Intravascular lymphomas

Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other types of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, other parts of the lymphatic system (e. g. the spleen), and various non lymphatic organs (e. g. bone marrow and liver) but not in blood vessels. IVL fall into three different forms based on the type of lymphocyte causing the disease. Intravascular large B cell lymphoma (IVBCL), which constitutes ~90% of all IVL, is a lymphoma of malignant B cell lymphocytes as classified by the World Health Organization, 2016. The remaining IVL types, which have not yet been formally classified by the World Health Organization, are defined based mainly on case reports; The malignant cells in IVNK/TL are typically infected with the Epstein–Barr virus suggesting that these lymphomas are examples of the Epstein Barr virus associated lymphoproliferative diseases. and intravascular NK/T cell Subsequent studies reported in 1982, 1985, and 1986 led to the conclusion that these malignant cells were derived from lymphocytes rather than endothelial cells. These along with other studies termed the disease angioendotheliomatosis, neoplastic angiotheliomatosis, intravascular lymphomatosis, angioendotheliotropic (intravascular) lymphoma, angiotropic large cell lymphoma, diffuse large cell lymphoma, intralymphatic lymphomatosis, and, less specifically, malignant angioendotheliomatosis or intravascular lymphoma. By 2001, the World Health Organization had defined the disease as a malignant B cell lymphoma termed intravascular large B cell lymphoma. Santucci et al. first reported a case of IVL that involved malignant NK cells. Some 2 dozen other cases of intravascular NK cell lymphoma have been reported by 2018. In 2008, 29 case reports of purported intravascular T cell lymphoma were reviewed; only two of these cases were associated with evidence strongly suggesting that the malignant cells were cytotoxic T cells. Subsequently, a few more cases of cytotoxic T cell based have been reported. There remains a possibility that future studies will find other T cell types may cause IVTCL.

Intravascular large B cell lymphomas fall into three distinct variants, all of which involve the intravascular accumulation of malignant B cells and appear to have a similar pathophysiology. However, they differ in the distribution of their lesions, types of populations affected, prognoses, and treatments. These three variants are: 1) intravascular large B cell lymphoma classical, 2) intravascular large B cell lymphoma, cutaneous variant, and 3) intravascular large B cell lymphoma, hemophagocytic syndrome associated variant. and some or the mutations in CD79B occur in diverse types of lymphoma. Other abnormalities seen in the small numbers of cases that have been studied so far include translocations between chromosome 14 and 18; tandem triplications of both the BCL2 gene located on the long arm of chromosome 18 at position q21 and the KMT2A gene located on the long arm of chromosome 11 between positions 22 and 25. and KMT2A are associated with other types of B cell lymphomas. It seems likely that these or other gene, chromosome, and/or gene expression abnormalities contribute to the development and/or progression of IVBCL. The malignant B cells in IVBCL fail to express the CD29 protein while the endothelial cells in close proximity to the intravascular accumulations of the malignant B cells fail to express key CXC chemokine receptor proteins particularly CxcL12 but also Cxcr5, Ccr6, and/or Ccr7. The failure of the endothelial cells to express these receptor proteins may be due to the action of nearby malignant B cells. In any event, all of the cited proteins are involved in the movement of B cells from the intravascular space across the vascular endothelium and into tissues. The lack of these proteins may explain the accumulation of the malignant B cells of IVLBC within blood vessels. rather than the "germinal center B cells" that are commonly found in less aggressive B cell lymphomas. This factor may contribute to the aggressiveness of IVBCL. These findings are based primarily on studies of 740 patients conducted in Europe; a study conducted in Quebec, Canada on 29 patients gave similar results. anemia, decreases in blood platelet levels, and decreases in white blood cell levels in 25% >50% of cases. The diagnosis of IVBCL, classical variant is solidified by finding these pathological features in more than one site.

The cutaneous variant, which comprises a small percentage of all IVBCL cases, occurs almost exclusively in females and younger individuals (median age 59 years) than the classical variant (median age 72 years).

Historically, individuals with the cutaneous variant survive significantly longer than that those with the classical variant (3 year overall survival 56% versus 22%). Early intervention in the cutaneous variant would appear to be highly desirable. Rituximab may improve the latter situation.

The hemophagocytic syndrome associated variant of IVBCL is a very rare variant of IVBCL. Its previous name, intravascular large B cell lymphoma, Asian variant, was recently changed to its current name by the world Health Organization, 2016. Unlike the classical and cutaneous variants, the hemophagocytic syndrome associated variant presents with the hemophagocytic syndrome. This syndrome is characterized by bone marrow involvement, reduced numbers of circulating blood platelets and enlarged liver and spleen. Less often, it is also associated with overt hemophagocytosis (i. e. the engulfment by non malignant histiocytes of red blood cells, white blood cells, platelets, and their precursor cells that is most commonly found in the bone marrow and other tissues. A study of two patients with IVNKL identified mutations in genes that produce histone proteins (HIST1H2BE, HIST1H2BN and H3F3A), the histone deacetylase gene, HDAC5, two genes that produce helicase proteins (WRN and DDX3X), two genes that make DNA methylation related enzymes (TET2 and DNMT1) and a gene in the SWI/SNF family of chromatin remodeling genes, ARID1A. In a third study of a single patient, copy number analysis identified driver gene alterations in ARID1B, HACE1, and SMAD4 genes and gain of the SOX2 gene. including in extremely rare cases IVNK/TL. It seems likely that the virus acts similarly to cause IVNK/TL.

Individuals (age range 23–81 years Rituximab does not target NK or T cells and therefore is not used to treat IVNK/TL.