An analysis of 1000 consecutive, adequate renal biopsies from patients of the University Hospital Kuala Lumpur between 1982 and 1991 revealed: minimal change nephritis (20.7%), focal glomerulosclerosis (2.9%), proliferative glomerulonephritides (16.0%), membranous glomerulonephritis (5.5%), IgA nephropathy (18.5%), lupus nephritis (24.9%), end stage nephropathy (3.1%) and others (8.4%). Compared with the previous decade, IgA nephropathy has emerged as a common entity. Lupus nephritis forms the largest diagnostic entity and is probably related to the selected referral of SLE patients to this hospital.
Congo red screening of routine biopsies at the University Hospital Kuala Lumpur revealed the following categories of amyloidosis: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). Unlike in the West, AA amyloidosis in this population was usually secondary to leprosy or tuberculosis. Liver involvement in AL amyloidosis was shown to exhibit a sinusoidal pattern and differed from the vascular pattern of AA amyloidosis. Within the category of AA amyloidosis, there were two patterns of renal involvement--glomerular and vascular, with the glomerular pattern carrying a more ominous clinical picture. Notable among the localized amyloidoses were isolated atrial amyloidosis complicating chronic rheumatic heart disease, intratumour amyloidosis within nasopharyngeal carcinomas and dystrophic amyloidosis which occurred in fibrotic tissues.
Congo red screening of 211 consecutive cardiac biopsy specimens obtained during cardiac surgery from 167 patients revealed 26 (16%) instances of isolated atrial amyloidosis (IAA). The ages of IAA-positive patients ranged from 25 to 52 years (mean age, 39 years). Twenty-three (88%) IAA-positive biopsy specimens were from patients with chronic rheumatic heart disease (CRHD) while three (12%) were from patients with an atrial septal defect (ASD). The prevalence of IAA in the CRHD patients was 23%, appreciably higher than that in the ASD patients (15%) and in other patients with atrial biopsies. The prevalence of IAA in both CRHD and ASD patients was significantly higher (P < .001) than in controls. Controls consisted of 247 healthy adults who were autopsied after traumatic deaths, with an age range of 18 to 89 years (mean age, 38 years). Only seven (3%) control subjects were IAA positive; all were over 40 years of age. Isolated atrial amyloidosis deposits were permanganate resistant and immunohistochemically positive for human amyloid P (AP) protein and negative for human amyloid-associated (AA) protein and immunoglobulin light chains. They were observed as fine congophilic and birefringent deposits in intramyocardial vessel walls, along the myocardial sarcolemma, and in the subendocardium. There was associated myocyte hypertrophy but no atrophy. Electron microscopy demonstrated typical nonbranching amyloid fibrils. It is postulated that stretching of the atria in chronic heart disease results in a raised prevalence of IAA. Recent reports that IAA contains atrial natriuretic peptide, a polypeptide hormone product of atrial myocytes, supports this view.
Vulvar ulceration is a rare manifestation of histiocytosis X. A 13-year-old girl had a nonhealing vulvar ulcer for 1 year. She had been in remission from histiocytosis X and the ulcer was not recognised as a sign of disease recurrence until tissue biopsy was obtained for histopathological and immunohistochemical studies. This article stresses the importance of establishing an accurate diagnosis when chronic vulvar ulcers are encountered and reviews the literature on this uncommon presentation of histiocytosis X.
A serological investigation for human T cell leukemia virus I (HTLV-I) infection was carried out at the University Hospital, Kuala Lumpur. A total of 626 sera from a non-patient population and 1,038 sera from unselected in-patients were screened for HTLV-I antibodies using an enzyme-linked immunosorbent assay (ELISA). 27/1664 (1.6%) were found to be reactive. However, on Western blotting, only 2 sera were confirmed positive, both showing reactions for the major core (p19 and p24) and the envelope (gp46) proteins. Both of the serum samples were from unselected hospital patients. Most of the remaining sera which were reactive on screening showed indeterminate results on Western blotting. These were further tested by radioimmunoprecipitation assay (RIPA) and none of these sera gave a positive reaction. Therefore, only 2/1038 (0.19%) unselected patients could be confirmed to have antibodies to HTLV-I. None of the normal individuals screened showed a positive Western blot result. Our data indicate that HTLV-I infection is present in our population, but at a low prevalence rate.
Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.
A five-month-old male baby presented with an abdominal mass which was found on computerised tomography (CT) to be involving the left kidney. Nephrectomy and histopathological study showed morphological featues of a malignant rhabdoid tumour. The tumour cells stained strongly for cytokeratin and epithelial membrane antigen and less intensely for vimentin. Electron microscopy revealed concentric whorled arrays of intermediate filaments within the tumour cell cytoplasm. The child was put on post-operative chemotherapy and radiotherapy but developed bilateral lung metastases and died three months after surgery.
The use of the colloidal-gold technique in electron microscopy immunocytochemistry has provided important information on the in situ localisation of intracellular antigens. We have developed a post-embedding technique for prolactin localisation on resin-embedded human pituitary tissue sections by the use of the protein-A gold conjugate. Human pituitary tissue obtained at autopsy was processed for electron microscopical study without post-osmication and then embedded in Epon. The indirect immunoperoxidase method was used for light microscopical targetting of lactotroph cells for subsequent electron microscopical antigen localisation. Ultra-thin sections were labelled with human anti-human prolactin followed by protein-A gold conjugate. Specific labelling was observed over secretory granules with a density of 15-30 particles per granule, as determined by the Quantimet 570 image analysis system. This technique provides a means of studying the pathophysiology of hormonal secretion at ultrastructural level and can be a useful tool in diagnostic and research investigations.
A review of consecutive biopsies of adnexal tumours from 112 patients, received by the Department of Pathology, University of Malaya, over a 13-year period was undertaken. The age range of the patients was from 1 to 84 years, with a mean of 29.8 years. Thirty-three (32%) patients were under 20 years of age. There were 68 females with a male to female ratio of 1.0:1.5. In 105 cases (93.7%), the neoplasm was solitary. The tumour measured less than 2 cm in the largest dimension in 103 cases (92%). The common sites of occurrence were the head and neck region (59%) and extremities (25%). Neoplasms of hair follicle origin accounted for 63.4% (71 cases) of all lesions. Intra-tumour deposition of amyloid was noted in one of the 14 cases of trichoepithelioma.
Although most anatomical pathologists have encountered breast lesions with the composite histological features of fibroadenoma (FA) and fibrocystic change (FC), referred to as fibroadenomatosis or fibroadenomatoid mastopathy (FAM), little is known about its prevalence or clinico-pathological significance. In a retrospective histological review of 400 consecutive breast lesions, among both East and West Malaysians, coded either as FA or FC in the files of the Department of Pathology, University of Malaya, we found 45 (11.3%) cases of FAM. Typically, FAM lesions showed fibroadenomatoid foci in a background of fibrocystic change. The finding of FAM among lesions coded as FC was higher (18.5%) than among FA (4%). The mean age of patients with FAM (32.1 years) was similar to FC (35.1 years) but significantly older than that of FA (26.1 years). The notion that FA and FC are lesions at two ends of a spectrum of growth disorder of breast related to oestrogen-progesterone interplay, and that FAM occupies a position intermediate between the two, may explain its morphological and age patterns, but remains speculative. It is hoped that increasing awareness of this condition will lead to better understanding of breast pathophysiology. Nevertheless, until its biological nature, histogenesis and malignant potential are more clearly understood, defining FAM as a distinct form of breast disease may not be meaningful to patient management.
Congo red screening of tumour material examined at the Department of Pathology, University of Malaya revealed intratumour deposits of amyloid in 12% of nasopharyngeal carcinomas, 66% of basal cell carcinomas, 100% of medullary carcinomas of the thyroid, 56% of islet cell tumours of the pancreas, 1 out of 16 carcinoids and 1 out of 100 thyroid adenomas. All the deposits were permanganate resistant and did not contain AA protein, indicating that what was encountered was not secondary amyloid. The deposits showed variable staining for immunoglobulin light chains and amyloid P component with a standard peroxidase antiperoxidase method. The possibility that intratumour amyloid has a neoplastic origin is discussed.
Thirty-one patients with systemic lupus erythematosus had membranous lupus nephropathy (MLN). They were divided into two groups. Group I consisted of 13 patients who had pure MLN but the patients in Group 2 had segmental proliferation in up to 35 per cent of their glomeruli. The rest of the glomeruli had purely membranous change. The patients of Group 2 were no different from the other MLN patients in terms of age, sex and race. The extrarenal disease in both groups was extensive and severe. The renal disease was usually associated with the nephrotic syndrome or oedema but was asymptomatic throughout in one patient. Both renal and extrarenal features responded to treatment initially but relapses were frequent and often severe. Relapses often occurred as treatment was discontinued or medication reduced. Survival at six years in Group I was 62 per cent and in Group 2 was 50 per cent. Only one patient died with renal failure although five patients had impaired renal function at death. The chief causes of death were disease of the central nervous system and infection.
Nineteen out of 121 consecutive cardiac biopsies from 107 patients were found to contain amyloid deposits on routine Congo red screening. Seventeen were left atrial appendages removed during mitral valvotomy for chronic rheumatic mitral valve disease while the remaining two were right atrial appendages excised during surgical repair of atrial septal defects. The distribution of amyloid deposits within the atria and their tinctorial characteristics are described. The high prevalence of atrial amyloidosis observed could not be attributed to generalized or senile amyloidosis. The possibility that this is a distinctive localized form of amyloidosis secondary to chronic heart disease is discussed.
Congo-red screening demonstrated intratumor deposits of amyloid in 35 of 53 unselected cases of basal cell carcinoma. Male subjects had a higher amyloid positivity rate than female subjects. The amyloid deposits were permanganate-resistant and located in the stroma between clumps of tumor cells, as well as abutting the advancing front of the neoplasm. Solar elastosis was often observed in the overlying and adjacent subepidermis. The relationship between amyloid positivity and the different histological subtypes of basal cell carcinoma, tumor ulceration, and density of the lymphoplasmacytic stromal infiltrate were also studied. The possibility that amyloid originates from the tumor cells and is a result of tumor apoptosis (degeneration) is discussed.
In West Malaysia, hepatocellular carcinoma (HCC) is common in the Chinese and in the members of the Senoi aboriginal tribe, two racial groups with diametrically opposite life-styles. Certain fundamental differences exist between the liver tumors in the two races. In the Senoi, the tumor occurs in a younger age group and there is a greater male preponderance than in the Chinese. There is also a very close relationship between hepatitis B virus infection, chronic active hepatitis, cirrhosis, liver cell dysplasia, and HCC in the Senoi and the tumors generally present as multiple nodules studding both lobes of the liver. In the Chinese, although a relationship between hepatitis B virus infection, HCC, and cirrhosis exists, this association is not as strong as in the Senoi and the tumors are generally large and solitary. The data suggest that, although the hepatitis B virus is probably an important oncogenic agent in both racial groups, there may be a difference in the pathogenesis of HCC in the two races.
Adequately biopsied renal tissue received in the Department of Pathology, University Hospital, Kuala Lumpur from 1,000 consecutive Malaysian patients during an eleven year period between 1970 and 1981 was reviewed. The youngest patient was 6 days old and the oldest 80 years. Both sexes were equally represented. The majority of the patients were Chinese (71%) with Malays and Indians comprising most of the remainder. Over half the patients (50.4%) presented with the nephrotic syndrome. Other modes of presentation included systemic lupus erythematosus, proteinuria and haematuria separately or in combination and hypertension. Minimal change (25.7%) and proliferative glomerulonephritis (24.8%) were present in about equal numbers and together accounted for over half of the cases (50.5%). Lupus nephritis was the third most common diagnosis (18.4%). In addition, there were patients with focal glomerulonephritis (5.4%), membranous glomerulonephritis (5.5%), Berger's disease (5.8%), amyloidosis (0.6%) and end stage renal disease (4.0%).
Seventeen consecutive patients with dystrophic amyloidosis are reported here (eight Chinese, three Indian, three Iban, two Malay and one Caucasian). Ten were females and seven males, with ages ranging from 12 to 80 years (mean of 48 years). Five instances of dystrophic amyloidosis occurred in areas of tissue damage in the cardiovascular system, including fibrotic cardiac valves and an atheromatous plaque. Three occurred in osteoarthritic joint tissue. Of note were three occurrences in endometriotic cyst walls, four in the fibrotic walls of epidermal cysts, one in a hernial sac and one at the edge of a skin ulcer. All deposits were congophilic and exhibited green-birefringence and permanganate-resistance. Immunohistochemistry did not reveal reactivity for AA protein or immunoglobulin lambda or kappa light-chains. AP protein was detected in 35% of cases. Our results show that, besides the usual sites of osteoarthritic joints and damaged heart valves, dystrophic amyloidosis can complicate other areas of chronic tissue damage and fibrosis such as walls of cysts and ulcers. While the pathogenesis and biochemical nature remain unresolved, immunohistochemistry indicates that neither AA nor AL proteins are present in the deposits, and suggests that a different amyloid protein is involved.
Congo red screening of 27,052 routine biopsy specimens from 22,827 patients over a 5 1/2-year period in the Department of Pathology, University of Malaya detected 186 cases of amyloidosis. The categories of amyloidosis encountered and their prevalences in relation to each other were: systemic AL (5.9%); systemic AA (3.2%); isolated atrial (14%); primary localized cutaneous (7.5%); other primary localized deposits (3.2%); localized intratumour (58%); and dystrophic (8.6%). A third of patients with systemic AL amyloidosis had coexistent immunocyte abnormality. The commonest underlying pathology for systemic AA amyloidosis was leprosy. Notable among the types of localized amyloidosis revealed by this study were isolated atrial amyloidosis, which appeared to complicate chronic rheumatic heart disease, and intratumour amyloidosis complicating nasopharyngeal carcinoma. Other tumours in which amyloid deposits were observed included basal cell carcinoma, islet cell tumour and medullary carcinoma of the thyroid. Dystrophic amyloidosis was observed in fibrotic tissues, such as damaged cardiac valves and osteoarthritic joints. Heredofamilial amyloidosis, senile systemic amyloidosis and degenerative cerebral amyloidosis were notably absent from this study.