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Biomedical subjects

J K Chan

Publications and source records attributed to J K Chan.

At least 91 records · Page 5Linked to original sources
PubMed1998

Drug use concomitant with cyclosporine immunosuppressive therapy for 3 years after renal transplantation.

Little is known about outpatient drug use concomitant with cyclosporine immunosuppressive therapy following renal transplantation. In part, this stems from the difficulty in monitoring drugs not covered by Medicare. Using several linked state and federal program data bases, a cohort of dually eligible Medicare/Medicaid California residents aged > or = 18 years with a first cadaver transplant in 1988 was followed for 3 years to examine drug use and medical expenditures: 99, 122, and 90 patients met these inclusion criteria in each study year, respectively. More than one third of the study population received one or more drugs that inhibit metabolism and increase cyclosporine circulating blood levels (class I) in each year posttransplant. The most commonly prescribed were diltiazem, verapamil, metoclopramide, and ketoconazole. Patients receiving class I drugs had a lower mean cyclosporine dose compared with those not receiving such drugs in all three study years, suggesting that overall cost savings were obtained among patients using class I drugs. Less than one tenth of the study population in any given year received a drug that induces metabolism and decreases cyclosporine blood levels (class II), the most common of which was phenytoin. Use of nephrotoxic drugs (eg, trimethoprim-sulfamethoxazole, gentamicin, and tobramycin) that exhibit nephrotoxic synergy when used with cyclosporine was common. Almost half of all posttransplant patients were prescribed a nephrotoxic drug during the study period. Pharmaceuticals (primarily cyclosporine) accounted for 35% to 43% of the approximately $17,000 to $19,500 per patient annual health care expenditures incurred in the first 3 years following kidney transplantation.

Adolescent↗
PubMed1998

Angiosarcoma of the ovary: clinicopathologic and immunohistochemical analysis of four cases with a broad morphologic spectrum.

Angiosarcoma most frequently occurs in the skin of the head and neck region of elderly persons, lymphedematous limbs, or in deep soft tissue but only rarely has been described to occur in the female genital tract. Four cases of angiosarcoma of the ovary are described herein. They occurred in patients 25 to 42 years old (median, 31 years). The most common clinical presentation was abdominal pain. All of the tumors were unilateral, hemorrhagic, and ranged from 3.5 cm to 14 cm (median, 13 cm). The histologic appearance of the tumors was varied, and often the vascular nature of the tumor was not apparent immediately. Some of the tumors had a fascicular growth pattern composed of spindle-shaped cells with ovoid nuclei and ample eosinophilic cytoplasm closely mimicking leiomyosarcoma. Other tumors resembled ovarian yolk sac tumor with a reticular growth pattern, whereas, in other areas, cystic structures lined by hobnailed hyperchromatic enlarged nuclei simulated clear cell carcinoma of the ovary. Despite these misleading morphologic findings, all cases were characterized, at least focally, by vasoformative channels or discrete cytoplasmic vacuoles, and all were immunoreactive for vascular markers. Two patients with spread of tumor outside of the ovary died 1 month and 2 years after initial diagnosis, respectively. Two patients with tumor confined to the ovary are alive without evidence of disease 3 and 14 months after diagnosis, respectively. The differential diagnosis of this unusual neoplasm is discussed, and the literature is reviewed.

Adult↗
PubMed1998

Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile.

Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, or p53 protein, and loss of CD99+ immature T lymphocytes, and is occasionally associated with a change in the expression of CD5 or vimentin.

Adult↗
PubMed1998

Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.

PURPOSE: To study the clinical features and outcome for primary non-Hodgkin's lymphomas of the nose/nasopharynx (NNP-NHLs) according to immunophenotype. PATIENTS AND METHODS: One hundred thirteen Chinese patients with primary NNP-NHLs that belonged to the categories E, F, G, or H according to the Working Formulation (WF), with full immunophenotypic data and complete clinical follow-up data, were analyzed in this retrospective study. RESULTS: Ninety (79.6%) patients had localized (stage I or II) disease, while 23 (20.4%) had stage III or IV disease. The lymphomas in 51 (45.1%), 24 (21.3%), and 38 (33.6%) patients showed natural killer (NK)/T- (CD56-positive), T-cell, and B-cell immunophenotype, respectively. Seventy-three patients (65.8%) achieved a complete remission, of whom 34 (46.6%) subsequently relapsed. The median follow-up time for those alive was 88 months. The 5-year actuarial disease-free and overall survival rates were 34.4% and 37.9%, respectively. Multivariate analysis showed that only stage and immunophenotype were significant for survival. NK/T lymphomas were distinctive among the three immunophenotypes in the following aspects: the highest male-to-female ratio, more frequent involvement of the nasal cavity alone, higher risk of dissemination to the skin, more frequent development of hemophagocytic syndrome, and the worst prognosis (overall median survival, 12.5 months). CONCLUSION: The three immunophenotypes studied are shown to exhibit different clinical patterns. Since the NK/T phenotype carries the worst prognosis, patients who present with NNP-NHL should have their tumors analyzed for CD56 expression.

Adolescent↗
PubMed1997

Preferential dissemination of B-cell gastric mucosa-associated lymphoid tissue (MALT) lymphoma to the splenic marginal zone.

The tendency for gastric mucosa-associated lymphoid tissue (MALT) lymphoma cells preferentially to localize around reactive B-cell follicles, both in the mucosa and regional lymph nodes, coupled with their immunophenotype, has led to the proposal that the normal cell counterpart of this lymphoma is the marginal zone B cell. In keeping with this proposition, lymphocytes expressing the lymphoma idiotype have been detected in the splenic marginal zone in a single case of gastric MALT lymphoma. To confirm that this truly represented preferential homing of MALT lymphoma to the splenic marginal zone, we have now re-examined this case, together with 17 other cases, using both immunohistochemical and molecular methods in an attempt to establish clonal identity between the gastric lymphoma and cells in the splenic marginal zone. In three cases, the spleen was characterized by marked expansion of marginal zones by cells showing the same pattern of Ig light chain restriction as the gastric lymphoma. None of the remaining 15 cases showed histologic evidence of lymphomatous infiltration. Analysis of the Ig genes by polymerase chain reaction (PCR), cloning, and sequencing confirmed clonal identity between the splenic marginal zone infiltrates and the gastric lymphoma in the histologically involved cases. Amplifiable DNA could be extracted from only 5 of the remaining 15 cases. In 3 of these cases, including the case previously studied using an anti-idiotype, involvement of the splenic marginal zone could be confirmed using microdissection and clone-specific PCR. No involvement could be detected in the remaining 2 cases. In addition, we have shown that mucosal addressin cell adhesion molecule-1 (MAdCAM-1), the primary homing receptor of gut-mucosa for lymphocytes, was strongly expressed by the sinus lining cells of the splenic marginal zone. These results provide strong evidence for preferential involvement of the marginal zone when gastric MALT lymphomas disseminate to the spleen, which is in keeping with the notion that the marginal zone B cells are the normal counterparts of MALT lymphoma cells.

Adult↗
PubMed1997

Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.

Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Adolescent↗
PubMed1997

Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data.

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+ years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR = 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process.

Adolescent↗
PubMed1997

Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized.

BACKGROUND: The goal of this study was to characterize the clinicopathologic features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS: The 17 cases were collected from the consultation and surgical pathology files of the authors, including 8 previously reported cases. The histologic and immunohistochemical features and outcome were analyzed. RESULTS: The patients had a median age of 40 years, with a slight female predominance. Seven patients presented with enlarged lymph nodes, and ten presented with tumor in extranodal sites. Two cases were associated with hyaline-vascular Castleman's disease. The tumors had an average greatest dimension of 6.7 cm. The most common histologic feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin, distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm. There were often scattered multinucleated forms. The tumor cells sometimes formed sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular spaces. There was a sprinkling of small lymphocytes, with or without cuffing around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17 cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17 cases), but not cytokeratin. Ultrastructural studies showed villous processes connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13 patients with a median follow-up of 3 years, local recurrence occurred in 6, metastasis in 6, and 3 died of disease. CONCLUSIONS: Follicular dendritic cell sarcoma exhibits distinctive histologic features that permit its presumptive recognition, but a firm diagnosis requires confirmation with special studies. Because it has a significant recurrent and metastatic potential (the latter risk having been previously underestimated), it should be viewed as an intermediate grade malignancy. An intraabdominal location is associated with a particularly aggressive clinical course.

Adolescent↗
PubMed1997

T- and T/natural killer-cell lymphomas of the salivary gland: a clinicopathologic, immunohistochemical and molecular study of six cases.

Primary salivary gland lymphomas are almost always of B lineage, with most being represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue. This study characterizes the rare non-B-cell lymphomas of the salivary gland based on an analysis of six cases. All patients were men, with a mean age of 53.5 years. They presented with submandibular or parotid mass, which on histological examination showed extensive interstitial infiltration by small, medium-sized, or large lymphoid cells. There was prominent invasion and expansion of the ducts and acini in five cases. Angioinvasion was evident in two cases. Three cases were of T lineage and were CD56 negative; one of these cases expressed CD30. Three cases showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative cases by polymerase chain reaction on paraffin sections using primers for the T-cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died within 3 years, and two were disease free at 4 and 1.5 years, respectively. This study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably distinguished from B-cell lymphomas on morphological grounds alone, because both can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas, which are often extranodal in localization and strongly associated with Epstein-Barr virus (EBV), show a predilection to involve the salivary glands as well.

Aged↗
PubMed1997

CD56+ putative natural killer cell lymphomas: production of cytolytic effectors and related proteins mediating tumor cell apoptosis?

Apoptosis is a regulated form of cell death that may be triggered by natural killer (NK) or cytotoxic T cells, which effect target cell lysis by cytolytic effector and related proteins through complex intracellular signals. This study was aimed to investigate whether there is selective expression of these cytolytic markers in the putative NK-cell lymphomas and whether there is correlation with zonal tumor cell death in these tumors. Expression of the cytolytic effectors perforin, granzyme B9, and the granule membrane protein TIA1 were examined in 24 putative NK-cell lymphomas, 18 postthymic T-cell lymphomas (one case CD8+ CD56+ and three anaplastic large cell lymphomas (ALCL), three T-lymphoblastic lymphomas, and 20 B-cell lymphomas. Nineteen (79%) putative NK-cell lymphomas expressed perforin, and all 24 cases expressed granzyme B9 and TIA1. The only CD8+ CD56+ postthymic T-cell lymphoma also expressed all three cytolytic markers, two CD8- ALCL expressed TIA1; other postthymic T-cell, T-lymphoblastic, and B-cell lymphomas were consistently negative. There was strong correlation between percentage perforin-positive cells and zonal tumor cell death. Angioinvasion, in contrast, was present only in a proportion (37%) of these lymphomas despite the frequent presence of zonal tumor cell death (71%). We propose that cytolytic effector and related proteins produced by putative NK and some CD8+ CD56+ postthymic T-cell lymphomas, probably in conjunction with other mechanisms, may effect massive tumor cell apoptosis. The frequent expression of cytolytic effector markers in the CD2+ surface CD3- CD56+ putative NK-cell lymphomas lends further support to their probable NK cell origin.

Apoptosis↗
PubMed1997

Nasal pleomorphic adenoma with skeletal muscle differentiation: potential misdiagnosis as rhabdomyosarcoma.

Pleomorphic adenoma can show diverse lines of differentiation in the epithelial and myoepithelial elements, such as cartilage, bone, and fat. Myoid differentiation, however, has not been documented. We report an unusual case of nasal pleomorphic adenoma which shows focal skeletal muscle differentiation. The tumor was discovered only after successful radiation therapy for an undifferentiated carcinoma of the nasopharynx. Apart from being of morphological interest, the presence of cells with skeletal muscle differentiation also raises the practical issue of possible confusion with rhabdomyosarcoma in a biopsy. The distinguishing features are lack of cytological atypia and presence of a neoplastic glandular element.

Adenoma, Pleomorphic↗
PubMed1997

Identification of del(6)(q21q25) as a recurring chromosomal abnormality in putative NK cell lymphoma/leukaemia.

The putative natural killer (NK) cell lymphomas/leukaemias are a group of recently characterized haematolymphoid malignancies sharing an immunophenotype of CD3/Leu4- CD3epsilon+ CD56+, and a genotype of germline T-cell receptor genes. They frequently present in extranodal sites and exhibit a highly aggressive clinical course. Information on the cytogenetic or molecular events leading to the tumourigenesis in this group of tumours is very scarce. In this study we analysed the cytogenetic findings of seven patients with CD56-positive putative NK cell lymphoma/leukaemia. Three cases, including one nasal, one extranasal and one leukaemic form, showed a common region of deletion at 6q21-q25, suggesting that this may be a nonrandom chromosomal aberration.

Adult↗