Congenital orofacial teratoma in a 22-week foetus.

No abstract available.

Distribution of cord inflammation in cases with clinical suspicion of chorioamnionitis.

INTRODUCTION: Identification of acute funisitis, a sign of foetal inflammatory response (FIR), is crucial as their presence is associated with ominous neonatal outcomes. Recommendation on which part of umbilical cord should be sampled to facilitate optimal identification of acute funisitis is limited. METHODS: This is a retrospective cross-sectional study over a seven-month duration recruiting all patients with clinical suspicion of chorioamnionitis and/or maternal intrapartum pyrexia. The distribution and the degree of cord inflammation were assessed. The cases were also evaluated for maternal inflammatory response (MIR) and chorionic vasculitis (CV). RESULTS: Of the 191 placentas, 88 (46.1%) had some degree of cord inflammation. Forty-nine (55.7%) had a differential in cord inflammation, with distal cord section (n = 38) demonstrating significant greater inflammation than that of proximal cord section (n = 11) (p<0.001). There were 20 cases with phlebitis only and 8 cases demonstrated arteritis only in either proximal or distal cord sections. Increasing magnitude of cord inflammation was significantly associated with increasing severity of MIR and the rate of CV (p<0.001). CV was observed in 25 (24.3%) cases showing absence of cord inflammation, while 12 (13.6%) cases with cord FIR demonstrated no CV. DISCUSSION: Inflammatory reaction can occur variably throughout the length of the umbilical cord and chorionic plate vessels, with greater inflammation seen in the distal cord section. We affirm the current Amsterdam recommendation of submitting at least two cross sections of the cord representing proximal and distal sites and two sections from placental parenchyma to facilitate the identification of FIR.

MicroRNA profiling in complete and partial hydatidiform moles.

INTRODUCTION: Hydatidiform mole is one of the gestational trophoblastic disease and comprises complete (CM) and partial moles (PM), which carries a risk of developing persistence disease, invasive mole or choriocarcinoma. MicroRNAs (miRNAs) have been discovered in various tissues, including neoplastic tissues. Its role in the pathogenesis of molar pregnancy or as biomarkers are still largely uncertain. The aim of this study is to identify the differentially expressed miRNAs in CM and PM. MATERIALS AND METHODS: Using next-generation sequencing, the miRNAs profiles of CM (n=3) and PM (n=3) moles, including placenta of non-molar abortus (n=3) as control were determined. The differentially expressed miRNAs between each group were analysed. Subsequently, bioinformatics analysis using miRDB and Targetscan was utilised to predict target genes. RESULTS: We found 10 differentially expressed miRNAs in CMs and PMs, compared to NMAs, namely miR- 518a-5p, miR-423-3p, miR-503-5p, miR-302a-3p, and miR-1323. The other 5 miRNAs were novel, not listed in the known database. The 3 differentially expressed miRNAs in CMs were predicted to commonly target ZTBT46 and FAM73B mRNAs. DISCUSSION: miR-518 was consistently observed to be downregulated in CM versus PM, and CM versus NMA. Further bioinformatic analysis to provide insight into the possible role of these miRNAs in the pathogenesis of HMs, progression of disease and as potential diagnostic biomarkers as well as therapeutic targets for HMs is needed.

MJP going green.

No abstract available.

Globus pharyngeus due to a lymphangiomatous polyp arising from the tonsil.

INTRODUCTION: Lymphangiomatous polyp of the tonsil is generally accepted as a hamartomatous lesion. Its differential diagnosis includes fibroepithelial polyp, squamous papilloma, angiofibroma, haemangioma, arteriovenous malformation, hamartoma and lymphangioma. CASE REPORT: A 33-year-old man presented with 2 months history of feeling of foreign body sensation in the throat. Examination revealed a nodular red coloured polyp on the left tonsil. Histologically, the polyp was covered by squamous epithelium and is composed of numerous vascular channels containing lymphocytes and eosinophilic material, in a fibrous stroma. Immunohistochemically, the endothelial cells were positive toward CD31 and D2-40. DISCUSSION: The characteristic histological features of a lymphangiomatous polyp are benign vascular proliferation with variable fibrous, adipose and lymphoid stromal components. Nested intraepithelial epidermotropism of lymphocytes can be observed. The vascular channels are typically thin-walled and contain eosinophilic proteinaceous material and lymphocytes. There is no reported incidence of recurrent or malignant transformation.

Eosinophilic/ T cell chorionic vasculitis.

No abstract available.

Medical record archives in the era of digitalisation.

No abstract available.

Guidelines on retention of pathology records and materials (Version 2/2022).

No abstract available.

Antibiotic use reduces efficacy of tyrosine kinase inhibitors in patients with advanced melanoma and non-small-cell lung cancer.

BACKGROUND: Antibiotic (ABX) use can reduce the efficacy of immune checkpoint inhibitors and chemotherapeutics. The effect for patients treated with targeted therapies, namely, small-molecule tyrosine kinase inhibitors (TKIs), is less known. PATIENTS AND METHODS: Retrospective data were analysed for TKI-treated patients with advanced melanoma and non-small-cell lung cancer (NSCLC) between January 2015 and April 2017 at The Christie NHS Foundation Trust. Data on demographics, disease burden, lactate dehydrogenase (LDH) level, presence of brain metastases, ECOG performance status (PS) and ABX use were collected. Progression-free survival (PFS) and overall survival (OS) were compared between the ABX+ group (ABX within 2 weeks of TKI initiation-6 weeks after) and the ABX- group (no ABX during the same period). RESULTS: A total of 168 patients were included; 89 (53%) with NSCLC and 79 (47%) with melanoma. 55- (33%) patients received ABX. On univariable analysis, ABX+ patients demonstrated shorter PFS (208 versus 357 days; P = 0.008) and OS (294 versus 438 days; P = 0.024). Increased age, poorer PS and higher LDH were associated with shorter PFS and OS. On multivariable analysis, ABX use was independently associated with shorter PFS [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.05-2.34, P = 0.028] and OS (HR 2.19, 95% CI 1.44-3.32, P = 0.0002). The negative impact of ABX on OS was particularly pronounced for patients with PS of ≥2 (HR 3.82, 95% CI 1.18-12.36, P = 0.025). CONCLUSION: For patients treated with TKIs, ABX use is independently associated with reduced PFS and OS and judicious use is warranted, particularly in patients with poorer PS.

SARS-CoV-2: Reflection beyond the lungs.

No abstract available.

Opportunity in a time of crisis: New technology in pathology.

No abstract available.

Diagnostic utility of p57 immunohistochemistry and DNA ploidy analysis by fluorescence in situ hybridisation in hydatidiform moles.

INTRODUCTION: Hydatidiform moles (HMs) include complete and partial moles, are the result of abnormal fertilisation. The accurate classification of HMs and its distinction from non-molar specimens is utmost important for clinical management and risk assessment. It is diagnostically challenging if the distinction is based solely on histomorphology with poor interobserver reproducibility, especially in early gestations. This study aimed to investigate the diagnostic ability of combined p57 immunohistochemistry and DNA ploidy analysis to distinguish between complete moles, partial moles and non-molar abortus. MATERIALS AND METHODS: We included all HMs cases diagnosed in our centre over a six-year period. p57 immunohistochemistry stain was performed. Only nuclear immunoreactivity in >50% of cytotrophoblasts and villous stromal cells was regarded as positive for p57. DNA ploidy status was determined by fluorescence in situ hybridisation. A total of 250 cells from five chorionic villi were counted and were scored as diploid or triploid if more than 10% of nuclei demonstrated two or three signals, respectively. RESULTS: A total of 51 cases originally diagnosed by histomorphology as complete mole (n = 18), partial mole (n = 24) and non-molar abortus (n = 9) were recruited. The cases were reclassified based on the p57 immunostaining pattern and DNA ploidy status, into 27 complete moles (p57-/diploid), 9 partial moles (p57+/triploid) and 15 non-molar abortus (p57+/diploid). The diagnostic accuracy by histomorphological features alone in each category: complete moles, partial moles and non-molar abortus was 78.4%, 70.6% and 88.2% respectively. CONCLUSION: This study highlighted the importance of the utility of combined p57 immunostain and DNA ploidy analysis in arriving at an accurate diagnosis in HMs. An algorithmic approach utilising these ancillary techniques is advocated in routine diagnostic workup for a more refined diagnostic approach to HMs.

Digital pathology as a solution for working from home.

No abstract available.

Virtual meeting in pathology: Time to adapt to the new-norm.

No abstract available.

Primary extragonadal vaginal yolk sac tumour: A case report.

INTRODUCTION: Yolk sac tumour (YST) or endodermal sinus tumour is rare and typically seen in gonads. CASE REPORT: We described a case of extragonadal vaginal YST in a one year and seven months old girl who presented with vaginal discharge and bleeding, and discuss its differential diagnosis and potential pitfalls in immunohistochemistry. She was found to have a suprapubic mass on examination. The serum alpha fetoprotein was 11919.4 ng/mL. Computed tomography of the pelvis revealed a large 6.4 cm heterogenous pelvic mass. Colposcopic examination of the pelvis showed a fungating vaginal mass that was subsequently confirmed as a yolk sac tumour. Immunohistochemically, the malignant cells were positive toward CKAE1/AE3, AFP and glypican-3, as well as CD117. DISCUSSION: Solid pattern extragonadal vaginal YST may morphologically resemble dysgerminoma that is also CD117 positive, while the glandular pattern YST may have clear cytoplasm and is positive for cytokeratin; hence, may resemble clear cell carcinoma. Being mindful of these potential diagnostic caveats is necessary to prevent misdiagnosis.

Challenges of Covid-19 testing.

No abstract available.

Construction of a doxycycline inducible lentivirus that expresses stem cell-specific miR-302 cluster.

INTRODUCTION: The polycistronic miR-302 cluster encodes five miRNA genes that have an important role in the regulation of embryonic stem cell function. Studies showed that the miR-302 cluster can reprogram both mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) with high efficiency. The aim of this study was to generate an inducible lentivirus that expresses miR-302 cluster in order to further investigate somatic cell reprogramming by these miRNAs. MATERIALS AND METHODS: The miR-302 cluster was amplified by polymerase chain reaction technique from human genomic DNA and was ligated into pTRIPz, an inducible lentiviral vector. RESULTS: MRC5 fibroblasts and HEK293 (human embryonic kidney) cells were infected with pTRIPz-302 cluster lentivirus and the family of 302 miRNAs were strongly expressed in HEK293 cells but lowly expressed in MRC5 fibroblasts. When cultured in hESC conditions, MRC5 cells expressed only low levels of DNMT3B, Nanog, Oct4 and Lin28 and failed to show stem cell induction. The red fluorescent expression seen in the majority of MRC5 cells, indicated that the rate of infection by lentivirus was efficient. DISCUSSION: The efficiency of reprogramming may be improved perhaps by either using a different cell type or a high expression vector with a different type of promoter.

Occult primary breast carcinoma presented as an axillary mass: A Diagnostic Challenge.

INTRODUCTION: Occult primary breast carcinoma (OBC) manifesting as axillary nodal metastasis without an identifiable breast primary is exceptionally rare. It continues to pose a diagnostic challenge to pathologists. Here, we report a case of OBC with emphasis on the usefulness of immunohistochemistry to determine the primary site of tumour. CASE REPORT: A 58-year-old female presented with a 3-cm painless right axillary mass. Extensive radiological investigations that include mammography, ultrasonography of the breasts and positron emission tomography (PET) scan failed to conclude the primary site of the tumour. Histological examination of the lymph node revealed loosely cohesive sheets of poorly differentiated malignant cells, without discernible glandular or squamous differentiation. Immunohistochemically, the malignant cells exhibited diffuse immunoreactivity toward pan-cytokeratin and CK7, while leukocyte common antigen, S100 and CK20 were negative. A second panel of immunomarkers was carried out. The malignant cells expressed breast-specific markers (GATA-3, GCDFP-15 and mammaglobin), and were negative for ER, PR and TTF-1 immunohistochemistry. A diagnosis of OBC was rendered. DISCUSSION: Breast primary must always be considered in the differential diagnosis in patients with sole presentation of axillary lymphadenopathy. The breast-specific immunomarkers play a pivotal role in the diagnosis of ER, PR-negative occult breast cancer.

Androgen receptor expression in triple negative breast carcinoma and its association with the clinicopathological parameters.

INTRODUCTION: Androgen receptor (AR) is the most frequently expressed biomarker in all subtypes of breast carcinoma. Triple negative breast carcinoma (TNBC) is breast carcinoma that lacks oestrogen and progesterone receptors immunoexpression as well as absence of HER2/neu gene amplification. This makes targeted therapy not feasible in this cancer and hence has poorer prognosis. Detecting AR expression could be another milestone in the management of TNBC, as AR is a prognostic, predictive marker and potential index for targeted treatment. This study aimed to assess expression of AR in TNBC by immunohistochemistry and its association with clinicopathological parameters. METHODS: We analysed the expression of AR in 97 TNBC cases from Penang General Hospital for a period of 3 years (2014 to 2017). Androgen receptor immunoreactivity was considered positive if ≥ 1% of tumour cells nuclei were stained irrespective of staining intensity. RESULTS: The prevalence of AR expression in TNBC was 31% (30/97), with the proportion of AR-positive tumour cells ranged from 1% to 90%. These include 23 invasive carcinomas, no special type (NST) and 7 other invasive carcinoma subtypes (papillary, lobular, clear cell and medullary carcinomas). Sixty-seven cases (69%) that showed AR immunonegativity were invasive carcinomas, NST (n=60), clear cell carcinoma (n=1) and metaplastic carcinoma (n=6). Androgen receptor immunoexpression was inversely correlated with tumour grade (p=0.016), but not the tumour stage, tumour size and nodal status. CONCLUSION: AR is expressed in about one-third of TNBC and loss of AR immunoexpression does not predict adverse clinical outcomes. Larger cohorts for better characterisation of the role of AR immunoexpression in TNBC are warranted.

CNS germinoma with extensive calcification: An unusual histologic finding.

INTRODUCTION: Intratumoral calcification is a feature that is more often observed in pineal parenchymal tumour than germinoma. We describe a 13-year-old male with pineal region germinoma demonstrating extensive intratumoral calcification. CASE REPORT: He presented with worsening headache that was associated with fatigue, nausea and vomiting. Radiologic examination revealed a multilobular mass in the pineal region with internal calcifications. Biopsy showed a pure germinoma with unusually extensive calcification. DISCUSSION: Although a diagnosis may be suggested with a careful evaluation of imaging, there is no pathognomonic pattern. Thus, histologic verification is necessary for most pineal region masses.