (CIN) with cervical lymphoma. We describe a 42-year-old woman with CIN 3 and malignant lymphoma of the cervix. The Papanicolaou cytology only revealed dysplastic cells of CIN 3, but not the malignant lymphoid cells. The histology of the cervix revealed diffuse infiltration of monotonous medium-sized lymphoid cells with dispersing tingible bodies, and a Burkitt's lymphoma in combination with a small CIN 3 lesion was diagnosed. Neither human papillomavirus nor Epstein-Barr virus was identified by polymerase chain reaction or in situ hybridization. The patient developed leukemic spreading and died soon after surgery.

Adult↗

Bone marrow that is positive for Epstein-Barr virus encoded RNA-1 by in situ hybridization is related with a poor prognosis in patients with extranodal natural killer/T-cell lymphoma, nasal type.

BACKGROUND AND OBJECTIVES: Extranodal NK/T-cell lymphoma, nasal type is an aggressive lymphoma that is always associated with Epstein-Barr virus (EBV). This study was done to evaluate the use of EBV-encoded RNA-1 in situ hybridization (EBER-1 ISH) to detect occult micrometastasis in the bone marrow (BM) of patients with nasal NK/T-cell lymphoma. DESIGN AND METHODS: A total of 23 patients who underwent BM biopsy for routine pre-therapeutic evaluation were enrolled in the study. We used EBER-1 ISH to investigate the expression of EBER-1 in 30 BM specimens. The clinical correlation and therapeutic outcomes of these patients were analyzed. In addition, genomic analysis of EBV was performed in five patients. RESULTS: Conventional morphologic examinations failed to identify any lymphoma involvement in the 23 BM specimens obtained at initial staging. However, 10 of the 23 BM were positive for EBER-1. A lower survival rate was seen in patients with BM positive for EBER-1. Only the BM EBER-1 ISH result was shown to be an independent variable predicting overall survival in stage I and II patients (p=0.027; hazard ratio for death 0.066, 95% confidence interval, 0.006 to 0.733), suggesting that EBER-1 positivity in BM is the major determinant of a poor prognosis. However, discrepancies in the EBV strains between the primary tumor and BM existed in two of the five studied patients. INTERPRETATION AND CONCLUSIONS: We suggest that EBER-1 ISH should be performed on BM specimens of patients with nasal NK/T-cell lymphoma to identify the presence of EBER-1 positive cells, which appears to carry a poor prognosis. Whether or not the EBER-1 positive cells in the BM of nasal NK/T-cell lymphoma patients are true tumor cells requires further study.

Adult↗

Natural killer cell lymphoma of small intestine with features of enteropathy but lack of association with celiac disease.

A primary small intestinal natural killer (NK) cell lymphoma with pathologic features of enteropathy but lack of association with celiac disease is reported. A 37-year-old man presented with tarry stool, coffee-ground vomitus, and mild fever. He did not have chronic diarrhea or malabsorption. Segmental resection of the duodenum and jejunum showed multicentric transmural infiltration by medium-sized lymphoma cells expressing CD3, CD8, cytotoxic granules, and Epstein-Barr virus by in situ hybridization. The nontumorous mucosa away from the main tumor revealed enteropathy with villous blunting and increased intraepithelial lymphocytes sharing the same immunophenotype as the lymphoma cells. Both lymphoma and nontumorous areas were germline for T-cell receptor-gamma and immunoglobulin heavy chain gene rearrangement. Serologic test by ELISA was negative for anti-transglutaminase. The patient died of repeated gastrointestinal bleeding and sepsis at 2 months. Differential diagnosis of this unique nasal-type NK-cell lymphoma with enteropathy-associated T-cell lymphoma is discussed.

Adult↗

t(1;14) and t(11;18) in the differential diagnosis of Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia is caused by several B-cell proliferative disorders including lymphoplasmacytic lymphoma, marginal zone B-cell lymphoma, B-cell chronic lymphocytic leukemia and multiple myeloma. Differential diagnosis between lymphoplasmacytic lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue is particularly difficult as there is a considerable overlap in histological presentation. We report a case of Waldenström's macroglobulinemia with involvement of the peripheral blood, bone marrow and stomach. Serum chemistry revealed an IgM of 5.4 g/dl, but Bence-Jones protein in urine was negative. Abnormal lymphoid cells were detected in both blood and the bone marrow. Flow cytometry of the bone marrow aspirate showed that majority of cells were CD20(+), CD38(+), expressing immunoglobulin lambda light chain, but CD5(-) and CD10(-). Gastric biopsies revealed infiltration of the gastric mucosa by small lymphoid cells showing plasmacytoid differentiation and occasional Dutcher bodies. Lymphoepithelial lesions and Helicobacter pylori were not seen. Thus, the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma was raised. To resolve this, we performed BCL10 immunohistochemistry and reverse transcriptional polymerase chain reaction (RT-PCR) for the API2-MALT1 fusion transcript of t(11;18)(q21;q21). Both bone marrow and gastric biopsies showed strong BCL10 nuclear staining, similar to that seen in t(1;14)(p22;q32) positive mucosa-associated lymphoid tissue lymphoma, but absence of the API2-MALT1 fusion transcript. To further ascertain whether the detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) can be reliably used for the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma, we screened for these translocations by BCL10 immunohistochemistry in 58 lymphoplasmacytic lymphomas and RT-PCR for t(11;18)(q21;q21) in 40 lymphoplasmacytic lymphomas, respectively. None of the lymphoplasmacytic lymphomas studied harbored these translocations. Thus, detection of t(1;14)(p22;q32) and t(11;18)(q21;q21) is useful in the differential diagnosis between lymphoplasmacytic lymphoma and mucosa-associated lymphoid tissue lymphoma.

ADP-ribosyl Cyclase↗

T-cell and NK/T-cell lymphomas in southern Taiwan: a study of 72 cases in a single institute.

In an attempt to better understand the clinicopathologic features of T- and natural killer (NK)/T-cell lymphomas in Taiwan and the distribution and relative frequency of each subtype according to the new WHO classification, the pathology file of a medical center in southern Taiwan during 1989-2002 was retrospectively searched. The results of light microscopy, immunohistochemistry, in situ hybridization for Epstein-Barr virus (EBER), and T-cell receptor (TCR)-gamma chain gene rearrangement were correlated with clinical findings. A total of 72 cases were identified. They were peripheral T-cell lymphoma, unspecified (PTLu; n = 23, 31.9%), NK/T-cell lymphoma (n = 14, 19.4%), anaplastic large cell lymphoma (n = 13, 18.0%), angioimmunoblastic T-cell lymphoma (AITL; n = 9, 12.5%), precursor T-lymphoblastic lymphoma (n = 8, 11.1%), enteropathy-type intestinal T-cell lymphoma (n = 2, 2.8%), adult T-cell leukemia/lymphoma (n = 2, 2.8%), and subcutaneous panniculitis-like T-cell lymphoma (n = 1, 1.4%). The male to female ratio was 1.5:1. Forty patients (55.6%) had extranodal presentation. Eleven cases including 9 of 14 (64.3%) NK/T-cell lymphomas expressed CD56. All 14 NK/T-cell lymphomas are EBER-positive. Seven of nine (77.8%) AITLs expressed CD10. The overall 5-year survival rate was 10.2%. In conclusion, we have characterized a large series of T- and NK/T-cell lymphomas in southern Taiwan, where there is male predominance and poor prognosis. CD56 is a specific but not very sensitive marker while EBER is most reliable for the diagnosis of NK/T-cell lymphoma. CD10 is a useful marker to differentiate AITL from PTLu.

CD56 Antigen↗