295P - PAX-5 downregulation is pivotal for transformation of non-Hodgkin's lymphoma into histiocytic sarcoma: a meta-analysis

Date 19 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 1
Topics Lymphomas
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Presenter Abdul Naqash
Citation Annals of Oncology (2015) 26 (suppl_9): 85-92. 10.1093/annonc/mdv526
Authors A.R. Naqash1, O.S. Akhtar2, J.M. Ansari3, M. Hafiz4
  • 1Internal Medicine, Catholic Health SUNY Buffalo & Roswell Park Cancer Institute, 14214 - Buffalo/US
  • 2Internal Medicine, Division Of Haem Oncology, Weill Medical college, 10065 - New York/US
  • 3Heamatology/oncology, LSU Feist Weiller Cancer Center, 71130 - Shreveport/US
  • 4Clinical Research, Harvard Clinical Research Institute, 02215 - Boston/US



Histiocytic sarcoma (HS) is a rare malignancy with an aggressive clinical course and no well-established treatment protocols. Sporadic cases of HS, having synchronous or metachronous occurrence with various malignancies, most often non-Hodgkin's lymphoma (NHL) have been described previously. Molecular analysis in certain instances has suggested a clonal relationship between HS and the primary lymphoma. It has been postulated that downregulation of PAX-5, a transcription factor that plays a decisive role in maintaining B-cell identity, may contribute to lineage switching and trans-differentiation of the primary B-Cell lymphoma. Our aim was to assess the association of PAX-5 in cases of B-cell NHL transforming into HS.


A literature review was conducted in PubMed/Medline to identify cases of synchronous or metachronous HS associated with mature B-cell NHL, reported between the years 2000-2015. Only cases with presence of cytogenetic or gene rearrangement assay data were included. Seventeen such cases of HS with NHL sharing a common clonal origin were thus identified.


Median age of diagnosis of HS was 61 (range 30-85), 64.7% (11/17) were males. Most cases of HS cases were diagnosed in lymph nodes (52.9%), followed by skin (17.6%). 70.6% (12/17) had follicular lymphoma (FL) associated HS. Median interval between diagnosis of NHL and evolution into HS was 24 ± 11.83 months. Grading of FL did not impact time to diagnosis of HS (P = 0.13). All cases that had PAX-5 done (15/17), showed its downregulation. CEBP and PU-1 upregulation was seen in 7 and 9 patients respectively and this observation did not seem restricted to cases of FL only. All patients with reported survival time (4/17), died within 1 year of diagnosis of HS.


PAX-5 downregulation is consistently found in patients with HS arising out of NHL. Lack of somatic hyper-mutation as seen previously, strongly suggests other factors including perhaps, alterations in critical epigenetic switches may contribute to PAX-5 downregulation. Further studies to elucidate the underlying processes including the contribution of epigenetic mechanisms in regulating lineage switching, are needed to understand the evolution of secondary HS.

Clinical trial identification


All authors have declared no conflicts of interest.