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Journal of clinical pathology [journal]
- Bone marrow trephine biopsy involvement by lymphoma: review of histopathological features in 511 specimens and correlation with diagnostic biopsy, aspirate and peripheral blood findings. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Dec 10.
This study aimed to evaluate the key features of bone marrow trephine (BMT) biopsy involvement by lymphoma.511 cases were assessed for percentage of marrow involvement, pattern of involvement (diffuse, nodular, paratrabecular, interstitial or intrasinusoidal), presence/absence of granulomas, stromal fibrosis and necrosis, presence/absence of neoplastic/reactive follicles and discordance with other biopsy sites. Correlation with aspirate and peripheral blood findings was made in a subset of 345 patients (167 aspirates, 178 blood).The most frequent subtype was follicular lymphoma (26.2%) followed by extranodal marginal zone (23.1%), lymphoplasmacytic (19.2%), diffuse large B cell (DLBCL) (12.5%), Hodgkin (HL) (5.7%) and mantle cell lymphomas (4.3%). The predominant pattern in follicular lymphoma was paratrabecular. Marginal zone lymphomas of all types and lymphoplasmacytic lymphoma showed a relatively even distribution between diffuse, interstitial, paratrabecular and nodular patterns. The majority of mantle cell lymphoma cases showed either diffuse or nodular patterns. A diffuse pattern was common in DLBCL and Burkitt lymphomas. An intrasinusoidal pattern was seen only in extranodal and splenic marginal zone lymphomas. Granulomas and fibrosis were uncommon in small cell B cell lymphomas but frequent in DLBCL and HL. Aspirate and trephine results concurred in 73.8% of cases overall, but this varied widely between subtypes. Peripheral blood involvement rates by lymphoma also varied, with a mean of 37.1%.Different lymphomas often demonstrate reliably characteristic architectural patterns of marrow involvement which can help differentiate them even when cytological features do not permit this, and marrow stromal and other background changes may also be useful pointers towards a particular lymphoma subtype.
- The association of serum antiphospholipid antibodies and dilute Russell's viper venom times. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Dec 10.
We hypothesised that there is a threshold value for the association of dilute Russell's viper venom times (dRVVT) with positive immunoglobin G antiphospholipid antibody (IgG-APLA) test results.We tested 120 controls and a cohort of 2412 outpatients who had concomitant test results for dRVVT and IgG-APLA (IgG antibodies to cardiolipins and β2-glycoprotein I). We also selected a subgroup who had repeated IgG-APLA tests at least 12 weeks apart (1398 patients with multiple β2-glycoprotein I tests and 672 with multiple aCL tests). We cross tabulated the proportion of IgG-APLA single positive, double positive and persistently positive antibodies with dRVVT values.The distribution of the dRVVT results from the reference population was consistent with an upper limit of the reference interval of 1.22 to >1.48. A consistent increase in the proportion of IgG-APLA single, double positive and persistently positive antibody tests occurred in the group with a normalised dRVVT ratio of 1.40-1.49. IgG-APLA double positivity was found in 12.5% (4 of 32) patients with a ratio of dRVVT 1.40-1.49 compared with 3.3% (6/181) of those with a ratio of dRVVT 1.20-1.39 (p=0.045).We conclude that there is an association between dRVVT positivity and elevated proportions of single, double and persistently positive IgG-APLA test results with an apparent threshold effect. These findings may provide a general guide to risk and suggest a way to choose from a wide range of possible upper limits of the reference interval.
- Quantitative flow cytometric identification of aberrant T cell clusters in erythrodermic cutaneous T cell lymphoma. Implications for staging and prognosis. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Dec 6.
Assessment of peripheral blood tumour burden for staging of cutaneous T cells lymphoma is most often accomplished by flow cytometry (FC) using various non-standarised strategies. We report the results of calculating absolute Sezary cell counts (SCCs) by FC, based on the identification of aberrant T cell clusters on a virtual 6-dimensional space and independently of the expected immunophenotype (6D-FC SCC).6D-FC SCCs were calculated on 65 peripheral blood specimens from 28 patients with erythrodermic cutaneous T cells lymphoma (stage III or IV). Comparisons were made with recommended FC strategies and correlations with overall mortality were studied.At first visit, 17 of 28 patients (61%) had 6D-FC SCCs meeting current criteria for Stage IV disease (≥1000 SC/μL); while only 2 patients (7%) met Stage IV criteria on other tissues. As defined by comprehensive staging using clinicomorphological criteria and 6D-FC SCCs, Stage IV disease identified a subgroup of patients with worse overall survival (p=0.0227). Residual non-aberrant CD4 T cells were markedly decreased in Stage IV disease (p=0.018). Among 65 specimens, discrepancies were observed between 6D-FC SCCs and usual FC thresholds for Stage IV disease, namely a CD4:CD8 ratio ≥10:1 (9 discrepancies, 14%), and ≥40% aberrant CD4 T cells (4 discrepancies, 6%). Surprisingly, 8 cases (12%) from 6 patients exhibited two distinctively separate clusters of aberrant CD4 T cells with different CD7 and/or CD26 expression.Visual 6-dimensional identification of aberrant T cell clusters by FC allows for the calculation of clinically significant SCCs. Simplified gating strategies and relative quantitative values might underestimate the immunophenotypical complexity of Sezary cells.
- Comparison of D-dimer point of care test (POCT) against current laboratory test in patients with suspected venous thromboembolism (VTE) presenting to the emergency department (ED). [JOURNAL ARTICLE]
- J Clin Pathol 2013 Dec 4.
To compare quantitative point of care (POC) with laboratory d-dimer testing in patients with suspected venous thromboembolism (VTE) presenting to the emergency department.A prospective single centre diagnostic study in adults presenting with suspected VTE (pleuritic chest pain or leg swelling) RESULTS: Main outcome measures were the statistical correlation of the two methods. Secondary outcome measures were: test turnaround times, correlation between D-dimer levels, Wells score and final diagnosis. The results showed that there was strong evidence of POC D-dimer being sufficiently accurate to be used as a screening device. The correlation between the two logged assay scores was good. Both logged scores correlated similarly with the Wells score. Once an equivalent cut-off value for POC D-dimer (412 ng/mL) was established, there were only 4 of 100 cases all of which were extremely close to the cut-off. D-dimer turnaround time decreased by 83%. A further recent analysis of laboratory times done in 2013 demonstrates that POC D-dimer results remain 62% quicker. Based on the D-dimer results 27 patients were scanned. The median Wells score in this group was 3.0 (range 2-10) median POC D-dimer levels of 2590 (412-5000) and median lab D-dimer levels of 864 (230-13 000) showing good correlation between D-dimer positive patients and the Wells score. Seven patients had positive scans. There was a significant difference in both logged D-dimer scores between the negative and positive groups indicating that raised D-dimer levels correlate well with final diagnosis.The POC device was comparable with the laboratory device and was sufficiently accurate to be used as a screening tool in the emergency department setting.
- Expression of thymoproteasome subunit β5t in type AB thymoma. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Dec 10.
Type AB thymoma is a thymic epithelial tumour composed of lymphocyte-poor type A and lymphocyte-rich type B components. Although it is categorised as a single entity in the classification of WHO, it shows a broad range of morphology. To investigate whether the functional characteristic of neoplastic cells in type AB thymoma relates to morphological diversity, we performed immunohistochemical analysis using anti-β5t antibody in 20 cases of type AB thymoma. β5t is a recently discovered proteasomal β subunit expressed exclusively in cortical thymic epithelial cells and tumour epithelial cells of thymomas with cortical differentiation. Consistent with our previous observation, β5t was predominantly expressed in the type B component. When the type B component was divided into three groups morphologically, β5t was expressed more frequently in cases with round to polygonal than spindle to oval tumour cells. Furthermore, the ratio of terminal deoxynucleotidyl transferase (TdT)-positive lymphocytes was increased in components with higher expression of β5t. These results indicate that the histological diversity of type AB thymoma correlates with expression of a functional marker β5t and abundance of TdT-positive lymphocytes.
- Alteration of energy metabolism in the pathogenesis of bile duct lesions in primary biliary cirrhosis. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Nov 29.
Primary biliary cirrhosis (PBC) is characterised by antimitochondrial antibody against the pyruvate dehydrogenase complex (PDC) and chronic non-suppurative destructive cholangitis (CNSDC). Pyruvate oxidation to acetyl-CoA by PDC is a key step in the glycolytic system. Oestrogen-related receptor-α (ERRα) is functionally activated by inducible coactivators such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and Bcl-3. Moreover, the PGC-1α-ERRα axis interrupts glycolytic metabolism through the upregulation of pyruvate dehydrogenase kinase, isozyme 4 (PDK4), which functionally inhibits PDC-E1α and stimulates fatty acid oxidation. In this study, we investigated the PGC-1α-ERRα axis to clarify PDC dysfunction in CNSDC of PBC.The expression of PGC-1α, Bcl-3, ERRα, PDK4 and PDC-E1α was examined by immunohistochemistry in liver sections from patients with PBC and controls. The expression of these molecules, the activity of mitochondrial dehydrogenase and PDC, and their alterations by starvation, a treatment used to induce PGC-1α expression, were examined in cultured human biliary epithelial cells (BECs).The nuclear expression of PGC-1α, Bcl-3 and ERRα was exclusively observed in CNSDC of PBC. Moreover, the expression of PDK4 and PDC-E1α was enhanced in CNSDC of PBC. In cultured BECs, the amplification of Bcl-3 and PDK4 mRNAs by reverse-transcription-PCR and mitochondrial dehydrogenase activity were markedly increased but PDC activity was decreased according to the upregulation of PGC-1α.In CNSDC of PBC, the activation of the ERRα-PGC-1α axis was exclusively observed, suggesting the interference of PDC-related glycolytic function and the induction of the fatty acid degradation system. The switching of the cellular energy system is possibly associated with the pathogenesis of CNSDC in PBC.
- Chromogenic in situ hybridisation (CISH) is a powerful method to detect ALK-positive non-small cell lung carcinomas. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Nov 29.
We assessed the potential of a chromogenic in situ hybridisation (CISH) assay in comparison with quantitative reverse transcription (RT)-PCR (qPCR) to detect anaplastic lymphoma kinase (ALK) break apart-positive lung carcinomas.Dual-colour CISH using a break apart probe for the ALK gene on 2p23 was performed with 181 formalin-fixed, paraffin-embedded tissue and agar block sections from 175 cases of non-small cell lung carcinomas (NSCLC). Stained slides were analysed with a standard bright-field microscope at 1000× magnification by counting signals from 60 non-overlapping nuclei from three different tumour areas. Samples with ≥15% of positive nuclei were judged as ALK break apart-positive. All samples were simultaneously analysed by qPCR for EML4-ALK to validate CISH results, and positive samples were subject to Sanger sequencing.CISH was successful with 173 of 181 hybridised samples (96%), and seven ALK break apart-positive cases were detected. CISH signals were specific and distinct for both colours. All positive cases were confirmed by qPCR and Sanger sequencing, and concordance between CISH and qPCR was 100%. Nearly all samples (9/10) which failed by qPCR were accessible to CISH analysis.CISH is a very reliable, convenient and inexpensive method to detect ALK-positive NSCLC. CISH success rate is comparably high as with qPCR, and it detects all ALK break apart events in a single assay. It is of special value when RNA quality is poor, or when small biopsies with a very limited amount of tumour cells have to be analysed.
- Mucinous tumours of appendix and ovary: an overview and evaluation of current practice. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Nov 21.
Mucinous lesions of the appendix and ovary are commonly encountered in routine practice. There are several published classification schemes for appendiceal mucinous neoplasms with resultant inconsistent use of terms and clinical doubt. While nomenclature is more settled with regards to ovarian mucinous neoplasms, the difficulty here lies with distinguishing primary from secondary mucinous tumours. This review highlights the terminology and nomenclature for appendiceal mucinous tumours, the relationship with ovarian mucinous neoplasms and pseudomyxoma peritonei, and the features that assist in separating primary from secondary ovarian mucinous tumours.
- Neuromuscular and vascular hamartoma: is it a true hamartoma? [JOURNAL ARTICLE]
- J Clin Pathol 2013 Nov 21.
- Phosphorylated Akt expression is a prognostic marker in early-stage non-small cell lung cancer. [JOURNAL ARTICLE]
- J Clin Pathol 2013 Nov 21.
To determine the prognostic significance of pAkt expression in order to identify high-risk stage IB patients with non-small cell lung cancer (NSCLC) in an exploratory study.We identified 471 consecutive patients with stage IB primary NSCLC according to the American Joint Commission on Cancer 6th edition tumour-node-metastasis (TNM) staging system, who underwent surgical resection between 1990 and 2008. Patients who received neoadjuvant or adjuvant treatments were excluded. Pathology reports were reviewed, and pathological characteristics were extracted. Expression of phosphorylated Akt (pAkt) in both cytoplasmic and nuclear locations was assessed by immunohistochemistry, and clinicopathological factors were analysed against 10-year overall survival using Kaplan-Meier and Cox proportional hazards model.455 (96.6%) cancers were adequate for pAkt immunohistochemical analysis. The prevalence of pAkt expression in the cytoplasm and nucleus of the cancers was 60.7% and 43.7%, respectively. Patients whose cancers expressed higher levels of cytoplasmic pAkt had a trend towards longer overall survival than those with lower levels (p=0.06). Conversely, patients whose cancers expressed higher levels of nuclear pAkt had a poorer prognosis than those with lower levels of expression (p=0.02). Combined low cytoplasmic/high nuclear expression of pAkt was an independent predictor of overall survival (HR=2.86 (95% CI 1.35 to 6.04); p=0.006) when modelled with age (HR=1.05 (95% CI 1.03 to 1.07); p<0.001), extent of operation (HR=2.11 (95% CI 1.48 to 3.01); p<0.001), visceral pleural invasion (HR=1.63 (95% CI 1.24 to 2.15); p<0.001), gender, tumour size, histopathological type and grade (p>0.05).Level of expression of pAkt in the cytoplasm and nucleus is an independent prognostic factor that may help to select patients with high-risk disease.