Journal of clinical pathology [journal]
- DOG1 expression in phosphaturic mesenchymal tumour. [LETTER]
- J Clin Pathol 2016 Jul 19.
- β-Catenin activation in fundic gland polyps, gastric cancer and colonic polyps in families afflicted by 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS). [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 12.
To evaluate possible colon involvement in the 'gastric adenocarcinoma and proximal polyposis of the stomach' (GAPPS) gastrointestinal polyposis syndrome.Prospective clinicopathological evaluation of two GAPPS families and expression of nuclear β-catenin, p53 and Ki67 measured by immunohistochemistry on endoscopic and surgical specimens from patients with GAPPS.Patients with the GAPPS phenotype were more frequently affected by colonic polyps than patients at risk within the same families (p<0.01). Colonic polyps shared immunohistochemical features of fundic gland polyps and gastric cancers including increased expression of nuclear β-catenin, Ki67 and p53. Both gastric and colonic lesions harboured activating somatic variants of β-catenin signalling.Similarities in expression markers in fundic gland and colonic polyps, together with an enrichment of colonic adenomas in family members affected by GAPPS phenotype compared with family members at risk, support mild colonic involvement of this rare cancer syndrome. Colonoscopic screening might be warranted.#09-C-0079; Results.
- Review of the national external quality assessment (EQA) scheme for breast pathology in the UK. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 12.
The National Health Service Breast Screening Programme (NHSBSP; pathology) external quality assurance (EQA) scheme aims to provide a mechanism for examination and monitoring of concordance of pathology reporting within the UK. This study aims to review the breast EQA scheme performance data collected over a 24-year period following its introduction.Data on circulations, number of cases and diagnosis were collected. Detailed analyses with and without combinations of certain diagnostic entities, and over different time periods were performed.Overall, of 576 cases (172 benign, 11 atypical hyperplasia, 98 ductal carcinoma in situ/microinvasive and 295 invasive disease), consistency of assessment of diagnostic parameters was very high (overall k=0.80; k for benign diagnosis=0.79; k for invasive disease=0.91). For distinguishing benign versus malignant lesions, no further improvement is considered possible in view of the limitations of the scheme methodology. Although diagnostic consistency of atypical hyperplasia remains at a low level, combining it with the benign category results in a high level of agreement (k=0.93). The level of consistency of reporting prognostic information is variable and some items such as lymphovascular invasion and tumour size measurement may need further intervention to improve their reporting consistency. Although the level of consistency of reporting of histological grade remained at a moderate level overall (k=0.48), it was variable among cases and appears to have levelled off; no further significant improvement is expected and no significant impact of the previous publication of guidelines is observed.These results provide further evidence to indicate the value of the breast EQA scheme in monitoring performance and the identification of specific areas where improvement or new approaches are required. For most parameters, the concordance of reporting reached a plateaux a few years after the introduction of the EQA scheme. It is important to maintain this high level and also to tackle specific low-performance areas innovatively.
- Evaluation of the Metasin assay for intraoperative assessment of sentinel lymph node metastases in breast cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 12.
Sentinel lymph node (SLN) biopsy is the preferred surgical technique for staging the axilla in clinically node-negative breast cancer. Accurate intraoperative staging allows for the immediate performance of an axillary clearance in node-positive patients. We assessed the Metasin assay for the intraoperative analysis of SLNs in a prospective evaluation of 250 consecutive patients undergoing intraoperative SLN analysis at the Breast Unit, University Hospital, Southampton, UK.Metasin uses a quantitative reverse transcription PCR to detect two markers of metastasis: cytokeratin 19 (CK19) an epithelial marker and mammaglobin (MGB) a breast specific marker. Metasin results were compared with the results from routine paraffin block histopathology.Metasin was robust, with a failure rate of <1%, and demonstrated excellent accuracy and reproducibility. The average turnaround time for the Metasin assay was 42 min, the largest variable being the number of nodes assayed. A total of 533 SLNs were evaluated with 75 patients testing positive for MGB and/or CK19. Based on the analysis of individual SLNs, the overall concordance between Metasin and histology was 92.3% (sensitivity 88.7%, specificity 92.9%). When adjusted for tissue allocation bias, the concordance was 93.8% (sensitivity 89.8%, specificity 94.6%). In this evaluation, 57/250 patients (23%) proceeded to axillary clearance based on Metasin results and were considered spared a second operative procedure.Metasin has proven to be an accurate, reproducible and reliable laboratory test. The analysis time is acceptable for intraoperative use, and in comparison to routine histology demonstrates acceptable concordance, sensitivity and specificity.
- Different expression patterns of LGALS1 and LGALS3 in polycythemia vera, essential thrombocythemia and primary myelofibrosis. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 11.
Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.
- Assessment of myeloid and monocytic dysplasia by flow cytometry in de novo AML helps define an AML with myelodysplasia-related changes category. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 7.
In recent years, multiparameter flow cytometry has been increasingly recognised as an important tool in diagnosis of myelodysplastic syndrome and acute myeloid leukaemia (AML). Assessment of myeloid and monocytic 'immunophenotypic' dysplasia by flow cytometry in de novo AML has not been evaluated.97 cases of de novo AML cases were identified and reviewed by three hematopathologists. 'Immunophenotypic' dysplasia was assessed on blasts, monocytes and granulocytes by mean fluorescence intensity.Using the 2008 WHO classification criteria, there were 53 AML-not otherwise specified (NOS) (55%) and 28 AML with myelodysplasia-related changes (AML-MRC) (29%), while 16 cases were ambiguous as to AML-MRC status due to limited maturing cells for morphologic but adequate events number for immunophenotypic evaluation (AML-not evaluable, 16%). Compared with AML-NOS, granulocytic cells in AML-MRC had higher CD33 expression but lower CD45, CD11b and CD15. Monocytes in AML-MRC had lower expression of CD14, CD56 and CD45. Morphologic dysplasia was associated with significantly lower granulocytic forward scatter, side scatter and CD10 but higher CD33 expression.Our results suggest that the workup of AML cases should include flow cytometric assessment of granulocytes and monocytes. This analysis can aid a morphologic impression of multilineage dysplasia in distinguishing AML-MRC from AML-NOS, especially in cases with limited maturing myeloid cells.
- Single thyroid tumour showing multiple differentiated morphological patterns and intramorphological molecular genetic heterogeneity. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 7.
A 49-year-old man presented with a single thyroid tumour that showed a combination of conventional papillary carcinoma, follicular variant of papillary carcinoma, clear cell papillary carcinoma, columnar cell carcinoma and poorly differentiated carcinoma. As all of the morphologies have been associated with papillary carcinoma in the literature, we wished to determine if they contained identical or different molecular abnormalities.Targeted next generation sequencing (NGS) of each morphological component and metastases was performed.NGS revealed a BRAF p.K601E mutation in both the clear cell papillary carcinoma and poorly differentiated carcinoma and a KRAS p.G12R mutation in the papillary carcinoma, follicular variant. Two different areas of columnar cell variant were tested, with one showing a KRAS p.G12D mutation but no mutation in the other area. A KRAS p.G12R mutation was seen in the metastatic clear cell variant. Two different lymph nodes had metastatic columnar cell carcinoma, one negative for mutations but the other with a compound KRAS p.G12R and KRAS p.G12V mutation on different alleles. No mutations including BRAF and KRAS were seen in the conventional papillary carcinoma.Although all of the morphological patterns in this tumour have been reported as having aetiological or other association with one another, there was only partial concordance with their molecular signatures. There was significant molecular discordance, however, even with identical morphologies.
- Extranodal extension of lymph node metastasis is a marker of poor prognosis in oesophageal cancer: a systematic review with meta-analysis. [REVIEW, JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 7.
The extranodal extension (ENE) of nodal metastasis is the extension of neoplastic cells through the nodal capsule into the perinodal adipose tissue. This histological feature has recently been indicated as an important prognostic factor in different types of malignancies; in this manuscript, we aim at defining its role in the prognosis of oesophageal cancer with the tool of meta-analysis. Two independent authors searched SCOPUS and PubMed until 31 August 2015 without language restrictions. The studies with available data about prognostic parameters in subjects with oesophageal cancer, comparing patients with the presence of ENE (ENE+) versus only intranodal extension (ENE-), were considered as eligible. Data were summarised using risk ratios (RRs) for number of deaths/recurrences and HRs together with 95% CIs for time-dependent risk related to ENE+, adjusted for potential confounders. Fourteen studies were selected; they followed-up 1437 patients with oesophageal cancer for a median follow-up of 39.4 months. The presence of ENE was associated with a significantly increased risk of all-cause mortality (RR=1.33; 95% CI 1.18 to 1.50, p<0.0001, I(2)=49%; HR=2.72, 95% CI 2.03 to 3.64, p<0.0001, I(2)=0%), cancer-specific mortality (RR=1.35; 95% CI 1.14 to 1.59, p=0.001, I(2)=57%; HR=1.97, 95% CI 1.41 to 2.75, p<0.0001, I(2)=41%) and of risk of recurrence (RR=1.50, 95% CI 1.20 to 1.88, p<0.0001, I(2)=9%; HR=2.27, 95% CI 1.72 to 2.90, p<0.0001, I(2)=0%). On the basis of these results, in oesophageal cancer, ENE should be considered from the gross sampling to the pathology report, and in future oncological staging system.
- Haemoglobinopathies that occur with decreased HbA2 levels: a gene mutation set involving the δ gene at a Spanish centre. [JOURNAL ARTICLE]
- J Clin Pathol 2016 Jul 7.
Haemoglobin A2 (HbA2) consists of two globin chains, α and β. Alterations in any of these genes influences the level of HbA2. Here, we present cases of structural Hb variants and thalassaemias which present either alone or together and reduce the level of HbA2 at varying degrees. Furthermore, we present a novel structural mutation in the δ globin gene, called Hb A2-Madrid.The levels of HbA2 and HbF and the different haemoglobin variants were measured and analysed by ion exchange high performance liquid chromatography (HPLC, VARIANT II), the types of haemoglobins were determined by capillary zone electrophoresis (CZE) (Sebia) and the globin chains were determined by reversed-phase HPLC. Genetic analysis was performed by automatic sequencing of the α and δ genes as well as by multiple PCRs for the α globin genes.In α thalassaemia (n=94), the HbA2 levels ranged from 1.39% to 2.43%. Among individuals with δ thalassaemia (n=5), the HbA2 level of those with δ(+) thalassaemia was 1.77%, and that of those with δ(0) thalassaemia was 1.70%. Among the individuals with δβ thalassaemia (n=13), those who were homozygous lacked HbA2. All structural haemoglobinopathies (n=97) were heterozygous; the α chain variants (n=84) presented with an HbA2 level of 1.76%, while the δ chain variants (n=13) presented with a level of 1.75%.HbA2 is an essential parameter in the diagnostics of haemoglobinopathies. HPLC-EC and CZE allow the quantification of HbA2. Here, we show that quantification of HbA2 is critical for the identification of α, δ and βδ thalassaemias. Structural variants are discovered by HPLC. Molecular genetics is required for the proper identification of the mutations. Only with this knowledge is genetic counselling possible.