TY - JOUR
T1 - Diagnostic dilemmas of high-grade transformation (Richter's syndrome) of chronic lymphocytic leukaemia
T2 - results of the phase II National Cancer Research Institute CHOP-OR clinical trial specialist haemato-pathology central review
AU - Soilleux, Elizabeth J.
AU - Wotherspoon, Andrew
AU - Eyre, Toby A.
AU - Clifford, Ruth
AU - Cabes, Maite
AU - Schuh, Anna H.
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Ltd
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Aims: Richter's syndrome (RS) refers to high-grade transformation of B-cell chronic lymphocytic leukaemia (CLL), usually to diffuse large B-cell lymphoma, as assessed according to strict World Health Organization (WHO)-defined histological criteria. Although this is a relatively evidence-poor area, the recommended clinical management of high-grade transformation differs considerably from that of relapsed CLL. The ‘CHOP-OR’ trial was a single-arm, multicentre, non-randomized phase II National Cancer Research Institute trial in patients with newly diagnosed RS, recruited from across the UK from April 2011 to December 2014. Forty-three patients were enrolled, of whom 37 were ultimately evaluable for response. The aim was to verify the presence of RS in the trial patients and identify pitfalls in the diagnosis of RS. Methods and results: Two independent, specialist haematopathologists reviewed histological material from 40 available cases enrolled in the CHOP-OR trial to determine whether the submitted diagnosis of RS was correct. Three cases were unavailable for central review. This series represents the largest central review of RS within a prospective trial in the literature to date. Thirty-three of the 40 (82.5%) submitted cases showed features consistent with WHO-defined RS. Reasons for diagnostic uncertainty in discrepant cases included large proliferation centres, variably confluent and serpiginous proliferation centres, and an apparently high proliferation index, sometimes attributable to a thick section or associated normal bone marrow proliferation. Conclusions: We discuss the importance of high-quality histological and immunohistochemical sections and strict adherence to WHO criteria in the diagnosis of RS. This study further reinforces the importance of centralized review of cases of haematological malignancy.
AB - Aims: Richter's syndrome (RS) refers to high-grade transformation of B-cell chronic lymphocytic leukaemia (CLL), usually to diffuse large B-cell lymphoma, as assessed according to strict World Health Organization (WHO)-defined histological criteria. Although this is a relatively evidence-poor area, the recommended clinical management of high-grade transformation differs considerably from that of relapsed CLL. The ‘CHOP-OR’ trial was a single-arm, multicentre, non-randomized phase II National Cancer Research Institute trial in patients with newly diagnosed RS, recruited from across the UK from April 2011 to December 2014. Forty-three patients were enrolled, of whom 37 were ultimately evaluable for response. The aim was to verify the presence of RS in the trial patients and identify pitfalls in the diagnosis of RS. Methods and results: Two independent, specialist haematopathologists reviewed histological material from 40 available cases enrolled in the CHOP-OR trial to determine whether the submitted diagnosis of RS was correct. Three cases were unavailable for central review. This series represents the largest central review of RS within a prospective trial in the literature to date. Thirty-three of the 40 (82.5%) submitted cases showed features consistent with WHO-defined RS. Reasons for diagnostic uncertainty in discrepant cases included large proliferation centres, variably confluent and serpiginous proliferation centres, and an apparently high proliferation index, sometimes attributable to a thick section or associated normal bone marrow proliferation. Conclusions: We discuss the importance of high-quality histological and immunohistochemical sections and strict adherence to WHO criteria in the diagnosis of RS. This study further reinforces the importance of centralized review of cases of haematological malignancy.
KW - central pathology review
KW - chronic lymphocytic leukaemia
KW - Richter's syndrome
UR - http://www.scopus.com/inward/record.url?scp=84987651066&partnerID=8YFLogxK
U2 - 10.1111/his.13024
DO - 10.1111/his.13024
M3 - Article
C2 - 27345622
AN - SCOPUS:84987651066
SN - 0309-0167
VL - 69
SP - 1066
EP - 1076
JO - Histopathology
JF - Histopathology
IS - 6
ER -