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Biomedical subjects

I S Luk

Publications and source records attributed to I S Luk.

At least 19 recordsLinked to original sources

Distinct clinical features associated with microsatellite instability in colorectal cancers of young patients.

The Hong Kong Chinese population has an unusually high incidence of colorectal cancer in the young, suggestive of hereditary susceptibility. To search for a genetic basis for this predisposition, we studied the incidence of microsatellite instability (MSI) in paraffin-embedded colectomy specimens of 124 young (<50 years old) Chinese colorectal cancer patients referred to the Hong Kong Hereditary Gastrointestinal Cancer Registry from 1995 to 1998. By medical record review and personal interview, we searched for distinct clinical features associated with the manifestation of MSI in this group of patients. For patients with MSI tumours, blood was taken for detection of germline mutation in 2 mismatch repair (MMR) genes. MSI was present in 33 tumours from 23 males and 10 females (26.6%). Ongoing mutation analysis has so far identified MMR gene mutations in 8 patients with MSI tumours. The incidence of MSI increased significantly with decreasing age at cancer diagnosis. For patients aged 30 to 49, MSI tumours were located mainly at the proximal colon. However, for exceptionally young patients (<30 years), MSI tumours tended to be at the distal large bowel. This observation suggested a differential activity of the MMR pathway in colorectal carcinogenesis in different age groups. On multivariate analysis, young age at cancer diagnosis, proximal tumour location, a strong family history of colorectal cancer, and a personal history of metachronous cancer were independent predictors for MSI status. This knowledge may have an impact on the management of young colorectal cancer patients and their families.

Adaptor Proteins, Signal Transducing↗

Metanephric adenofibroma: report of a case and review of the literature.

The recent recognition of a variety of pediatric renal tumors of different biologic behavior places an ever-increasing demand on the surgical pathologist for an accurate diagnosis. Although metanephric adenofibroma is one of the rarest benign renal tumors, the clinical importance of correctly diagnosing it cannot be overemphasized because it can potentially be mistaken as Wilms' tumor. We describe the clinical, radiologic, and pathologic features of a case of metanephric adenofibroma and discuss its differential diagnosis. The neoplasm was composed of two discrete components: a major fibroblastic element and a minor immature epithelial element. The latter formed a small nodule beneath the renal capsule, which could barely be detected by magnetic resonance imaging. This subcapsular nodule, however, was slightly soft and tan and was distinctly different from the white, whorled cut surface of the main tumor. It was formed by closely packed small immature epithelial cells in a slightly edematous background, which was histologically identical to metanephric adenoma and closely resembled epithelial Wilms' tumor. Unlike Wilms' tumor, however, the epithelial cells were very bland with no mitoses. The main bulk of the tumor was formed by spindle fibroblastic cells that were cytologically similar to the spindle cells in congenital mesoblastic nephroma. The tumor, however, was well demarcated without the irregular infiltrating edges of congenital mesoblastic nephroma. In contrast to the randomly distributed epithelial element throughout the stromal component in previous reported cases of metanephric adenofibroma, our finding of the exceedingly small and discrete epithelial component expands the known histologic spectrum of the disease. In addition, the presence of such minute epithelial nodule underscores the importance of diligent pathologic examination and careful sampling of tissue for histologic examination.

Adenofibroma↗

Interdigitating dendritic cell tumor of the testis: a novel testicular spindle cell neoplasm.

Interdigitating dendritic cell tumor is an extremely rare neoplasm that mainly occurs in lymph nodes. An example of such a tumor in the testis, a hitherto unreported site, is described. Grossly, the tumor was light tan with a uniform solid appearance, replacing virtually the entire testis. Microscopically, it was formed by whorls and fascicles of spindle cells intermingling with small lymphocytes. Such a histologic appearance can, however, mimic a wide variety of other tumors and tumor-like lesions, among which mesenchymal sarcoma, spindle cell carcinoma, follicular dendritic cell tumor, and inflammatory pseudotumor are the main differential diagnoses. Immunohistochemical studies showed that the spindle tumor cells were strongly and diffusely positive for S-100 protein and vimentin. They were also focally positive for CD68 and CD4, but were uniformly negative for leukocyte common antigen, CD1a, CD3, CD20, CD21, CD23, CD34, CD35, actin, desmin, HMB45, cytokeratins, and placental alkaline phosphatase. Ultrastructurally, the tumor cells possessed complex interdigitating cytoplasmic dendritic processes, with abundant rough endoplasmic reticulum and mitochondria in their cytoplasm. An in situ hybridization study for Epstein-Barr virus was negative. The pathologist should be aware of such an entity and consider it in the list of differential diagnoses for unusual spindle cell lesions with a significant background population of small lymphocytes. However, because of its nonspecific histologic appearance, additional immunohistochemical and electron microscopic studies are generally required for its definitive diagnosis.

Adolescent↗

Colorectal carcinoma in Hong Kong: epidemiology and genetic mutations.

The incidence of colorectal carcinoma is rising at an alarming pace in Asian urban societies such as Hong Kong. Detailed examination of the epidemiological pattern and genetic mutation of colorectal cancer in the Hong Kong Chinese population is overdue. We compared the reported age incidence of colorectal carcinoma in Hong Kong with that of Scotland and other countries. Hong Kong showed a much higher incidence of colorectal carcinoma among the young age groups. By comparison with other countries, this raised incidence among the young appeared to be related to southern Chinese societies. The recent dramatic rise in colorectal cancer in Hong Kong was largely attributable to an increase in the over 50 years age group, while the young incidence remained unchanged. We also defined the mutation spectrum of p53 and Ki-ras in 67 unselected cases by direct DNA sequencing. Interestingly, insertion/deletion mutations in p53 from colorectal carcinoma in Hong Kong showed a significantly higher frequency (17.2%) than the Scottish data (0%) and the world database (6.6%), although the overall frequency of p53 mutation (43%) in Hong Kong was similar to others. The high incidence of colorectal carcinoma in young people and the raised proportion of frameshift mutations in p53 encourage further search for a genetic basis for susceptibility to this disease in the Hong Kong Chinese population.

Adolescent↗

Clear cell carcinoid tumor of stomach. A variant mimicking gastric xanthelasma.

We report a rare case of gastric carcinoid composed entirely of clear cells with foamy cytoplasm. The patient was a 75-year-old Hispanic woman with atrophic fundic (oxyntic) gland gastritis leading to hypochlorhydria, secondary hypergastrinemia, endocrine cell hyperplasia, and multiple gastric carcinoids. Grossly, the lesion was yellow and distinct from other carcinoids in the gastric mucosa, mimicking gastric xanthelasma. Histologically, the tumor consisted of uniform clusters of polygonal cells with foamy cytoplasm. The formation of cell packets and abundant vascular stroma provided clues to its neuroendocrine nature. This was confirmed by immunoreactivity for chromogranin A and the demonstration of dense core granules ultrastructurally.

Aged↗

Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis.

Pituitary adenomas may cause significant difficulties in histological diagnosis when presenting in unusual sites either as extension from an intrasellar lesion or as ectopic tumor. Three such cases, involving the sinonasal tract are described herein, and the differential diagnoses are discussed. Two of them were invasive intrasellar macroadenomas that presented as unilateral nasal polyp, and one was an ectopic pituitary adenoma involving the sphenoid sinus. There was notable cellular atypia in two cases, with nuclear pleomorphism, giant cells, chromatin clumping, and distinct nucleoli, leading to serious consideration of the possibility of poorly differentiated carcinoma. In none of the cases was the diagnosis of pituitary adenoma suspected clinically. The clues to diagnosis were an endocrine growth pattern comprising tumor cells arranged in packets, ribbons, or rosettes, with prominent delicate vascularized stroma; a high index of suspicion; and immunohistochemical showing of neuroendocrine markers and pituitary hormones in the tumor cells. A correct diagnosis is important because in contrast to neuroendocrine carcinoma as a whole or to poorly differentiated carcinoma, pituitary neoplasms have a much more favorable prognosis and a low metastatic potential.

Adenoma↗

Lymphoepithelioma-like carcinoma of the thyroid gland: lack of evidence of association with Epstein-Barr virus.

Lymphoepithelioma-like carcinomas (LELC) occurring in sites derived from the primitive pharynx and foregut have been reported to show a strong association with Epstein-Barr virus (EBV), especially in the Oriental population. Primary lymphoepithelioma-like carcinoma of the thyroid is an extremely rare neoplasm which has been known under many different names, such as intrathyroidal epithelial thymoma, primary thyroid thymoma, carcinoma of the thyroid showing thymoma-like features, and carcinoma showing thymus-like differentiation (CASTLE). We report one such case in a Chinese woman, whose tumor was negative for EBV by in situ hybridization technique. This finding suggests that LELC of the thyroid may be biologically different from other LELCs, and that detection of EBV may aid in diagnosis when the LELC presents initially in lymph nodes or other metastatic sites.

Adult↗

Lymphoepithelioma-like carcinoma of the skin.

The histopathological findings of two cases of primary lymphoepithelioma-like carcinoma (LELC) of the skin occurring in two elderly Chinese individuals are presented. Microscopically, they were well circumscribed and were composed of irregular nests of malignant epithelial cells in a background of reactive lymphoid cells including mature plasma cells. A focus of epithelial dysplasia was noted in the adjacent epidermis in one case, suggesting that the LELC might have originated from the overlying epidermis. The epithelial nature of the tumors was confirmed by cytokeratin staining. In situ hybridization for Epstein-Barr virus-encoded RNA (EBER) showed that the tumor cells were uniformly negative, although positive signals were detected in scattered background lymphocytes in case 1. Our results confirm the previous observation that LELC of skin is not related to Epstein-Barr virus, even in Chinese subjects. Nevertheless, such negative findings may prove to be of diagnostic value in excluding the alternative more common diagnosis of metastatic nasopharyngeal carcinoma, which is uniformly positive for EBER.

Aged↗

Inflammatory cell-rich gastrointestinal autonomic nerve tumor. An expansion of its histologic spectrum.

Gastrointestinal autonomic nerve (GAN) tumor is an uncommon neoplasm of the gastrointestinal tract. Its histologic appearance is similar to other gastrointestinal stromal tumors. Ultrastructural demonstration of neural differentiation is required for its definitive diagnosis. Recently, we encountered two examples of GAN tumor that occurred in the body of the stomach and the cervical esophagus; the latter site has never been reported previously. These tumors showed unequivocal evidence of neural differentiation ultrastructurally, confirming the diagnosis of GAN tumor. Histologically, they were composed of swirling fascicles of spindle cells as well as a minor component of epithelioid cells, similar to that described previously. In addition, a cuff of lymphoid cells was noted at the peripheral part of both tumors and a scattering of mature plasma cells, lymphocytes, and foam cells was intermingled with the tumor cells. Such histologic features have not been described hitherto and can potentially be misinterpreted as features of inflammatory pseudotumor, inflammatory fibrosarcoma, or follicular dendritic cell tumor. There is a lack of CD34 expression in both tumors, but it would be premature to draw any conclusions about the potential usefulness of this observation.

Adult↗

Germ cell tumour as a diagnostic pitfall of metastatic carcinoma.

AIM: Testicular germ cell tumours may present as metastases in cervical lymph nodes, yet the primary tumours remain clinically occult. The aim of the study is to alert pathologists and clinicians to this uncommon but important presentation and highlight the clues and the diagnostic adjuncts to its correct diagnosis. METHODS: The clinical, cytological, histological, and immunohistochemical features of two patients with germ cell tumour initially presenting as cervical lymphadenopathy were described and analysed. RESULTS: Both patients were young adult males, who were found to have metastatic undifferentiated carcinoma on fine needle aspiration of the enlarged cervical lymph nodes. The tumour cells in both cases were positive for placental alkaline phosphatase (PLAP) and negative for epithelial membrane antigen (EMA). CONCLUSIONS: Clinicians and pathologists should be aware of the possibility of germ cell tumour when encountering a young adult male with metastatic poorly differentiated carcinoma. Positivity for PLAP and negativity for EMA are helpful adjuncts in arriving at the correct diagnosis.

Adult↗

Paclitaxel-induced cardiotoxicity. An ultrastructural study.

The ultrastructural appearance of the myocardium in a fatal case of paclitaxel-induced cardiotoxicity is reported, which includes swelling of the sarcoplasmic reticulum, loss of myofibrils, and accumulation of lipofuscin as well as laminated myelinoid figures. Such changes are very similar to those seen in anthracycline-induced cardiotoxicity and may suggest a pathogenetic final common pathway. While endomyocardial biopsy is a recognized means of monitoring anthracycline-induced cardiotoxicity, whether more liberal use of endomyocardial biopsy can prevent fatal cases of paclitaxel-induced cardiotoxicity needs to be further assessed.

Antineoplastic Agents, Phytogenic↗

Melanotic oncocytic metaplasia of the nasopharynx.

Two cases of melanotic oncocytic metaplasia occurring in the nasopharynx are reported. One presented with serous otitis media and the other with tinnitus. Nasoscopic examination revealed a small brown nodule obstructing the Eustachian tube in both cases. While oncocytic metaplasia of the nasopharynx is not too uncommon, melanin pigmentation of the nasal or nasopharyngeal mucosa is very rare. To our knowledge, their combination has not been described.

Aged↗

The effect of nicotine and its interaction with carbon tetrachloride in the rat liver.

In order to study the effects of nicotine on liver, groups of rats were given nicotine doses that simulated those seen in chronic smoking (54 and 108 mumol/l of nicotine) for 10 days. A subgroup was also given a single subcutaneous injection of 6 g/kg of carbon tetrachloride (CCl4) shortly before the animals of the group were killed. Histology demonstrated a significant hepatotoxic effect in the group receiving 108 mumol/l of nicotine when compared with the control group in the form of fatty change, focal or confluent necrosis and dark-cell change. The effects in pregnant rats were less severe. Carbon tetrachloride alone induced significant fatty change and focal necrosis in non-pregnant rats but not in pregnant rats. Nicotine also aggravated the CCl4 induced pathological changes in livers of both non-pregnant and pregnant animals. Thus nicotine alone, when given at a concentration of 108 mumol/l, exerted hepatotoxic effects; the alkaloid also aggravated the hepatotoxicity of CCl4. Pregnant rats were more resistant to the hepatotoxic effects produced by nicotine and CCl4.

Animals↗

In situ detection of Epstein-Barr virus in gastric and colorectal adenocarcinomas.

The association of Epstein-Barr virus (EBV) with lymphoepithelioma-like carcinoma in the nasopharynx, which is common in Chinese from the southern region, is well established. Recently, EBV has also been found to be associated with lymphoepithelioma-like carcinomas (LELCs) and carcinomas with prominent lymphoid infiltrates in the stomach. We investigated for the presence of EBV in 74 cases of gastric adenocarcinoma and 36 cases of colorectal adenocarcinoma from Chinese patients by in situ hybridization (ISH) using an antisense EBER probe. In seven cases (9.5%) of gastric carcinoma, EBER was highly expressed in the adenocarcinoma cells and metastatic tumor cells in regional lymph nodes. In all these cases, the normal gastric epithelium was EBV negative. None of the colorectal carcinomas showed a positive signal. Isolated positive lymphoid cells were frequently found in both tumors. Of the seven positive cases, only one was LELC, and the others were conventional adenocarcinomas of the intestinal type. Five showed expression of the viral RNA in all tumor cells as well as the surrounding dysplastic epithelium. Interestingly, the sixth case showed distinct negative islands of dysplastic glands adjacent to strongly positive dysplastic glands and invasive carcinoma cells. This pattern of positivity, together with negative normal gastric epithelium and positive metastatic tumor, suggested that EBV infection occurred in the dysplastic phase and that an apparent growth advantage was conferred by the EBV infection.

Adenocarcinoma↗

Influence of chronic nicotine intake and acute ethanol challenge on gastric mucus level and blood flow in rabbits.

The effects of nicotine pretreatment on ethanol-induced gastric mucosal lesions and changes of gastric mucosal mucus levels and blood flow (GBF) were studied in anaesthetized rabbits. Nicotine treatment 25 or 50 micrograms/ml drinking water did not affect the volume of water consumption during the 10-day experimental period. It did not produce gastric mucosal lesions or affect the superficial adherent mucus content. The length of mucus-containing cells and the basal GBF were also unaffected. Intragastric administration of absolute ethanol reduced GBF, this effect was not altered by nicotine. However, the alkaloid potentiated the ulcerogenic actions of ethanol both on lesion formation and mucus depletion evoked by graded oral doses of ethanol (50 or 100%, v/v). Ultrastructurally, the mucous cells were more degenerated in the animals co-treated with nicotine and ethanol. It is concluded that reductions of mucus-containing cells and adherent mucus on the gastric mucosa are likely to be the contributory factors involved in the aggravating action of nicotine on ethanol-induced gastric mucosal lesions in rabbits.

Animals↗