title: Herpes simplex infection simulating Richter transformation: a series of four cases and review of the literature.
abstract: OBJECTIVE
  Richter transformation (RT) occurs in 5-10% of patients with chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL), and is associated with a poor outcome. The histological manifestations of RT are variable, and include an increase in the proportion of prolymphocytes, immunoblasts, and other pleomorphic cells, along with an increased proliferation rate and often necrosis. Rarely, superimposed herpes simplex virus (HSV) infection involving lymph nodes in patients with CLL/SLL may mimic RT clinically and histologically. In this study, we describe four cases of CLL/SLL with superimposed HSV lymphadenitis, and we review the literature.
  
  
  RESULTS
  We describe the clinicopathological and immunophenotypic findings of four cases of CLL/SLL with superimposed HSV infection. The patients presented with B-type symptoms, and laboratory and imaging findings suggested progression of lymphoma. Histologically, there were geographical areas of necrosis and increased numbers of prolymphocytes and immunoblasts, in some areas forming sheets, with increased mitotic figures and a high proliferation (Ki67) rate. However, the necrotic regions were associated with acute inflammatory cells and larger cells, mostly necrotic, showing viral cytopathic effects. Therapy with antiviral agents resulted in improvement of clinical symptoms and laboratory and imaging findings. Additionally, we identified 11 cases of CLL/SLL with superimposed HSV infection described in the English-language literature, and integrated the cases that we report here into this wider context.
  
  
  CONCLUSIONS
  Herpes simplex virus infection of lymph nodes in patients with CLL/SLL results in clinicopathological and radiological findings that may mimic RT. It is essential to refrain from misclassifying these cases as RT, as patients can respond remarkably well to antiviral therapy.
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Alireza
authors.initials: A
authors.lastname: Salem
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Sanam
authors.identifier: http://orcid.org/0000-0001-8980-3202
authors.initials: S
authors.lastname: Loghavi
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Joseph D
authors.identifier: http://orcid.org/0000-0003-2621-3584
authors.initials: JD
authors.lastname: Khoury
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Rose Lou Marie C
authors.identifier: http://orcid.org/0000-0002-5309-7104
authors.initials: RL
authors.lastname: Agbay
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Jorgensen
authors.affiliation: Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: L Jeffrey
authors.identifier: http://orcid.org/0000-0001-6577-8006
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D000368:Aged; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D005260:Female; D005434:Flow Cytometry; D006561:Herpes Simplex / Q000150:complications / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D017403:In Situ Hybridization; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology* / Q000821:virology; D008198:Lymph Nodes / Q000473:pathology / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008297:Male; D008875:Middle Aged
keywords: CLL/SLL; Richter; Transformation; herpes