Publications by authors named "Ayoma D Attygalle"

32 Publications

Early detection of T-cell lymphoma with T follicular helper phenotype by RHOA mutation analysis.

Haematologica 2021 Feb 11. Epub 2021 Feb 11.

Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK; Department of Histopathology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge.

Angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma with T follicular helper phenotype (PTCL-TFH) are a group of complex clinicopathological entities that originate from TFH cells and share a similar mutation profile. Their diagnosis is often a challenge, particularly at an early stage, due to a lack of specific histological and immunophenotypic features, paucity of neoplastic T cells and prominent polymorphous infiltrate. We investigated whether the lymphoma associated RHOA Gly17Val (c.50G>T) mutation, occurring in 60% of cases, is present in the early 'reactive' lesions, and whether mutation analysis can help advance early lymphoma diagnosis. The RHOA mutation was detected by quantitative PCR with a locked nucleic acid (LNA) probe specific to the mutation, and a further PNA clamp oligonucleotide to suppress the amplification of the wild-type allele. The qPCR assay was highly sensitive and specific, detecting RHOA Gly17Val at an allele frequency of 0.03%, but not other changes in Gly17, nor in 61 controls. Among the 37 cases of AITL and PTCL-TFH investigated, RHOA Gly17Val was detected in 62.2% (23/37) of which 19 had multiple biopsies including preceding biopsies in 10 and follow up biopsies in 11 cases. RHOA Gly17Val was present in each of these preceding or follow up biopsies including 18 specimens that showed no evidence of lymphoma by combined histological, immunophenotypic and clonality analyses. The mutation was seen in biopsies 0-26.5 months (mean=7.87 months) prior to lymphoma diagnosis. Our results show that RHOA Gly17Val mutation analysis is valuable in the early detection of AITL and PTCL-TFH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3324/haematol.2020.265991DOI Listing
February 2021

Lymphomatoid papulosis mimicking relapsed angioimmunoblastic T-cell lymphoma on histology: the importance of clinicopathological correlation.

Histopathology 2021 Feb 8;78(3):470-473. Epub 2020 Dec 8.

Gastrointestinal and Lymphoma Unit, The Royal Marsden Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14287DOI Listing
February 2021

Aggressive B-cell lymphomas with a primary bone marrow presentation.

Histopathology 2020 Sep 14;77(3):369-379. Epub 2020 Jul 14.

Institute of Pathology and Comprehensive Cancer Centre, Tübingen University Hospital, Tübingen, Germany.

Aggressive B-cell lymphomas present as a heterogeneous spectrum of disease. A primary diagnosis in the bone marrow (BM) may be challenging in terms of diagnostic classification and clinical handling, owing to limited architectural information. Aggressive B-cell lymphomas can be subdivided into entities that typically present primarily in the BM, and cases with BM involvement in which the bulk of disease is present in other organs. One main topic at the 2018 BM workshop of the European Association of Haematopathology/Society of Hematopathology was therefore aggressive B-cell lymphomas with a primary BM presentation. The spectrum of cases submitted to this topic gave a good overview of commonly encountered problems, as well as unusual manifestations, and highlighted areas of imprecise disease definitions and diagnostic grey zones. The categories submitted to the workshop included cases of Burkitt lymphoma (BL) with unusual features, high-grade B-cell lymphomas (HG-BCLs) with and without so-called double/triple-hit, and diffuse large B-cell lymphomas (DLBCLs) with a primary BM presentation. Areas of difficulties included the morphological boundaries of HG-BCL not otherwise specified, cases with MYC and bcl-2 or bcl-6 translocations and terminal deoxynucleotidyl transferase (TdT) expression, which were categorised as B-cell lymphoblastic leukaemia/lymphoma if most cells showed TdT positivity, and the clinicopathological overlap between intravascular large B-cell lymphoma, CD5-positive DLBCL, and DLBCL with primary presentations in the BM, spleen, and liver. This review summarises our understanding of the main aggressive B-cell lymphoma categories with a common primary BM presentation and potential problem areas, and makes suggestions for the immunophenotypic and genetic work-up, illustrated by the interesting and challenging cases submitted to the workshop.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14124DOI Listing
September 2020

Breast Implant-associated Anaplastic Large Cell Lymphoma: Review and Multiparametric Imaging Paradigms.

Radiographics 2020 May-Jun;40(3):609-628. Epub 2020 Apr 17.

From the Departments of Radiology (B.S., E.P.), Hematopathology (A.D.A., A.C.W.), Oncology (C.B.), and Hematology (S.S., S.I., D.E.S.), Royal Marsden Hospital, Fulham Road, London SW3 6JJ, England; Department of Medical Oncology, Royal Marsden Hospital Chelsea, London, England (A.J.R.); and University of Exeter Medical School, Exeter, England (R.S.).

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a new provisional category in the 2016 World Health Organization (WHO) classification of lymphoid neoplasms, and its incidence is rising owing to increasing recognition of this complication of breast implant insertion. At a median of 10 years after implant insertion, the typical presenting features are sudden-onset breast swelling secondary to peri-implant effusion and less frequently mass-forming disease. Histologic features comprise pleomorphic cells expressing CD30 and negative anaplastic lymphoma kinase (ALK) receptor, similar to systemic and cutaneous ALK-negative anaplastic large cell lymphoma (ALCL). The effusion-only subtype is generally indolent and curable with surgery, unlike the more aggressive mass-forming disease, for which systemic therapy is advocated. High clinical suspicion and pertinent use of radiologic and pathology modalities are essential for timely and accurate diagnosis of BIA-ALCL. Contemporary imaging techniques including US, mammography, breast MRI, CT, and PET/CT are routinely used in breast disease and lymphomas; however, the unique behavior of BIA-ALCL presents significant diagnostic and radiologic interpretative challenges, with numerous nuanced imaging features being pertinent, and current lymphoma staging and response guidelines are not easily applicable to BIA-ALCL. The authors evaluate available evidence in this evolving field; detail key indications, strengths, and limitations of the panoply of radiologic techniques for BIA-ALCL; and propose multiparametric imaging paradigms for management of the peri-implant effusion and mass-forming or advanced disease subtypes, with the goal of accurate optimal patient care. The authors also predict a future model of multimodal assessment using novel imaging and molecular techniques and define key research directions. RSNA, 2020.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/rg.2020190198DOI Listing
April 2020

Diagnosis of classic Hodgkin lymphoma on bone marrow biopsy.

Histopathology 2020 06 7;76(7):934-941. Epub 2020 May 7.

Department of Histopathology, Royal Marsden Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14085DOI Listing
June 2020

Challenges and limitations in the primary diagnosis of T-cell and natural killer cell/T-cell lymphoma in bone marrow biopsy.

Histopathology 2020 07 12;77(1):2-17. Epub 2020 Jun 12.

Pathology and Cytology Department, Centre Hospitalo-Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse-Oncopole, Centre de Recherche en Cancerologie de Toulouse, Inserm, UMR1037 laboratoire d'excellence TOUCAN, Paul Sabatier University Toulouse III, Toulouse, France.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14093DOI Listing
July 2020

Angioimmunoblastic T-cell lymphoma contains multiple clonal T-cell populations derived from a common TET2 mutant progenitor cell.

J Pathol 2020 03 16;250(3):346-357. Epub 2020 Jan 16.

Division of Cellular and Molecular Pathology, Department of Pathology, University of Cambridge, Cambridge, UK.

Angioimmunoblastic T-cell lymphoma (AITL) is a neoplastic proliferation of T follicular helper cells with clinical and histological presentations suggesting a role of antigenic drive in its development. Genetically, it is characterized by a stepwise acquisition of somatic mutations, with early mutations involving epigenetic regulators (TET2, DNMT3A) and occurring in haematopoietic stem cells, with subsequent changes involving signaling molecules (RHOA, VAV1, PLCG1, CD28) critical for T-cell biology. To search for evidence of potential oncogenic cooperation between genetic changes and intrinsic T cell receptor (TCR) signaling, we investigated somatic mutations and T-cell receptor β (TRB) rearrangement in 119 AITL, 11 peripheral T-cell lymphomas with T follicular helper phenotype (PTCL-TFH), and 25 PTCL-NOS using Fluidigm polymerase chain reaction (PCR) and Illumina MiSeq sequencing. We confirmed frequent TET2, DNMT3A, and RHOA mutations in AITL (72%, 34%, 61%) and PTCL-TFH (73%, 36%, 45%) and showed multiple TET2 mutations (2 or 3) in 57% of the involved AITL and PTCL-TFH. Clonal TRB rearrangement was seen in 76 cases with multiple functional rearrangements (2-4) in 18 cases (24%). In selected cases, we confirmed bi-clonal T-cell populations and further demonstrated that these independent T-cell populations harboured identical TET2 mutations by using BaseScope in situ hybridization, suggesting their derivation from a common TET2 mutant progenitor cell population. Furthermore, both T-cell populations expressed CD4. Finally, in comparison with tonsillar TFH cells, both AITL and PTCL-TFH showed a significant overrepresentation of several TRB variable family members, particularly TRBV19*01. Our findings suggest the presence of parallel neoplastic evolutions from a common TET2 mutant haematopoietic progenitor pool in AITL and PTCL-TFH, albeit to be confirmed in a large series of cases. The biased TRBV usage in these lymphomas suggests that antigenic stimulation may play an important role in predilection of T cells to clonal expansion and malignant transformation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/path.5376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064999PMC
March 2020

Sarcomatous Transformation in Undifferentiated/Dedifferentiated Endometrial Carcinoma: An Underrecognized Phenomenon and Diagnostic Pitfall.

Int J Gynecol Pathol 2020 Sep;39(5):485-492

Department of Cellular Pathology, The Royal Marsden Hospital, London, UK.

Undifferentiated/dedifferentiated carcinoma is an aggressive endometrial carcinoma which remains underrecognized but may account for up to 9% of all endometrial malignancies. We describe 3 cases in which the undifferentiated component was associated with sarcomatous differentiation, characterized by spindled cells in 2 cases and heterologous malignant cartilage in 1 case. Two of the 3 cases demonstrated mismatch repair deficiency by immunohistochemistry. This phenomenon has not previously been formally reported and increases the likelihood of misdiagnosis, especially within biopsy samples; differential diagnoses may include endometrial stromal sarcoma and grade 3 endometrioid adenocarcinoma with spindled morphology. We review the current literature and provide strategies for resolving the differential diagnoses, with a suggested panel of antibodies which includes EMA, E-cadherin, and mismatch repair proteins as approximately 50% of cases show loss of mismatch repair expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000635DOI Listing
September 2020

Florid T follicular helper cell hyperplasia associated with extranodal marginal zone lymphoma: a diagnostic pitfall which may mimic T cell lymphoma.

Histopathology 2019 08 10;75(2):287-290. Epub 2019 Jun 10.

Department of Cellular Pathology, The Royal Marsden Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13858DOI Listing
August 2019

Expanding the morphological spectrum of ovarian microcystic stromal tumour.

Histopathology 2019 Feb 5;74(3):443-451. Epub 2018 Dec 5.

Cancer Research Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada.

Aims: To expand the morphological spectrum of ovarian microcystic stromal tumour, a rare neoplasm considered to have a relatively constant morphology with microcysts, solid cellular regions and hyalinised fibrous stroma.

Methods And Results: We report four ovarian neoplasms in patients aged 45, 56, 61 and 71 years with the characteristic immunophenotype of microcystic stromal tumour (diffuse nuclear positivity with beta-catenin, cyclin D1 and WT1; diffuse cytoplasmic positivity with CD10; negative inhibin, calretinin, oestrogen receptor and progesterone receptor). The tumours had variant morphology (diffuse, nested and corded arrangements in three cases, including one with spindle cell elements; nested, corded and tubular in the other). A CTNNB1 point mutation in exon 3 (c.98C>G,p.S33C; c.100G>A,p.G34R; c.97T>G,p.S33A) was present in the three cases with material available for testing.

Conclusions: We feel that the cases we report are related to microcystic stromal tumour but with variant morphology; as such, the morphological spectrum of ovarian microcystic stromal tumour is broader than hitherto reported.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13755DOI Listing
February 2019

CHOP versus GEM-P in previously untreated patients with peripheral T-cell lymphoma (CHEMO-T): a phase 2, multicentre, randomised, open-label trial.

Lancet Haematol 2018 May;5(5):e190-e200

The Royal Marsden NHS Foundation Trust, London and Surrey, UK. Electronic address:

Background: Outcomes with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like chemotherapy in peripheral T-cell lymphoma are poor. We investigated whether the regimen of gemcitabine, cisplatin, and methylprednisolone (GEM-P) was superior to CHOP as front-line therapy in previously untreated patients.

Methods: We did a phase 2, parallel-group, multicentre, open-label randomised trial in 47 hospitals: 46 in the UK and one in Australia. Participants were patients aged 18 years and older with bulky (tumour mass diameter >10 cm) stage I to stage IV disease (WHO performance status 0-3), previously untreated peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, enteropathy-associated T-cell lymphoma, or hepatosplenic γδ T-cell lymphoma. We randomly assigned patients (1:1) stratified by subtype of peripheral T-cell lymphoma and international prognostic index to either CHOP (intravenous cyclophosphamide 750 mg/m, doxorubicin 50 mg/m, and vincristine 1·4 mg/m [maximum 2 mg] on day 1, and oral prednisolone 100 mg on days 1-5) every 21 days for six cycles; or GEM-P (intravenous gemcitabine 1000 mg/m on days 1, 8, and 15, cisplatin 100 mg/m on day 15, and oral or intravenous methylprednisolone 1000 mg on days 1-5) every 28 days for four cycles. The primary endpoint was the proportion of patients with a CT-based complete response or unconfirmed complete response on completion of study chemotherapy, to detect a 20% superiority of GEM-P compared with CHOP, assessed in all patients who received at least one cycle of treatment and had an end-of-treatment CT scan or reported clinical progression as the reason for stopping trial treatment. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov (NCT01719835) and the European Clinical Trials Database (EudraCT 2011-004146-18).

Findings: Between June 18, 2012, and Nov 16, 2016, we randomly assigned 87 patients to treatment, 43 to CHOP and 44 to GEM-P. A planned unmasked review of efficacy data by the independent data monitoring committee in November, 2016, showed that the number of patients with a confirmed or unconfirmed complete response with GEM-P was non-significantly inferior compared with CHOP and the trial was closed early. At a median follow-up of 27·4 months (IQR 16·6-38·4), 23 patients (62%) of 37 assessable patients assigned to CHOP had achieved a complete response or unconfirmed complete response compared with 17 (46%) of 37 assigned to GEM-P (odds ratio 0·52, 95% CI 0·21-1·31; p=0·164). The most common adverse events of grade 3 or worse in both groups were neutropenia (17 [40%] with CHOP and nine [20%] with GEM-P), thrombocytopenia (4 [10%] with CHOP and 13 [30%] with GEM-P, and febrile neutropenia (12 [29%] with CHOP and 3 [7%] with GEM-P). Two patients (5%) died during the study, both in the GEM-P group, from lung infections.

Interpretation: The number of patients with a complete response or unconfirmed complete response did not differ between the groups, indicating that GEM-P was not superior for this outcome. CHOP should therefore remain the reference regimen for previously untreated peripheral T-cell lymphoma.

Funding: Bloodwise and the UK National Institute of Health Research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S2352-3026(18)30039-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946805PMC
May 2018

Optimised ARID1A immunohistochemistry is an accurate predictor of ARID1A mutational status in gynaecological cancers.

J Pathol Clin Res 2018 07 20;4(3):154-166. Epub 2018 Jul 20.

The Breast Cancer Now Toby Robins Research Centre, Division of Breast Cancer, The Institute of Cancer Research, London, UK.

ARID1A is a tumour suppressor gene that is frequently mutated in clear cell and endometrioid carcinomas of the ovary and endometrium and is an important clinical biomarker for novel treatment approaches for patients with ARID1A defects. However, the accuracy of ARID1A immunohistochemistry (IHC) as a surrogate for mutation status has not fully been established for patient stratification in clinical trials. Here we tested whether ARID1A IHC could reliably predict ARID1A mutations identified by next-generation sequencing. Three commercially available antibodies - EPR13501 (Abcam), D2A8U (Cell Signaling), and HPA005456 (Sigma) - were optimised for IHC using cell line models and human tissue, and screened across a cohort of 45 gynaecological tumours. IHC was scored independently by three pathologists using an immunoreactive score. ARID1A mutation status was assessed using two independent sequencing platforms and the concordance between ARID1A mutation and protein expression was evaluated using Receiver Operating Characteristic statistics. Overall, 21 ARID1A mutations were identified in 14/43 assessable tumours (33%), the majority of which were predicted to be deleterious. Mutations were identified in 6/17 (35%) ovarian clear cell carcinomas, 5/8 (63%) ovarian endometrioid carcinomas, 2/5 (40%) endometrial carcinomas, and 1/7 (14%) carcinosarcomas. ROC analysis identified greater than 95% concordance between mutation status and IHC using a modified immunoreactive score for all three antibodies allowing a definitive cut-point for ARID1A mutant status to be calculated. Comprehensive assessment of concordance of ARID1A IHC and mutation status identified EPR13501 as an optimal antibody, with 100% concordance between ARID1A mutation status and protein expression, across different gynaecological histological subtypes. It delivered the best inter-rater agreement between all pathologists, as well as a clear cost-benefit advantage. This could allow patients to be accurately stratified based on their ARID1A IHC status into early phase clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cjp2.103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065117PMC
July 2018

Epstein-Barr virus-positive mucocutaneous ulcer with a background of Crohn's disease and Waldenström macroglobulinaemia: a case report highlighting diagnostic pitfalls.

Histopathology 2018 04 21;72(5):874-877. Epub 2017 Dec 21.

Histopathology Department, The Royal Marsden Hospital, Sutton, Surrey, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.13420DOI Listing
April 2018

Cyclin D1 overexpression in proliferation centres of small lymphocytic lymphoma/chronic lymphocytic leukaemia.

J Clin Pathol 2017 Oct 13;70(10):899-902. Epub 2017 Apr 13.

Histopathology Department, The Royal Marsden Hospital, London, UK.

The recent publication reviewing the updated WHO classification commented on the presence of cyclin D1-positive cells in the proliferation centres (PC) of small lymphocytic lymphoma/chronic lymphocytic leukaemia (SLL/CLL). The figure quoted was 30%, which appeared higher than our experience. To assess cyclin D1 expression in PC of SLL/CLL cases, we performed a review of SLL/CLL cases diagnosed at the Royal Marsden Hospital between 1996 and 2009. Of 105 SLL/CLL cases, 16.2% showed expression of cyclin D1 in PC with none carrying the translocation t(11;14)(q13;q32). Our study and a review of the published literature suggest that this phenomenon occurs with a significantly lower prevalence than that described in the recent review of the updated WHO classification. We confirm that cyclin D1 expression is confined to PC with the typical small lymphocytes being negative. This finding is apparently unrelated to the translocation involving and genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2017-204364DOI Listing
October 2017

An Unusual Case of YWHAE-NUTM2A/B Endometrial Stromal Sarcoma With Confinement to the Endometrium and Lack of High-Grade Morphology.

Int J Gynecol Pathol 2017 Mar;36(2):165-171

Departments of Histopathology (A.D.A, K.V., S.J.H.) Surgery (D.P.J.B.), Royal Marsden Hospital Institute of Cancer Research (K.K.), London Department of Pathology (W.G.M.), Belfast Health and Social Care Trust, Belfast Department of Molecular Diagnostics (D.W.), Royal Marsden Hospital, Sutton, Surrey, UK Department of Pathology (P.D.C.), Brigham and Women's Hospital, Boston, Massachusetts.

Endometrial stromal sarcoma (ESS) characterized by YWHAE-NUTM2A/B genetic fusion is a recently recognized entity that is classified as a high-grade (HG) ESS in the 2014 World Health Organization Classification. These are myoinvasive neoplasms and typically contain a monomorphous HG round-cell cyclinD1-positive component with or without an accompanying low-grade (LG) component that is only focally positive/negative for cyclinD1. We report a case of YWHAE-NUTM2A/B ESS in a 46-yr-old woman that showed a number of unusual histologic features, including being entirely confined to the endometrium with no myoinvasion or lymphovascular space invasion. The initial hysteroscopic biopsy showed a cyclinD1-positive classic LG ESS-like component which merged with a smaller cyclinD1 negative/focally positive fibroblastic component with no HG areas. YWHAE-NUTM2A/B genetic fusion was shown by real-time quantitative polymerase chain reaction and Sanger sequencing. In the subsequent hysterectomy specimen, the tumor was entirely confined to the endometrium and was largely composed of cellular and classic LG ESS-like areas (80%) which were strongly and diffusely positive for cyclinD1 and a focal fibroblastic component (20%) which was largely cyclinD1 negative. Despite the cellular areas showing mild nuclear enlargement, the entire tumor had a very low mitotic and proliferation index and showed strong and diffuse positivity for estrogen and progesterone receptors. The patient remains alive and well with no evidence of disease 14 mo following diagnosis. To our knowledge, this is the first reported case of YWHAE-NUTM2A/B ESS that is confined to the endometrium and which exhibits entirely LG morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PGP.0000000000000286DOI Listing
March 2017

Comparison of optimised endovaginal vs external array coil T2-weighted and diffusion-weighted imaging techniques for detecting suspected early stage (IA/IB1) uterine cervical cancer.

Eur Radiol 2016 Apr 11;26(4):941-50. Epub 2015 Jul 11.

CRUK Cancer Imaging Centre, The Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Downs Road, Surrey, SM2 5PT, UK.

Objective: To compare sensitivity and specificity of endovaginal versus external-array coil T2-W and T2-W + DWI for detecting and staging small cervical tumours.

Methods: Optimised endovaginal and external array coil MRI at 3.0-T was done prospectively in 48 consecutive patients with stage Ia/Ib1 cervical cancer. Sensitivity/specificity for detecting tumour and parametrial extension against histopathology for a reading radiologist were determined on coronal T2-W and T2W + DW images. An independent radiologist also scored T2-W images without and with addition of DWI for the external-array and endovaginal coils on separate occasions >2 weeks apart. Cohen's kappa assessed inter- and intra-observer agreement.

Results: Median tumour volume in 19/38 cases positive on subsequent histology was 1.75 cm(3). Sensitivity, specificity, PPV, NPV were: reading radiologist 91.3 %, 89.5 %, 91.3 %, 89.5 %, respectively; independent radiologist T2-W 82.6 %, 73.7 %, 79.1 %, 77.8 % for endovaginal, 73.9 %, 89.5 %, 89.5 %, 73.9 % for external-array coil. Adding DWI improved sensitivity and specificity of endovaginal imaging (78.2 %, 89.5 %); adding DWI to external-array imaging improved specificity (94.7 %) but reduced sensitivity (66.7 %). Inter- and intra-observer agreement on T2-W + DWI was good (kappa = 0.67 and 0.62, respectively).

Conclusion: Endovaginal coil T2-W MRI is more sensitive than external-array coil for detecting tumours <2 cm(3); adding DWI improves specificity of endovaginal imaging but reduces sensitivity of external-array imaging.

Key Points: • Endovaginal more accurate than external-array T2-W MRI for detecting small cervical cancers. • Addition of DWI improves sensitivity and specificity of endovaginal T2-W imaging. • Addition of DWI substantially reduces sensitivity of external-array T2-W imaging.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00330-015-3899-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778155PMC
April 2016

Helicobacter pylori infection in gastric extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma: a re-evaluation.

Gut 2014 Sep 20;63(9):1526-7. Epub 2014 Jun 20.

Department of Histopathology, Royal Marsden Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/gutjnl-2014-307389DOI Listing
September 2014

CD4-positive small T-cell lymphoma of the intestine presenting with severe bile-acid malabsorption: a supportive symptom control approach.

Br J Haematol 2014 Oct 26;167(2):265-9. Epub 2014 May 26.

Department of Histopathology, Royal Marsden Hospital, London, UK.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.12953DOI Listing
October 2014

Preoperative imaging in patients undergoing trachelectomy for cervical cancer: validation of a combined T2- and diffusion-weighted endovaginal MRI technique at 3.0 T.

Gynecol Oncol 2014 May 26;133(2):326-32. Epub 2014 Feb 26.

CRUK and EPSRC Cancer Imaging Centre, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, UK. Electronic address:

Aim: The aim of this study is to validate high-resolution endovaginal T2- and diffusion-weighted MRI measurements (tumour size, volume and length of uninvolved cervical canal) against histology in patients undergoing trachelectomy.

Patients/interventions: 55 consecutive patients 25-44 years with cervical cancer being considered for trachelectomy were prospectively assessed with endovaginal T2-W and diffusion-weighted MRI. Two independent observers blinded to histology recorded maximum tumour dimension, volume and distance from the superior aspect of the tumour to the internal os. Following trachelectomy, pathologist-outlined tumour sections were photographed with a set scale and similar measurements were recorded.

Results: Fifteen of 45 patients subsequently treated with fertility-sparing surgery had residual tumour (median histological volume: 0.28 cm(3), IQR=0.14-1.06 cm(3)). Sensitivity, specificity, positive and negative predictive values for detecting tumour: Observer 1: 86.7%, 80.0%, 68.4%, and 92.3%, respectively; Observer 2: 86.7%, 90.0%, 81.0%, and 93.1%, respectively. Size and volume correlated between observers (r=0.96, 0.84, respectively, p<0.0001). Size correlated between each observer and histology (observer 1 r=0.91, p<0.0001; observer 2 r=0.93, p<0.0001), volume did not (observer 1: r=0.08, p=0.6; observer 2: r=0.21, p=0.16); however, differences between observer measurements and histology were not significant (size p=0.09, volume p=0.15). Differences between MRI and histology estimates of endocervical canal length were not significant (p=0.1 both observers).

Conclusion: In subcentimetre cervical cancers, endovaginal MRI correlates with pathology and is invaluable in assessing patients for fertility-sparing surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2014.02.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4012135PMC
May 2014

Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward - report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology.

Histopathology 2014 Jan 16;64(2):171-99. Epub 2013 Oct 16.

Department of Histopathology, Royal Marsden Hospital, London, UK.

Mature T-cell and T/NK-cell neoplasms are both uncommon and heterogeneous, among the broad category of non-Hodgkin lymphomas. Owing to the lack of specific genetic alterations in the vast majority, most currently defined entities show overlapping morphological and immunophenotypic features, and therefore pose a challenge to the diagnostic pathologist. In the light of recent immunophenotypic, cytogenetic and molecular genetics advances in the field of T-cell and T/NK-cell lymphomas, the focus of the lymphoma workshop of the European Association for Haematopathology/Society for Hematopathology meeting in Lisbon, Portugal, in October 2012 was to refine existing diagnostic criteria and clarify the borders between overlapping entities. The panel reviewed over 200 submitted cases, which were grouped into five categories: (i) angioimmunoblastic T-cell lymphoma and T-follicular-helper-cell-associated lymphomas; (ii) CD30-positive T-cell lymphomas/lymphoproliferative diseases; (iii) extranodal T-cell and NK-cell neoplasms; (iv) EBV-associated T-cell/NK-cell lymphomas/lymphoproliferative diseases; and (v) peripheral T-cell lymphoma, not otherwise specified, post-transplant lymphoproliferative disorders, and mimics. This report summarizes the discussions and conclusions of the workshop, which question current diagnostic criteria and provide recommendations for refining existing classifications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.12251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6364972PMC
January 2014

ITK/SYK translocation in angioimmunoblastic T-cell lymphoma.

Am J Surg Pathol 2013 Sep;37(9):1456-7

*Department of Histopathology, Royal Marsden Hospital, London, UK †Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/PAS.0b013e3182991415DOI Listing
September 2013

Relationship between imaging biomarkers of stage I cervical cancer and poor-prognosis histologic features: quantitative histogram analysis of diffusion-weighted MR images.

AJR Am J Roentgenol 2013 Feb;200(2):314-20

CRUK/EPSRC Cancer Imaging Centre, MRI Unit, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Royal Marsden Hospital, Downs Rd, Sutton, Surrey SM2 5PT, UK.

Objective: The purpose of this study was to determine whether histogram analysis of apparent diffusion coefficient (ADC) values from diffusion-weighted MRI can be used to differentiate cervical tumors according to their histologic characteristics.

Subjects And Methods: Sixty patients with International Federation of Gynecology stage I cervical cancer underwent MRI at 1.5 T with a 37-mm-diameter endovaginal coil. T2-weighted images (TR/TE, 2000-2368/90) followed by diffusion-weighted images (TR/TE, 2500/69; b values, 0, 100, 300, 500, and 800 s/mm(2)) were acquired. An expert observer drew regions of interest around a histologically confirmed tumor on ADC maps by referring to the T2-weighted images. Pixel-by-pixel ADCs were calculated with a monoexponential fit of data from b values of 100-800 s/mm(2), and ADC histograms were obtained from the entire tumor volume. An independent samples Student t test was used to compare differences in ADC percentile values, skew, and kurtosis between squamous cell carcinoma and adenocarcinoma, well or moderately differentiated and poorly differentiated tumors, and absence and presence of lymphovascular space invasion.

Results: There was no statistically significant difference in ADC percentiles between squamous cell carcinoma and adenocarcinoma, but the median was significantly higher in well or moderately differentiated tumors (50th percentile, 1113 ± 177 × 10(-6) mm(2)/s) compared with poorly differentiated tumors (50th percentile, 996 ± 184 × 10(-6) mm(2)/s) (p = 0.049). Histogram skew was significantly less positive for adenocarcinoma compared with squamous cell carcinoma (p = 0.016) but did not differ between tumor grades. There was no significant difference between any parameter with regard to lymphovascular space invasion.

Conclusion: Median ADC is lower in poorly compared with well or moderately differentiated tumors, while lower histogram-positive skew in adenocarcinoma compared with squamous cell carcinoma is likely to reflect the glandular content of adenocarcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2214/AJR.12.9545DOI Listing
February 2013

Endovaginal magnetic resonance imaging of stage 1A/1B cervical cancer with A T2- and diffusion-weighted magnetic resonance technique: effect of lesion size and previous cone biopsy on tumor detectability.

Gynecol Oncol 2011 Mar 19;120(3):368-73. Epub 2010 Nov 19.

Cancer Research UK Clinical Magnetic Resonance Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey SM2 5PT, UK.

Objective: To evaluate the effects of previous cone biopsy and lesion size on detectability of stage 1a/1b cervical cancer using endovaginal T2- and diffusion-weighted magnetic resonance imaging.

Methods: One hundred and thirteen patients with cervical tumor were imaged using an endovaginal coil with T2-weighted (T2-W) and diffusion-weighted single-shot echo-planar sequences; 85 managed surgically (58 with prior cone biopsy/LLETZ) were evaluated. T2-W images and ADC maps viewed simultaneously were scored positive or negative for tumor and compared with histology at surgery. MRI tumor volumes, maximum radiological and histological dimensions were recorded. ROC analysis determined the MRI volume with optimal sensitivity/specificity for identifying tumor in those without and with prior cone biopsy/LLETZ and the maximum histological dimension for correctly identifying tumor with MRI. Mean apparent diffusion coefficients (ADCs) from tumor and adjacent normal epithelium were compared.

Results: Sensitivity and specificity for detecting tumor in those without (100%; 100% respectively) and with (80%; 78.9% respectively) prior cone biopsy/LLETZ were significantly different (p<0.001). Following cone biopsy/LLETZ, MRI tumor volume of 83 mm3 detected tumor with 80% sensitivity, 94.7% specificity; a 5.3mm maximal histological dimension was detected on MRI with 100% sensitivity, 100% specificity. Tumor ADCs were significantly lower (p<0.001) than paired normal epithelial tissue (median, 988×10(-6) mm2/s vs. 1564×10(-6) mm2/s) but neither tumor nor epithelial ADCs differed significantly between patients with or without prior cone biopsy/LLETZ (p=0.48 and 0.15, respectively).

Conclusions: Endovaginal MRI with T2- and diffusion-weighted sequences has significantly lower sensitivity and specificity for tumor detection following cone biopsy/LLETZ.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygyno.2010.10.013DOI Listing
March 2011

Imaging of uterine malignancies.

Semin Ultrasound CT MR 2010 Oct;31(5):377-87

Department of Radiology, Royal Marsden Hospital, London, UK.

This article reviews the role of imaging in malignant neoplasms of the uterine corpus. Endometrial cancer is the most common uterine malignancy, and diagnosis is made by histology. Staging of these tumors remain surgical-pathologic on the 2009 International Federation of Gynecology and Obstetrics staging system. However, imaging is important in treatment planning, with magnetic resonance imaging providing the best staging for the primary tumor; more advanced disease may be evaluated with computed tomography or positron emission tomography-computed tomography. Uterine sarcomas are uncommon and heterogeneous group of malignancies. International Federation of Gynecology and Obstetrics have introduced a new staging system for uterine sarcoma that is also surgical-pathologic. Imaging is used in evaluating these tumors and in defining the extent of disease. Other malignant tumors involving the uterus and discussed here include lymphoma and metastases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1053/j.sult.2010.07.005DOI Listing
October 2010

Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers.

Mod Pathol 2009 Jun 27;22(6):753-61. Epub 2009 Mar 27.

Department of Histopathology, University College, London, UK.

Angioimmunoblastic T-cell lymphoma is an aggressive peripheral T-cell lymphoma whose natural history is not fully understood. Up to 17% of cases can present histologically with hyperplastic germinal centres (pattern I). The accurate recognition of Angioimmunoblastic T-cell lymphoma with pattern I remains a challenge and therefore the aim of this study is to phenotypically and morphologically characterize this variant with the use of the follicular helper T-cell (T(FH)) markers PD1, CXCL-13 and ICOS. Out of the 88 Angioimmunoblastic T-cell lymphoma cases reviewed, 10 showed hyperplastic follicles. Molecular probe methods for the detection of T-cell and B-cell clonality, as well as in-situ hybridization probes for EBV RNA expression, were carried out to leave no question as to the establishment of the diagnosis in each case. Of the 10 cases, all (100%) showed strong positive PD1 staining in perifollicular areas and in neoplastic cells surrounding small veins. CXCL13 and ICOS showed a similar staining pattern. By contrast, CD10 was found to only weakly label the neoplastic T cells, with only 5-10% of the target cell population staining for this marker. EBV was found in 9/10 cases. Clinically, 8/9 cases presented with stage IIIB/IVB and in 2/10 cases consecutive biopsies showed 'progression' from pattern I to classical Angioimmunoblastic T-cell lymphoma. In conclusion we have shown that the T(FH) cells markers PD1, CXCL13 and ICOS are useful adjuncts in the diagnosis of Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres. PD1 also highlighted the presence of neoplastic cells in the outer zone of lymphoid follicles, suggesting that Angioimmunoblastic T-cell lymphoma (pattern I) may originate from T(FH) cells in this region, in accordance with previous immunological studies. As the majority of cases in our series presented clinically with advanced stage disease, progression from pattern I to classical Angioimmunoblastic T-cell lymphoma may represent histological evolution rather than clinical progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.2009.12DOI Listing
June 2009

Diffusion-weighted imaging in cervical cancer with an endovaginal technique: potential value for improving tumor detection in stage Ia and Ib1 disease.

Radiology 2008 Nov;249(2):541-50

Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, England.

Purpose: To establish apparent diffusion coefficients (ADCs) of invasive cervical carcinoma compared with nontumor cervical epithelium and determine sensitivity and specificity of diffusion-weighted (DW) magnetic resonance (MR) imaging used in conjunction with T2-weighted MR imaging to help detect invasive cervical carcinoma in patients with stage Ia and Ib1 disease.

Materials And Methods: Local research ethics committee approval was obtained with written consent from each subject. Group 1 comprised patients (mean age, 38.7 years +/- 13.2 [standard deviation]) with histologically confirmed cervical intraepithelial neoplasia (CIN) found on smear (n = 20) or stage Ib1 cervical tumors (n = 18). Patients were imaged with endovaginal T2-weighted fast spin-echo and single-shot DW echo-planar MR imaging of the cervix. ADCs from invasive cervical carcinoma and nontumor regions were compared within (t test) and between (U test) patients. A derived threshold ADC level indicative of invasive cervical carcinoma was used with T2-weighted imaging by two independent observers to identify possible invasive cervical carcinoma in group 2, patients with suspected disease (n = 21; mean age, 42.0 years +/- 16.4). Surgical specimens were the reference standard. Interobserver agreement was assessed.

Results: In group 1, ADCs from cervical carcinoma (757 x 10(-6) mm(2)/sec +/- 110) and adjacent epithelium (1331 x 10(-6) mm(2)/sec +/- 159) or CIN (1291 x 10(-6) mm(2)/sec +/- 156) were significantly different (P < .0001). In group 2, respective sensitivity and specificity to help detect invasive cervical carcinoma on T2-weighted images were 55.6% and 75% for observer 1 and 66.7% and 41.7% for observer 2, and 88.9% and 66.7% for observer 1 and 77.8% and 58.3% for observer 2 when ADC maps with a threshold level of 1100 x 10(-6) mm(2)/sec were added. Interobserver agreement was fair (kappa = 0.37) for T2-weighted images alone and good (kappa = 0.80) with ADC included.

Conclusion: ADCs from invasive cervical carcinoma are significantly lower than those from nontumor epithelium; good interobserver agreement by using T2-weighted and DW MR imaging makes this technique potentially useful to help detect early-stage disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1148/radiol.2491072165DOI Listing
November 2008

Angioimmunoblastic T-cell lymphoma: histological progression associates with EBV and HHV6B viral load.

Br J Haematol 2007 Jul;138(1):44-53

Department of Pathology, University of Cambridge, Cambridge, UK.

The clinical and histological presentations of angioimmunoblastic T-cell lymphoma (AITL) often mimic an infectious process. Epstein-Barr virus (EBV) and human herpes virus (HHV6) are known to be associated with AITL, but whether these viral infections play a role in its pathogenesis is unclear. It also remains to be investigated whether there might be other viruses associated with AITL. We first screened 26 well-characterised cases of AITL for herpesvirus by polymerase chain reaction (PCR) with universal primers and found evidence of only EBV and HHV6B infection. Subsequent PCR using virus-specific primers demonstrated EBV and HHV6B infection in 40/49 biopsies (36/42 cases) and 21/49 biopsies (19/42 cases) of AITL respectively with both viral infections found in 17/49 specimens (15/42 cases). Importantly, simultaneous infection with both viruses was found only in specimens showing histological pattern II (n = 2) or III (n = 15). Interestingly, among specimens containing both viruses, there was a tendency towards an inverse correlation between the EBV and HHV6B viral load as shown by quantitative PCR. In specimens positive only for EBV, the viral load was significantly higher in specimens with histological pattern III than those with pattern II. High EBV load was also significantly associated with B-cell monoclonality. Double EBV encoded small RNA (EBER) in situ hybridisation and immunohistochemistry indicated that EBV-infected B cells had a late postgerminal centre immunophenotype. Our results demonstrate an association between EBV and HHV6B infection and the histological progression of AITL, suggesting that these viruses may play a role in the pathogenesis of this lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1365-2141.2007.06620.xDOI Listing
July 2007

Expression of CXCL13, a chemokine highly upregulated in germinal center T-helper cells, distinguishes angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified.

Mod Pathol 2006 Aug 5;19(8):1101-7. Epub 2006 May 5.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905, USA.

The germinal center T-helper cell has been proposed as the cell of origin for angioimmunoblastic T-cell lymphoma. Our recent report of expression of CXCL13, a chemokine critical for germinal center formation and one of the most highly upregulated genes in the germinal center T-helper cell subset, in the majority of angioimmunoblastic T-cell lymphoma cases, provided further support for this theory. To determine the specifity of this marker for angioimmunoblastic T-cell lymphoma, we evaluated CXCL13 expression in 26 nodal-based peripheral T-cell lymphomas and 14 lymph nodes showing paracortical lymphoid hyperplasia. No significant paracortical CXCL13 staining was seen in the reactive lymph nodes. By WHO classification criteria, 20 of the lymphoma cases were considered peripheral T-cell lymphoma, unspecified, and six were reclassified as angioimmunoblastic T-cell lymphoma after immunohistochemical detection of disorganized follicular dendritic cell meshworks. Combining the results of our studies, 31 of 35 angioimmunoblastic T-cell lymphoma cases (89%) showed CXCL13 expression, in contrast to two out of 20 peripheral T-cell lymphoma, unspecified cases (10%). The two peripheral T-cell lymphoma, unspecified cases that were positive for CXCL13 showed a Lennert lymphoma-like histology. While these cases did not meet all histologic criteria for angioimmunoblastic T-cell lymphoma, they did show an increase in EBV-positive B cells, suggesting they may be histologic variants of angioimmunoblastic T-cell lymphoma. In conclusion, CXCL13 expression is a distinctive feature of angioimmunoblastic T-cell lymphoma, providing further support for the germinal center T-helper cell as the cell of origin for this neoplasm. Given its specificity when compared to cases of peripheral T-cell lymphoma, unspecified as well as paracortical lymphoid hyperplasia, it may be a useful marker in the diagnosis of angioimmunoblastic T-cell lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/modpathol.3800625DOI Listing
August 2006

Atypical marginal zone hyperplasia of mucosa-associated lymphoid tissue: a reactive condition of childhood showing immunoglobulin lambda light-chain restriction.

Blood 2004 Nov 15;104(10):3343-8. Epub 2004 Jul 15.

Department of Histopathology, Royal Free and University College Medical School, Rockefeller Bldg, University St, London WC1E 6JJ, United Kingdom.

Mucosa-associated lymphoid tissue (MALT) lymphomas usually arise at sites of acquired MALT and are uncommon in native MALT (eg, Peyer patches and tonsil). Malignancy in these low-grade lymphomas is often inferred by immunoglobulin light-chain restriction and expression of CD43; molecular genetic evidence is sought only if these are in doubt. We report 6 cases (4 tonsils, 2 appendixes) of marginal zone (MZ) hyperplasia in children aged 3 to 11 years that, despite histologic and immunophenotypic features indicative of lymphoma, were polyclonal by molecular analysis. No lymphoma-directed therapy was given and patients remain alive and well (5 cases, median follow-up 35.3 months). The involved tonsil and appendix showed florid MZ hyperplasia with prominent intraepithelial B cells (IEBCs). The MZ B cells and IEBCs showed a high-proliferation fraction and a CD20(+), CD21(+), CD27(-), immunoglobulin (Ig) superfamily receptor translocation-associated 1-positive (IRTA-1(+)), CD43(+), multiple myeloma oncogene 1 (MUM-1), IgM(+)D(+) phenotype. Polymerase chain reaction (PCR), cloning, and sequencing of rearranged IgH and Iglambda genes (whole tissue sections [6 cases]; microdissected cells [2 cases]) showed that the MZ B cells and IEBCs were polyclonal and the IgH genes nonmutated. In contrast, MZ (intraepithelial) B cells of 6 control tonsils had a similar immunophenotype, except for expression of CD27 and polytypic light chains, whereas molecular studies showed that they were polyclonal with mutated Ig genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2004-01-0385DOI Listing
November 2004