Presence of Hepatic Steatosis Does Not Increase the Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Over Long Follow-Up.

BACKGROUND: Chronic hepatitis B (CHB) infection and nonalcoholic fatty liver disease (NAFLD) are liver diseases which may lead to hepatocellular carcinoma (HCC) formation. Both disease entities have been attributed independently to increase risk of HCC development. While concomitant hepatic steatosis in patients with CHB are becoming more frequent in view of increasing NAFLD prevalence, there is no conclusive evidence linking presence of hepatic steatosis and increased HCC risk in patients with CHB infection. This study explores the association of hepatic steatosis among CHB-infected individuals in HCC development. METHODS: This is a retrospective study on a cohort of patients with CHB who underwent liver biopsy between January 2000 and December 2014. They were stratified according to presence and severity of histologically proven hepatic steatosis and subsequently followed up to evaluate the association between hepatic steatosis and HCC development. RESULTS: Among 289 patients with a median follow-up of 111.1 months, hepatic steatosis was present in 185 patients (64.0%). In all, 27 patients developed HCC on follow-up and 21 of them had hepatic steatosis. Univariate Cox analysis showed that age (hazard ratio [HR] = 1.08, 95% CI = 1.042-1.12), type 2 diabetes mellitus (T2DM) (HR = 4.00, 95% CI = 1.622-9.863), and Ishak score (HR = 1.221, 95% CI = 1.014-1.472) were associated with HCC development, whereas multivariate Cox analysis demonstrated that age and T2DM (HR = 2.69, 95% CI = 1.072-6.759) were significant risk factors for development of HCC. CONCLUSIONS: Concurrent hepatic steatosis in patients with CHB infection is not a risk factor for hepatocellular carcinoma formation.

An integrated automated multispectral imaging technique that simultaneously detects and quantitates viral RNA and immune cell protein markers in fixed sections from Epstein-Barr virus-related tumours.

BACKGROUND/AIM: Epstein-Barr virus (EBV) is an oncovirus that is commonly associated with the development of lymphomas and epithelial carcinomas. In the era of immunotherapy, histological evaluation of EBV-related cancers is currently a multi-sample, multi-technique process requiring separate time-consuming detection of EBV-encoded small RNAs by in situ hybridisation (ISH), and parallel labelling of sections for cancer-associated protein markers. METHODS: Using EBV-associated tumours as proof-of-concept for feasibility, here we developed an approach that allows simultaneous detection of EBV RNAs and multiple protein markers such as PD-L1, EBV-LMP, CD8, CD4, CD20, CD30 and CD15on a single tissue section based on our recently reported automated staining protocol. RESULTS: We successfully combined multiplex immunofluorescence (mIF) to detect 3 abovementioned protein markers involved in cancer, with ISH, and applied the protocol to f tissue samples from patients diagnosed with EBV-associated pulmonary lymphoepithelioma-like carcinoma (LELC), gastric carcinoma and Hodgkin's Lymphoma. Empowered by the Vectra 3 Automated Quantitative Pathology Imaging System, we demonstrate the utility and potential of this integrated approach to concurrently detect and quantitate viral RNA and protein biomarkers of immune and tumour cells. CONCLUSION: This study represents an important step forward in the research and diagnosis of EBV-associated cancers, and could be readily modified to include other proteins and RNA markers to apply to other malignancies. More importantly, the novel automated ISH-mIF protocol that we detailly described here could also be readily reproduced by most of the diagnostic and research lab to future projects that aim to look at both RNA and protein markers.

Diagnostic pitfall: Adenoid cystic carcinoma of the tongue presenting as an isolated hypoglossal nerve palsy, case report and literature review.

INTRODUCTION: We describe a patient with an unusual presentation of an isolated hypoglossal nerve palsy as a result of perineural invasion (PI) from adenoid cystic carcinoma (ACC). We will also discuss the diagnostic pitfalls as well as present a short literature review of adenoid cystic carcinomas and suggest improvement to the current diagnostic algorithm for isolated hypoglossal nerve palsies. PRESENTATION OF CASE: A 63year old Malay female presented with progressive dysphagia and slurred speech for one year. Physical examination showed unilateral right tongue wasting, fasciculation and deviation to the right. An MRI showed atrophy of the tongue due to denervation and subsequently she was treated in a neurology clinic for 8 months. Due to lack of improvement, she was referred to our surgical unit and underwent examination under anaesthesia (EUA) and biopsy. Histology showed adenoid cystic carcinoma with perineural involvement, resulting in lower motor neuron signs. She underwent radiotherapy to the base of her tongue (70Gy/35#). A PET-CT one month post treatment showed complete response. DISCUSSION: Adenoid cystic carcinoma (ACC) is a salivary gland neoplasm. It is characterized by local invasiveness with frequent recurrence and indolent growth. It affects major salivary glands more than minor salivary glands. In malignancies that have a propensity for PI such as ACC, patients may present atypically with nerve palsies. In infiltrative lesions, the primary tumour may not be evident on magnetic resonance imaging. Therefore, to achieve a diagnosis, a high index of suspicion is required. When the diagnosis is in question, deep biopsy and positron emission tomography may be useful.

Enabling digital pathology in the diagnostic setting: navigating through the implementation journey in an academic medical centre.

AIMS: As digital pathology (DP) and whole slide imaging (WSI) technology advance and mature, there is an increasing drive to incorporate DP into the diagnostic environment. However, integration of DP into the diagnostic laboratory is a non-trivial task and filled with unexpected challenges unlike standalone implementations. We share our journey of implementing DP in the diagnostic laboratory setting, highlighting seven key guiding principles that drive the progression through implementation into deployment and beyond. METHODS: The DP implementation with laboratory information system integration was completed in 8 months, including validation of the solution for diagnostic use in accordance with College of American Pathologists guidelines. We also conducted prospective validation via paired delivery of glass slides and WSI to our pathologists postdeployment. RESULTS: Common themes in our guiding principles included emphasis on workflow and being comprehensive in the approach, looking beyond pathologist user champions and expanding into an extended project team involving laboratory technicians, clerical/data room staff and archival staff. Concordance between glass slides and WSI ranged from 93% to 100% among various applications on validation. We also provided equal opportunities for every pathologist throughout the department to be competent and confident with DP through prospective validation, with overall concordance of 96% compared with glass slides, allowing appreciation of the advantages and limitations of WSI, hence enabling the use of DP as a useful diagnostic modality. CONCLUSIONS: Smooth integration of DP into the diagnostic laboratory is possible with careful planning, discipline and a systematic approach adhering to our guiding principles.

Single centre experience of transjugular liver biopsy in 152 patients.

INTRODUCTION: Liver biopsy is considered the definitive investigation in the diagnosis and management of liver disease. This study describes the experience of performing transjugular liver biopsy (TJLB) over the last 9 years in a local single centre. MATERIALS AND METHODS: A retrospective review of consecutive TJLB procedures performed at our institution was conducted. A total of 152 patients (74 males and 78 females), with a mean age of 47.4 years (range, 13 to 83 years) underwent a total of 154 TJLB procedures at our institution between March 2003 and November 2011. The principal indication for TJLB was severe coagulopathy in over 80% of patients. The technical success, number of passes, histological adequacy and complication rates were analysed. RESULTS: The procedural success rate was 98.7% (152 out of 154 procedures). Adequate material for diagnosis was obtained in 149 out of 152 (98.0%) technically successful procedures. There was procedure related morbidity in 8 patients (5.2%) of which all but one were self-limiting requiring no further intervention. We also performed hepatic venous pressure gradient (HVPG) measurements in 19% of patients at the time of TJLB. CONCLUSION: TJLB performed at our institution is a safe and reliable technique in patients in whom traditional percutaneous liver biopsy may be hazardous. TJLB has a high technical success rate as well as a high diagnostic yield with a low complication rate. TJLB also has the added benefit of performing HVPG, which is of increasing importance in management and prognostication of chronic liver disease.

Plasmacytoma of the pancreas: an unusual manifestation of multiple myeloma.

Extramedullary plasmacytoma of the pancreas is a rare entity. Although this condition is uncommon, it should be considered in the differential diagnosis of solid mass in the pancreas, especially in patients with underlying multiple myeloma. We report a case of pancreatic plasmacytoma in a 56-year-old woman with newly diagnosed multiple myeloma. We highlight this rare manifestation of multiple myeloma among other better recognised presentations.

IgG4-related disease in Singapore: a description of two cases and review of the literature.

We describe a 42-year-old man who presented with painless obstructive jaundice, organomegaly and lymphadenopathy. Biopsy of the ampulla of Vater revealed the presence of increased populations of plasma cells which stained positively for immunoglobulin G4. He was treated with prednisolone and demonstrated significant clinical improvement 1 month later. A further case is described and a review of the literature is also provided.

A deleterious BRCA1 mutation in a young Pakistani woman with metaplastic breast carcinoma.

Metaplastic breast carcinoma (MBC) is a relatively rare subtype of breast cancer that encompasses a pathologically heterogeneous group of tumors. Pathogenic germ line mutations in the major breast cancer susceptibility genes BRCA1 and BRCA2 genes have been rarely found or described in MBC. We report the identification of the BRCA1 185delAG mutation in a 22-year-old Pakistani woman with triple-negative MBC that showed biphasic morphological features, including sarcomatous and malignant epithelial components. A comprehensive description of the clinical, histopathological, morphological, and immunohistochemical features of the tumor and the patient's treatment course is presented.

Central mucoepidermoid carcinoma, a case report with molecular analysis of the TORC1/MAML2 gene fusion.

Mucoepidermoid carcinoma is the most common salivary gland malignancy. The majorities of these tumors arise in the parotid and minor salivary glands, but may rarely develop intraosseously. The latter is not uncommonly associated with diagnostic and management difficulties. We report an example of intraosseous mucoepidermoid carcinoma with positive TORC1/MAML2 gene fusion transcript and discuss the clinical implications.

Differentiated thyroid carcinoma in a juvenile patient.

Juvenile differentiated carcinoma thyroid is a rare entity. It differs from adult differentiated thyroid carcinoma in a variety of ways, including large tumor volume at presentation with early involvement of the capsule, more frequent nodal and distant metastases, greater expression of sodium-iodide symporter and early recurrence. The overall survival seems to be better than for adult patients; however, due to high and early recurrence rates, prompt and adequate treatment is advocated. The mainstay of treatment includes total thyroidectomy, central lymphadenectomy with modified radical lateral lymphadenectomy, followed by ablation with radioactive iodine (RAI). Both modalities improve the final outcome, but RAI ablation decreases cause-specific death risk independent of the extent of surgery. We present the case of a 5-year-old girl, the youngest ever treated in our country with surgery and RAI therapy successfully after being diagnosed as papillary carcinoma of the thyroid, follicular variant.

Skin metastasis from prostate adenocarcinoma.

We are presenting an interesting case of skin metastasis from adenocarcinoma prostate. Interestingly bone metastasis were absent as documented on radioisotope bone scan and PSA levels were normal. As it was a hormone refractory disease, he was started on mitoxantrone and prednisolone chemotherapy. Lung metastatis appeared after 2 cycles of chemotherapy. He died of progressive disease 4 months later.