A comparative analysis of coronary adventitial T-lymphocytes--an autopsy study.

BACKGROUND: Recent clinical and histopathologic data suggests that inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. The intima has received much attention as a site of inflammation, while the adventitia has remained relatively unexplored. The aim of the present study was to investigate the frequency of inflammatory activity in the cap and shoulder region of unruptured, atherosclerotic lesions in coronary arteries and to correlate these findings with distribution of inflammatory cells in adventitia. METHODS: The study was carried out in Histopathology Department, Army Medical College, Rawalpindi and National University of Sciences & Technology (NUST), from August 2008 to July 2009. Sixty-seven autopsy cases performed at Military Hospital Rawalpindi, Pakistan were selected. The cases were divided into study group and control group. Case group (n = 35) included those where cause of death was ischemic heart disease. Those coronary arteries were taken as control (n = 32) where atherosclerotic changes were found by chance (death without history of ischemic heart disease). Plaques in each group were assessed by light microscopy and by immunohistochemistry. RESULTS: The ages of the deceased ranged from 38 to 49 years. Within study group, adventitial lymphocytes exhibited strong correlation with erosion, thrombus formation in culprit plaque (p = 0.001). No correlation was found between adventitial T-lymphocytes and erosion of plaque (p = 0.700) in control group. In 72% of culprit plaques moderate staining for T-lymphocytes was observed in adventitia as well as intima. In control group, most of the cases contained scattered cells. Few cases of stable plaques revealed lymphocytes as clusters, both in adventitia and in intima. CONCLUSION: Adventitial inflammation may play a pivotal role for atherosclerotic lesion histology and atheroma instability. With the help of these autopsy findings, we hope to be able to reduce the incidence of culprit plaques related to inflammatory reaction in patients of ischemic heart disease.

Correlation of steatosis with fibrosis and necro-inflammation in chronic hepatitis C infection in the absence of confounding factors.

OBJECTIVE: To assess the frequency and degree of hepatic steatosis in patients of chronic hepatitis C infection and determine its correlation with stages of fibrosis and necro-inflammatory grades. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: The study was carried out in the Department of Pathology (Histopathology), Army Medical College, Rawalpindi, from March 2006 to March 2007. METHODOLOGY: Patients who had undergone a liver biopsy for evaluation of hepatitis C virus infection were included in the study. Demographic characteristics and laboratory data were collected at the time of biopsy. First hundred biopsy specimens meeting the inclusion criteria were assessed for steatosis, necro-inflammation and fibrosis. RESULTS: Steatosis was present in 46 patients and graded as mild (41.3%), moderate (54.3%) and severe (4.3%). An overall significant correlation was found between grades of steatosis with stage of fibrosis (p < 0.0001) but no correlation was found with necro-inflammatory grades. Only focal necrosis revealed weak correlation with grades of steatosis (p < 0.003). CONCLUSION: These results suggest a possible role of the hepatitis C virus itself in the pathogenesis of steatosis and indicate its close relationship with fibrosis and focal degeneration in chronic hepatitis C. Necro-inflammation seen in liver biopsy is host immune reaction to hepatitis C virus and is not related to steatosis.

An autopsy study of sudden cardiac death.

OBJECTIVE: To determine the cause of sudden cardiac death and observe the morphological changes in the heart after death. METHODS: A cross sectional survey of 66 cases was carried out at Armed Forces Institute of Pathology (AFIP) Rawalpindi from 1992 to 1994. A detailed autopsy including external and internal postmortem examination was done. Representative sections were taken for histopathological examination and some viscera were sent to Chemical Examiner at Lahore for chemical analysis. RESULTS: All the cases were male with age range from 21 to 58 years. These cases died within 60 minutes with or without onset of symptoms. Fifty two cases revealed mild to severe atherosclerosis. Coronary occlusion with thrombosis was seen in 37 cases whereas 9 cases showed critical narrowing without evidence of thrombosis. Five showed both symmetric and asymmetric hypertrophy. Changes in conduction system of the heart were seen in 4 individuals. Myocarditis was noted in 2 cases only. The cause of death could not be determined in 3 cases. CONCLUSION: Majority of the cases died of coronary atherosclerosis whereas 17% cases revealed hypertrophic cardiomyopathy, changes in conduction system and myocarditis and 4% cases were undetermined. A detailed and thorough postmortem examination is mandatory to ascertain the cause of sudden cardiac death.

Usefulness of needle biopsy in the diagnosis of paediatric liver disorders.

OBJECTIVE: To see the usefulness of liver biopsy in the diagnosis and to document the spectrum of paediatric liver diseases. METHODS: A retrospective, cross sectional survey at Histopathology Department of Army Medical College Rawalpindi from January 2000 to December 2003. The liver biopsies were taken with Menghini needle. The fixed tissues were processed under standard conditions. RESULTS: During four years period, a total of 100 cases with age range of 1.5 months to 16 years were studied. The most common histological findings in order of frequency were secondary haemochromatosis (30%), biliary atresia (20%), storage disorders (16%), cirrhosis of liver (10%) and neonatal hepatitis (10%). The less common entities were chronic hepatitis (6%), nonspecific reactive hepatitis (3%) and granulomatous hepatitis (1%). One case each of hepatoblastoma, haemophagocytic lymphohistiocytosis and congenital fibrosis was also noted. These findings have been compared with local and international histological studies. CONCLUSION: Liver biopsy is a useful diagnostic technique in the diagnosis of paediatric liver diseases. Biliary atresia, strorage disorders and neonatal hepatitis are the most common entities in our set up.

Morphological features correlation with serum tumour markers in prostatic carcinoma.

OBJECTIVE: To find out Gleason grades, scores and to see the correlation of these morphological features with tumour markers in prostatic carcinoma. DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: The study was conducted at the Departments of Histopathology and Chemical Pathology, Armed Forces Institute of Pathology, Rawalpindi, over a period of one year. MATERIALS AND METHODS: Fifty cases of prostatic carcinoma were studied. Gleason grades and score of tumour were determined by doing haematoxylin and eosin (HE) staining. Pre-operative serum prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) assays were carried out in these cases. RESULTS: The patients seen were between 50-102 years of age with an average of 70.9 years. There were 49 cases of adenocarcinoma and 01 case of mixed adeno and transitional cell carcinoma of prostate. Twenty-eight (56%) patients had Gleason score of 5-7. Twenty-nine (58%) patients were having serum PSA levels between 10.0 ng/ml and 50.0 ng/ml. Thirteen (26%) cases showed PSA assays >50 ng/ml. The sensitivity of PSA test was 84 % in these cases. Thirty-five (70%) patients were having PAP values >3.7 U/l (sensitivity 70 %). CONCLUSION: The Gleason grading system is a specific morphological predictor. The serum PSA showed better sensitivity and specificity with Gleason grades and scores as compared to serum PAP. The serum PAP levels showed better correlation with morphological features as compared to serum PSA.

Morphometric analysis of hepatic steatosis in chronic hepatitis C infection.

BACKGROUND/AIMS: To quantitatively assess steatosis by a morphometric method and to study its relationship with other histological features of chronic hepatitis C (CHC). This was a comparative descriptive study. The study was carried out in the Department of Histopathology, Army Medical College, Rawalpindi, Pakistan, from March 2006 to March 2007. METHODS: Patients who had undergone a liver biopsy for the evaluation of hepatitis C virus (HCV) infection were included in the study. Demographic characteristics and laboratory data were collected at the time of biopsy. The first hundred biopsy specimens that met the inclusion criteria were assessed for grades of steatosis (semiquantitatively), diameter of fat globules (by a morphometric method), necroinflammation, and fibrosis (semiquantitatively). Liver biopsies were processed for paraffin embedding, stained with hematoxylin and eosin, whereas Gomori's Reticulin stain was used for the evaluation of fibrosis. RESULTS: Out of 46 cases showing fatty change, pansteatosis was observed in 24 (52%) patients: 12 (26%) cases had a pericentral and mid zonal distribution of fat globules and eight (17.5%) cases revealed a mid zonal pattern only. There were two (4.5%) cases in which fat globules were found in periportal and mid zonal areas. None of the histological parameters (the stage of fibrosis and grades of inflammation) had any significant correlation with these distribution patterns of steatosis. The diameter of fat droplets was quantified by morphometry. A mixed pattern of steatosis was observed more frequently (21 out of 46 cases): 17 cases had microglobules and eight biopsies showed macroglobules. The size of the fat globules exhibited a significant correlation with the stage of fibrosis (P < 0.0001). The analysis of the grades of necroinflammation did not reveal any significant relationship with the diameter of fat globules. CONCLUSIONS: A mixed pattern of fat globules is more frequently observed in CHC, but macrovesicular steatosis is associated with a higher stage of fibrosis. Morphometry is recommended as one of the important tools for the follow-up of HCV-infected patients. Whether an accurate assessment of fat globule size by morphometry is preferred for the evaluation of patients before and after the antiviral therapy needs further research.

Frequency of bcl-2 gene rearrangement in B-cell Non-Hodgkin's lymphoma.

OBJECTIVE: The objective of the study was to determine the frequency of bcl-2 gene rearrangement in B-cell Non-Hodgkin's lymphoma (NHL) and identify different breakpoints of bcl-2 gene. METHODS: Thirty cases of B-cell lymphoma (including 8 cases of follicular lymphoma, 19 cases of diffuse large B-cell lymphoma and 3 cases of T-cell rich B-cell lymphoma) were included in the study. Good quality of DNA was extracted in 4 cases from formalin fixed paraffin embedded tissue and in 26 cases from fine needle aspirate. The polymerase chain reaction was done for major break point region (mbr), minor cluster region (mcr) and intermediate cluster region (icr) of the bcl-2 gene. RESULTS: The bcl-2 gene rearrangement was identified in 23.3% of B-cell lymphoma, 50% of follicular lymphoma, 15% of diffuse large B-cell lymphoma and no bcl-2 rearrangement was identified in any of the T-cell rich B-cell lymphomas. Further analysis showed the icr breakpoint in 16.7% of B-cell lymphoma, 37.5% of follicular lymphoma and 10.5% of diffuse large B-cell lymphoma. Involvement of the mbr breakpoint was found in 6.7% of B-cell lymphoma, 12.5% of follicular lymphoma, and 5.3% of diffuse large B-cell lymphoma. Involvement of the mcr breakpoint was not seen in any of the cases. CONCLUSION: The bcl-2 gene rearrangement is quite frequent in follicular lymphoma, followed by diffuse large B-cell lymphoma. The commonest breakpoint in present series is icr followed by mbr. This indicates that primers for bcl-2 gene must include icr primer, whenever the bcl-2 gene is being evaluated for B-cell NHL in this part of the world and this might reduce the variability of frequency of bcl-2 gene rearrangement within and between different regions.

Estrogen receptor, progesterone receptor, HER2/neu, P53 and Ki-67 status of male breast carcinomas in Pakistan.

OBJECTIVE: The aim of present study was to assess the status of estrogen and progesterone receptors, HER2/neu, p53 and ki-67 in male breast carcinomas in our institute. STUDY DESIGN: A descriptive study, carried out in the Department of Pathology (Histopathology), Army Medical College, Rawalpindi, Pakistan from June 2008 to January 2009. SUBJECTS AND METHODS: In this study 45 cases of male breast carcinoma, including all the histological subtypes were assessed with original pathology reports of each case investigated for the age, laterality of breast, histological type of tumour and tumour grade. Tumour blocks of each case were retrieved for immunohistochemical staining of estrogen and progesterone receptors and HER2/neu, ki-67 and p53 scoring was accomplished using established protocols. RESULTS: The majority of the cases were above 65 years of age. Histologically, the invasive ductal carcinoma was the predominant lesion. In total 95.5% of the cases were estrogen and progesterone (ER and PR) receptor positive. The HER2/neu staining was positive in 84.4% cases. According to the percentage of nuclear staining, 77.7% of the cases were p53 positive and 35.6% of the cases had strong nuclear staining intensity. A total of 55.5% of the tumours showed proliferation by ki-67. CONCLUSION: The majority of male breast carcinomas in Pakistan are ER and PR positive and demonstrate immunoreactions for prognostic markers. The results point to a relatively aggressive nature of such lesions in our institute.