Malaysian Journal of Pathology最新文献

Introduction: Podocyte infolding glomerulopathy (PIG) is a rare glomerular disorder characterised by the infolding of podocytes into the glomerular basement membrane (GBM) with the presence of intramembranous cytoplasmic microspherules or microtubules. Most patients with PIG presented with nephrotic or subnephrotic proteinuria accompanied with microscopic haematuria. The condition is often associated with autoimmune diseases.

Case report: Recently, two cases of PIG were reported in Malaysia for the first time involving two female patients aged 25 and 36 years. The first patient had a history of systemic lupus erythematosus (SLE), peripheral neuropathy, anti-nuclear matrix protein 2 (NXP2)-positive antibody, autoimmune hypothyroidism, and primary ovarian failure. She presented with persistent nephrotic range proteinuria and haematuria. Meanwhile, the second patient with history of SLE presented at rheumatology clinic with bilateral pedal oedema, frothy urine, and haematuria. The electron microscopy (EM) analysis of the first patient revealed widespread and extensive invagination of podocyte cytoplasmic processes into the GBM, forming subepithelial clusters of microspherules and microtubules and separated by an intervening basement membrane. Likewise, extensive infolding of podocyte cytoplasmic processes into the GBM were found in the second case, and the intervening basement membrane separated the microspherules and microtubules.

Discussion: These findings confirmed the diagnosis of PIG, and the patients were treated with Prednisolone, maintaining normal creatinine level during follow-up. In summary, PIG is a rare and new glomerular disease which has been known to be associated with connective tissue diseases, predominantly affecting young individuals with a favourable clinical outcome.

Introduction: Renal angiomyolipoma is one of the members of the perivascular epithelioid cell (PEC) tumour family. It has a characteristic triphasic morphology featuring varying proportions of dysmorphic blood vessels, smooth muscle cells, and mature adipose tissue. Large angiomyolipomas pose a risk of haemorrhagic complications.

Case report: A 47-year-old woman presented with right abdominal pain for 2 months, and radiological investigation revealed a 14.2 cm renal mass causing hydronephrosis. The symptoms persisted after arterial embolisation and hence, nephrectomy was performed. The excised renal tumour weighed 1,442 grams. There was a well-circumscribed yellow mass confined within the Gerota's fascia. Histological examination revealed a classic triphasic morphology comprising mature adipose tissue, dysmorphic blood vessels, and smooth muscle. Notably, there were post-embolisation histological changes in extensive fat necrosis and foreign body giant cell reaction. Immunohistochemically, it expressed HMB45, MelanA, and SMA, while it was negative for PAX8 and pan-cytokeratin.

Discussion: We described a case of renal angiomyolipoma with classic gross appearance of adipose-rich tumour and the triphasic histological features and discussed the post-embolisation histological changes.

Introduction: In Malaysia, acute coronary syndrome is the leading cause of hospitalisation. Identification of patients with low 30-day risk of major adverse cardiac event (MACE) may facilitate an early and safe discharge from overcrowding emergency departments (ED). This study aimed to determine the diagnostic accuracy of high-sensitivity-cardiac-troponin-I (hs-cTnI) for ruling out 30-day MACE among chest pain patients in ED.

Materials and methods: A prospective observational study using an Accelerated Diagnostic Protocol (ADP) which included Thrombolysis-in-Myocardial-Infarction (TIMI) score, electrocardiogram, and 0- and 3-hour hs-cTnI. TIMI = 0 and ≤1 was used in ADP-1 and ADP-2, respectively.

Results: 20 (10%) and 64 (32%) of 201 patients were low-risk, whereby none of whom developed MACE in ADP-1 and ADP-2, respectively. Using the overall hs-cTnI cut-off, ADP-1 had a Sensitivity (Sn) of 100% [95% Confidence Interval (CI)] (51.7 to 100), Specificity (Sp) of 10.2% (6.5 to 15.6), Negative Predictive Value (NPV) of 100% (80.0 to 100) and Positive Predictive Value (PPV) 3.3% (1.4 to 7.4). ADP-2 yielded a Sn of 100% (51.7 to 100), Sp of 32.8% (26.4 to 40.0), NPV of 100% (92.9 to 100) and PPV of 4.4% (1.8 to 9.7). Using gender-specific hs-cTnI cut-off, either that of Abbott or a Malaysian population, yielded similar diagnostic accuracy; except the former produced slightly higher Sp of 75.4% (68.7-81.1).

Conclusion: Using either the overall or gender-specific cut-offs, both protocols yielded 100% diagnostic accuracy for ruling out MACE which may enable a safe early discharge of up to 32% of chest pain patients in ED.

Introduction: Sudden unexpected death (SUD) in a healthy young adult presents a challenging scenario that forensic pathologists often encounter. Although they are rare, thyroid diseases such as hyperthyroidism, hypothyroidism, and lymphocytic thyroiditis can contribute to SUD. Comprehensive investigations, including thyroid histological evaluation, are critical to identify underlying causes. This report discusses a rare case of lymphocytic thyroiditis in a young male who died unexpectedly, highlighting the forensic value of thyroid pathology in SUD cases.

Case report: A 25-year-old Bangladeshi male, with no known comorbidities, was found unresponsive in bed and was brought to the hospital, where resuscitation efforts in the emergency department were unsuccessful. He had no complaints of health issues in the past two weeks before his death. There was no family history of SUD. Externally, there was no evidence of injury or systemic disease. Gross examination of vital organs, including the heart and brain, was unremarkable. A cricothyroidotomy incision partially obscured the thyroid gland. However, histological analysis revealed lymphocytic infiltration, follicular destruction in the thyroid glands, and fibrosis in the sinoatrial (SA) node. Extensive toxicological tests were negative and no thyroid function tests or molecular autopsy were performed.

Conclusion: Lymphocytic thyroiditis should be considered in SUD cases, even with unremarkable gross findings or nonspecific clinical history. Routine microscopic thyroid examination could reveal subtle yet significant conditions contributing to SUD. Establishing standardised autopsy guidelines focusing on thorough thyroid assessment may improve post-mortem diagnostics and enhance the understanding of thyroid pathology in SUD.

Introduction: To investigate the major causes of neonatal deaths in Malaysian neonatal intensive care units (NICUs).

Materials and methods: This retrospective observational study analysed prospectively collected data of neonates (gestation ≥22 weeks, birthweight ≥500g) admitted to 44 NICUs in the years 2015-2020 in the Malaysian National Neonatal Registry. Causes of death were reported using the modified Wigglesworth classification.

Results: Out of 759,435 neonates, 1.2% (n=9470) died. Most (72.3%) were early neonatal deaths (0-7days of life), 17.5% were late neonatal deaths (8-28 days of life), and 10.2% were post-neonatal deaths (>28 days of life). Inborn extremely preterm (EPT, <28 weeks gestation) neonates had the highest death rates (427.5/1000 livebirths) and term neonates (1.7/1000 livebirths) had the lowest. Congenital malformations accounted for 33.0% of deaths; the majority were of gestation ≥28 weeks. Trisomy 18 (n=542), trisomy 13 (n=397), cardiovascular (CVS) malformations (n=371) and neurological malformations including neuro-tube defects (NTD) (n=252) were the four most common types of malformations. The three most common causes of non-malformation deaths were EPT (n=1424), sepsis (n=867, affecting all gestations), and hypoxic-ischaemic encephalopathy (HIE) in term neonates with/without multiorgan failure (n=570). Less than one-third of EPT neonates who died received respiratory support at birth. Most (85.3%) sepsis death was late-onset sepsis (≥72 hours of age). Only 27.8% term neonates dying from HIE received adequate therapeutic hypothermia.

Conclusions: Extreme prematurity, nosocomial sepsis, HIE in term neonates, chromosomal abnormalities due to trisomy 18 and trisomy 13, ductal-dependent CVS malformations, and NTD were the six most common causes of neonatal deaths in Malaysian NICUs.

Introduction: Individuals with alpha(α)-thalassaemia usually have evidence of microcytosis but showed normal haemoglobin A2 and F, except those with three or four gene deletions or those with abnormal Haemoglobin (Hb) such as Hb Constant Spring (HbCS). Definitive diagnosis requires molecular analysis. Multiplex amplification refractory mutation system (ARMS) and gap PCR are reliable for detecting common α-gene mutations; however, many rare or novel mutations remain unidentified. Using principle of primer-specific amplification, abnormality analysed is primer-dependent. This study aimed to compare the detection of HBA gene rearrangements by multiplex ligation-dependent probe amplification (MLPA) with multiplex PCR (ARMS and Gap).

Materials and methods: MLPA facilitates amplification of multiple nucleic acid sequences with a single primer pair via identical end probe amplification, thus giving wide α-globin analysis in a single experiment to provide high-resolution detection. Amplification products only require capillary electrophoresis separation followed by software analysis. Seventy-three samples that have been analysed by multiplex PCR were selected for this study. Fifty-five confirmed cases of α-thalassaemia and 18 normal samples were tested using MLPA. Discordant cases suspected of α-thalassaemia underwent sequencing analysis.

Results: All normal samples and 50 positive cases showed consistent findings between both methods. MLPA showed 100% sensitivity and specificity in detecting HbCS mutation. However, MLPA could not determine zygosity of three homozygous HbCS cases detected by multiplex PCR. The concordant rate was 93.2% between both methods. MLPA results in five discordant cases.

Conclusion: MLPA is a reliable and accurate technique for characterising HBA gene rearrangements. Overall, both methods showed excellent concordance rate and statistically good agreement. The simplicity of wide α-globin cluster analysis makes MLPA as favourable diagnostic method for the detection both common and unresolved HBA gene abnormalities involving HBA gene cluster.

Introduction: Ameloblastoma is a benign but locally aggressive odontogenic tumour broadly divided into conventional, unicystic, peripheral, adenoid and metastasising types. The first three entities compose the majority and especially the conventional type which has different histopathological subtypes such as follicular, plexiform, acanthomatous, granular cell, basal cell and desmoplastic have been described. We report the largest series of ameloblastoma in a single study to analyse the demographic characteristics according to histopathological subtypes of ameloblastoma.

Materials and methods: 1,312 cases of ameloblastoma reported from two centres in Sri Lanka and Malaysia were analysed according to age, site and histopathological subtype.

Results: Of the total of 1,312 cases, the mean age for conventional ameloblastoma (excluding desmolastic subtype) was 36.82±16.57. It was 46.3±15.21 for categorisewhile peripheral and unicystic ameloblastoma occurred at 40.77±16.35 and 31.00±17.37, respectively. Ninety percent of the cases were in the mandible (p=0.00001) with significant predilection for the right side. Unicystic and plexiform subtypes were mostly seen in the 11-20 age group while the desmoplastic subtype was seen in the 51-60 age group. The commonesthistological subtype was follicular subtype and acanthomatous changes were observed predominately in combination with follicular subtype. Majority of the acanthomatous subtype was observed inposterior mandible (p=0.00001). The frequency of luminal (243) and mural (246) subtypes werealmost similar.

Conclusion: This study provides a comprehensive demographic detail of differenthistological subtypes of ameloblastoma using the largest sample in the literature. The present findingswill be helpful in classification and understanding of different subtypes of the tumours.

Introduction: In bladder cancer, the presence of lamina propria invasion (pT1) poses a significant clinical challenge due to varied tumour behaviours and risk of disease progression. Efforts to substage pT1 urothelial carcinoma (UC) using diverse systems have been made, but challenges persist in accurately predicting disease progression. This study introduces a novel risk stratification approach focusing on pT1b UC cases based on the spatial relationship between invasive carcinoma and the muscularis propria (MP) in transurethral resection of bladder (TURB) specimens.

Materials and methods: Retrospective analysis of pathology reports from 2017 to 2023 identified pT1 cases in TURB specimens, subcategorised using a 2-tiered approach. Exclusions were applied based on specific criteria, leading to a final cohort of 24 patients. We evaluated the tumour diameter and proximity to the MP from a "Tumour-MP (T-M) angle" perspective. A novel pT1b risk stratification method focusing on the T-M angle to differentiate low- and high-risk groups was developed, in which pT1b low-risk is defined as a T-M angle less than 180 degrees, and pT1b high-risk is defined as a T-M angle greater than 180 degrees.

Results: In this study of 24 pT1b UC cases, 16 were categorised as pT1b low-risk and 8 as pT1b high-risk. Notably, the high-risk group showed a higher upstaging rate to advanced tumour stages (≥pT2) in radical cystectomy (RC) specimens compared to the low-risk group (88% vs. 56%, p = 0.015).

Conclusion: This new risk stratification method presents promise in guiding early aggressive treatment decisions, though larger prospective studies are essential for further validation and clinical integration.

Introduction: Chronic kidney disease (CKD) poses a global public health challenge, necessitating accurate assessment of renal function for timely intervention. Glomerular filtration rate (GFR) is a crucial indicator, traditionally measured using creatinine-based equations. However, Cystatin C-based equations offer potential advantages. We aim to evaluate the performance of estimated GFR (eGFR) equations for accurate renal function assessment in diverse Asian populations.

Materials and methods: Following PRISMA guidelines, the systematic review covered studies from 1991 to 2023 across Asian populations, incorporating equations based on both creatinine and Cystatin C. Eligibility criteria included adults aged 18 or older, either healthy or with CKD. Data extraction included study details, population characteristics, disease conditions, and formulas used. Quality assessment was conducted using the QUADAS-2 tool.

Results: The study analysed 26 studies focusing on South Asia and 66 on East Asia. In South Asia, the CKD-Epi-Pak equation demonstrated superior accuracy, achieving high percentages of eGFR values within specified ranges of measured GFR (P15: 70.39%, P30: 89.35%) with minimal bias (-1.33). The traditional MDRD equation exhibited poor performance, registering the lowest agreement percentages (P15: 7.8%, P30: 25.4%, P50: 71.1%) and the highest bias (-26.13). In East Asia, the CKD-Epi-2021 formula displayed the best accuracy, with high percentages of eGFR values within specified ranges (P15: 65.4%, P30: 97.6%). The simplified MDRD formula showed suboptimal performance, indicating lower agreement percentages (P15: 15.46%, P50: 56.59%). Variations of the MDRD formula in Japan exhibited bias while modified Gates Method demonstrated inferior precision.

Conclusion: CKD-Epi-Pak and CKD-Epi-2021 show potential suitability in South and East Asia, respectively. Future research should prioritise ethnicity-specific equation development to enhance accuracy and clinical utility in Asian populations.