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Biomedical subjects

J K Chan

Publications and source records attributed to J K Chan.

At least 127 records · Page 7Linked to original sources

Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density.

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.

Adult↗

T-cell form of chronic lymphocytic leukaemia: a reaffirmation of its existence.

Early in the 1980s three categories of T-cell chronic lymphocytic leukaemia were recognized: CD4+ CD8- knobby type, CD4- CD8+ azurophilic type and CD4+ CD8- adult T-cell leukaemia (ATL) type. Both azurophilic and ATL types were later shown to be distinctive disorders, whereas the knobby type has been largely neglected and even considered non-existent by some authors. In this report we describe two patients with leukaemia of CD3+ CD4+ CD8- post-thymic T lymphocytes presenting with marked lymphocytosis, generalized lymphadenopathy and hepatosplenomegaly. We believe that CLL of the post-thymic T-lymphocytes is a distinct entity, and merits a separate designation from other T-cell leukaemias.

Adult↗

Paucicellular variant of anaplastic thyroid carcinoma. A mimic of Reidel's thyroiditis.

Anaplastic thyroid carcinomas usually pose no problems in histologic diagnosis because of the obvious invasive growth, high cellularity, and frank anaplasia. Two cases of a variant of anaplastic thyroid carcinoma with peculiar gross and histologic features closely mimicking those of Riedel's thyroiditis are described in this report. The clinical features were no different from those of the usual anaplastic thyroid carcinomas: occurrence in elderly subjects, presentation with rapidly enlarging neck mass associated with compression symptoms, and rapidly fatal outcome. The tumors were infiltrative, hard, fibrotic masses that partly or completely replaced one lobe of the thyroid, and extended to perithyroid tissues. Histologically, they were predominated by acellular fibrous or infarcted tissue with central dystrophic calcification, as well as hypocellular foci comprising mildly atypical spindle cells intermingled with collagen and small lymphocytes. Both cases showed permeation and plugging of the arteries by tumor. Lymph node metastasis was documented in one case. The spindle cells were positive for epithelial membrane antigen in both cases, and cytokeratin in one. The qualifying term "paucicellular variant" accurately describes this uncommon morphologic variant of anaplastic thyroid carcinoma. It is important to recognize this variant so as not to mistaken it for Riedel's thyroiditis, which is a reactive condition with a very favorable prognosis. The distinguishing features are as follows: presence of infarction, atypical cells in at least some areas, atypical spindle cells obliterating large blood vessels, and immunoreactivity for epithelial markers.

Aged↗

Tubular adenosis of the breast. A distinctive benign lesion mimicking invasive carcinoma.

Tubular adenosis, a term first coined by Oberman, is an uncommon benign lesion of the breast that may mimic invasive carcinoma. There is no formal description of this condition in the literature. We report the findings on six specimens from five patients (one with bilateral disease), including three that showed cancerization by intraductal carcinoma (DCIS). The ages of the patients ranged from 40 to 82 years. One patient presented with a 3-cm breast mass, and the others were found in specimens resected for infiltrating ductal carcinoma (two specimens) or DCIS (three specimens). The histologic hallmark of tubular adenosis was haphazard proliferation of elongated tubules that were noncrowded, narrow, and sometimes branching. There was no lobular arrangement or, at most, vague lobular grouping, with some tubules often extending into the fat. The tubules contained basophilic or granular eosinophilic secretion. The stroma was sclerotic to edematous. The tubules were lined by bland-looking ductal cells and were surrounded by an intact myoepithelial layer, a phenomenon well highlighted by immunostaining for muscle-specific actin (HHF-35) or S-100 protein. In three specimens, the tubular adenosis was cancerized by noncomedo DCIS, producing a pattern strongly mimicking infiltrating carcinoma; the in situ nature of the carcinoma was confirmed by actin immunoreactivity in the residual myoepithelium as well as by the presence of architecturally similar tubular adenosis in the vicinity. Tubular adenosis shows an infiltrative growth similar to microglandular adenosis and adenomyoepithelial adenosis, but it differs from them by the interdigitating tubular configuration and also differs from microglandular adenosis by the presence of myoepithelium. Tubular adenosis can be distinguished from sclerosing adenosis by the lack of obvious lobular architecture or whorled arrangement and wider separation of the tubules. Tubular adenosis appears to be a benign lesion per se, but whether it has premalignant potential remains to be determined. The importance of recognizing this entity lies in its being potentially mistaken for invasive carcinoma, especially at intraoperative frozen section or when the lesion is cancerized by DCIS.

Adult↗

Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology.

A workshop jointly sponsored by the University of Hong Kong and the Society for Hematopathology explored the definition, differential diagnosis, and epidemiology of angiocentric lymphomas presenting in the nose and other extranodal sites. The participants concluded that nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity highly associated with Epstein-Barr virus (EBV). In situ hybridization for EBV an be very valuable in early diagnosis, especially if tissue is sparse. The cytologic spectrum is broad, ranging from small or medium-sized cells to large transformed cells. Histologic progression often occurs with time. Necrosis is nearly always present, and angioinvasion by tumor cells is seen in most cases. Nasal T/NK cell lymphoma has a characteristic immunophenotype: CD2-positive, CD56-positive, but usually negative for surface CD3. Cytoplasmic CD3 can be detected in paraffin sections. Clonal T-cell receptor gene rearrangement is not found. Tumors with an identical phenotype and genotype occur in other extranodal sites, most commonly in the skin, subcutis, and gastrointestinal tract, and should be referred to as nasal-type T/NK cell lymphomas. The differential diagnosis includes lymphomatoid granulomatosis, blastic or monomorphic NK cell lymphoma/leukemia, CD56-positive peripheral T-cell lymphoma, and enteropathy-associated T-cell lymphoma.

Diagnosis, Differential↗

Utility of a paraffin section-reactive CD56 antibody (123C3) for characterization and diagnosis of lymphomas.

Although expression of CD56 (neural cell adhesion molecule, a natural killer cell marker) is uncommon among lymphomas, this feature has defined a distinctive and important category of lymphoma: the putative natural killer (NK) cell lymphoma, which shows a predilection for the upper aerodigestive tract, skin, skeletal muscle, and other extranodal sites and pursues an aggressive clinical course. Thus far, CD56 expression can be reliably analyzed only on fresh or frozen tissues. In this study, we evaluated the sensitivity and specificity of a CD56 antibody, 123C3, when applied on routine formalin-fixed, paraffin-embedded tissues for analysis of lymphomas, by comparing the staining results with those obtained on frozen tissues using the CD56 antibody NKH1. The 123C3 antibody worked on paraffin sections only with prior antigen retrieval using a pressure cooker or a microwave oven. Among 32 CD56+ T/NK cell lymphomas and one CD56+ B-lymphoblastic lymphoma, the neoplastic cells showed crisp membrane staining with 123C3 in all cases. None of the 24 CD56- T-cell lymphomas and 50 CD56-B-cell lymphomas stained with 123C3. In normal or reactive lymphoid tissues from a variety of sites, there were few small lymphocytes (< 0.1%) that showed cell membrane staining with 123C3, although occasional plasma cells might show cytoplasmic staining. We conclude that with suitable antigen retrieval procedures, 123C3 can be reliably applied on routine paraffin sections for detection of CD56 expression in lymphomas. Furthermore, this antibody can be used to support a diagnosis of lymphoma or to detect residual disease for cases of CD56+ T/NK cell lymphoma in which the neoplastic lymphoid cells are small and show minimal atypia, especially in small biopsies.

Adult↗

Endocrine ductal carcinoma in situ (E-DCIS) of the breast: a form of low-grade DCIS with distinctive clinicopathologic and biologic characteristics.

Endocrine ductal carcinoma in situ (E-DCIS), first characterized by Cross et al. in 1985, is an uncommon entity, and there is little information on its pathobiologic features and natural history in the literature. This report describes the largest series of 34 cases: 14 cases were pure in situ (group A), and 20 were accompanied by an invasive component (group B). All except three patients were over the age of 60 years, with the mean being 69.5 years for group A and 72.6 years for group B. Except for six patients in group A who had nipple discharge, all had a breast mass. On follow-up, one of five group A patients developed local recurrence 5 years after mastectomy, and two of seven group B patients developed another invasive primary in the contralateral breast. Histologically, E-DCIS showed expansile intraductal growths forming solid sheets and festoons traversed by delicate fibrovascular septa. Accumulation of basophilic mucin might be found within the growth and the fibrovascular septa. There were variable degrees of stromal sclerosis. In some cases, the solid intraductal cellular proliferations were focally punctuated by microglandular spaces and rosettes. Comedo necrosis was absent. Intraductal papillomas were found in the immediate vicinity of the tumors in 18 cases and invariably showed pagetoid involvement by E-DCIS. Pagetoid spread into the adjacent ducts and ductules was also a common feature (17 cases). The tumor cells were polygonal, oval, or spindly, often with eccentrically placed, bland-looking, ovoid nuclei and abundant eosinophilic granular cytoplasm. Intracellular mucin was commonly demonstrable. Immunostaining for myoepithelium using muscle-specific actin antibody confirmed the in situ nature of the E-DCIS component. The majority of tumor cells showed strong staining with the neuroendocrine markers chromogranin, synaptophysin, and neuron-specific enolase (monoclonal). Immunostaining also dramatically highlighted the pagetoid spread into the papillomas and ductules by outlining the tumor cells between the negatively stained residual ductal epithelium and myoepithelium. All cases were immunoreactive for estrogen and progesterone receptor, but not p53 and c-erbB2. The Ki-67 index was < 5%. Ultrastructural studies on four cases showed many dense-core neurosecretory granules and larger mucigen granules. In group B cases, the invasive component, which comprised 5-95% of the tumor, included colloid carcinoma, 12; "carcinoid" tumor, 3; mixed "carcinoid"/colloid carcinoma, 4; and small cell neuroendocrine carcinoma, 1. Neuroendocrine markers were also consistently demonstrable in the invasive component. In conclusion, E-DCIS is predominantly a disease of older women that is frequently accompanied by papillomas in the vicinity and may present as nipple discharge (an uncommon presentation in the usual forms of DCIS). It can mimic epitheliosis histologically, but the pagetoid spread is a helpful clue to its neoplastic nature. The bland nuclear morphology, lack of necrosis, and biologic marker profile suggest that E-DCIS is a form of low-grade DCIS despite its solid growth pattern. The invasive carcinomas associated with E-DCIS are also neuroendocrine programmed rather than the usual types of ductal carcinomas, suggesting that E-DCIS represents a biologically distinctive category of DCIS.

Adult↗

Gastrointestinal lymphomas: an overview with emphasis on new findings and diagnostic problems.

The first section of this article summarizes the salient clinicopathologic features of the more common types of primary gastrointestinal lymphomas, the recent explosion of information on the low grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT), and new findings on multiple lymphomatous polyposis and ulcerative jejunitis. The second section discusses the practical problems that may be encountered in the diagnosis of gastrointestinal lymphomas, including diagnosis of large cell malignancies, distinction between lymphoma and reactive lymphoid hyperplasia, classification of diffuse small B-cell lymphomas (including the potential pitfall of mistaking Burkitt's lymphoma for small B-cell lymphoma), recognition of large cell transformation in low-grade B-cell MALT lymphoma, assessment of gastric biopsies from MALT lymphoma patients after anti-Helicobacter therapy, and assessment of nodal or splenic involvement in low-grade MALT lymphoma.

Colitis, Ulcerative↗

Basaloid-squamous carcinoma of the nasopharynx. An Epstein-Barr virus-associated neoplasm compared with morphologically identical tumors occurring in other sites.

BACKGROUND: Basaloid-squamous carcinoma is a newly characterized, highly aggressive neoplasm occurring mostly in the base of tongue, hypopharynx, larynx, and esophagus. Its occurrence in the nasopharynx is rare. METHODS: The clinicopathologic features of three cases of basaloid-squamous carcinoma of the nasopharynx are described and were studied for the presence of Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small nuclear RNA (EBER). For comparison, basaloid-squamous carcinomas occurring in other sites also were studied for the presence of EBV. RESULTS: EBER was detected in all 3 cases of basaloid-squamous carcinoma occurring in the nasopharynx, but in none of the 13 cases from other sites including the esophagus, larynx, pharynx, hypopharynx, and nasal cavity. The nasopharyngeal basaloid-squamous carcinomas occurred in two male and one female patients with an age range of 48-70 years. The serum immunoglobulin A against the EBV-viral capsid antigen was elevated in all three cases. Two patients developed cervical lymph node involvement during the course of the disease. All three patients were treated by radiotherapy and survived for longer than 34 months compared with the average reported median survival of approximately 2 years for basaloid-squamous carcinomas occurring in the usual sites. CONCLUSION: Based on this limited study, basaloid-squamous carcinoma occurring in the nasopharynx appears to be an EBV-associated neoplasm, whereas the same tumor occurring in other sites is not. The prognosis is potentially better for patients with nasopharyngeal basaloid-squamous carcinoma, which appears to be pathogenetically and biologically more related to the much more common nasopharyngeal undifferentiated carcinoma.

Aged↗

Primary lymphoepithelioma-like carcinoma of the lung. A clinicopathologic study of 11 cases.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, and skin. Primary LELC of the lung is very rare, with only limited information in the literature. METHODS: The clinicopathologic features of 11 patients with pulmonary LELC collected from two regional hospitals in Hong Kong are described. RESULTS: The patients, all Chinese, were aged 38 to 73 years (median, 54 years), with equal sex incidence. Two of the 8 patients were smokers. Four presented with coin lesions incidentally discovered on chest X-ray, five with cough and blood-stained sputum, and two with pleural effusion. The tumor formed a discrete (9 patients) or an ill-defined (1 patient) nodule in the lung, or, rarely, showed extensive bilateral pulmonary involvement (1 patient). The major bronchi were not involved except in 1 patient. Three patients had lymph node metastasis at presentation; two of them had bone metastasis, one at presentation and one after 9 months. The tumors had pushing margins, and grew in the form of anastomosing islands and sheets, comprising syncytial-appearing large cells with vesicular nuclei and prominent nucleoli. They were infiltrated by an appreciable number of small lymphocytes and plasma cells. Intratumoral amyloid globules were found in one tumor. In five patients, the tumor showed intraepithelial growth within the small bronchi; this could represent either the in-situ phase of the tumor or pagetoid spread into the bronchial epithelium. The neoplastic cells of all patients harbored Epstein-Barr virus (EBV) as demonstrated by in situ hybridization for EBV-encoded small nuclear RNAs. All eight Asian patients with pulmonary LELC previously reported in the literature similarly have been EBV-positive, whereas the four reported Caucasian patients all have been EBV-negative. CONCLUSION: Lymphoepithelioma-like carcinoma of lung occurring in Asians is an EBV-associated neoplasm; it also appears to occur at a higher frequency in Asians than Caucasians. It usually presents as a solitary subpleural nodule, and there is no strong association with cigarette smoking. Most patients have early stage disease at presentation. From the limited available data, the behavior of LELC of lung is highly variable, ranging from apparent curability by excision (particularly for localized disease) to highly aggressive, extensive disease at presentation.

Adult↗

Aggressive pleomorphic CD2+, CD3-, CD56+ lymphoma with t(5;9)(q31;q34) abnormality.

CD56-positive lymphoma is a recently described entity which is characterized by predominantly extranodal involvement and an aggressive clinical course. We report one such case with involvement of the bone marrow and spinal cord at presentation, and associated with reactive hemophagocytic syndrome. The lymphoma cells had a highly pleomorphic appearance which is uncommon in CD56-positive lymphoma. Cytogenetic studies revealed a t(5;9)(q31;q34) abnormality. Analysis of more cases is required to determine if this is a recurring chromosomal translocation characteristic of the group of aggressive CD56-positive lymphoma.

Antigens, CD↗