Peripheral T-cell lymphomas represent a rare, heterogeneous group of nodal and extra-nodal mature T-cell lymphomas. Among those, the subtype of PTCL not otherwise specified (PTCL-NOS) account for about 25% of all PTCL. While other PTCL subtypes are increasingly recognized as discrete entities based on specific genotypic and phenotypic alterations, the diagnosis of PTCL-NOS is currently performed on an "exclusion criteria" model, since PTCL-NOS lack pathognomonic features. In this review, we describe the classical pathological features of PTCL-NOS and integrate them with the most recent molecular findings. Thanks to gene expression profiling and next generation sequencing approaches, we have recently improved our knowledge of PTCL in general and PTCL-NOS in particular. Indeed, specific patterns of gene expression were reported to segregate PTCL into more homogeneous subtypes associated with distinct clinical outcome. Furthermore, we describe how immunophenotypic, expression and mutational data helped to better define a new subgroup of PTCL-NOS displaying a global profile close to T Follicular Helper cell elements. Finally, we review how these new acquisitions are changing the current diagnostic approach to PTCL-NOS, and how phenotypic features and oncogenic pathways operative in these lymphomas are becoming targets of novel treatments. Although no recurrent and specific biological aberrations have been discovered yet, novel integrated genomic and transcriptomics approaches are significantly improving our knowledge of PTCL biology and support the development of new powerful diagnostic and prognostic markers, as well as targets of future therapies.
Multiple sclerosis (MS) is an autoimmune disease that attacks the central nervous system, causing the appearance of focal areas of inflammation and demyelination. A detailed study of MS would offer a better understanding of the causes of increased number of MS cases in the Arab Gulf countries. A comprehensive literature search was performed to extract data regarding MS in general and MS in Arabian Gulf countries in specific. Only peer-reviewed, full-text articles published in English were included. Data have shown a noticeable increase in cases of MS in the Arab Gulf countries. Although the underlying causes still remain elusive, many factors have been proposed to influence MS. This review will discuss the factors influencing MS, correlate their effects with disease pathology, their interaction in the context of disease development, and try to explain the increased number of MS in Arabian Gulf countries. Understanding MS development could open new doors for the treatment of MS, as well as initiate novel target therapies for citizens of Arab Gulf countries.
Optimal cancer treatment with targeted agents requires rapid, comprehensive and accurate molecular assays to analyse actionable oncogenic mutations across multiple tumour types. We describe a PCR panel based on the 384 well TaqMan Array® (Thermo Fisher Scientific). This allows measurement of common RAS (NRAS and KRAS), EGFR and BRAF mutations in a single assay (the REB Array), analysing 44 mutations in 7 samples per plate. This retrospective study includes 96 patients with NSCLC (n = 42), colorectal cancer (n = 26), and melanoma (n = 28) with previous mutational analysis. Samples with discrepant results were sequenced to confirm the result. The REB achieved 93% concordance with the Therascreen EGFR assay (Qiagen), 95% concordance with the KRAS castPCR assay (Thermo Fisher), and 100% concordance with the cobas BRAF assay (Roche). There were 2 true discrepancies, most likely a result of sample quality or differences in sensitivity between the assays that depend on set thresholds to determine the presence of mutations. Analysis of the performance of the REB Array gave an overall sensitivity of 92%, with a positive predictive value of 100% and negative predictive value of 84.24%. The REB array is comparable to competing PCR methods with the additional advantages of a broader range of mutations, simplified manual handling, and reduced overall cost per sample.
We report an audit of skin cancers reported by pathologists across the North of England Cancer Network. We examined 386 reports to determine whether core data items recommended by the National Minimum dataset had been included in the pathology reports. Only 115 of the 386 reports (30%) had all the expected data items compared to the expected standard of 90%. Melanoma reports were more often fully compliant (42%) compared with non-melanoma skin cancer (26%). Of 203 proforma reports, 112 were considered complete compared to only 3 of 183 free text reports. This confirms once again the value of a structured report in capturing all required core data items. The data items accounting for the majority of the deficiencies were tumour subtype, T stage and particularly risk status. We consider the reasons behind the poor level of compliance and consider opportunities that may exist to aid pathologists in generating clinically more useful reports of skin cancers.
Next-generation sequencing (NGS) technologies have begun to revolutionize the field of haematological malignancies through the assessment of a patient's genetic makeup with a minimal cost. Significant discoveries have already provided a unique insight into disease initiation, risk stratification and therapeutic intervention. Sequencing analysis will likely form part of the routine diagnostic testing in the future. However, a number of important issues need to be addressed for that to become a reality with regard to result interpretation, laboratory workflow, data storage and ethical issues. In this review we summarize the contribution that NGS has already made to the field of haematological malignancies. Finally, we discuss the challenges that NGS technologies will bring in relation to data storage, ethical and legal issues and laboratory validation. Despite these challenges, we predict that high-throughput DNA sequencing will redefine haematological malignancies based on individualized genomic analysis.
HER2, a member of the human epidermal growth factor (HER) family of transmembrane tyrosine kinases, has been of considerable interest in oncology due to its significant role in the pathogenesis of various cancer types. In this article, we review current data on HER2 as a potential biomarker in cancers other than breast and gastric by conducting an electronic database search using Pubmed. The existing literature provides evidence that HER2 protein overexpression and genomic alterations exist in a subset of patients with non-breast and non-gastric cancers, and hints at the promise of anti-HER2 targeted therapy in these patients. Moving forward, the rigorous evaluation of HER2 (protein and genomic) status as a predictive biomarker will be necessary to bring anti-HER2 therapeutics for non-breast and non-gastric cancers to the clinic.
Splenic marginal zone lymphoma (SMZL) is a distinct low grade B-cell lymphoma with an immunophenotype similar to that of splenic marginal zone B-cells. Like the normal splenic marginal zone B-cells, SMZLs also show variable features in somatic mutations of their rearranged immunoglobulin genes, with ∼90% of cases harbouring somatic mutations but at remarkably variable degrees, suggesting that SMZL may have multiple cell of origins, deriving from the heterogeneous B-cells of the splenic marginal zone. Notably, ∼30% of SMZLs show biased usage of IGHV1-2*04, with the expressed BCR being potentially polyreactive to autoantigens. Recent exome and targeted sequencing studies have identified a wide spectrum of somatic mutations in SMZL with the recurrent mutations targeting multiple signalling pathways that govern the development of splenic marginal zone B-cells. These recurrent mutations occur in KLF2 (20–42%), NOTCH2 (6.5–25%), NF-κB (CARD11 ∼7%, IKBKB ∼7%, TNFAIP3 7–13%, TRAF3 5%, BIRC3 6.3%) and TLR (MYD88 5–13%) signalling pathways. Interestingly, the majority of SMZL with KLF2 mutation have both 7q32 deletion and IGHV1-2 rearrangement, and these cases also have additional mutations in NOTCH2, or TNFAIP3, or TRAF3. There is a potential oncogenic cooperation among concurrent genetic changes, for example between the IGHV1-2 expressing BCR and KLF2 mutation in activation of the canonical NF-κB pathway, and between KLF2 and TRAF3 mutations in activation of the non-canonical NF-κB pathway. These novel genetic findings have provided considerable insights into the pathogenesis of SMZL and will stimulate the research in both normal and malignant marginal zone B-cells.
Liquid biopsy has the potential to provide information about cancers without invasive biopsy, using circulating biomarkers. These include proteins, RNA and DNA. They can be used in detection, diagnosis, monitoring and detection of recurrence. While protein-based tumour markers have been used in routine pathology for many years, the ability to detect mutations in circulating DNA is relatively new, and poised to enter clinical practice. A number of issues remain, and it is important that such markers are fully validated before they enter clinical practice. Evidence of clinical utility and cost effectiveness are major hurdles, but it is likely that the use of liquid biopsy in defined settings could benefit cancer patients substantially.
Rapid diagnosis of bacterial infection is an important for patient management and appropriate therapy during the early phase of bacteria-induced disease. Among the existing techniques for identifying pathogens were less sensitive and time-consuming processes. PCR has the benefits of excellent sensitivity, resolution and reproducibility. A multiplex PCR assay was designed for simultaneous detection and diagnosis of C. perfringens, P. aeruginosa and K. pneumoniae in different clinical samples. A total of 46 clinical samples of patients suspected with the infections were obtained from Sri Venkateswara Institute of Medical Sciences, and used in the present study as test samples for detecting the pathogens. Through this approach, the above pathogens were detected simultaneously with high specificity in pure cultures and from the blood and urine samples. The results were correlated with normal diagnostic process, and proved to be more sensitive and specific diagnostic technique in the simultaneous detection of C. perfringens, P. aeruginosa and K. pneumoniae.
A 52 year old lady presented with non-specific abdominal symptoms and menorrhagia. Ultrasound scan revealed an incidental finding of a large soft tissue mass. This was further characterised with a CT scan which revealed a 15 cm × 10 cm × 7 cm multilobulated mass. This was removed via a subtotal colectomy. Initial histology was reported as a most likely diagnosis of gastro-intestinal stromal tumour (GIST) but further characterisation revealed this to be a low-grade fibromyxoid sarcoma.
