Intravascular lymphomatosis presenting as skin lesions and subacute encephalopathy

Inimioara Mihaela Cojocaru 1 , 2 , Adina Mitru 1 , Dana Nica 2 , 3 ,  and Carmen Maria Ardeleanu 2 , 4
  • 1 Department of Neurology, “Colentina” Clinical Hospital, Bucharest, Romania
  • 2 “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
  • 3 Department of Dermatology, “Colentina” Clinical Hospital, Bucharest, Romania
  • 4 “Victor Babeş” National Institute for Research and Development in the Domain of Pathology, Bucharest, Romania


Intravascular lymphomatosis is a neoplastic multisystemic disease; it is a rare subtype of diffuse large cell lymphoma characterized by the presence of lymphoma cells in the lumina of small vessels. A 49-year-old Caucasian woman was admitted to the Department of Internal Medicine for fatigue, night sweats, loss of weight, and multiple nodules in the forearms. Three months ago the patient’s family noticed problems with her cognitive function, she displayed difficulties with common daily tasks. The neurological examination revealed bradypsychia. Laboratory data showed modestly high levels of lactate dehydrogenase, and C-reactive protein. The day after admission, the patient had headache which raised in intensity; his mental status deteriorated, she was disoriented to time and place. She presented nucal rigidity. The CSF examination revealed a hemorrhagic aspect, elements 30/mm3, cytology: lymphocytes 90%, numerous erythrocytes, proteinorachia 96 mg/dL, glycorrachia 60 mg/dL. Intravenous Methylprednisolone (0.5 g two times a day) and Mannitol 20% 1g/kgw/day were administered for five days without response. She became comatose and she died six days after hospitalization. The post-mortem macroscopical brain examination showed a swallen brain, with diffuse hemorrhagic areas in the supratentorial subcortical regions. Microscopical examination showed capillaries, venules, and many arterioles distended by large malignant cells suggesting malignant lymphocytes which were intraluminal. Every organ was involved, except for bone marrow and lymph nodes. Immunohistochemical studies showed intensive staining for B cells and negative staining for factor VIII related antigen, a specific endothelial cell marker. Intravascular lymphomatosis was the post-mortem diagnostic. It represents a difficult diagnostic challenge which involves laboratory, imagistic and immunohistochemical investigations.

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  • 1. GATTER K.C., WARNKE R.A. Intravascular large B-cell lymphoma. Pathology and genetics of tumors of haematopoietic and lymphoid tissues, Jaffe E.S., Harris N.L., Stein H., Vardiman J.W. (eds), 177-78, IARC Press: Lyon, 2001.

  • 2. SUKPANICHNANT S., VISUTHISAKCHAI S. Intravascular lymphomatosis: a study of 20 cases in Thailand and a review of the literature. Clin Lymphoma Myeloma 2008; 6: 319-28.

  • 3. CROISILE B., TOMMASI M., JOUVET A., TRUFFERT A., TRILLET M. Lymphome malin endovasculaire à grandes cellules. Rev Neurol (Paris) 1990; 146: 184-90.

  • 4. WICK M.R., MILLS S.E. Intravascular lymphomatosis: clinico-pathologic features and differential diagnosis. Semin Diagn Pathol 1991; 8: 91-101.

  • 5. YEGAPPAN S., COUPLAND R., ARBER D.A., WANG N., MIOCINOVIC R., TUBBS R.R., HSI E.D. Angiotropic lymphoma: an immunophenotypically and clinically heterogenous lymphoma. Mod Pathol 2001; 14; 1147-56.

  • 6. MATSUE K., HAYAMA B.Y., IWAMA K., KOYAMA T., FUJIWARA H., YAMAKURA M., TAKEUKI M., O’UCHI T. High frequency of neurolymphomatosis as a relapse disease of intravascular large B-cell lymphoma. Cancer 2011; 117: 4512-21.

  • 7. YAMADA S., TANIMOTO A., NABESHIMA A., TASAKI T., WANG K.-Y., KITADA S., NOGUCHI H., SASAGURI Y. Diffuse large B-cell lymphoma presenting with neurolymphomatosis and intravascular lymphoma: a unique autopsy case with diverse neurological symptoms. Diagnostic Pathology 2012; 7: 94.

  • 8. KANDA M., SUZUMIYA J., OSHIMA K., TAMURA K., KOKUCHI M. Intravascular large cell lymphoma: clinicopathological, immuno-histochemical and molecular genetic studies. Leuk Lymphoma 1999; 34: 569-80.

  • 9. PONZONI M., ARRIGONI G., GOULD V.E., DEL CURTO B., MAGGIONI M., SCAPINELLO A., PAOLINO S., CASSISA A., PATRIARCA C. Lack of CD29 (β1 integrin) and CD54 (ICAM-1) adhesion molecules in intravascular lymphomatosis. Hum Pathol 2000; 31: 220-26.

  • 10. MACHADO G.F., CASTRO M.B., MELO G.D., FERREIRA W.L., AYLON E.G., ALESSI A.C. Intravascular lymphomatosis in the central nervous system of dogs: inmmunohistochemical investigation in two cases. Braz J Vet Path 2011; 4: 47-51.

  • 11. OEI M.E., KRAFT G.H., SARNAT H.B. Intravascular lymphomatosis. Muscle Nerve 2002; 25; 742-6.

  • 12. ZUCKERMAN D., SELIEM R., HOCHBERG E. Intravascular lymphoma: The Oncologist’s “great imitator”. The Oncologist h

  • 13. GLASS J., HOCHBERG F.H., MILLER D.C. Intravascular lymphomatosis. A systemic disease with neurologic manifestations. Cancer 1993; 71: 3156-64.

  • 14. CALAMIA K.T., MILLER A., SHUSTER A., PERMICIARO C., MENKE D.M. Intravascular lymphomatosis. A report of ten patients with central nervous system and a review of the disease process. Adv Exp Med Biol 1999; 455: 249-65.

  • 15. VIEREN M., SCIOT R., ROBBERECHT W. Intravascular lymphomatosis of the brain: a diagnostic problem. Clin Neurol Neurosurg 1999; 101: 33-6.

  • 16. BEQUET D., GUILLAMO J.S., MOKHTARI K. Confrontation de la Salpetrière. Syndrome confusionnel, troubles de langaje, troubles moteurs des membre inferieures à rechutes chez un homme de 48 ans. Rev Neurol (Paris) 2000; 156: 821-27.

  • 17. KONIKKARA J.J., PERURENA O.H., WARACH S., BAUSERMAN S.C. A 62-year-old man with fluctuating neurological deficits and skin lesions. JAMA Neurol 2013; 70: 120-24.

  • 18. BILLÉ J., BILLÉ-TURC F., LEHMANN G., GAMBARELLI D., PADOVANI R., PELISSIER J.F. Un cas anatomo-clinique de demence au cours d’un lymphome endovasculaire à grandes cellules. Rev Neurol (Paris) 1995; 151: 576-79.

  • 19. JOTPRATOOM P., YUCKPAN P., SITTHINASUWAN P., CHOTINAIWATTARAKUL W., CHINTHAMMITR Y. Progressive multifocal infarction from intravascular large B cell lymphoma presenting in a man: a case report. J Medical Case Reports 2011; 5: 24.

  • 20. AWAD A., ESTHPHAN B., STILVE O. CNS intravascular lymphoma: A case report. Case Reports in Neurological Medicine 2011; artcle ID 515182, 4 pages doi: 10.1155/2011/515182.

  • 21. OJEDA V.J. Neoplastic angioendotheliosis of spinal cord. Case report. Acta Neuropathol (Berlin) 1983; 62: 164-6.

  • 22. HAMADA K., HAMADA T., SATOH M., TASHIRO K., KATOH I., NAGANUMA M., SHIMA K., OGATA A., NAGASHIMA K. Two cases of neoplastic angio-endotheliomatosis presenting with mielopathy. Neurology 1991; 41: 1139-40.

  • 23. DUBAS F., SAINT-ANDRE J.P., POULARD BARTHELAIZ A., DELESTRE F., EMILE J. Intravascular malignant lymphomatosis (so-called malignant angioendotheliomatosis): a case confined to the lombosacral spinal cord and nerve roots. Clin Neuropathol 1990; 9: 115-20.

  • 24. NAKAHARA T., SAITO T., MUROI A., SUGURA Y., OGATA M., SUGIYAMA., YAMAMOTO T.A. Intravascular lymphomatosis presenting as an ascending cauda equina: conus medullaris syndrome: remission after biweekly CHOP therapy. J Neurol Neurosurg Psychiatry 1999; 67: 403-6.

  • 25. ABUZINADAH A., ALMALIK Y., SHABANI-RAD M.-T., HO C.H., GEORGE D., ALANT J., ZOCHODNE D. Cauda equina syndrome secondary to intravascular lymphoma. Neurology Clinical Practice 2012; 2: 158-61.

  • 26. ROUX S., GROSSIN M., DE BRANDT M., PALAZZO E., VACHON F., KAHN M.F. Angiotropic large cell lymphoma with mononeuritis multiplex mimicking systemic vasculitis. J Neurol Neurosurg Psychiatry 1995; 58: 363-6.

  • 27. VANDENHEEDE M., DIOH A., DE NOORDHOUT M., DEPREZ M., SCHOENEN J. Intravascular malignant lymphomatosis: report of 2 cases. Acta Neurol Belg 2002; 102: 76-81.

  • 28. LEVIN K.H., LUTZ G. Angiotropic large-cell lymphoma with peripheral nerve and skeletal muscle involvement: early diagnosis and treatment. Neurology 1996; 94: 311-5.

  • 29. MATSUE K., HAYAMA B.Y., IWAMA K.-I., KOYAMA T., FUJIWARA H., YAMAKURA M., TAKEUCHI M., O’UCHI T. High frequency of intravascular neurolymphomatosis as a relapse disease of intravascular large B-cell lymphoma. Cancer 2011; 117: 4512-21.

  • 30. HSU Y.H., TSENG B.Y., SHYU W.C., YEN P.S. Intravascular lymphomatosis mimicking acute disseminated encephalomyelitis: a case report. Kaohsiung J Med Sci 2005; 21: 93-7.

  • 31. LEGERTON C.W. 3rd, SERGENT J.S. Intravascular malignant lymphoma mimicking central nervous system lupus. Arthritis Rheum 1993; 36: 135.

  • 32. FREDERICKS R.K., WALKER F.O., ELSTER A. Angiotropic intravascular large-cell lymphoma (malignant angioendotheliomatosis): report of a case and review of the literature. Surg Neurol 1991; 35; 218-23.

  • 33. SUMER M., OZON A.O., BAKAR B., CILA A., RUACAN S. Intravascular lymphoma masquerading as multiembolic stroke developing after coronary artery by-pass surgery. Neurologist 2009; 15: 98-101.

  • 34. BAEHRING J.M., LONGTINE J., HOCHBERG F.H. A new approach to the diagnosis and treatment of intravascular lymphoma. J Neurooncol 2003; 61: 237-48.

  • 35. SONG D.K., NOULIS N.M., MCKEEVER P.E., QUINT D.J. Angiotropic large cell lymphoma with imaging characteristics of CNS vasculitis. Am J Neuroradiol 2002; 23: 239-42.

  • 36. LIOW U., ASMAR P., LIOW M. Intravascular lymphomatosis: contribution of cerebral MRI findings to diagnosis. J Neuro-imaging 2000; 10: 116-8.

  • 37. BAEHRING J.M., HENCHCLIFFE C., LEDEZMA C.J., FULBRIGHT R., HOCHBERG F.H. Intravascular lymphoma: magnetic resonance imaging correlates of disease imaging dynamics within the central nervous system. J Neurol Neurosurg Psychiatry 2005; 76: 540-4.

  • 38. YAMAMOTO A., KITUCHI Y., HOMMA K., O’UCHI T., FURUI S. Characteristics of intravascular large B-cell lymphoma on cerebral MR imaging. AJNR 2012; 33: 292-6.

  • 39. WILLIAMS R.I., MELTRER C.C., SMIRNIOTOPOULOS J.G., FUKUI M.B., INMAN M. Cerebral MR imaging in intravscular lymphomatosis. AJNR 1998; 19: 427-31.

  • 40. HUNG L.-C., TSAI J.-H., WU C.-S., DAI Y.-C., CHEN C.-C., SUNG S.-F. Brain biopsy-proven intravscular lymphomatosis presenting as rapidly recurrent strokes-two case reports. Acta Neurol Taiwan 2014; 23: 11-8.

  • 41. SCULLY R.E., MARK E.J., MCNEELY W.F., EBELING S.H. Case records of the Massachusetts General Hospital. N Engl J Med 1996; 335: 952-9.

  • 42. OSSEGER L.M., POSTLER E., PLEGER B., MULLER K.-M., MALIN J.-P. Neoplastic cells in the cerebrospinal fluid in intravascular lymphomatosis. J Neurol 2000; 247: 656-8.

  • 43. BILLÉ J., BILLÉ-TURC F., LEHMANN G., GAMBARELLI D., PADOVANI R., PELISSIER J.F. Un cas anatomo-clinique de demence au cours d’un lymphome endovasculaire à grandes cellules. Rev Neurol (Paris) 1995; 151: 576-9.

  • 44. FERRERI A.J.M., CAMPO E., SEYMOUR J.F., WILLEMZE R., ILARIUCCI F., AMBROSETTI A., ZUCCA E., ROSSI G., LOPEZ-GUILLERMO A., PAVLOVSKY M.A., GEERTS M.-L., CANDONI A., LESTANI M., ASIOLI S., MILANI M., PIRIS M.A., PILERI S., FACCHETTI F., CAVALLI F., PONZONI M., ON BEHAF OF THE INTERNATIONAL EXTRANODAL LYMPHOMA STUDY GROUP (IELSG). 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: 173-83.

  • 45. GILL S., MELOSKY B., HALEY A. Use of random skin biopsy to diagnose intravascular lymphoma presenting as fever of unknown origin. Am J Med 2003; 114: 56-8.

  • 46. KIDSON-GERBER G., BOSCO A., MACCALUM S., DUNKLEY S. Two cases of intravascular lymphoma: highlighting the diagnostic difficulties in pyrexia of unknown origin. Intern Med J 2005; 35: 569-70.

  • 47. MURASE T., NAKAMURA S., KAWAUCHI K., MATSUZAKI H., SAKAI C., INABA T., NASUN K., TASHIRO K., SUCHI T., SAITO H. 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: 826-34.

  • 48. MURASE T., NAKAMURA S., TASHIRO K., SUCHI T., HIRAGA J., HAYASAKI N., KIMURA N., SAITO H. Malignant histiocytosis-like B-cell lymphoma, a distinct pathologic variant of intravascular lymphomatosis: a report of five cases and review of the literature. Br J Haematol 1997; 99: 459-73.

  • 49. MURASE T., NAKAMURA S. An Asian variant of intravascular lymphomatosis: an updated review of malignant histiocytosis-like B-cell lymphoma. Leuk Lymphoma 1999; 33: 459-73.

  • 50. NINOMIYA T., NAKAMURA T., FUJI N., HIRAKI A., IMEMURA S., YAMANE H., SHIRAKAWA A., KAMEI H. Unusual spontaneous improvement in Asian variant of intravascular large B-cell lymphoma. Open Journal of Internal Medicine 2012; 2: 15-8.

  • 51. HOSHINO A., KAWANDA E., UKITA T., ITOH K., SAKAMOTO H., FUJITA K., MANTANI N., KOGURE T., TAMURA J. Usefulness of FDG-PET to diagnose intravascular lymphomatosis presenting as fever of unknown origin. Am J Haematology 2004; 76: 236-9.

  • 52. ASADA N., ODAWARA J., KIMURA S., AOKI T., YAMAKURA M., TAKEUKI M., SEKI R., TANAKAN A., MATSUE K. Use of random skin biopsy for the diagnosis of intravascular large B-cell lymphoma. Mayo Clin Proc 2007; 93: 1525-7.

  • 53. OOMURA M., SAKAKIBARA N., SUZUKI S., WAKITA A., MORI Y., KAMIMOTO K. Intravascular lymphomatosis mimicking primary central nervous system lymphoma: A case report and literature review. Case Reports in Neurology 2014; 6: 101-8.

  • 54. BAUMANN T.P., HURWITZ N., KARAMITOPOLOU-DIAMANTIS E., PROBST A., HERRMANN R. Diagosis and treatment of intravascular lymphomatosis. Arch Neurol 2000; 57: 374-7.

  • 55. SHIMADA K., KINOSHITA T., NAOE T., NAKAMURA S., Presentation and management of intravascular B-cell lymphoma. Lancet Oncol 2009: 10: 895-902.

  • 56. HARRIS C.P., SIGMAN J.D., JAECKLE K.A. Intravascular malignant lymphomatosis: amelioration of neurologic symptoms with plasmapheresis. Ann Neurol 1994; 35; 357-9.

  • 57. NAKAHARA T., SAITO T., MUROI A., SUGIURA Y., OGATA M. Intravascular lymphomatosis presenting as an ascending cauda equina conus medularis syndrome: remission after biweekly CHOP therapy. J Neurol Neurosurg Psychiatry 1999; 67: 403-6.

  • 58. ROSE C., STAUMONT D., JOUET J.-P. Successful autologous bone marrow transplantation in intravscular lymphomatosis. Br J Haematol 1999; 105: 313-20.

  • 59. BAEHRING J.M., LONGTINE J., HOCHBERG F.H. A new approach to the diagnostic and treatment of intravascular lymphoma. J Neurooncol 2003; 61: 237-48.

  • 60. ANGHEL G., PETRINATO G., SEVERINO A., REMOTTI D., INSABATO L., DE RENZO A., ROTOLI B., MAJOLINO I. Intravascular B-cell lymphoma: report of two cases with different clinical presentation but rapid central nervous system involvement. Leuk Lymphoma 2003; 44: 1353-9.

  • 61. INOUE D., HAMAMURA T., UEHARA T., MIYOSHI K., KATSURAGI T., TAKESHITA I., HAMATA T. Intravascular lymphoma confirmed by brain biopsy, quickly treated by chemotherapy: a case report. No Shinkei Geka 2008: 37: 369-74.

  • 62. SAWAMOTO A, NARIMATSU H., SUZUKI T., KURAHASHI, SUGIMOTO T., SUGIURA I. Long-term remission after autologous peripheral blood stem cell transplantation for relapsed intravascular lymphoma (Letter). Bone Marrow Transplantation 2009; 37: 233-4.


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