Oculopharyngeal muscular dystrophy: underdiagnosed disease in Hong Kong.

Despite the advances in the understanding of the molecular basis for oculopharyngeal muscular dystrophy in the last decade, it remains an underdiagnosed disease, especially among the Chinese. In the presence of a positive family history and late-onset ptosis, dysphagia, and proximal muscle weakness (its cardinal features), we suggest that PABPN1 gene analysis should be the first-line investigation to rule out this condition. Muscle biopsy can be reserved for atypical cases. Non-specific mitochondrial changes in the muscle specimens of these patients should be appreciated, so as to avoid diagnostic confusion. It is hoped that greater awareness among medical professionals and judicious use of PABPN1 gene analysis will lead to earlier diagnosis, better management, and avoidance of unnecessary invasive investigations of affected patients.

Polymorphic reticulosis and conventional lymphomas of the nose and upper aerodigestive tract: a clinicopathologic study of 70 cases, and immunophenotypic studies of 16 cases.

Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions.

Chromosomal 11 alterations in non-small-cell lung carcinomas in Hong Kong.

We examined 60 non-small-cell lung cancer (NSCLC) patients for evidence of genetic alterations on chromosome 11 with nine polymorphic markers by Southern blot and microsatellite marker analysis. These analyses detected genetic alterations at both the 11p and 11q arms. At the 11p15 Ha-ras locus, the loss of heterozygosity (LOH) occurred in three out of 11 (27.3%) of the informative cases; at the 11p11-q12 D11S149 locus, the LOH occurred in two out of nine (22.2%) of the informative cases; and at the 11q13 INT-2 locus, the LOH occurred in four out of 18 (22.2%) of the informative cases. Microsatellite markers in the 11q12-q13 region revealed genetic alterations for PYGM in eight out of 54 (14.8%) of the specimens studied and 10 out of 55 (18.2%) of the specimens for the INT-2 marker. The data suggest genetic alterations occur in some of the lung cancer patients in both the 11p and 11q regions.

The angiopoietins, tie2 and vascular endothelial growth factor are differentially expressed in the transformation of normal lung to non-small cell lung carcinomas.

The successful establishment of angiogenesis depends on a complex process of endothelial proliferation and organization. The angiopoietins (Ang-1 and Ang-2) and Tie2 ligand-receptor system is essential for the regulation of vascular maturation and stability during embryonic development. Together with the vascular endothelial growth factor (VEGF)-mediated pathway, they have been implicated in the control of normal physiological angiogenesis. We investigated their potential role and interaction in the development of lung cancers by comparing the expression pattern and inter-relationship of Ang-1 and 2, Tie2 and VEGF levels in 28 pairs of primary non-small cell lung cancers (NSCLC) and normal lung. Using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in-situ hybridization (ISH), we showed that in NSCLC, there was significantly up-regulated VEGF expression by the tumour cells and an increased intensity of Ang-2 expression in the tumour vessels. The number of Ang-2-expressing vessels also correlated with the grades of tumour cell expression of VEGF. On the other hand, normal lung expressed constitutively high and correlated levels of Ang-1 and Tie2, which were significantly reduced in the carcinomas. The findings suggested a role of the Ang-1/Tie2 pathway in the maintenance of the complex vasculature in normal lung, while collaborative activities between the Ang-2 and VEGF pathways might be important in promoting tumour angiogenesis in NSCLC.

Comparative study of automated versus manual extraction of DNA from clinical specimens.

The authors have compared an automated method for DNA extraction with an established manual method using routine clinical specimens. The purity, yield, and quality of the extracted DNA was assessed by ultraviolet absorbency measurements, gel electrophoresis, and DNA probe hybridization. The automated DNA extractor can provide high molecular weight DNA equivalent in purity, yield, and quality to that obtained by the manual method with substantial savings in technologist time and overall costs associated with the procedure.

Value of routine histopathological examination of appendices in Hong Kong.

A retrospective study of the histopathological findings of more than 11,443 appendices submitted as surgical specimens over 14 years was performed in this department. In most cases routine histopathological examination added little clinically important information to other clinical and operative gross findings, but a variety of interesting and uncommon lesions were identified. In 85 cases clinically important pathological findings were first discovered on routine histopathological examination. These included enterobiasis, schistosomiasis, mucocele, trichuriasis, tuberculosis, ascariasis, endometriosis, mucinous cystadenoma, granuloma, carcinoid tumour, neuroma, clonorchiasis, primary adenocarcinoma and secondary carcinoma.

Immunologic studies in patients with premature ovarian failure.

Tests for a range of autoantibodies, and counts of lymphocytes, B cells, T cells, and T cell subsets were performed in 45 Chinese patients with premature ovarian failure and 45 age-matched normal control subjects. Eight patients (18%) were positive for at least one autoantibody. Only one patient was positive for antiovarian antibody. Patients with autoantibodies had a significantly higher percentage of circulating B cells. The lymphocyte, T cell, CD4+, and CD8+ counts in patients with premature ovarian failure were significantly higher than those in the control group, but the CD4:CD8 ratio was significantly lower in women with premature ovarian failure. There was a significant negative correlation between plasma estradiol levels and CD8+ counts, and a significant positive correlation between plasma estradiol levels and CD4:CD8 ratios. The changes in lymphocytes and lymphocyte subpopulations in premature ovarian failure may be due to estrogen deficiency.

p53 intron 2 genotypes detected in normal specimens and lung carcinomas in Hong Kong.

Previous studies suggest that the polymorphic p53 intron 2 displays a high frequency of mutations, occurring with different frequencies in tumor tissues versus peripheral blood of lung cancer patients as compared to healthy individuals. We evaluated the significance of these polymorphisms and mutations utilizing matched triple specimens from the lung tumor, normal lung tissue, and peripheral blood of cancer patients. Identical genotypes were observed in normal tissues and blood, while 4 mutations were observed in tumors. The A1 allelic frequency was increased in the adenocarcinoma tissues as compared to normal tissues. Two p53 exon 2 polymorphisms were detected, appearing with equal frequencies among cancer patients and healthy individuals. The p53 intron 2 polymorphic locus is a hot spot for mutations in Hong Kong lung cancer patients.

Observer variability in microcomputer-assisted morphometric study of nuclear parameters.

To evaluate observer variability during microcomputer-assisted planimetry, nuclear features (area, perimeter, and form factor) were studied in a case of malignant lymphoma. Tissue fixed in glutaraldehyde, embedded in plastic and sectioned at 1 micron was studied using a Zeiss Kontron IBAS 2000 image analysis system. Manual tracing of nuclear outline was performed to obtain the parameters. Both interindividual and intraindividual reproducibilities were evaluated, the former among 8 observers and the latter by the observers repeating the measurements. With the present technique, intraindividual reproducibility was high and correlation was excellent for area, perimeter and form factor measurements. A high degree of interindividual inconsistency was demonstrated for all parameters. Interindividual correlation was poor for form factor. It is concluded that poor interindividual reproducibility even when the objective method of morphometry is used may be a significant problem in tissue investigations, especially when results from different laboratories are being compared.

Significant changes in the distribution of histologic types of lung cancer in Hong Kong.

A retrospective study of 2385 Chinese patients with proven carcinoma of lung was performed. The autopsy incidence was 3.3%. Most patients presented in the seventh decade. The age distribution was 24-94 yrs with a mean age of 63 yrs. The four major histologic types (37.3% of adenocarcinoma, 33.4% of squamous cell carcinoma, 13.7% of small cell carcinoma and 14.7% of large cell carcinoma) accounted for 99.1% of the cases. Among the four, adenocarcinoma was the most common histologic type, particularly for females and there has been an increase in the incidence of adenocarcinoma in recent years. This trend has been observed and reported in many affluent countries. In Hong Kong, the frequency of adenocarcinoma among Chinese females is exceptionally high.

Recurrent aortic valve prosthesis dehiscence secondary to aortoarteritis: three case reports and literature review.

We report three young Chinese male patients who underwent aortic valve replacement for severe aortic regurgitation of subacute onset, complicated by recurrent dehiscence of the aortic valve prosthesis, due to aortitis. One of the three patients underwent aortic valve replacement three times and progression of the prosthesis dehiscence was arrested with the use of corticosteroids. A review of the literature on the prognosis and treatment of aortoarteritis with particular reference to the management of recurrent valvular dehiscence is discussed.

Nonsecretory immunoglobulin-derived amyloidosis of the heart: diagnosis by immunohistochemistry of the endomyocardium.

Primary amyloid light chain (AL) amyloidosis of the heart is a rare cause of congestive heart failure. Approximately 15% of patients with primary AL amyloidosis demonstrate no monoclonal proteins on serum or urine immunoelectrophoresis:(so-called nonsecretory immunoglobulin-derived amyloidosis). The histologic findings of endomyocardial biopsy from these patients may be indistinguishable from those with senile cardiac amyloidosis. However, the AL type may respond favourably to chemotherapy while the latter type does not. The prognosis is also better in the senile cardiac amyloid type. The precise diagnosis in the present case was made by applying immunohistochemical techniques on cardiac tissues.

Sclerosing hemangioma of lung: A close cytologic mimicker of pulmonary adenocarcinoma.

We report the fine-needle aspiration biopsy findings of sclerosing hemangioma of lung occurring in a 40-yr-old Chinese woman. Cytologically, there were hyalinized stromal tissue fragments admixed with clusters of nondescript mononuclear tumor cells. Scattered foamy macrophages and red blood cells were also noted in the background. Focal papillary and acinar configurations were seen. However, some of the epithelial cells show nuclear pleomorphism with nuclear hyperchromasia, prominent nucleoli, and occasional intranuclear inclusions. Mitotic activity was virtually absent. The cytologic atypia present may result in misdiagnosis of well-differentiated pulmonary adenocarcinoma, especially bronchioloalveolar carcinoma. Recognition of the subtle cytologic differences, together with cell block examination, immunocytochemistry, and proper clinicoradiologic correlation, is crucial for an accurate preoperative diagnosis.

A new model of AA-amyloidosis induced by oral pristane in BALB/c mice.

Fifteen male BALB/c mice were given six intermittent oral doses of O.I. ml pristane (2, 6, 10, 14 tetramethylpentadecane) within a period of 9 weeks. Fifteen mice receiving tap water using the same schedule formed the control group. Amyloidosis was first detected in the spleen of a mouse which had died 33 weeks after the first dose and 24 weeks after the last. All six mice which were subsequently autopsied 34-51 weeks after the first dose also showed amyloidosis involving liver and spleen. The most extensive tissue deposits were seen at 37-38 weeks whereas the older mice showed predominantly chronic renal lesions with papillary necrosis, scars and cystic change. Electron microscopy confirmed the identity of the amyloid fibrils and the presence of globular stellate amyloid 'bodies' in liver and spleen. The amyloid deposits were shown to be made up of AA (amyloid associated) protein using an indirect immunoperoxidase method and a monoclonal rat anti-murine AA protein antibody. We did not find any plasmacytomas or increased numbers of plasma cells in the bone marrow. None of the control mice developed amyloidosis. This new experimental model promises to provide a means of studying several aspects of secondary amyloidosis which may be relevant to the clinical situation.

Percutaneous transthoracic needle biopsies in the rapid diagnosis of pulmonary tuberculosis.

From May, 1987, to December, 1990, 173 percutaneous transthoracic needle biopsies (PTNB) using a 19-gauge spinal needle under uniplane fluoroscopic guidance were performed in 160 patients. Thirty-one patients had a final diagnosis of pulmonary tuberculosis. These patients with tuberculosis underwent a total of 35 biopsies. Twenty of 35 (57%) had definite histologic features of tuberculosis with stainable acid-fast bacilli, 4/35 (11.5%) had granulomatous or caseous lesion consistent with tuberculosis, and 11/35 had nonspecific inflammatory changes. When results were matched with the sputum culture results, 15/35 specimens (43%) provided the exclusive means of diagnosis of tuberculosis. Five of 35 (14%) patients developed postbiopsy pneumothoraces. The overall acceptance by patients was good. This report indicates the potential usefulness of PTNB in the rapid diagnosis of selected cases of suspected pulmonary tuberculosis. The yield was comparable to fiberoptic bronchoscopy, currently commonly used in the diagnosis of pulmonary mycobacterial disease. The procedure was noted for its simplicity.

Clonal Epstein-Barr virus genome in T-cell-rich lymphomas of B or probable B lineage.

Seventeen nodal lymphomas (originally diagnosed as T-cell lymphomas based on histological features and immunohistochemical staining results) were studied for the presence of Epstein-Barr virus (EBV) genome, and the results correlated with immunoglobulin and T-cell receptor gene rearrangement analyses performed on the same tissue samples. All four EBV positive cases had clonal rearrangement of the joining region of the immunoglobulin heavy chain (IgJH) gene without clonal T-cell receptor beta-chain (TCR beta) gene rearrangement. Of these, two cases also showed clonally rearranged light chain gene, and they were reclassified as T-cell rich B-cell lymphomas (TRBL). The other two cases lacked clonal kappa or lambda light chain rearrangement and they were reclassified as T-cell rich lymphomas of probable B lineage, based on their isolated IgJH clonal rearrangement. These B-cell lymphomas may be easily misdiagnosed as T-cell lymphomas owing to the presence of an abundant reactive T-cell infiltrate masking the tumor population. The florid T-cell reaction may represent an unusual host response towards a clonal proliferation of EBV bearing B cells.

A case of malignant pleural mesothelioma with unexpectedly long survival without active treatment.

Malignant pleural mesothelioma (MPM) is a disease with a very dismal prognosis. A median survival of 6-18 months is expected in most patients. Rarely, patients may survive unexpectedly long. We present the case of a patient with MPM who survived for more than 10 years without active treatment after the disease had been diagnosed.

Antineutrophil cytoplasmic antibody and gallium lung scintiscan in usual interstitial pneumonitis.

A 2 year old Chinese boy was reported in whom there was an association between usual interstitial pneumonitis (UIP) and serum antineutrophil cytoplasmic antibody of the classical cytoplasmic type (cANCA). The concentration of cANCA reflected disease activity and decreased during a 6-week course of prednisolone. The gallium lung scintiscan index correlated with his disease activity. Both the serum cANCA concentration and the gallium lung scan could be used to monitor responses to treatment in this patient with UIP.