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Intravascular large cell lymphoma

Arnold S Freedman, MD
Jon C Aster, MD
Almut Böer-Auer, MD
Section Editors
Richard A Larson, MD
John A Zic, MD
Deputy Editor
Alan G Rosmarin, MD


Intravascular large cell lymphoma (ILCL) is a rare subtype of large cell lymphoma that is characterized by the proliferation of lymphoma cells within the lumina of small blood vessels, particularly capillaries and post-capillary venules, without an obvious extravascular tumor mass or readily observable circulating lymphoma cells in the peripheral blood.

This type of lymphoma has also been described as intravascular lymphomatosis, angiotropic large cell lymphoma, and malignant angioendotheliomatosis. The clinical presentation is varied and often includes symptoms related to organ dysfunction caused by occlusion of blood vessels. Particularly in the past, the diagnosis was usually only recognized at autopsy. In recent years, the heightened awareness of ILCL has resulted in more patients being diagnosed during life, thereby allowing for treatment.

Most information on ILCL comes from case reports and small case series of patients. In addition, an expert panel of pathologists and clinicians, convened under the sponsorship of the International Extranodal Lymphoma Study Group, has proposed practical guidelines [1].

The clinical presentation, diagnosis, and treatment of ILCL will be discussed here. Other types of large cell lymphoma are presented separately. (See "Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma" and "Initial treatment of advanced stage diffuse large B cell lymphoma".)


ILCL is a rare subtype of large cell lymphoma; the true incidence is unknown. Median age at diagnosis is in the sixth to seventh decades; there is no sex predilection [2-4].

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Literature review current through: Nov 2017. | This topic last updated: Nov 01, 2017.
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  1. Ponzoni M, Ferreri AJ, Campo E, et al. Definition, diagnosis, and management of intravascular large B-cell lymphoma: proposals and perspectives from an international consensus meeting. J Clin Oncol 2007; 25:3168.
  2. Ferreri AJ, Campo E, Seymour JF, et al. Intravascular lymphoma: clinical presentation, natural history, management and prognostic factors in a series of 38 cases, with special emphasis on the 'cutaneous variant'. Br J Haematol 2004; 127:173.
  3. Murase T, Yamaguchi M, Suzuki R, et al. Intravascular large B-cell lymphoma (IVLBCL): a clinicopathologic study of 96 cases with special reference to the immunophenotypic heterogeneity of CD5. Blood 2007; 109:478.
  4. Shimada K, Matsue K, Yamamoto K, et al. Retrospective analysis of intravascular large B-cell lymphoma treated with rituximab-containing chemotherapy as reported by the IVL study group in Japan. J Clin Oncol 2008; 26:3189.
  5. Brunet V, Marouan S, Routy JP, et al. Retrospective study of intravascular large B-cell lymphoma cases diagnosed in Quebec: A retrospective study of 29 case reports. Medicine (Baltimore) 2017; 96:e5985.
  6. Chapin JE, Davis LE, Kornfeld M, Mandler RN. Neurologic manifestations of intravascular lymphomatosis. Acta Neurol Scand 1995; 91:494.
  7. Detsky ME, Chiu L, Shandling MR, et al. Clinical problem-solving. Heading down the wrong path. N Engl J Med 2006; 355:67.
  8. Shimada K, Murase T, Matsue K, et al. Central nervous system involvement in intravascular large B-cell lymphoma: a retrospective analysis of 109 patients. Cancer Sci 2010; 101:1480.
  9. Murase T, Nakamura S, Kawauchi K, et al. An Asian variant of intravascular large B-cell lymphoma: clinical, pathological and cytogenetic approaches to diffuse large B-cell lymphoma associated with haemophagocytic syndrome. Br J Haematol 2000; 111:826.
  10. Kojima K, Kaneda K, Yasukawa M, et al. Specificity of polymerase chain reaction-based clonality analysis of immunoglobulin heavy chain gene rearrangement for the detection of bone marrow infiltrate in B-cell lymphoma-associated haemophagocytic syndrome. Br J Haematol 2002; 119:616.
  11. Narimatsu H, Morishita Y, Saito S, et al. Usefulness of bone marrow aspiration for definite diagnosis of Asian variant of intravascular lymphoma: four autopsied cases. Leuk Lymphoma 2004; 45:1611.
  12. Röglin J, Böer A. Skin manifestations of intravascular lymphoma mimic inflammatory diseases of the skin. Br J Dermatol 2007; 157:16.
  13. Tsuda M, Nakashima Y, Ikeda M, et al. Intravascular Large B-Cell Lymphoma Complicated by Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis that was Successfully Treated with Rituximab-Containing Chemotherapy. J Clin Exp Hematop 2015; 55:39.
  14. Sugiyama A, Kobayashi M, Daizo A, et al. Diffuse Cerebral Vasoconstriction in a Intravascular Lymphoma Patient with a High Serum MPO-ANCA Level. Intern Med 2017; 56:1715.
  15. Shinkawa Y, Hatachi S, Yagita M. Intravascular large B-cell lymphoma with a high titer of proteinase-3-anti-neutrophil cytoplasmic antibody mimicking granulomatosis with polyangiitis. Mod Rheumatol 2016; :1.
  16. Cobcroft R. Images in haematology. Diagnosis of angiotropic large B-cell lymphoma from a peripheral blood film. Br J Haematol 1999; 104:429.
  17. Williams G, Foyle A, White D, et al. Intravascular T-cell lymphoma with bowel involvement: case report and literature review. Am J Hematol 2005; 78:207.
  18. Song DE, Lee MW, Ryu MH, et al. Intravascular large cell lymphoma of the natural killer cell type. J Clin Oncol 2007; 25:1279.
  19. Martinez-Escala ME, Guggina LM, Cotliar J, et al. Cutaneous Involvement in a Case of Intravascular T-Cell Lymphoma With a γδ Phenotype. Am J Dermatopathol 2016; 38:e27.
  20. Ganguly S. Acute intracerebral hemorrhage in intravascular lymphoma: a serious infusion related adverse event of rituximab. Am J Clin Oncol 2007; 30:211.
  21. Kiyohara T, Kumakiri M, Kobayashi H, et al. A case of intravascular large B-cell lymphoma mimicking erythema nodosum: the importance of multiple skin biopsies. J Cutan Pathol 2000; 27:413.
  22. Gill S, Melosky B, Haley L, ChanYan C. Use of random skin biopsy to diagnose intravascular lymphoma presenting as fever of unknown origin. Am J Med 2003; 114:56.
  23. Odawara J, Asada N, Aoki T, et al. 18F-Fluorodeoxyglucose positron emission tomography for evaluation of intravascular large B-cell lymphoma. Br J Haematol 2007; 136:684.
  24. Martusewicz-Boros M, Wiatr E, Radzikowska E, et al. Pulmonary intravascular large B-cell lymphoma as a cause of severe hypoxemia. J Clin Oncol 2007; 25:2137.
  25. Asada N, Odawara J, Kimura S, et al. Use of random skin biopsy for diagnosis of intravascular large B-cell lymphoma. Mayo Clin Proc 2007; 82:1525.
  26. Le EN, Gerstenblith MR, Gelber AC, et al. The use of blind skin biopsy in the diagnosis of intravascular B-cell lymphoma. J Am Acad Dermatol 2008; 59:148.
  27. Pongpudpunth M, Rattanakaemakorn P, Fleischer AB Jr. Usefulness of Random Skin Biopsy as a Diagnostic Tool of Intravascular Lymphoma Presenting With Fever of Unknown Origin. Am J Dermatopathol 2015; 37:686.
  28. Adachi Y, Kosami K, Mizuta N, et al. Benefits of skin biopsy of senile hemangioma in intravascular large B-cell lymphoma: A case report and review of the literature. Oncol Lett 2014; 7:2003.
  29. Cho HG, Sheu SL, Kuo KY, et al. Limited Role of Random Skin Biopsy in the Diagnosis of Intravascular Lymphoma in Adult Patients with Hemophagocytic Lymphohistiocytosis. Acta Haematol 2017; 138:33.
  30. Sitthinamsuwan P, Chinthammitr Y, Pattanaprichakul P, Sukpanichnant S. Random skin biopsy in the diagnosis of intravascular lymphoma. J Cutan Pathol 2017; 44:729.
  31. Arai T, Kato Y, Funaki M, et al. Three Cases of Intravascular Large B-Cell Lymphoma Detected in a Biopsy of Skin Lesions. Dermatology 2016; 232:185.
  32. Yamada S, Nishii R, Oka S, et al. FDG-PET a pivotal imaging modality for diagnosis of stroke-onset intravascular lymphoma. Arch Neurol 2010; 67:366.
  33. Gatter KC, Warnke RA. Intravascular large B-cell lymphoma. In: World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds), IARC Press, Lyon 2001. p.177.
  34. Alhumidi A. Cutaneous Intravascular NK/T-cell lymphoma mimic panniculitis clinically, case report and literature brief review. Diagn Pathol 2015; 10:107.
  35. Wang L, Chen S, Ma H, et al. Intravascular NK/T-cell lymphoma: a report of five cases with cutaneous manifestation from China. J Cutan Pathol 2015; 42:610.
  36. Requena L, El-Shabrawi-Caelen L, Walsh SN, et al. Intralymphatic histiocytosis. A clinicopathologic study of 16 cases. Am J Dermatopathol 2009; 31:140.
  37. Kempf W, Keller K, John H, Dommann-Scherrer C. Benign atypical intravascular CD30+ T-cell proliferation: a recently described reactive lymphoproliferative process and simulator of intravascular lymphoma: report of a case associated with lichen sclerosus and review of the literature. Am J Clin Pathol 2014; 142:694.
  38. Tsukadaira A, Okubo Y, Ogasawara H, et al. Chromosomal aberrations in intravascular lymphomatosis. Am J Clin Oncol 2002; 25:178.
  39. Bouzani M, Karmiris T, Rontogianni D, et al. Disseminated intravascular B-cell lymphoma: clinicopathological features and outcome of three cases treated with anthracycline-based immunochemotherapy. Oncologist 2006; 11:923.
  40. Koizumi M, Nishimura M, Yokota A, et al. Successful treatment of intravascular malignant lymphomatosis with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 2001; 27:1101.
  41. Ferreri AJ, Dognini GP, Govi S, et al. Can rituximab change the usually dismal prognosis of patients with intravascular large B-cell lymphoma? J Clin Oncol 2008; 26:5134.
  42. Juweid ME, Stroobants S, Hoekstra OS, et al. Use of positron emission tomography for response assessment of lymphoma: consensus of the Imaging Subcommittee of International Harmonization Project in Lymphoma. J Clin Oncol 2007; 25:571.
  43. Shimada K, Kosugi H, Shimada S, et al. Evaluation of organ involvement in intravascular large B-cell lymphoma by 18F-fluorodeoxyglucose positron emission tomography. Int J Hematol 2008; 88:149.
  44. Hoshino A, Kawada E, Ukita T, et al. Usefulness of FDG-PET to diagnose intravascular lymphomatosis presenting as fever of unknown origin. Am J Hematol 2004; 76:236.