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Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate

The Malaysian Journal of Pathology.2018;40(2):103-110.

Introduction: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. Methods: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. Results: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). Conclusion: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.
ethnic variation

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CD56 expression in benign and malignant thyroid lesions

Santhia Muthusamy

The Malaysian Journal of Pathology.2018;40(2):111-119.

Introduction: Thyroid cancer is the most common endocrine malignancy with more than 95% originating from follicular epithelial cells. Diagnostic dilemma may arise in occasional cases such as when an encapsulated nodule with a follicular growth pattern exhibits clear nuclei with grooves making it difficult to distinguish a follicular adenoma from encapsulated follicular variant papillary thyroid carcinoma. This study aimed to evaluate the diagnostic utility of an immunohistochemical marker, CD56, to distinguish between benign and malignant thyroid lesions. Materials and Methods: We retrospectively studied CD56 expression in 54 benign and 54 malignant thyroid lesions using archival formalin fixed paraffin-embedded tissue blocks for the study period from January 2010 to December 2015, diagnosed in a tertiary hospital. Results: CD56 was expressed in 52/54 (96.3%) of benign specimens and only 24/54 (44.4%) of malignant ones. The malignant specimens comprised 31 (57.4%) papillary thyroid carcinomas (PTC), 11 (20.3%) follicular carcinomas (FC), seven (13%) medullary thyroid carcinomas (MC), one (1.9%) poorly differentiated carcinoma (PC) and four (7.4%) anaplastic carcinomas (AC). CD56 was not expressed in 28/31 (90.3%) of the PTCs, 1/11 (9.1%) FCs, 1/4 (25%) of ACs while all MCs and the PD were positive. The benign group comprised nodular hyperplasias (29/54), lymphocytic thyroiditis (10/54), follicular adenomas (FA) (14/54) and one hyalinising trabecular tumour. CD56 was expressed in all the benign cases except one FA and one nodular hyperplasia. Thirteen of the 14 FAs were CD56 positive. The difference in expression between benign and malignant tumours was statistically significant as the p value was <0.01. Conclusion: CD56 is a potentially good immunohistochemical marker for differentiating papillary thyroid carcinoma from other benign follicular lesions of the thyroid especially in differentiating follicular variant PTC from FA in equivocal cases.
benign thyroid lesions

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Intraoperative frozen section sentinel lymph node assessment in breast cancer: A tertiary institution experience

Lai Shau-Kong

The Malaysian Journal of Pathology.2018;40(2):121-128.

Introduction: Intraoperative frozen section lymph node assessment helps to predict axillary lymph node metastasis in breast cancer. However, the accuracy of this frozen section analysis may vary among institutions. This study describes our institution’s experience in intraoperative analysis of sentinel lymph node and aims to determine the accuracy, sensitivity and specificity of our assessment. Materials and Methods: We retrospectively analysed the histopathological material and data from 82 breast cancer patients diagnosed over a period of four years who underwent intraoperative frozen section evaluation of sentinel lymph nodes. Results: Frozen section analysis detected metastasis in 13 out of 82 cases and definitive pathological examination on the paraffin section confirmed these positive findings. There was no false positive case (specificity of 100%). The true positive cases comprised seven macrometastases, five micrometastases and one isolated tumour cells. Sampling error was noted in two cases in which the malignant cells were only present in the deeper final paraffin sections (false negative rate of 13.3%). The test sensitivity was 86.7% and the accuracy rate was 97.5%. These findings are comparable to other published data. Conclusion: Intraoperative frozen section analysis is a safe and reliable method for assessment of sentinel lymph node. Knowledge on limitation of frozen section analysis with diligent evaluation of frozen section specimen will be beneficial in reducing interpretation error.
lymph node

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A clinicopathologic study of 173 odontogenic tumours in Northern Peninsular Malaysia (2007-2014)

Sumairi Ismail

The Malaysian Journal of Pathology.2018;40(2):129-135.

Introduction: The objectives of this study were to analyse, compare and contrast the demographic, clinical and pathological data of odontogenic tumours seen at a regional oral pathology centre in the Northern part of Peninsular Malaysia with other international data as an aid to clinicians in diagnosing odontogenic tumours. Materials and Methods: This was a descriptive, retrospective study of odontogenic tumours diagnosed from January 2007 to December 2014 at this centre. The odontogenic tumours were classified using the 2005 World Health Organization classification system. Results: Among 2,733 biopsy specimens, 173 cases were diagnosed as odontogenic tumours (6.3%), of which 171 (98.8%) are benign and 2 (1.2%) are malignant. The most frequently encountered tumour was ameloblastoma (n=96, 55.5%), followed by keratocystic odontogenic tumour (KCOT) (n=38, 22.0%) and odontomas (n=16, 9.2%). Malignant tumours accounted for 1.2% of the tumours. Most ameloblastomas and KCOTs affected the mandible preferentially. The mean age was 33.5 (± 17.8) years and 64.7% of patients were in the age group of 10 to 39. Odontogenic tumours were slightly more common in males, with a male to female ratio of 1.4:1. Conclusion: The findings of this study are similar to the other studies in Asia in which the most common tumour encountered is the ameloblastoma, followed by KCOT. The most common signs and symptoms are pain and swelling, while paraesthesia and root resorption are less frequently reported. Such clinical and radiographic features should alert the clinician of a possible odontogenic tumour and though rare, malignant tumours should also be included in the differential diagnoses.
Odontogenic tumour

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Stromal podoplanin expression and its clinicopathological role in breast carcinoma

Kumcu Emrah

The Malaysian Journal of Pathology.2018;40(2):137-142.

Introduction: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters. Materials & Methods: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ≥ 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive. Results: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032). Discussion: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.
tumour stroma

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Post mortem troponin T analysis in sudden death: Is it useful?

Razuin Rahimi

The Malaysian Journal of Pathology.2018;40(2):143-148.

Introduction: Cardiac-related diseases contributed approximately 50-60% of sudden natural death cases. This study aimed to describe the cardiac troponin T (cTnT) findings in post mortem subjects irrespective of the cause and manner of death, and the possible use of post mortem serum cTnT as a modality in investigating sudden natural death. Methods: The study samples comprised 140 subjects aged 18 to 50 years old, natural and unnatural causes of sudden death brought to the Department of Forensic Medicine, Hospital Sungai Buloh (HSgB) and Hospital Sultanah Aminah Johor Bahru (HSAJB) for a period of 12 months. The subjects were categorised into 5 groups: cardiovascular disease (CVD), sudden unexplained death (SUD), thoracic trauma (TT), non-thoracic trauma (NTT) and other diseases (OD). Results: Median troponin concentration in cases of CVD, SUD, TT, NTT, and OD were 0.51 µg/L, 0.17 µg/L, 0.62 µg/L, 0.90 µg/L and 0.51 µg/L respectively. We found no significant difference of troponin T level in different causes of death (p ≥ 0.05). NTT has the highest median troponin concentration with 0.90 µg/L, SUD possessed the lowest median concentration with 0.17 µg/L. Conclusion: Troponin T is neither specific nor useful as cardiac biomarker for post mortem sample. Therefore, it may not be a useful diagnostic tool at autopsy.
cardiac death

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Pregnancy outcomes in women with non-transfusion dependent thalassaemia (NTDT): A haematology centre experience

Lee Bee Sun

The Malaysian Journal of Pathology.2018;40(2):149-152.

Introduction: Non-transfusion dependent thalassaemia (NTDT) is a term used for thalassaemia patients who do not require lifelong regular transfusions for survival. Pregnancy in these women, whether spontaneous or through assisted reproductive technology, represents a challenge for the physician. Materials and Methods: The maternal and foetal outcomes of patients with NTDT followed up in a tertiary haematology centre over 6 months period were studied. A total of 36 pregnancies in 26 pregnant women with NTDT were analysed. Results: Among these women, all of the pregnancies resulted in successful delivery of singleton live-born neonates. There were four clinically distinct forms of NTDT among these women which include Hb E/β-thalassemia (mild and moderate forms), HbH disease, HbH-Constant Spring, and homozygous δβ-thalassemia. No blood transfusion was needed in 15 of the 36 pregnancies (41.6%). The lowest mean Hb level in which no blood transfusion was given was 8.21 g/dL. The mean of packed-cell units received during pregnancy was 6.95 units per pregnancy. There was no worsening of serum ferritin observed during pregnancy with mean serum ferritin pre- and post-pregnancy of 409.35 ug/L and 418.18 ug/L respectively. The mean gestational age at delivery was 38.6 weeks with no preterm delivery reported. The mean foetal birth weight was 2729 grams. There was no intrauterine growth restriction (IUGR) or congenital malformation. There was a case of small for gestational age (SGA) and a case of oligohydramnios. Conclusion: This study showed that pregnancy was possible, safe and has a favourable outcome in patients with NTDT with multidisciplinary care.
Non-transfusion dependent thalassaemia

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The effect of Resveratrol and Octreotide on peritoneal adhesions in a rat model

Ü ; reyen Orhan

The Malaysian Journal of Pathology.2018;40(2):153-160.

Introduction: The aim of this study was to investigate the efficacy of resveratrol and octreotide, agents that are used to prevent intra-abdominal adhesions in experimental models, in preventing intraperitoneal adhesions when used alone or in combination. Materials and Methods: The study employed 28 young female Wistar albino rats weighing 250-300 grams. An experimental adhesion model was created in each rat using serosal abrasion and peritoneal excision. They were divided into four groups, each comprising seven rats: Group 1, adhesion induction only; Group 2, resveratrol administration only; Group 3, octreotide administration only; and Group 4, administration of resveratrol and octreotide combination. The rats were monitored under appropriate conditions for 14 days and then underwent laparotomy. Macroscopic intensity and extensiveness of adhesions and microscopic changes in the granulation tissue (cellular intensity, reticular and collagen fibers, capillaries, elastic and smooth muscle fibers, fibrosis) were evaluated and graded. Kruskal-Wallis and Mann-Whitney U-test were used in statistical analysis and the level of statistical significance was established as p <0.05. Results: There was no significant difference between the groups in terms of the intensity and extensiveness of macroscopic adhesions (p=0.377 and p=0.319). There was a statistically significant difference between the microscopic scores of the groups according to Zühlke’s classification (p=0.026). The Bonferroni correction used to test for the differences revealed that the rats in Group 1 achieved significantly higher scores than the rats in Group 3 (p=0.016). Conclusion: Octreotide showed higher efficiency compared to the control group in microscopic classification; however, the two agents were not superior to each other or their combination was not superior in preventing intra-abdominal adhesions.
Octreotide ; resveratrol

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ALK-positive anaplastic large-cell lymphoma with primary bone involvement: A rare case and review of the literature

Noh Byeong-Joo

The Malaysian Journal of Pathology.2018;40(2):161-167.

Primary bone lymphoma (PBL) is an uncommon type of extranodal lymphoma involvement. An anaplastic large-cell lymphoma (ALCL) is an extremely rare type of PBL, and it remains unclear whether ALCLs that primarily involve the bone exhibit favourable or unfavourable biological behaviour, and whether they are similar to ALCLs in general, or not. We reported a case of ALKpositive ALCL with primary bone involvement, and reviewed the clinicopathological features of 22 previously reported cases. An ALCL with primary bone involvement mostly affects younger patients with a preponderant towards the involvement of axial-bone. The prognosis of an ALCL that primarily involves bone is unfavourable, compared with PBL generally. The ALK-positive ALCLs in PBLs had less decedents than the ALK-negative ALCLs with a statistical non-significance (p=0.198).
primary-bone lymphoma

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Leptospirosis in pregnancy: A lesson in subtlety

Razuin Rahimi

The Malaysian Journal of Pathology.2018;40(2):169-173.

Introduction: Leptospirosis is a zoonotic disease caused by spirochaete of the genus Leptospira. Human infection occurs after exposure to water or soil contaminated by urine from an infected animal. Most patients manifest as self-limited systemic illness. However 10% of patients manifest as severe disease associated with high fatality. The disease affects mostly men, cases involving pregnant women are uncommon. We presented a case of leptospirosis in a pregnant woman leading to mortality of both mother and foetus. Case Report: A 28-year-old woman at 18 weeks of gestation, had shortness of breath and collapsed. She was brought unconscious to the emergency department and died shortly after arrival. A week prior to this, she had presented to the same hospital with pain on both thighs. Examination of the patient and ultrasound of the foetus revealed normal findings. Post mortem examination revealed hepatosplenomegaly and congested lungs; no jaundice, meningeal inflammation or cardiac abnormalities was evident. Histopathology examination of the lungs revealed pulmonary haemorrhages and oedema. Multiple infarcts were seen in the spleen and the kidneys showed foci of acute tubular necrosis. Laboratory investigations revealed Leptospira IgM antibody and PCR for leptospira were positive. This case illustrates the subtleness of clinical presentation of leptospirosis. The diagnosis was obscure even at post-mortem and was only suspected following histopathological examination, leading to further investigations. Conclusion: Leptospirosis may have a subtle presentation and a high index of suspicion for this infection is required for early identification of the disease.
Leptospirosis

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