Intravascular NK/T-Cell Lymphoma: What We Know about This Diagnostically Challenging, Aggressive Disease

Abstract

Intravascular lymphoma is a form of lymphoid malignancy characterized by neoplastic cells growing almost exclusively within the lumina of small- to medium-sized blood vessels. Most cases are of B-cell origin with rare cases of natural killer or T-cell lineage. Extranodal sites are affected, mainly the skin and central nervous system, although any organ may be involved. Intravascular NK/T-cell lymphoma deserves special attention because of its clinicopathologic features and the need for adequate immunophenotyping combined with clonality test for a proper diagnosis. Moreover, intravascular NK/T-cell lymphoma is strongly linked to Epstein–Barr virus (EBV), which is considered to play a role in tumorigenesis and to be responsible for the aggressive behavior of the disease. In this paper, we review the current knowledge on this rare lymphoma and, in particular, the most recent advances about its molecular landscape. The main distinguishing features with other EBV-related entities, such as extranodal NK/T-cell lymphoma, EBV-positive primary nodal T/NK-cell lymphoma, and aggressive NK-cell leukemia, are discussed to help pathologists obtain the correct diagnosis and consequently develop an adequate and prompt therapy response.

Cutaneous Intravascular Hematolymphoid Entities: A Review

“…Intravascular natural killer/T-cell lymphoma (IVNKTL) is a highly aggressive form of non-Hodgkin lymphoma that primarily impacts the CNS and the skin [40]. It typically affects small to medium-sized vessels and does not form a mass lesion [40].…”

“…Intravascular natural killer/T-cell lymphoma (IVNKTL) is a highly aggressive form of non-Hodgkin lymphoma that primarily impacts the CNS and the skin [40]. It typically affects small to medium-sized vessels and does not form a mass lesion [40]. IVNKTL is an extremely rare disease, with a recent literature review indicating that just 27 cases with sufficient immunohistochemical and molecular data have been reported since the disease was first described by Santucci et al in 2003 [41,42].…”

“…Given its rarity, optimal disease classification remains unclear; IVNKTL was formerly considered to be a variant of extranodal NK/T-cell lymphoma [43,44]; however, the most recent edition of the WHO classification of lymphoid neoplasms categorizes IVNKTL as a subtype of aggressive NKcell leukemia instead [45]. IVNKTL has predominantly been reported in adult patients without a clear age or sex predilection [40,42].…”

“…In addition to the cutaneous manifestations, other organs and organ systems including the CNS, bone marrow, lungs, and kidneys may be affected, with CNS manifestations being the most common [46,47]. Due to the potential for many different organ systems to be involved, presentation is highly variable; symptoms may include fever and other B-symptoms, malaise, jaundice, neurologic symptoms, arthralgias and other musculoskeletal symptoms, or rash [40,46,47,51]. To further complicate matters, some patients present only with cutaneous manifestations with no symptomatic evidence of systemic disease [40,42,48,52].…”

CD30 in Cutaneous Pathology

“…Although most intravascular lymphomas are of B-cell nature, some T-cell lymphomas, such as LyP, ALCL, or ENKTCL, can sometimes show an intravascular presentation. 107 In the intravascular type of ENKTCL, the vessels are blood vessels; therefore, they should be negative when studied with lymphatic endothelial markers such as D2-40. However, LyP and ALTCL can sometimes be intralymphatic.…”