hasan rizvi | St Barts Medical College (original) (raw)

Papers by hasan rizvi

Research paper thumbnail of Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Infectious Agents and Cancer

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized a... more Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis.

Research paper thumbnail of O07 Randomised, open labelled clinical trial to investigate synovial mechanisms determining response: resistance to rituximab versus tocilizumab in RA patients failing TNF inhibitor therapy

Rheumatology

Background Biologic therapies have transformed the outlook for RA but the significant health econ... more Background Biologic therapies have transformed the outlook for RA but the significant health economic impact of these therapies has highlighted the need to define predictive markers of response. Rituximab (RTX) is licensed for use following failure of csDMARDs and TNF inhibitor (TNFi) therapy. However, in this increasing therapeutically resistant cohort only 30% of patients achieve an ACR50 response. The observation in early RA that 50% of patients show low/absence of synovial B-cells prompted us to test the hypothesis that in these patients a biologic agent targeting alternative pathways maybe more effective. We report results from the first pathobiology-driven randomised controlled trial (RCT) in RA (R4RA) evaluating whether patient stratification according to the synovial B-cell rich/poor status enriches for response/non response to RTX. Methods R4RA is a phase IV open-label RCT conducted in 19 European centres recruiting patients failing or intolerant to csDMARD therapy and at l...

Research paper thumbnail of Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key fact... more The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tum...

Research paper thumbnail of Novel markers in pediatric-type follicular lymphoma

Virchows Archiv

The aim of this study was to review the histopathological, phenotypic, and molecular characterist... more The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)–associated markers stathmin and LLT-1 were positive in most of the cases (1...

Research paper thumbnail of The Role of Human Papillomaviruses and Polyomaviruses in BRAF-Inhibitor Induced Cutaneous Squamous Cell Carcinoma and Benign Squamoproliferative Lesions

Frontiers in Microbiology

Research paper thumbnail of Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood

In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL)... more In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separ...

Research paper thumbnail of A Virtual Microscopy Learning Platform - a High Quality, Innovative and Interactive Tool for Training Haematologists of the Future: A UK Pilot Study

Blood

Introduction: Virtual microscopy (VM) allows a whole slide once scanned, to be visualised, naviga... more Introduction: Virtual microscopy (VM) allows a whole slide once scanned, to be visualised, navigated and annotated at different magnifications on a digital viewing platform. Advantages for trainees are numerous; slides can be viewed simultaneously by large numbers of students or accessed remotely at the student’s time and place of preference. In the UK all Haematology trainees are required to be competent in diagnostic evaluation of blood films, bone marrow aspirates and trephines. The drive towards laboratory centralisation, increasing automation and full shift working patterns has decreased access to traditional small group teaching using a multi-headed microscope. VM has the potential to realise new modes of training delivery and to prepare haematologists for the advent of VM as a mainstream diagnostic tool. Aim: To review the utility and acceptability of incorporating virtual microscopy into a virtual learning environment (VLE) for haematology trainees. Methods : Over a 6 month ...

Research paper thumbnail of THU0058 B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis at Different Disease Stages

Research paper thumbnail of Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma

Journal of Investigative Dermatology

Research paper thumbnail of The Undergraduate Training in Genomics (UTRIG) Initiative: early & active training for physicians in the genomic medicine era

Personalized medicine, Jan 30, 2018

Genomic medicine is transforming patient care. However, the speed of development has left a knowl... more Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

Research paper thumbnail of Microscopic-Observation Drug-Susceptibility (Mods) for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance

Journal of clinical microbiology, Jan 28, 2015

In the study, 132 patients with lymphadenopathy were investigated. 52 (39.4%) were diagnosed with... more In the study, 132 patients with lymphadenopathy were investigated. 52 (39.4%) were diagnosed with TB. MODS provided rapid (13 days), accurate diagnosis (sensitivity 65.4%), and reliable DST. Despite lower sensitivity than other methods, faster results and simultaneous DST are advantageous in resource-poor settings, supporting incorporation of MODS into diagnostic algorithms for extrapulmonary TB.

Research paper thumbnail of Expression of the CD2AP adaptor molecule in normal, reactive and neoplastic human tissue

Pathologica, 2012

To study the expression of CD2-associated protein (CD2AP), an adaptor protein involved in T-cell ... more To study the expression of CD2-associated protein (CD2AP), an adaptor protein involved in T-cell signalling and renal function, in normal, reactive and neoplastic human lymphoid tissues. We used immunohistochemical techniques to evaluate monoclonal antibodies against CD2AP on over 400 formalin fixed paraffin embedded tissue blocks retrieved from the host institutions of three authors. The samples tested included normal, reactive and neoplastic lymphoid tissue. In lymphoid tissues, strong CD2AP staining was observed in plasmacytoid dendritic cells (pDCs), weak and variable in mantle zone B cells and moderate in rare germinal center cells. CD2AP labeled cortical and rare medullary thymocytes and isolated mononuclear cells in bone marrow trephines. Furthermore, epithelial and endothelial cells expressed CD2AP. Among neoplasms, the greatest number of CD2AP-positive cases were found in diffuse large B cell (21/94), NK T-cell lymphomas (7/67), "blastic plasmacytoid dendritic cell neo...

Research paper thumbnail of United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings

British Journal of Haematology, 2015

Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with throm... more Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities.

Research paper thumbnail of Intracellular TCR-signaling Pathway

The American Journal of Surgical Pathology, 2014

Despite the immunologic functions of T-cell receptor signaling molecules being extensively invest... more Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

Research paper thumbnail of Pathology Education

Pathology, 2014

The postgraduate education programs in the Arab countries have intra- and intercountry difference... more The postgraduate education programs in the Arab countries have intra- and intercountry differences in the availability of human resources and adequate training centers. The Arab Board of Pathology was established in 2010 to improve the health services in these countries, to set comprehensive and uniform standards for postgraduate training centers, and to establish uniform assessment of the training programs and the proficiency of the trainees. This presentation covers the foundations and the experience of the Arab Board of Pathology since its inception. It describes the structure of the exams and the performance of the trainees. Despite the noted improvement in the training programs over the past few years, many challenges remain and these relate to the growing populations of the countries of the region and the increasing demand for qualified pathologists, shortage of adequate training facilities and resources, disruptive political instability, differences in the adopted structure of the training programs based on external educational influences by European programs, and lack of national strategies to address these problems.The presentation also includes a brief comparison of the leading certification programs of postgraduate education in pathology in different regions of the world and questions the readiness for a global certification program.

Research paper thumbnail of NOTCH1 Mutations Occur Early during Cutaneous Squamous Cell Carcinogenesis

Journal of Investigative Dermatology, 2014

Research paper thumbnail of BRAF V600E mutation-specific antibody, a sensitive diagnostic marker revealing minimal residual disease in hairy cell leukaemia

British Journal of Haematology, 2013

Research paper thumbnail of A patient with CLL and a dry cough

BMJ, 2010

A 51 year old man was diagnosed with stage C chronic lymphocytic leukaemia (CLL) after he was fou... more A 51 year old man was diagnosed with stage C chronic lymphocytic leukaemia (CLL) after he was found incidentally to have marked lymphocytosis on a routine blood test with characteristic morphological and immunophenotypic features. He had massive ...

Research paper thumbnail of Cutaneous Mucinous Carcinoma Arising in Extramammary Paget Disease of the Perineum

The American Journal of Dermatopathology, 2011

We present the case of a 74-year-old woman with a 7-year history of an expanding vulval and peria... more We present the case of a 74-year-old woman with a 7-year history of an expanding vulval and perianal erythematous plaque, which failed to respond to topical treatments in the community. Biopsy of the affected skin showed typical features of extramammary Paget disease. No underlying associated malignancy was identified. After 2 months of treatment with 5% topical imiquimod, the patient developed a new tender nodule in the perineal region. Histological examination revealed a mucinous carcinoma, which, after careful clinical assessment, was deemed to be a primary cutaneous mucinous carcinoma. This is the second reported case of a primary cutaneous mucinous carcinoma arising on a background of extramammary Paget disease of the vulva and perineum.

Research paper thumbnail of Immune landscape in Burkitt lymphoma reveals M2-macrophage polarization and correlation between PD-L1 expression and non-canonical EBV latency program

Infectious Agents and Cancer

Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized a... more Background: The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. Methods: In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profiling (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by multiple immunohistochemistry (IHC) and multispectral immunofluorescence (IF), we investigated the TME of additional series of 40 BL cases to evaluate the role of the Programmed Death-1 and Programmed Death Ligand-1 (PD-1/PD-L1) immune checkpoint axis.

Research paper thumbnail of O07 Randomised, open labelled clinical trial to investigate synovial mechanisms determining response: resistance to rituximab versus tocilizumab in RA patients failing TNF inhibitor therapy

Rheumatology

Background Biologic therapies have transformed the outlook for RA but the significant health econ... more Background Biologic therapies have transformed the outlook for RA but the significant health economic impact of these therapies has highlighted the need to define predictive markers of response. Rituximab (RTX) is licensed for use following failure of csDMARDs and TNF inhibitor (TNFi) therapy. However, in this increasing therapeutically resistant cohort only 30% of patients achieve an ACR50 response. The observation in early RA that 50% of patients show low/absence of synovial B-cells prompted us to test the hypothesis that in these patients a biologic agent targeting alternative pathways maybe more effective. We report results from the first pathobiology-driven randomised controlled trial (RCT) in RA (R4RA) evaluating whether patient stratification according to the synovial B-cell rich/poor status enriches for response/non response to RTX. Methods R4RA is a phase IV open-label RCT conducted in 19 European centres recruiting patients failing or intolerant to csDMARD therapy and at l...

Research paper thumbnail of Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program

The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key fact... more The Tumor Microenviroment (TME) is a complex milieu that is increasingly recognized as a key factor in multiple stages of disease progression and responses to therapy as well as escape from immune surveillance. However, the precise contribution of specific immune effector and immune suppressor components of the TME in Burkitt lymphoma (BL) remains poorly understood. In this paper, we applied the computational algorithm CIBERSORT to Gene Expression Profile (GEP) datasets of 40 BL samples to draw a map of immune and stromal components of TME. Furthermore, by VECTRA multispectral immunofluorescence (IF) and multiple immunohistochemistry (IHC), we investigated the TME of an additional series of 40 BL cases and evaluated the possible role of the PD-1/PD-L1 immune checkpoint axis. Our results indicated that M2 polarized macrophages are the most prominent TME component in BL. In addition, we investigated the correlation between PD-L1 and latent membrane protein-2A (LMP2A) expression on tum...

Research paper thumbnail of Novel markers in pediatric-type follicular lymphoma

Virchows Archiv

The aim of this study was to review the histopathological, phenotypic, and molecular characterist... more The aim of this study was to review the histopathological, phenotypic, and molecular characteristics of pediatric-type follicular lymphoma (PTFL) and to assess the diagnostic value of novel immunohistochemical markers in distinguishing PTFL from follicular hyperplasia (FH). A total of 13 nodal PTFLs were investigated using immunohistochemistry, fluorescence in situ hybridization (FISH), and PCR and were compared with a further 20 reactive lymph nodes showing FH. Morphologically, PTFL cases exhibited a follicular growth pattern with irregular lymphoid follicles in which the germinal centers were composed of numerous blastoid cells showing a starry-sky appearance. Immunohistochemistry highlighted preserved CD10 (13/13) and BCL6 (13/13) staining, CD20 (13/13) positivity, a K light chain predominance (7/13), and partial BCL2 expression in 6/13 cases (using antibodies 124, E17, and SP66). The germinal center (GC)–associated markers stathmin and LLT-1 were positive in most of the cases (1...

Research paper thumbnail of The Role of Human Papillomaviruses and Polyomaviruses in BRAF-Inhibitor Induced Cutaneous Squamous Cell Carcinoma and Benign Squamoproliferative Lesions

Frontiers in Microbiology

Research paper thumbnail of Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood

In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL)... more In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separ...

Research paper thumbnail of A Virtual Microscopy Learning Platform - a High Quality, Innovative and Interactive Tool for Training Haematologists of the Future: A UK Pilot Study

Blood

Introduction: Virtual microscopy (VM) allows a whole slide once scanned, to be visualised, naviga... more Introduction: Virtual microscopy (VM) allows a whole slide once scanned, to be visualised, navigated and annotated at different magnifications on a digital viewing platform. Advantages for trainees are numerous; slides can be viewed simultaneously by large numbers of students or accessed remotely at the student’s time and place of preference. In the UK all Haematology trainees are required to be competent in diagnostic evaluation of blood films, bone marrow aspirates and trephines. The drive towards laboratory centralisation, increasing automation and full shift working patterns has decreased access to traditional small group teaching using a multi-headed microscope. VM has the potential to realise new modes of training delivery and to prepare haematologists for the advent of VM as a mainstream diagnostic tool. Aim: To review the utility and acceptability of incorporating virtual microscopy into a virtual learning environment (VLE) for haematology trainees. Methods : Over a 6 month ...

Research paper thumbnail of THU0058 B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis at Different Disease Stages

Research paper thumbnail of Epigenetic regulation of iASPP-p63 feedback loop in cutaneous squamous cell carcinoma

Journal of Investigative Dermatology

Research paper thumbnail of The Undergraduate Training in Genomics (UTRIG) Initiative: early & active training for physicians in the genomic medicine era

Personalized medicine, Jan 30, 2018

Genomic medicine is transforming patient care. However, the speed of development has left a knowl... more Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG's collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration.

Research paper thumbnail of Microscopic-Observation Drug-Susceptibility (Mods) for Rapid Diagnosis of Lymph Node Tuberculosis and Detection of Drug Resistance

Journal of clinical microbiology, Jan 28, 2015

In the study, 132 patients with lymphadenopathy were investigated. 52 (39.4%) were diagnosed with... more In the study, 132 patients with lymphadenopathy were investigated. 52 (39.4%) were diagnosed with TB. MODS provided rapid (13 days), accurate diagnosis (sensitivity 65.4%), and reliable DST. Despite lower sensitivity than other methods, faster results and simultaneous DST are advantageous in resource-poor settings, supporting incorporation of MODS into diagnostic algorithms for extrapulmonary TB.

Research paper thumbnail of Expression of the CD2AP adaptor molecule in normal, reactive and neoplastic human tissue

Pathologica, 2012

To study the expression of CD2-associated protein (CD2AP), an adaptor protein involved in T-cell ... more To study the expression of CD2-associated protein (CD2AP), an adaptor protein involved in T-cell signalling and renal function, in normal, reactive and neoplastic human lymphoid tissues. We used immunohistochemical techniques to evaluate monoclonal antibodies against CD2AP on over 400 formalin fixed paraffin embedded tissue blocks retrieved from the host institutions of three authors. The samples tested included normal, reactive and neoplastic lymphoid tissue. In lymphoid tissues, strong CD2AP staining was observed in plasmacytoid dendritic cells (pDCs), weak and variable in mantle zone B cells and moderate in rare germinal center cells. CD2AP labeled cortical and rare medullary thymocytes and isolated mononuclear cells in bone marrow trephines. Furthermore, epithelial and endothelial cells expressed CD2AP. Among neoplasms, the greatest number of CD2AP-positive cases were found in diffuse large B cell (21/94), NK T-cell lymphomas (7/67), "blastic plasmacytoid dendritic cell neo...

Research paper thumbnail of United Kingdom immune thrombocytopenia registry: retrospective evaluation of bone marrow fibrosis in adult patients with primary immune thrombocytopenia and correlation with clinical findings

British Journal of Haematology, 2015

Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with throm... more Fibrosis has been reported in some patients with immune thrombocytopenia (ITP) treated with thrombopoietin receptor agonists (TPO-RA). However, fibrosis has also been reported in patients with various stages of ITP, who were TPO-RA treatment-naïve. In our study, we looked for fibrosis in bone marrow trephine biopsies taken at initial diagnosis from 32 adult patients with ITP. Ten of the 32 evaluated samples (31·25%) showed increased reticulin (Grade 1-2 on Bauermeister scale and Grade 0-1 on the European Consensus scale), which showed a positive correlation with ethnicity (0·3%) but did not correlate with disease severity, any clinical features or co-morbidities.

Research paper thumbnail of Intracellular TCR-signaling Pathway

The American Journal of Surgical Pathology, 2014

Despite the immunologic functions of T-cell receptor signaling molecules being extensively invest... more Despite the immunologic functions of T-cell receptor signaling molecules being extensively investigated, their potential as immunohistochemical markers has been poorly explored. With this background, we evaluated the expression of 5 intracellular proteins-GADS, DOK2, SKAP55, ITK, and PKCα-involved in T-cell receptor signaling in normal and neoplastic hematologic tissue samples, using antibodies raised against fixation-resistant epitopes of the 5 molecules. All 5 antibodies were associated with normal T-cell differentiation. GADS, DOK2, SKAP55, and ITK turned out to be T-cell lineage-specific markers in the setting of lymphoid and myeloid precursor neoplasms but showed differential expression in peripheral T-cell lymphoma (PTCL) subtypes, being detected in PTCL/not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma but negative in anaplastic large cell lymphoma (ALCL). Peripheral B-cell lymphomas were consistently negative for ITK, with occasional cases showing expression of DOK2 and SKAP55, and a proportion (47%) of hairy cell leukemias were GADS. Notably, PKCα highlighted a defective antigen in both PTCL/NOS (6%) and angioimmunoblastic T-cell lymphoma (10%), mostly negative in ALCL, and was aberrantly expressed in classical Hodgkin lymphoma (65%), Burkitt lymphoma (48%), and plasma cell myeloma (48%). In conclusion, all five molecules evaluated play a role in T-cell differentiation in normal and neoplastic tissues. They can be applied confidently to routine sections contributing primarily to assignment of T-lineage differentiation in the setting of hematopoietic precursor neoplasms (GADS/DOK2/SKAP55/ITK) and for the differential diagnosis between ALCL and PTCL/NOS (GADS/DOK2/SKAP55/ITK) or classical Hodgkin lymphoma (PKCα). Finally, association with specific tumor subtypes may have therapeutic potential.

Research paper thumbnail of Pathology Education

Pathology, 2014

The postgraduate education programs in the Arab countries have intra- and intercountry difference... more The postgraduate education programs in the Arab countries have intra- and intercountry differences in the availability of human resources and adequate training centers. The Arab Board of Pathology was established in 2010 to improve the health services in these countries, to set comprehensive and uniform standards for postgraduate training centers, and to establish uniform assessment of the training programs and the proficiency of the trainees. This presentation covers the foundations and the experience of the Arab Board of Pathology since its inception. It describes the structure of the exams and the performance of the trainees. Despite the noted improvement in the training programs over the past few years, many challenges remain and these relate to the growing populations of the countries of the region and the increasing demand for qualified pathologists, shortage of adequate training facilities and resources, disruptive political instability, differences in the adopted structure of the training programs based on external educational influences by European programs, and lack of national strategies to address these problems.The presentation also includes a brief comparison of the leading certification programs of postgraduate education in pathology in different regions of the world and questions the readiness for a global certification program.

Research paper thumbnail of NOTCH1 Mutations Occur Early during Cutaneous Squamous Cell Carcinogenesis

Journal of Investigative Dermatology, 2014

Research paper thumbnail of BRAF V600E mutation-specific antibody, a sensitive diagnostic marker revealing minimal residual disease in hairy cell leukaemia

British Journal of Haematology, 2013

Research paper thumbnail of A patient with CLL and a dry cough

BMJ, 2010

A 51 year old man was diagnosed with stage C chronic lymphocytic leukaemia (CLL) after he was fou... more A 51 year old man was diagnosed with stage C chronic lymphocytic leukaemia (CLL) after he was found incidentally to have marked lymphocytosis on a routine blood test with characteristic morphological and immunophenotypic features. He had massive ...

Research paper thumbnail of Cutaneous Mucinous Carcinoma Arising in Extramammary Paget Disease of the Perineum

The American Journal of Dermatopathology, 2011

We present the case of a 74-year-old woman with a 7-year history of an expanding vulval and peria... more We present the case of a 74-year-old woman with a 7-year history of an expanding vulval and perianal erythematous plaque, which failed to respond to topical treatments in the community. Biopsy of the affected skin showed typical features of extramammary Paget disease. No underlying associated malignancy was identified. After 2 months of treatment with 5% topical imiquimod, the patient developed a new tender nodule in the perineal region. Histological examination revealed a mucinous carcinoma, which, after careful clinical assessment, was deemed to be a primary cutaneous mucinous carcinoma. This is the second reported case of a primary cutaneous mucinous carcinoma arising on a background of extramammary Paget disease of the vulva and perineum.