Immunohistochemistry

Positivity is limited to B-cell markers

Diagnosis : Angiotropic lymphoma, Large B-Cell

Skin biopsy

Bladder biopsy

The litterature about Angiotropic Lymphoma:

Lack of CD 29 (beta1 integrin) and CD 54 (ICAM-1) adhesion molecules in intravascular lymphomatosis.
Hum Pathol 2000 Feb;31(2):220-6
Ponzoni M, Arrigoni G, Gould VE, Del Curto B, Maggioni M, Scapinello A, Paolino S, Cassisa A, Patriarca
Department of Pathology, Scientific Institute Ospedale S. Raffaele HSR, Milan, Italy.

Intravascular Lymphomatosis (IL) is a rare and usually aggressive form of non-Hodgkin's lymphoma characterized by the growth of neoplastic cells within vascular lumina that usually presents with skin or central nervous system (CNS) involvement. The mechanism(s) for the selective intravascular growth of this neoplasm remain(s) unexplained. We now report clinical and immunohistologic data on surgical material from 6 cases of IL; in 4 of 6 cases, autopsies were performed. Our IL cases shared the following features: (1) B-cell lineage; (2) lack of skin involvement at presentation; (3) aggressive behavior; and (4) lack of extravascular lymphomatous masses; in addition, 1 case had an associated gastric low-grade MALT lymphoma. We studied by immunohistochemistry formalin-fixed, paraffin-embedded sections with monoclonal antibodies to molecules known to be involved in lymphocyte and endothelial adhesion phenomena, that is, CD29 (beta1 integrin subunit), CD43 (leukosialin), CD44 (H-CAM), CD54 (ICAM-1), embryonal N-CAM (e-NCAM), and EMA (episialin). In all cases, the surfaces of IL aggregates reacted for CD44 but were consistently negative for CD29; also absent was CD54. Conversely, the integrity of the endothelial cells was underscored by their even reactivity for CD29, CD44, and CD54. Given that CD29 is currently regarded as critical for lymphocyte trafficking in general and for transvascular migration in particular, and CD54 is also involved in transvascular lymphocyte migration, we conclude that their consistent absence in IL may contribute to its intravascular and disseminated distribution pattern.
The rather frequent association of IL with various conventional lymphomas is known; yet, one of our cases appears to be the first report of IL associated with a low-grade MALT lymphoma.

Angiotropic lymphoma manifesting as a solitary adrenal tumor in a case of ankylosing spondylitis.
Gau JP, Chiu CF, Liu SM, Hsu HC, Ho CH, Chau WK
Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.

Angiotropic lymphoma is an extremely rare disease characterized by intravascular accumulation of large neoplastic lymphocytes, with the clinical manifestations of fever, skin lesions and neurologic deficits. We report a patient who developed angiotropic lymphoma after a 10-year history of ankylosing spondylitis. The clinical disease manifested as a unilateral, solitary adrenal tumor, fever and body weight loss. The fever subsided after surgical removal of the adrenal tumor. Systemic chemotherapy was administered postoperatively. The patient was leading an uneventful life 44 months after the initial diagnosis. To our knowledge, this is the first case of angiotropic lymphoma associated with ankylosing spondylitis. It is also the second reported case manifesting with a unilateral solitary adrenal tumor without systemic involvement.





Angiotropic large B-cell lymphoma with clinical features resembling subacute combined degeneration of the cord.
Clin Neurol Neurosurg 1999 Dec;101(4):275-9
Waring WS, Wharton SB, Grant R, McIntyre M
Clinical Pharmacology Unit, University of Edinburgh, Western General Hospital, UK.

Angiotropic large cell lymphoma is a rare neoplastic disorder associated with a high mortality. The hallmark of the disease is lymphoid proliferation confined to the intravascular compartment without local tissue or vessel wall infiltration [1]. This feature is so striking that the disease was originally thought to arise from endothelial tissue and early cases were described as malignant angioendotheliomatosis. However, application of immunohistochemical methods for detection of lymphoid markers such as the CD45 and CD20 cell surface markers has confirmed its lymphoid origin, usually of B-cell lineage [2]. Clinical manifestations of the disease are protean and are due to multifocal medium and small vessel occlusion by tumour cells [3]. Characteristic sites of involvement are skin and central nervous system and although an ante-mortem diagnosis can be made from a biopsy specimen, it is often unsuspected [4]. We present a case of angiotropic large B-cell lymphoma in a 74-year-old man who presented with urinary symptoms and had a neurological picture resembling subacute combined degeneration of the cord.





Angiotropic (intravascular) large cell lymphoma of T-cell phenotype presenting as acute appendicitis in a patient with acquired immunodeficiency syndrome.
Arch Pathol Lab Med 1999 Apr;123(4):335-7
Malicki DM, Suh YK, Fuller GN, Shin SS
Department of Pathology, UCSD Medical Center, San Diego, Calif, USA.

We describe a patient with acquired immunodeficiency syndrome who presented with acute appendicitis but was found to have angiotropic large cell lymphoma (ALCL)by pathologic examination of the appendectomy specimen, without acute inflammation. Very rare cases of angiotropic large cell lymphoma have been reported in patients with human immunodeficiency virus infection, and most cases of this rare lymphoma are of B-cell origin, but in this instance immunohistochemical analysis showed a T-cell phenotype.


Angiotropic large cell lymphoma presenting as fever of unknown origin.
Am J Med Sci 1999 Apr;317(4):266-8
Kuvliev E, Glamour T, Shekar R, West BC
Department of Medicine, Meridia Huron Hospital, East Cleveland, Ohio 44112, USA.

BACKGROUND: Fever has never before been described as the chief complaint and major finding in angiotropic large cell lymphoma (ALCL). ALCL is a rare and usually fatal intravascular tumor characterized by a widespread proliferation of malignant mononuclear cells within vessels of small caliber, causing their blockage. The majority present as high-grade, B-cell lymphomas with a predilection for the central nervous system and the skin.
CASE REPORT: We report a 61-year-old woman who presented with a fever of unknown origin (FUO) that lasted 9 weeks from onset to death. To our knowledge, this is the first case of ALCL to present solely as a FUO, and the second case of ALCL to be diagnosed by muscle biopsy.
CONCLUSION: We suggest that this rare malignancy (ALCL) be considered in the differential diagnosis of FUO.




Generalized telangiectasia as the major manifestation of angiotropic (intravascular) lymphoma.
Br J Dermatol 1997 Sep;137(3):422-5
Ozguroglu E, Buyulbabani N, Ozguroglu M, Baykal C
Department of Dermatology, Istanbul Medical Faculty, University of Istanbul, Turkey.

We report a 60-year-old woman with B-cell angiotropic lymphoma who presented with generalized telangiectasia and indurated plaques. Cutaneous involvement in angiotropic lymphoma has a wide clinical spectrum. Telangiectasia on associated cutaneous lesions is expected, but generalized telangiectasia over normal skin was a striking feature of our patient.



Angiotropic (intravascular) large cell lymphoma: case report and short discussion of the literature.
Tumori 1997 Jul-Aug;83(4):772-5
Sanna P, Bertoni F, Roggero E, Quattropani C, Rusca T, Pedrinis E, Monotti R, Mombelli G, Cavalli F, Zucca E
Servizio Oncologico Cantonale, Ospedale San Giovanni, Bellinzona, Switzerland.

We report a case of angiotropic (intravascular) large B-cell lymphoma in an 84-year-old woman who underwent diagnostic procedures for progressive, painful induration of the legs. Physical examination and imaging studies revealed only widespread telangiectasias and significant panniculities-like lymphedema of the legs, with no masses or lymphadenopathies. The patient achieved a complete clinical remission after the first three cycles of polychemotherapy. Although angiotropic lymphoma is a rare entity with polymorphic clinical presentations,its early diagnosis appears very important since it may be curable with appropriate chemotherapy regimens.




T-cell intravascular lymphomatosis (angiotropic large cell lymphoma):
association with Epstein-Barr viral infection.
Histopathology 1997 Dec;31(6):563-7
Au WY, Shek WH, Nicholls J, Tse KM, Todd D, Kwong YL
University Department of Medicine, Queen Mary Hospital, Hong Kong.

AIMS: Intravascular lymphomatosis (IVL) is a very rare non-Hodgkin's lymphoma characterized by proliferation of lymphoma cells in the vascular lumina without involvement of adjacent parenchymal tissue. IVL is predominantly of B-cell lineage, but occasional cases of T lineage IVL involving almost exclusively the skin have been described. A case of IVL that occurred initially in the epididymis of a patient with an antecedent nasopharyngeal carcinoma was studied to define the clinicopathological features associated with this unique presentation.
METHODS AND RESULTS: This lymphoma was studied by standard histological and immunophenotyping methods. The results showed lymphoma cells confined within the blood vessels, which expressed leucocyte common antigen, and T-cell markers CD3 and UCHL-1. The T-cell origin of the IVL prompted investigations for an association with Epstein-Barr virus infection (EBV). In-situ hybridization with digoxigenin-labelled anti-sense RNA probes to EBV encoded RNA (EBER) showed strong signals in the nuclei of virtually all of the lymphoma cells.
CONCLUSIONS: EBV infection of the malignant cells was demonstrated by in-situ hybridization. This case suggests that T-cell IVL may be another EBV related human neoplasm. This observation will need to be validated by further studies.




Angiotropic lymphoma with endocrine involvement.
Histopathology 1997 Aug;31(2):161-6
Shanks JH, Harris M, Howat AJ, Freemont AJ
Department of Histopathology, Christie Hospital, Manchester, UK.

AIMS: Two cases of angiotropic high-grade B-cell lymphoma are described in which involvement of endocrine glands was a prominent feature.
METHODS AND RESULTS: One patient had marked unilateral adrenomegally due to lymphoma within adrenal blood vessels. He is alive 5 years after presentation following combination chemotherapy. The diagnosis was made at autopsy in the second patient who presented with pyrexia of unknown origin and had hypothyroidism and a thyroid nodule. The thyroid gland and pituitary showed striking involvement by angiotropic lymphoma and the thyroid nodule was a cavernous haemangioma heavily colonized by lymphoma cells.
CONCLUSIONS: Our cases illustrate endocrine organ manifestations of this rare disease. The condition may respond to combination chemotherapy.




Lymphoproliferative disorders and motor neuron disease: an update.
Neurology 1997 Jun;48(6):1671-8
Gordon PH, Rowland LP, Younger DS, Sherman WH, Hays AP, Louis ED, Lange DJ, Trojaborg W, Lovelace RE, Murphy PL, Latov N
Department of Neurology, Columbia-Presbyterian Medical Center, NY 10032-2699, USA.

We studied 26 patients with both motor neuron disease and lymphoproliferative disease (LPD). Twenty-three patients had definite or probable upper motor neuronsigns; none had electrophysiologic evidence of motor neuropathy. LPD syndromes comprised Waldenstrom's macroglobulinemia, multiple myeloma, chronic lymphocytic leukemia, follicular cell lymphoma, and Hodgkin's disease. In all but one patient, the cause of disability or death was neurologic. LPD was confined to bone marrow in 14 patients; eight of 14 had monoclonal paraproteinemia. One patient had LPD discovered at autopsy. Treatment of LPD in 20 patients resulted in neurologic improvement in 1 patient and arrest in another; both had progressive spinal muscular atrophy. Eleven patients were worse and 13 died. Atleast 30 cases have been reported from other centers, bringing the total to 56.
Among the unusual reported concomitants were POEMS (polyneuropathy, organomegaly, endocrinopathy, myeloma, and skin changes) syndrome of myeloma and angiotropic lymphoma.





Angiotropic lymphoma diagnosed by muscle biopsy.
Intern Med 1997 Apr;36(4):304-7
Suzuki S, Koizumi Y
Department of Internal Medicine, Shinonoi General Hospital, Nagano.

On hospitalization, the clinical examination of a 64-year-old female with polyarthralgia and an elevated fever revealed leukocytosis, an increased lactic acid dehydrogenase level, and a positivity for the C-reactive protein. Subsequently, the patient developed muscular pain in the lower limbs. Thus, a muscle biopsy was performed and B-cells with atypia were detected in the arteriolar lumen within the muscle. This led to the diagnosis of angiotropic lymphoma (AL). A combination chemotherapeutic regimen was initiated, and the patient's symptoms disappeared. AL is difficult to diagnose before death, but in this case, muscle biopsy facilitated an early diagnosis and subsequent chemotherapy resulted in the disappearance of the AL. We thus feel this report may be of value.




Malignant endovascular large-cell lymphoma: disclosing central nervous system involvement confirmed by cerebral biopsy.
Rev Med Interne 1997;18(6):4881-4
Viguier A, Alrich L, Faucheux JM, Delisle MB, Larrue V
Service de neurologie, CHU Rangueil, France.

Intravascular malignant lymphomatosis (IML) is characterised by proliferation of tumoral cells within small vessels. Angiotropic large cell lymphoma commonly affects the central nervous system and the skin, although any organ may be involved. Few cases are diagnosed ante mortem. We report a new case of IML in a 62-year-old woman who presented with the main clinical features of central nervous system involvement: cerebrovascular events, epileptic seizures, subacute dementia and spinal cord syndrome. Cranial magnetic resonance imaging demonstrated increased periventricular signal on T2-weighted images. Diagnosis was established by brain biopsy. Despite corticosteroid and radiation therapy no improvement occurred and the patient died 14 months after the onset of the first symptoms.




MR imaging of multiple cerebral infarctions in angiotropic lymphoma (neoplastic angio-endotheliosis).
Acta Neurochir (Wien) 1997;139(5):478-9
Takagi Y, Kikuchi H
Department of Neurosurgery, Kyoto University, School of Medicine, Japan.




Angiotropic lymphoma: report of a case with histiocytic features.
J Clin Pathol 1997 Jan;50(1):67-70
Snowden JA, Angel CA, Winfield DA, Pringle JH, West KP
Department of Haematology, Royal Hallamshire Hospital, Central Sheffield
University Hospitals Trust.

Angiotropic lymphoma, also known as intravascular lymphomatosis, is characterised by widespread intravascular proliferation of malignant lymphoid cells, usually without evidence of focal disease. A case of a 52 year old man referred for investigation of a two year history of pyrexia of unknown origin, skin rash and multiple organ failure is described. Angiotropic lymphoma was seen in gastric, colonic and skin biopsy specimens, and review of an earlier skin biopsy specimen showed similar morphological features. In contrast to previous cases which showed B or T cell differentiation, immunohistochemical examination was positive for histiocyte markers. Molecular studies showed no evidence of immunoglobulin heavy chain gene or T cell receptor gene rearrangement. The patient responded to combination chemotherapy, comprising cyclophosphamide,doxorubicin, etoposide, and prednisolone. This case highlights the fact that advanced lymphoma may be present without evidence of focal disease and that the diagnosis may be missed easily both clinically and histologically.



Angiotropic large cell lymphoma (intravascular lymphomatosis) occurring after follicular small cleaved cell lymphoma.
Mayo Clin Proc 1996 Sep;71(9):869-73
Carter DK, Batts KP, de Groen PC, Kurtin PJ
Division of Anatomic Pathology, Mayo Clinic Rochester, Minnesota 55905, USA.

Angiotropic large cell lymphoma is a rare, aggressive type of malignant lymphoma that primarily involves intravascular spaces and most often has clinical manifestations in the skin and central nervous system. Virtually any organ can be affected, however, including the lymph nodes and spleen. Peripheral blood involvement is usually not detectable morphologically. Conventional lymphoma in association with this entity has also been described. Herein we present a case of angiotropic lymphoma of B-cell lineage that affected the liver and skin. Reanalysis of a lymph node specimen that had been excised 3 years previously demonstrated a follicular small cleaved cell lymphoma. To our knowledge, this is the first reported case of possible evolution of follicular lymphoma to large cell lymphoma of angiotropic type.



Motor neuron disease and angiotropic lymphoma.
Arch Neurol 1997 Jan;54(1):92-5
Rubio A, Poole RM, Brara HS, Taylor N, Powers JM
Department of Pathology, University of Rochester, NY, USA.

BACKGROUND: The number of patients with motor neuron disease (MND) and a concomitant hematologic disorder appears to be overrepresented. Angiotropic large cell lymphoma, a rare and aggressive type of lymphoma, has been associated with MND only once (to our knowledge) prior to this report. There are more than 35 cases of MND associated with lymphoma or monoclonal gammopathy reported in the literature. The nature of this association remains disputable.
OBJECTIVE: To investigate whether the association between some MNDs and certain hematologic disorders is coincidental or pathogenetically related. CASE PRESENTATION: We describe the clinical and neuropathologic findings in a case involving a 70-year-old man with a rapidly progressive lower MND who at autopsy also exhibited angiotropic large cell lymphoma without ischemic lesions in the nervous system.
CONCLUSIONS: This case supports the notion that the association between some MNDs and certain hematologic disorders is not coincidental but pathogenetically related. A 2-hit hypothesis is proposed in which an initial abnormal glycosylation in motoneurons would require the production of an
appropriate autoantibody for disease expression.



Angiotropic large cell lymphoma: simultaneous peripheral nerve and skeletal muscle involvement.
Pathology 1996 Jan;28(1):25-7
Prayson RA
Department of Anatomic Pathology, Cleveland Clinic Foundation, Ohio, USA.

Angiotropic large cell lymphoma is a rarely encountered disorder characterized by a proliferation of malignant lymphoid cells within vascular lumina. Sites usually affected include the skin and central nervous system, although involvement of multiple other organ symptoms have been described including peripheral nerve and skeletal muscle. Simultaneous involvement of both skeletal muscle and peripheral nerve has rarely been reported. In most of those cases the diagnosis was made only at the time of autopsy. A case of an elderly male with angiotropic large cell lymphoma and in whom the diagnosis was made antemortem on a peripheral nerve and skeletal muscle biopsy is reported.



Angiotropic large cell lymphoma with mononeuritis multiplex mimicking systemic vasculitis.
J Neurol Neurosurg Psychiatry 1995 Mar;58(3):363-6
Roux S, Grossin M, De Bandt M, Palazzo E, Vachon F, Kahn MF
Department of Rheumatology, Bichat Hospital, Paris, France.

Angiotropic large cell lymphoma (ALCL), the so-called malignant angioendotheliomatosis, is characterised by proliferation of tumorous cells within small vessels. Manifestations in the CNS and cutaneous lesions prevail in the clinical presentation, although any organ can be involved. The recent classification of this lymphoma as part of the large cell lymphomas has modified the therapeutic approaches employed. This should improve the prognosis of this usually fatal disease. An unusual case presenting with fever, mononeuritis multiplex, and cutaneous lesions is reported. Peripheral neuropathy without other neurological symptoms is uncommon, and, to our knowledge, such isolated mononeuritis multiplex with nerve lesions has not been previously reported in ALCL. The clinical diagnosis was a systemic necrotising vasculitis and it is considered that its differential diagnosis must include angiotropic large cell lymphoma.




Angiotropic large cell lymphoma.
South Med J 1995 Feb;88(2):235-8
Collins KA, Davis GJ
Department of Pathology, Bowman Gray School of Medicine, Winston-Salem, NC
27157.

Lymphomas are malignant neoplasms of cells native to lymphoid tissue that can arise anywhere in the body. Angiotropic large cell lymphoma (ALCL) is characterized by a proliferation of neoplastic mononuclear cells within the lumina of small blood vessels. The clinical manifestations are usually neurologic, including progressive dementia and nonlocalizing deficits, cutaneous infiltration, adrenal masses, or fever of unknown origin. The diagnosis is made at autopsy or on skin biopsy, brain biopsy, or other surgical resection.
Differential diagnoses include metastatic malignant neoplasms and vasculartumors. We report the case of a 63-year-old white man who had neurologic signs and symptoms as well as dyspnea. Autopsy revealed ALCL involving multiple organ systems, including the central nervous system. Diagnostic techniques currently used to confirm the nature of this malignant neoplasm include immunohistochemistry, ultrastructural analysis, cytogenetics, and molecular biologic studies.