W. Bastiaan de Boer

Complex non-invasive fibrosis models are more accurate than simple models in non-alcoholic fatty liver disease

Background and Aim:  Significant hepatic fibrosis is prognostic of liver morbidity and mortality in non‐alcoholic fatty liver disease (NAFLD); however, it remains unclear whether non‐invasive fibrosis models can determine this end‐point. We therefore compared the accuracy of simple bedside versus complex fibrosis models across a range of fibrosis in a multi‐centre NAFLD cohort.

Can CD34 discriminate between benign and malignant hepatocytic lesions in fine-needle aspirates and thin core biopsies?

Distinguishing well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine‐needle aspiration (FNA) cytology. The endothelial cell marker CD34 is negative in normal hepatic sinusoids and stains vessels diffusely in HCC. This feature is useful in distinguishing benign from malignant hepatocytic lesions in histological specimens, although benign lesions may show focal positivity for CD34 confined to periportal and periseptal areas. In this study, we assess the role of CD34 in cell block and thin core biopsy material from benign and malignant hepatocellular lesions, and compare it with reticulin staining.

Medullary carcinoma of the thyroid

A preoperative diagnosis of medullary carcinoma of the thyroid (MCT) allows for the investigation of associated multiple endocrine neoplasia/pheochromocytoma, and definitive surgery without the need for frozen section. Criteria for cytodiagnosis are well known but variable patterns of presentation may cause diagnostic difficulty.

Pointers and pitfalls of mycophenolate-associated colitis

Aims Mycophenolate-associated colitis has been previously reported to show patterns of colonic mucosal injury mimicking a host of conditions, including graft-versus-host disease, ischaemia and inflammatory bowel disease (IBD). The aim of this study is to characterise, semiquantitatively, pathological changes of mycophenolate mofetil (MMF) mucosal injury. Methods Seven transplant patients receiving MMF who underwent colonoscopic examination and biopsy were identified retrospectively over a 2-year period. Multiple histologic parameters, including architectural distortion, cryptitis, stromal active inflammation, individual damaged crypts (IDC) and crypt apoptotic figures were evaluated in the biopsies semiquantitatively. Where biopsy site was identified, the parameters were assessed separately in biopsies from right and left colon. Results All cases showed mixed patterns of mucosal injury. All seven cases showed focal architectural distortion (in 58% of fragments per case), focal cryptitis (mean 3.0 foci per case), increased crypt apoptosis (mean 26.5/100 crypts) and IDC (mean 3.0 foci). Focal changes resembling acute self-limited colitis were noted in three cases. Possible proximal accentuation of some changes was noted with right side biopsies tending to show greater crypt apoptotic activity and more foci of architectural distortion. Three cases showed dual pathology (two with cytomegalovirus (CMV) infection and one with IBD). Conclusions Although a wide spectrum of changes may be seen in MMF-associated colitis, important microscopic clues include a mixed pattern of injury (typically a combination of crypt apoptosis, isolated crypt damage and architectural distortion), and possible proximal accentuation of pathologic changes. The need for clinical correlation and follow-up is emphasised by the occurrence of dual pathology in patients treated with MMF.

More than just counting eosinophils: proximal oesophageal involvement and subepithelial sclerosis are major diagnostic criteria for eosinophilic oesophagitis

Background According to American Gastroenterological Association Institute criteria, the diagnosis of eosinophilic oesophagitis (EOE) requires clinicopathological correlation. In the appropriate clinical context, a high eosinophil count (HEC, defined as ≥15/HPF) is considered pathological evidence of EOE. However, HEC may not always be identified in biopsies given its patchy distribution, and there may be histological overlap between EOE and gastro-oesophageal reflux disease (GORD) in the distal oesophagus. Aims To evaluate the utility of subepithelial sclerosis and HEC in proximal oesophageal biopsies as additional diagnostic criteria. Methods Cases between 2004 and 2008 with paired proximal and distal oesophageal biopsies and the mention of eosinophils in the reports were retrieved from PathWest Queen Elizabeth II Medical Centre archives. Biopsies were reviewed and assessed for eosinophilic count and presence of subepithelial stroma and sclerosis. A final diagnosis was made after review of both biopsy and clinical details. Results There were 23 cases of EOE and 20 cases of GORD in an adult cohort. In comparison to GORD, cases of EOE had significantly higher eosinophil counts in proximal (39.4 vs 0.6 eosinophils/HPF) and distal biopsies (35.6 vs 1.9), with HEC in proximal biopsies a feature exclusive to EOE (83% vs 0%). Subepithelial sclerosis was identified in at least one biopsy in 74% of EOE and in only a single case of GORD. Conclusions HEC in proximal oesophageal biopsies and subepithelial sclerosis should be considered major diagnostic findings in EOE.

Image analysis of liver biopsy samples measures fibrosis and predicts clinical outcome

BACKGROUND & AIMS Histopathological scoring of liver fibrosis mainly measures architectural abnormalities and requires a minimum biopsy size (⩾ 10 mm). Liver collagen quantification may allow use of small size biopsies and improve the prediction of clinical outcomes. This study evaluated the ability of the collagen proportional area (CPA) measurement to predict clinical outcomes. METHODS Clinical outcomes were determined using population based data-linkage for chronic hepatitis C (CHC) patients from 1992 to 2012. Quantitative digital image analysis of liver biopsies was used for CPA measurement. RESULTS 533 patients with a biopsy size ⩾ 5 mm were included. Median follow up was 10.5 years. 26 developed hepatocellular carcinoma (HCC), 39 developed liver decompensation and 33 had liver related death. 453 had Metavir F0-F2 and 80 had F3-F4. CPA ranged from 1.3% to 44.6%. CPA and Metavir stage were independently associated with liver related death. Metavir stage, CPA stage and age were independently associated with HCC. CPA stage (C1: 0%-5%, C2: 5%-10%, C3: 10%-20%, C4: >20%) stratified risk and a significant difference in outcomes was present between all CPA stages for HCC and between C2-C3 and C3-C4 for decompensation and liver related death. The 15 year composite endpoint-free survival was 97% for C1, 89% for C2, 60% for C3, 7% for C4. C4 had significantly worse survival than ⩽ C3 (p<0.001) in cirrhotic patients. CONCLUSIONS CPA stage gave additional information regarding risk stratification for adverse clinical outcomes independent of Metavir stage.

Cytodiagnosis of well differentiated hepatocellular carcinoma

Distinction of well differentiated hepatocellular carcinoma (HCC) from benign hepatocellular lesions is a well recognized problem in fine‐needle aspiration (FNA) cytology, sometimes leading to indeterminate reports. The aim of this study was to critically examine criteria that might allow definitive diagnosis in these cases.

Optimizing the multimodal approach to pancreatic cyst fluid diagnosis developing a volume-based triage protocol

The objective of this study was to develop a triage algorithm to optimize diagnostic yield from cytology, carcinoembryonic antigen (CEA), and v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing on different components of a single pancreatic cyst fluid specimen. The authors also sought to determine whether cell block supernatant was suitable for CEA and KRAS testing.

Addressing current problems in teaching pathology to medical students: blended learning

Background: Forces influencing the remodelling of medical curricula have clouded the visibility of pathology teaching yet its mastery is central to the study of medicine. The shortage in the workforce available for routine clinical diagnosis, research and teaching, and increasing student numbers have driven the development of innovative teaching methods. Aims: To develop teaching methods which improved student satisfaction and engagement in their learning of pathology, and which also accommodated larger classes. Methods: An iterative development cycle adopting effective use of the web and sound instructional design pedagogies was followed. Two face-to-face formats, i.e. small group and large group, and a self-directed web-based (online) format were implemented on a cohort of 220 third year medical students. Outcomes were evaluated by analysis of a student preceptions questionnaire and of students’ web footprints in the online resource. Results: Themes relating to teaching techniques, learning preferences and accessibility issues emerged as significant in the students’ perceptions. Measures of user “online avidity”, “case breadth compliance” and “formative assessment compliance/diligence” were determined by comparing historical behaviour in the web resource with patterns of use within these modules. Students who were proven avid online users entered the resource more frequently than less avid users. However less avid online users did not necessarily access a narrower breadth of cases than avid online users. Students who made maximal use of the web formative assessments tended to have better summative outcomes. Conclusions: The students adopted the online resource as a learning tool. The optimal combination of small group face-to-face tutorials and the self-directed web-based (online) format improved pathology teaching, partly because it satisfied a broader range of learning styles in students. The cycle used of develop, implement, evaluate was successful as it engaged the students, was evidence based and driven by discipline experts who were commited teachers.

Hepatic iron loading in patients with compound heterozygous HFE mutations.

Abstract: Aim: To assess the severity of hepatic iron loading in patients with a compound heterozygous C282Y/H63D HFE genotype.