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Journal of clinical pathology [journal]
- Reliability of small biopsy or cytology for the diagnosis of pulmonary mucinous adenocarcinoma. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 16.
In case of mucinous adenocarcinoma (MA), cytologic atypia is usually mild to moderate, or may be absent in some cases, incurring a diagnostic pitfall in recognising MA in small tissue biopsy and cytology specimens. The purpose of this study was to evaluate the diagnostic accuracy of transthoracic fine needle aspiration (FNA) or core needle biopsy (CNB) for making a diagnosis of pulmonary MA.We retrospectively reviewed a consecutive series of 185 patients who underwent curative operation for MA. Among those patients, 105 patients underwent preoperative percutaneous FNA (n=34) or CNB (n=79). Eight patients underwent FNA and CNB for the same tumour. Diagnostic accuracies of FNA and CNB for making a diagnosis of MA were evaluated, and the contribution of various clinicopathologic parameters to subtyping accuracy was analysed.Diagnostic accuracies of FNA and CNB in determining malignancy were 67.6% and 87.3%, respectively, and those for making a diagnosis of MA were 20.6% and 59.5%, respectively. Univariate analysis indicated that the type of biopsy procedure and prominent growth pattern of MA are significant factors for successful histologic diagnosis. Tumour nature on CT and the length of biopsy specimen were not related to successful diagnosis of histology subtyping of MA.CNB appears to be feasible and accurate for diagnosing a MA. Prominent growth patterns of MA are significant factors for successful histologic diagnosis of MA.
- The effect of delay in fixation on HER2 expression in invasive carcinoma of the breast assessed with immunohistochemistry and in situ hybridisation. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 15.
Accurate assessment of HER2 status is essential for selection of patients for HER2-targeted treatment such as trastuzumab. This study investigated the hypothesis that delayed fixation impairs HER2 assessment.9 carcinomas were received fresh, and samples were fixed immediately or put in fixative at time intervals up to 24 h. All carcinomas were scored as 3+ with immunohistochemistry in properly fixed tissue.2 of 9 carcinomas (95% CIs 6% to 56%) showed reduced immunohistochemical staining with delays in fixation of 1 and 8 h. One carcinoma showed low-level amplification with fluorescence in situ hybridisation (FISH) when properly fixed and was not amplified after delayed fixation. The other carcinomas were amplified at all time points.Delayed fixation impaired HER2 protein expression assessed using immunohistochemistry in 22% of 3+ carcinomas. HER2 amplification assessed using FISH may be less affected.
- Apoptotic enteropathy caused by antimetabolites and TNF-α antagonists. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 10.
To investigate whether drugs others than mycophenolic acid and ipilimumab might cause graft-versus-host-like apoptotic enteropathy, the clinicopathological findings in four patients were examined who had developed watery diarrhoea and apoptotic enteropathy (three cases from colon and one case from ileal pouch) after intake of antimetabolites (methotrexate and capecitabine) and/or tumour necrosis factor-α inhibitors (etanercept and infliximab).The clinical charts, endoscopy reports and intestinal biopsies from all endoscopies were reviewed for all patients. Biopsies were evaluated semiquantitatively for apoptosis of basal crypts, dilated damaged crypts, defined as cystically dilated crypts with flattened degenerated epithelium containing apoptotic debris and few neutrophils, and mucosal architecture. Further, the presence of intraepithelial lymphocytes, chronic inflammatory cells in the lamina propria and mucosal ulcerations was recorded and immunohistochemical analysis for human cytomegalovirus and herpes simplex virus was performed.Endoscopic examination revealed normal mucosa in two patients, whereas the other two showed focal ulcerations. Histological changes included increased apoptosis of basal crypts, the presence of dilated damaged crypts and architecture distortion. In all cases, a temporal association between drug intake and/or dose increase, and onset of diarrhoea, was observed, and no convincing evidence of other potentially underlying causes of colitis/enteritis was found, including infections.Pathologists should be aware of the expanding spectrum of drugs that can cause apoptotic enteropathy, including antimetabolites and tumour necrosis factor-α inhibitors.
- Pathology reporting of bone marrow biopsy in myelofibrosis; application of the Delphi consensus process to the development of a standardised diagnostic report. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 7.
The diagnosis of primary myelofibrosis (PMF) strongly relies on the bone marrow biopsy findings, but a report model has not been standardised. Our aim was to establish general recommendations for bone marrow evaluation and standardised reporting in a case suspicious of PMF.The Delphi method was employed to obtain expert consensus. An advisory panel of 10 leading members identifies a total of 37 haematopathology experts to participate. The first Delphi round included a questionnaire with three main groups of items: minimal clinical and laboratory data considered necessary before reporting, minimal descriptive aspects to record and main histological differential diagnosis. The final report content was based on consensus obtained after the second Delphi round.The minimal data considered necessary were age, splenomegaly, haemoglobin, leucocyte and platelet counts, differential blood cell count, leucoerythroblastic blood picture, lactate dehydrogenase (LDH) level, BCR-ABL and JAK2 mutational status, reticulin stain and the internal control for the reticulin staining. The minimal descriptive aspects to report were cellularity, osteosclerosis, megakaryocytic morphology and localisation, dense megakaryocytic clusters, quantity of granulocytic precursors, grade of myelofibrosis in a scale of 4, and a proposed final diagnostic approach. The entities to be considered for differential diagnosis were mainly the other classical chronic myeloproliferative neoplasms.The Delphi method is a robust tool to determine essential information to be included in a pathology report. A standardised good-quality histopathological report form may help to homogenise PMF diagnosis. A close collaboration between the pathologist and the haematologist is desirable according to our survey.
- The impact of different point-of-care testing lipid analysers on cardiovascular disease risk assessment. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 7.
Lipid point-of-care testing (POCT) analysers are being used to screen target populations to identify individuals at high risk of developing cardiovascular disease (CVD) as part of the National Health Service (NHS) Health Checks programme. We evaluated the performance of the Cholestech LDX and CardioChek PA POCT analysers against laboratory methods in CVD risk assessment.Ten-year QRISK2, Joint British Societies' II (JBSII), and Framingham CVD risk scores were calculated for subjects recruited from Wolverhampton City PCT community NHS Health Check clinics. CVD risk scores derived using POCT capillary whole blood total cholesterol and HDL-cholesterol measurements were compared with those derived from the laboratory analysis of paired venous serum samples. Data from subjects with diabetes, overt CVD, and those who did not meet the risk algorithm age criteria were excluded.All subjects classified as high risk (risk score >20%) by the three risk algorithms on the basis of the laboratory results were correctly identified by the LDX. One (2.2%) and four (7.0%) moderate-risk subjects were misclassified by the LDX as high risk, using the JBSII and Framingham risk algorithms, respectively. The CardioChek identified all subjects classed as high risk by QRISK2, but failed to identify 6/31 (19.4%) and 3/19 (15.8%) of subjects classed as high risk by the Framingham and JBSII algorithms, respectively. The CardioChek, however, did not misclassify any moderate-risk subjects as high risk.Identification of subjects at risk of CVD depends on the cardiovascular risk algorithm and also on the performance of the POCT device.
- Fat-soluble vitamin deficiency in children and adolescents with cystic fibrosis. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 7.
Determine the prevalence of fat-soluble vitamin deficiency in children with cystic fibrosis (CF) aged ≤18 years in New South Wales (NSW), Australia, from 2007 to 2010.A retrospective analysis of fat-soluble vitamin levels in children aged ≤18 years who lived in NSW and attended any of the three paediatric CF centres from 2007 to 2010. An audit of demographic and clinical data during the first vitamin level measurement of the study period was performed.Deficiency of one or more fat-soluble vitamins was present in 240/530 children (45%) on their first vitamin level test in the study period. The prevalence of vitamins D and E deficiency fell from 22.11% in 2007 to 15.54% in 2010, and 20.22% to 13.89%, respectively. The prevalence of vitamin A deficiency increased from 11.17% to 13.13%. Low vitamin K was present in 29% in 2007, and prevalence of prolonged prothrombin time increased from 19.21% to 22.62%. Fat-soluble vitamin deficiency is present in 10%-35% of children with pancreatic insufficiency, but only a very small proportion of children who are pancreatic-sufficient.This is one of few studies of fat-soluble vitamin deficiency in children with CF in Australia. Fat-soluble vitamin testing is essential to identify deficiency in pancreatic-insufficient children who may be non-compliant to supplementation or require a higher supplement dose, and pancreatic-sufficient children who may be progressing to insufficiency. Testing of vitamin K-dependent factors needs consideration. Further studies are needed to monitor rates of vitamin deficiency in the CF community.
- Enquiry time as part of turnaround time: when do our clinicians really consult our results? [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 4.
Traditionally, laboratories' turnaround times (TAT) have been calculated by only considering analytical or intralaboratory steps. The measure of the postanalytical impact in TAT has barely been studied and, more specifically, the running time from when finalised results are available to when clinicians make their first enquiry with an electronic medical record.During May-June of 2013, two 'Times' were collected from our laboratory information system for all the priority requests coming from our day hospitals: 'Validation time' (TV), as the request report time with full verified results and 'Enquiry time' (TQ), as the time when the first consult was made via electronic medical record. We classified requests in groups depending on time results, and TQ-TV (percentiles) were calculated for each group.654 (69%) requests were consulted by clinicians before 15 : 00 on the same day with available results. 191 (20%) were consulted after 15 : 00 and had complete results as well (p50 (TQ-TV): 5 days) while 61 (7%) were never consulted (up to 31/12/2013). 39 (4%) requests were finally consulted before 15 : 00 h with no available results, but the average time difference between validation and enquiry was 31 min.The results obtained lead us to reconsider the TAT established with our day hospitals in order to know if priority has to be reviewed or if there are failures in follow-up results. 'Enquiry time' appears to be a powerful tool in detecting these issues and shows that TATs are no longer just a 'laboratory problem'.
- New technology in thyroid fine-needle aspiration. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 2.
- Overexpression of integrin αv correlates with poor prognosis in colorectal cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 2.
Integrin αv subunits are involved in tumour angiogenesis and tumour progression in various types of cancers. Clinical trials evaluating agents targeting integrin αv are ongoing. Integrin αv expression has been reported in several cancers in association with tumour progression or poor survival. However, no study has addressed the prognostic influence of integrin αv expression on survival of patients with colorectal cancer (CRC).Immunohistochemical staining of integrin αv was performed in 198 CRC samples to evaluate its prognostic significance.High expression of integrin αv was observed in 58.1% (115/189) of colorectal adenocarcinoma samples, while only in 11.5% (3/26) of tubular adenoma samples and in none of normal mucosa or hyperplastic polyp samples. It was more frequently found in female patients and less frequently observed in well differentiated tumours. The proportion of cases with high expression of integrin αv showed an increasing trend with increased T stage (p=0.032), N stage (p=0.006) and TNM stage (p=0.001). Patients displaying exuberant expression of integrin αv showed shorter overall survival (p=0.001) and disease-free survival (p=0.004). Elevated integrin αv expression was an independent prognostic factor for overall survival (HR: 2.04, 95% CI 1.16 to 3.56; p=0.013) and disease-free survival (HR: 2.19, 95% CI 1.16 to 4.13; p=0.015).Overexpression of integrin αv is associated with advanced T and N stage and as an independent prognostic factor in CRC.
- Multigene profiling to identify alternative treatment options for glioblastoma: a pilot study. [JOURNAL ARTICLE]
- J Clin Pathol 2014 Apr 2.
Glioblastoma (GBM) is a highly aggressive malignancy and the most effective treatment regime has a high relapse rate. Increasingly, the development of therapies involves defining drug-diagnostic combinations where the presence of a molecular target or marker identifies patients who are most likely to respond to a specific therapy. Trials in other solid cancers have demonstrated clear utility in the incorporation of biomarkers to stratify patients to targeted treatment, however, there are no mutations that are currently used to inform treatment options for GBM.We piloted the use of high-throughput next-generation sequencing technology to identify genetic mutations in 44 GBM specimens that may be amenable to current or future targeted therapeutic strategies.Somatic mutation profiling was performed using the AmpliSeq Cancer Hotspot Panel v2 and semiconductor sequencing technology.A total of 66 mutations were detected in 35/44 (80%) patients. The number of mutations per tumour ranged from 0 to 4 (average per tumour=1.5). The most frequent mutations were in TP53 (n=12), PTEN (n=9), EGFR (n=8) and PIK3CA (n=5). Clinically actionable somatic mutations were detected in 24/35 (69%) patients.This study demonstrates that the use of an 'off-the-shelf' oncogene primer panel and benchtop next-generation sequencer can identify mutations and potentially actionable targets in the majority of GBM patients. Data from this pilot highlights the potential for targeted genetic resequencing to identify mutations that may inform treatment options and predict outcomes.