Intravascular Large T-cell or NK-cell Lymphoma

Abstract

Most cases of intravascular large cell lymphoma have a B-cell phenotype, but rare T-cell and natural killer (NK)-cell variants have been reported. We describe the clinicopathologic features of 4 patients (M:F=3:1; age range: 63 to 87; median age: 65) with intravascular large NK/T-cell lymphoma. The skin was the site of presentation in all patients (leg: 1 case; trunk: 1 case; trunk and extremities: 2 cases). Two patients had lesions confined to the skin; in 1 case concomitant involvement of the brain was detected and in 1 case no further studies were carried out. Immunohistology showed positivity for cytotoxic markers in 3/4 cases. One case had an NK phenotype similar to NK/T-cell lymphoma, nasal-type, whereas the other cases could not be precisely classified into specific categories (peripheral T-cell lymphoma, NOS). One of these cases was negative for cytotoxic markers and was positive only for CD2 and CD3 epsilon. Association with Epstein-Barr virus (EBV) was demonstrated in 2 cases by in situ hybridization, whereas 1 case was negative. All our patients had aggressive disease and died between 2 weeks and 7 months from presentation. Analysis of our cases and of those published in the literature shows that intravascular large NK/T-cell lymphoma is a rare, aggressive lymphoma with variable phenotypic features, frequent expression of cytotoxic proteins, true NK-cell phenotype and association with Epstein-Barr virus infection, and common presentation in the skin. Homogeneous studies on larger number of patients and reevaluation of cases published with incomplete phenotypic data would be necessary to gather more information on this extremely rare type of lymphoma.

Intravascular T-cell lymphoma in a patas monkey (Erythrocebus patas)

“…In contrast, 91 % of IVL in people is of B-cell phenotype (Estalilla et al, 1999;Ferreri et al, 2004), while only few reports exist on NK-cell and T-cell variants (Shimokawa et al, 1991;Wu et al, 2005;Cerroni et al, 2008). A further discrimination of neoplastic T-cells was not possible since neither neoplastic nor non-neoplastic lymphoid cells showed a reaction against anti-CD4 and anti-CD8 antibodies, suggesting a lack of cross-reactivity of the respective antibodies and the patas monkey epitopes.…”

“…In light of the clear association between T-cell IVL and EBV infection in people (Au et al, 1997;Cerroni et al, 2008) and a suspected connection of simian LCVs and nonHodgkin's lymphomas in macaques (Pingel et al, 1997;Mätz-Rensing et al, 1999;Blaschke et al, 2001;Hirata et al, 2015;Kahnt et al, 2002;Rivailler et al, 2004;Carville and Mansfield, 2008), the molecular detection of LCV made us initially suspect a gammaherpesviral-induced lymphomagenesis in the present case. However, since we were not able to demonstrate LCV immunohistochemically within neoplastic cells, the role of the LCV in oncogenesis remains elusive, in particular because of the high prevalence of the virus in nonhuman primates (Bruce et al, 2012).…”

“…Progressive occlusion of small vessels by neoplastic cells may result in thrombosis, hemorrhage, and infarction (Cullen et al, 2000;Bush et al, 2003). In humans, there is a clear relationship between Tcell IVL and Epstein-Barr virus (EBV, human herpes virus 4) infection, as demonstrated by detection of EBV RNA in lymphoma cells (Au et al, 1997;Cerroni et al, 2008).…”

“…In macaques, these agents include simian retroviruses, in particular simian immunodeficiency virus (SIV; Habis et al, 1999;Mätz-Rensing et al, 1999;Rivailler et al, 2004) and simian retrovirus (SRV) type D (Paramastri et al, 2002). In addition to the retrovirus-induced immunodeficiency, the development of lymphomas is thought to be associated with coinfection with one of two types of gammaherpesviruses, namely simian lymphocryptoviruses (LCVs), the simian equivalent of EBV (Blaschke et al, 2001;Bruce et al, 2012;Carville and Mansfield, 2008;Habis et al, 2000;Kahnt et al, 2002;Li et al, 1993;Mätz-Rensing et al, 1999;Pingel et al, 1997), and rhadinoviruses (Bruce et al, 2012;Orzechowska et al, 2008). In contrast to the aforementioned retroviruses, simian T-cell lymphotropic virus (STLV) associated lymphomagenesis in nonhuman primates does not seem to require a herpesviral co-infection (Allan et al, 2001;Homma et al, 1984;Hubbard et al, 1993).…”

“…The vast majority of them are associated with certain viral agents (Bruce et al, 2012;Hirata et al, 2015;Hubbard et al, 1993;Hunt et al, 1983;Miller, 2012;Paramastri et al, 2002;Suzuki et al, 2005), whose natural host spectrum covers different African and Asian nonhuman primate species (Carville and Mansfield, 2008;Lerche and Osborn, 2003). In macaques, these agents include simian retroviruses, in particular simian immunodeficiency virus (SIV; Habis et al, 1999;Mätz-Rensing et al, 1999;Rivailler et al, 2004) and simian retrovirus (SRV) type D (Paramastri et al, 2002).…”