Biomedical subjects
Publications and source records attributed to J K Chan.
A 66-year-old female who presented with cervical lymphadenopathy and splenomegaly was found to have large B-cell lymphoma on lymph node biopsy. However, trephine biopsy revealed involvement of the marrow by follicular lymphoma, and cytogenetic study showed an abnormal clone with 47,XX,+18.
Spindle epithelial tumor with thymus-like differentiation (SETTLE) is a very rare tumor of the thyroid believed to be derived from branchial pouch or thymic remnants and showing primitive thymic differentiation. Although this tumor is prone to develop delayed blood-borne metastases, the metastatic risk is unclear because the case reports in the recent literature had very short follow-up periods. We report one case, the oldest patient reported so far, who had been followed up until death. The 59-year-old man had an enlarged thyroid for all of his adult life, and presented with recent rapid enlargement of the thyroid. Neck exploration revealed a hard tumor in the right lobe, with adhesion to sternothyroid muscle. Histologic examination showed an invasive biphasic neoplasm traversed by sclerotic septa. Tight to loose fascicles of bland-looking spindly cells were intimately intermingled with tubulopapillary structures, diagnostic of the SETTLE. This patient developed left pulmonary metastases at 2 years and subsequently developed bilateral pulmonary and widespread metastases. He died 8 years after initial presentation. This case illustrates the protracted clinical course of the tumor, and survival for many years despite the occurrence of metastases. Review of the literature shows that SETTLE occurs predominantly in young patients with a median age of 15 years and male predominance. There is a significant metastatic rate of 71% for patients with more than 5 years of follow-up in spite of the otherwise indolent nature of the tumor.
The conventional positive control in immunohistochemistry consists of a separately immunostained slide containing tissue known to show positive reaction with the antibody. Although it can indicate that the reagents are sound, it cannot guarantee that the appropriate reagents have indeed been dispensed in the correct order on the test cases. Furthermore, positive controls are costly because they often account for 20% to 40% of all immunostained slides in a diagnostic surgical pathology laboratory. We describe a simple method to produce a multitissue spring-roll control block, comprising mostly normal tissues. The multitissue controls are mounted on the same slides of the test cases, and thus undergo the identical immunostaining procedures as the test tissues. Therefore they can provide the best assurance that the immunostains are working properly on the individual slides, the expected sensitivity is achieved, and the specificity is as expected. The wisdom of the conventional negative control is also questioned. When two or more immunostains are performed on a case, they should be sufficient to indicate the presence or absence of nonspecific staining.
Natural killer (NK)-cell lymphoma/leukemia is a group of rare but highly aggressive neoplasms. The associated genetic aberrations, as defined by conventional cytogenetics, include 6q deletion and chromosome X copy gain, while translocations have been suggested to be uncommon. In this study, three cases of NK cell lymphoma/ leukemia were investigated by spectral karyotyping (SKY). SKY permitted reinterpretation of the chromosomal alterations defined by G-banding and identified several cryptic translocations. In agreement with G-band, 6q deletion was detected in all 3 cases. Structural rearrangement involving chromosome X was observed in 2 cases, and fluorescence in situ hybridization (FISH) analysis indicated that both translocations involved Xp21-pter. Chromosome 8 translocation was also identified in 2 cases and shared a common breakpoint, 8p23. The present study shows the value of SKY in providing additional information on karyotypic abnormalities. The novel findings of recurring Xp21-pter rearrangements and 8p23 translocation should provide basis for further investigations into the tumorigenesis of NK cell lymphoma/leukemia.
The effects of different language backgrounds on trail making tasks were examined in this study. The measures adopted were the Color Trails Test (CTT) and the Trail Making Test (TMT), the former being the culturally fair analogue of the latter. Eighty-four right-handed participants belonging to the Chinese-English Bilingual (CEB) and English Monolingual (EM) groups participated in this study. The results of between-group comparisons revealed no significant differences in performance on the two measures between our Chinese bilingual and English monolingual participants, except on the TMT-A. However, a within-group correlation indicated that performances on the TMT and CTT were highly correlated for the English sample, but not for the Chinese. These observations suggest that trail making tasks like the TMT and CTT are themselves generally fair across Chinese and English, but equivalence between them may be more language-specific. Furthermore, mastery of a language loaded on temporal sequencing like English may give an advantage in the completion of trail making tasks.
Eight cases of a previously uncharacterized vascular neoplasm, showing varying combinations of benign, low-grade malignant, and malignant vascular components are described. Seven tumors occurred in the dermis and/or subcutis and one occurred in the oral submucosa. The patients were all adults with a median age of 39.5 years (range, 21-71 years). Five patients were men. The tumors arose predominantly in the hands and feet, and the lesions were usually of several years duration. The tumors were composed of a complex admixture of histologic components that varied from tumor to tumor, such that no two tumors looked precisely the same. This was due to variation in the proportions of each component as well as the manner in which each component was distributed throughout each lesion. The predominant histologic components were epithelioid hemangioendothelioma (HE) and retiform HE, which were each present in seven of the tumors. Areas of spindle cell HE were identified in four lesions. Angiosarcoma-like elements were identified in seven tumors. One of the tumors was associated with an arteriovenous malformation and one was associated with an area of lymphangioma circumscriptum. Of six cases with follow up (median duration, 6.5 years), three have recurred locally and, to date, only one has metastasized. We think composite HE is best regarded as a low-grade malignant vascular neoplasm, and the available data suggest that it behaves more favorably than conventional angiosarcoma. The existence of these composite lesions has led to careful reexamination of the concept of HE. The term HE, in that it is currently synonymous with a low-grade malignant vascular tumor, should be reserved for lesions that have true metastatic potential, albeit with low frequency.
The histogenesis of pulmonary sclerosing hemangioma has remained controversial despite extensive studies by many investigators. The availability of an antibody to thyroid transcription factor-1 (TTF-1), which is expressed in type II pneumocytes and Clara cells, has prompted us to readdress this issue. Sixteen cases were immunostained with a panel of antibodies including TTF-1. The patients were predominantly women with an age range of 30 to 73 years (mean, 52 yrs). All tumors were solitary. The single male patient showed regional lymph node metastases, an unusual occurrence reported only once in the literature. All cases exhibited the classic histologic features, with variegated patterns. TTF-1 expression was observed in both the surface lining cells and the pale polygonal cells. The surface lining cells were epithelial membrane antigen (EMA)+ cytokeratin+ surfactant apoprotein A+, whereas the polygonal cells were EMA+ cytokeratin- surfactant apoprotein A-. The neuroendocrine markers synaptophysin and chromogranin were both negative. The metastatic deposits in the lymph nodes comprised only polygonal cells and exhibited an EMA+ cytokeratin- surfactant apoprotein A- TTF- 1+ immunophenotype. These results suggest that pulmonary sclerosing hemangioma is an epithelial neoplasm derived from primitive respiratory epithelium or incompletely differentiated type II pneumocyte or Clara cell.
The subgroup of T/null-cell primary systemic anaplastic large cell lymphoma that expresses anaplastic lymphoma kinase (ALK) constitutes a distinctive clinicopathologic entity that exhibits a broad morphologic spectrum. The examples predominated by small cells or showing a mixed cell population can be difficult to recognize as being neoplastic. We report four such cases with a remarkably hypocellular granulation tissue-like appearance, mimicking an inflammatory or reparative process. All patients were young and presented with lymphadenopathy in multiple sites. The lymph node biopsies showed a hypocellular appearance, with wide separation of the small to medium-sized lymphoid cells by edematous or fibromyxoid stroma. There were interspersed spindly neoplastic cells resembling myofibroblasts, sometimes forming short, sweeping fascicles, as well as histiocytes. Occasional large cells with atypical nuclei were identified. The larger lymphoid cells tended to form cuffs around the venules. In two cases, the capsule and fibrous trabeculae were markedly broadened with increased spindly cells, mimicking inflammatory pseudotumor of lymph node. Immunostaining showed dispersed and clustered CD30+ ALK+ cells, confirming a diagnosis of anaplastic large cell lymphoma. In conclusion, a diagnosis of hypocellular anaplastic large cell lymphoma requires a high index of suspicion. The young age of the patients and the presence of perivascular cuffs of larger lymphoid cells should provide the strongest clues to the correct diagnosis.
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OBJECTIVES: To study the effects of augmentation of continuous positive airway pressure (CPAP) education and support on compliance and outcome in patients with obstructive sleep apnea (OSA). DESIGN: A randomized, controlled, parallel study of basic vs augmented CPAP education and support. SETTING: A university teaching hospital. PATIENTS: A total of 108 OSA patients randomized into basic-support (BS) and augmented-support (AS) groups. INTERVENTIONS: Patients in the BS group (n = 54) were given educational brochures on OSA and CPAP, CPAP education by nurses, CPAP acclimatization, and were reviewed by physicians and nurses at weeks 4 and 12. Patients in the AS group (n = 54) received more education, including a videotape, telephone support by nurses, and early review at weeks 1 and 2. MEASUREMENTS: Objective CPAP compliance, Calgary sleep apnea quality of life index (SAQLI), and cognitive function after 1 month and 3 months; and Epworth sleepiness scale (ESS) after 3 months of CPAP treatment. RESULTS: At 4 weeks, CPAP usage was 5.3 +/- 0.2 h/night (mean +/- SEM) vs 5.5 +/- 0.2 h/night in the BS and AS groups, respectively (p = 0.4). At 12 weeks, CPAP usage was 5.3 +/- 0.3 h/night vs 5.3 +/- 0.2 h/night in the two groups, respectively (p = 0.98). There was greater improvement of SAQLI at 4 weeks (p = 0.008) and at 12 weeks (p = 0.047) in the AS group. There was no significant difference between BS and AS groups in terms of improvement of ESS and cognitive function. CONCLUSION: Augmentation of CPAP education and support does not increase CPAP compliance, but leads to a greater improvement of quality of life during the reinforced period.
DNAse sensitive chromatin, putative transcriptionally competent sequences, exists either as pan-nuclear speckles in cells with nuclei which exhibit a flat geometry, or as a shell apposed to the nuclear envelope in cells with spheroidal nuclei. To test the hypothesis that DNAse sensitive chromatin is similarly associated with the nuclear periphery in cell types with a very flat geometry such as 3T3 fibroblasts, cells were subjected to hypotonic expansion to change their nuclei from a flat ellipsoid to a spheriod. This was based on the assumption that such a spatial association is not resolvable due to the interdigitation at the nuclear midplane of DNAse sensitive chromatin associated with the upper and lower nuclear surfaces. In situ nick translation was used to visualize the distribution of DNAse sensitive chromatin as a function of nuclear geometry. Both unexpanded and expanded cells exhibit DNAse sensitive chromatin as a dome at the apical side of the nucleus, i.e., that aspect of the cell facing the culture medium. The results argue for a polarized association of DNAse sensitive chromatin with the nuclear envelope and indicate that the nuclear periphery may function as a compartment for the spatial coupling of transcription and nucleo-cytoplasmic transport.
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Over the past decade, the many advances in immunohistochemical techniques have revolutionized the field of immunohistochemistry. Most notable is discovery of the use of heat for antigen retrieval, which permits consistent and reliable demonstration of antigens in routine surgical pathology specimens despite variations in the duration of fixation and tissue processing schedules. As a result, immunohistochemical studies play an increasingly important role in surgical pathology, such as help in rendering a diagnosis in a crushed specimen, classification of tumors, prediction of the likely origin of a carcinoma, demonstration of micrometastases, provision of prognostic information, and demonstration of microorganisms. To serve such purposes, immunohistochemical stains must be performed at a high standard with consistent and reproducible results. The stains must be interpreted cautiously in the appropriate context, and potential pitfalls such as endogenous biotin activity must be recognized. The increased demand for immunohistochemical tests raises the issue of cost containment, which can be achieved through a number of ways, such as deletion of nonvalue-added tests, deletion of antibodies that no longer serve a purpose, replacement of the conventional positive control with a multitissue control mounted on the same slides of the test cases, various means of savings on antibodies, and continuing to use "expired" antibodies. To keep abreast of modem developments in the field in this era of information explosion, the internet can play an important role by providing updated information or database and a platform for rapid exchange of knowledge.
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BACKGROUND: The extension of living donor liver transplantation to adult recipients is limited by the adequacy of the size of the graft. We evaluate the effect of the graft size on the survival of the recipient in order to establish a clinical guide for the minimum requirement. METHODS: The clinical records of 14 adults and 11 children (body weight 6.1-100 kg) who underwent living donor liver transplantation for chronic or acute liver failure were reviewed. The effect of the graft weight ratio (graft weight divided by standard liver weight of recipient) on graft function and survival was studied. RESULTS: The graft weight ratio ranged from 31 to 203%. The overall graft and patient survival rates were 84% at a median follow-up of 29 months. The survival rate was 95% for recipients with a graft weight ratio >40%, and 40% only for those with a ratio < or =40% (P = 0.016). It was 88% (7/8) when the ratio was >100%, 100% (5/5) when the ratio was 71 to 100%, 100% (7/7) when the ratio was 41 to 70%, and 40% (2/5) only when the ratio was < or =40%. When the graft weight ratio was < or =40%, early graft dysfunction was evident and contributed to the causes of death in three patients. CONCLUSIONS: Preoperative computed tomographic measurement of liver size of a living donor is essential. A graft that represented 40% or less of the recipient's standard liver weight should be regarded as a marginal graft with a lower success rate.
BACKGROUND: Mantle cell lymphoma is a mature, virgin B-cell neoplasm characterized immunologically by a panB+, CD5+, CD23-, cyclin D1+ phenotype and genetically by t(11;14)(q13;q32) with overexpression of the cyclin D1 (bcl-1) gene. It usually presents as advanced stage disease, involving lymph nodes, spleen, bone marrow, and extranodal sites, particularly the gastrointestinal tract. However, frank leukemic presentation with high white cell counts is uncommon and can be difficult to distinguish from other chronic lymphoproliferative disorders. The aim of this study was to characterize the morphologic spectrum of leukemic mantle cell lymphoma. METHODS: During the period July 1994 through October 1998, 14 patients with mantle cell lymphoma in leukemic phase were diagnosed at the Department of Pathology, Queen Elizabeth Hospital, Hong Kong. The diagnosis of mantle cell lymphoma was based on histologic and immunocytochemical findings and was confirmed by cyclin D1 immunoreactivity in all cases. The clinical records and laboratory results were reviewed. Peripheral blood smears, bone marrow, and other tissue biopsies were examined, with particular attention to the cytologic features of the leukemic mantle cells. RESULTS: Mantle cell lymphoma in leukemic phase showed a very aggressive clinical course. Eight patients died at a mean of 13 months, and only 1 patient was disease free. Morphologically, the leukemic mantle cells exhibited a broad morphologic spectrum, with several cytologic patterns identified: 1) mixed small and medium-sized cells, 2) predominantly medium-sized cells, 3) predominantly large cells, and 4) giant cells. Despite variations in the size and nuclear shape, the leukemic mantle cells could usually be recognized by the nuclear irregularity and clefting, moderately dense but evenly distributed chromatin, small nucleoli, and scant cytoplasm. CONCLUSIONS: Recognition of the characteristic cytologic features of leukemic mantle cells can help to distinguish them from other chronic lymphoproliferative disorders. In contrast to the latter, the clinical course is aggressive and response to conventional chemotherapy is poor.
Specific chromosomal abnormalities have been shown to be associated with certain types of leukemia and lymphoma. We and others have recently demonstrated del(6)(q21q25) as being strongly associated with natural killer cell lymphoma/leukemia. In this report, we describe a case of natural killer cell lymphoma with a clonal chromosomal abnormality of 46,X,-Y,+X,t(2;9)(q31;p24), del(4)(q21q25),del(6)(q21q23), and propose that the region 6q23 is probably an important site of genetic alteration in this group of tumors.