Intravascular lymphomatosis

Intravascular lymphomatosis (IVL) is a rare angiotrophic large cell lymphoma producing vascular occlusion of arterioles, capillaries, and venules. Antigenic phenotyping shows that these lymphomas are mostly of B cell type, and less commonly T cell or Ki-1 lymphomas. The central nervous system and skin are the two most commonly affected organs; patients usually present with progressive encephalopathy with mental status changes and focal neurological deficits and skin petechia, purpura, plaques, and discolouration. Other involved organs include adrenal glands, lungs, heart, spleen, liver, pancreas, genital tract, and kidneys. Bone marrow, blood, cerebrospinal fluid, and lymph nodes are typically spared. Fever of unknown origin is another common presentation. Only one case of IVL presenting with disseminated intravascular coagulation and anasarca (generalised oedema) has been reported in the literature. This report describes a postmortem case of a patient with IVL who initially presented with disseminated intravascular coagulation complicated by intracerebral haemorrhage.     

Intravascular lymphomatosis: a clinicopathological study of two cases presenting as an interstitial lung disease

 

Aims:

Intravascular lymphomatosis is an uncommon type of non-Hodgkin's lymphoma characterized by intravascular proliferation of neoplastic lymphoid cells. Although the tumour is basically a systemic disease, eventually involving multiple organs, primary presentation in the lung is rare.  

Methods and results:

We describe the clinicopathological features of two patients with intravascular lymphomatosis presenting in the lung. One patient complained of fever, headache and chest pain; the other, of dyspnoea on exertion and headache. Both patients showed reticulonodular density on chest radiography and decreased diffusion capacity. Lung biopsy showed features characteristic of intravascular lymphomatosis. Malignant lymphoid cells were CD30 positive T-cells of anaplastic large cell type in one patient and B-cells of large cell type in the other. There was a poor response to chemotherapy and both patients died of the disease within 3 months of diagnosis.  

Conclusions:

These cases and 10 previous reports illustrate the need to include intravascular lymphomatosis in the differential diagnosis of interstitial lung disease.     

Intravascular lymphomatosis: a case presenting with encephalomyelitis and reactive haemophagocytic syndrome diagnosed by renal biopsy

 

Aims:

To report an unusual instance of intravascular lymphomatosis presented with encephalomyelitis and reactive haemophagocytic syndrome. There was no skin involvement. The diagnosis was made on a renal biopsy. Methods and results : The marrow smear was air dried and stained with Diff-Quik. The tissue sections were stained with haematoxylin and eosin, Masson trichrome, periodic acid–Schiff's reagent, Elastic van Gieson's stain, modified hexamine-silver technique and Martius scarlet blue. Immunohistochemistry for CD45, CD20, CD45RO, Factor VIII related antigen, CD31 and CD34 was performed on paraffin-processed tissue. The marrow smear showed active haemophagocytosis in the histiocytes. The renal biopsy showed intravascular lymphomatosis with tumour cells positive for CD45 and CD20. Conclusion : The possibility of intravascular lymphomatosis should be considered in patients with reactive haemophagocytic syndrome where the underlying cause cannot be found after thorough investigation.     

Intravascular lymphomatosis presenting within angiolipomas

This report presents a case of intravascular lymphomatosis identified within an angiolipoma. The patient was a 73-year-old woman with a history of lobular carcinoma of the breast who presented with a chest wall nodule near the site of prior mastectomy. Microscopically, the nodule was composed of encapsulated adipose tissue with an associated vascular proliferation. Many of the vascular lumina were expanded by collections of large pleomorphic cells with vesicular nuclei and prominent nucleoli. These atypical cells displayed immunoreactivity for CD45RB (leukocyte common antigen) and the pan-B cell marker CD20 (L26). The patient subsequently developed multiple lesions of the extremities and died soon after developing symptoms referable to the central nervous system. Intravascular lymphomatosis most commonly presents with central nervous system and dermatologic involvement although any organ system may be affected. Intravascular lymphomatosis is an aggressive neoplasm that is generally diagnosed at postmortem examination. This case shows the protean manifestations of intravascular lymphomatosis and highlights the necessity of considering this malignancy in the differential diagnosis when entertaining the diagnosis of vascular invasion by carcinoma. Ann Diagn pathol 5:103-106, 2001. This is a US government work. There are no restrictions on its use.     

Angiotropic large cell lymphoma (intravascular malignant lymphomatosis) of the kidney: presentation as minimal change disease

We report the first case of angiotropic large-cell lymphoma (intravascular malignant lymphomatosis) presenting as minimal change disease (MCD) and diagnosed by renal biopsy. Neoplastic lymphoid cells were disseminated throughout the glomerular capillary bed and were associated with diffuse foot process effacement. The tumor had the immunophenotype of a B cell lymphoma (reactive with LCA and L-26 and unreactive with FVIII-R-Ag, Leu-M-1, alpha-1-antichymotrypsin, lysozyme, UCHL-1, Leu-22, kappa, and lambda). The temporal association between the onset of lymphoma and MCD, and the failure of the nephrotic syndrome to respond to immunosuppressive therapy support a role for lymphoma in the pathogenesis of MCD in this patient.     

Intravascular large B-cell lymphoma presenting with mass lesions in the central nervous system: a report of five cases

We have encountered five cases of intravascular large B-cell lymphoma (IVL) presenting with central nervous system (CNS) mass lesions during their clinical course. The age of the patients ranged from 50 to 74 years and three patients were male. All of these cases histopathologically showed typical intravascular localization of the neoplastic cells in the initial biopsy specimens obtained from sites other than the CNS. Despite multiagent chemotherapy, patients suffered from single or multiple CNS mass lesions 5-44 months after the initial diagnosis of IVL, except for one case in which IVL and the CNS mass lesion were diagnosed at the same time. The subsequent biopsy and autopsy specimens obtained from the CNS mass lesions revealed diffuse infiltration of the tumor cells with perivascular spreading, but minimal or no intravascular components. Immunohistochemical analysis of intravascular tumor cells and CNS mass lesions revealed expression of CD20, CD79a, bcl-2 and negative for CD3e and Epstein-Barr virus encoded RNA. The overall features of the CNS mass lesions were very similar to or indistinguishable from those of the primary CNS lymphomas. This implies that CNS mass lesions in the IVL cases can be correctly diagnosed only by careful attention to clinical and pathological findings. Moreover, there is the possibility that some cases previously diagnosed as primary CNS lymphomas may have include IVL cases. Further investigation is needed to explore this unusual phenomenon.     

Morphologie neurologischer Komplikationen bei der intravaskulären Lymphomatose

Intravascular lymphomatosis (IVL) is a rare lymphoproliferative disease characterized by intravascular growth of lymphoma cells in small vessels. Most frequently, its first manifestations occur in the central nervous system or skin. Based on autoptical findings in a 68-year-old-man with IVL, the pathological morphology in the central nervous system is compared to the course of neurological symptoms. The disease could not be diagnosed during his lifetime. The spectrum of neurological deficits can be explained histopathologically by occlusive intravascular aggregations of lymphomatous cells in small vessels of the spinal leptomeninges and nerve roots causing perfusion deficits and areas of ischemic necrosis of up to 4 mm in diameter in the medulla. Aggregations of lymphoma cells in the vessels of other organs are also found, but did not result in clinical symptoms. In reference to the present case, a survey of other literature reports on IVL with neurological and psychiatric manifestations is given. In patients with this condition, even an invasive biopsy has to be considered in order to make the correct diagnosis at an early clinical stage.     

Renal cell carcinoma with intravascular lymphomatosis: a case report of unusual collision tumors with review of the literature

We report the case of a 77-year-old white woman who presented with a left breast mass, lethargy, and weight loss. Pelvic computed tomographic scan revealed a 9.5-cm mass in the right kidney. Surgical pathology demonstrated a diffuse large B-cell lymphoma of the subcutaneous tissue of the breast and renal cell carcinoma with concurrent extensive intravascular lymphomatosis. Systemic dissemination of malignant lymphoma to a concurrent visceral primary neoplasm is rare. To the best of our knowledge, this is the first case illustrating a renal cell carcinoma collision with intravascular lymphomatosis.     

Intravascular lymphomatosis of the T cell type presenting as interstitial lung disease--a case report.

Intravascular lymphomatosis (IL) is a rare and generally fatal disease characterized by proliferation of large lymphoma cells almost exclusively within the lumen of small blood vessels. The skin and central nervous systems are typically affected, but involvement of other organs, such as lung, has been described. Predominant lung involvement without cutaneous and neurologic manifestation is very rare and difficult to diagnose. Originally considered as an endothelial disorder, IL has recently been reclassified as lymphoma. Most of the cases reported are of B cell lineage with a few cases of T cell type. We describe a case of the T-cell type IL manifested clinically as an interstitial lung disease without involvement of skin and central nervous systems. Immunohistochemical studies showed the T-cell nature of the neoplastic cells in open lung biopsy sample.     

Patient with intravascular lymphomatosis: Changes with time in concentrations of serum cytokines]

Serum cytokines were evaluated in a patient with intravascular lymphomatosis (IVL). A 62-year-old man was admitted to our hospital for his general malaise, arthralgia, and high-grade fever. He was diagnosed as dermatomyositis, initially. His symptoms were improved by high dose of corticosteroid and immunosuppressive therapy. However his condition deteriorated gradually, and died ten months after the onset of symptoms. Postmortem examination revealed IVL (B cell type). The serum concentrations of inflammatory cytokines, IL-6 and TNF-alpha, were elevated. Level of serum IFN-y was high only at the end of his illness. Serum IL-2 was not detected during the course. Serum IL-4 was slightly elevated. Elevated CRP and hypoalbuminemia might be related to the elevation of these inflammatory cytokines. The clinical diagnosis of IVL is usually difficult because of the absence of specific clinical manifestations and laboratory findings. The time course and/or concentrations of serum cytokines could be a key to make an early diagnosis.     

Angiotropic lymphoma (intravascular lymphomatosis)--2 case reports

Described are two cases of angiotropic lymphoma where eventually autopsy elucidated nonspecific neurologic symptoms. One patient suffering ambiguous encephalitic syndrome died three months later, the second one passed away after an unusually long three-year period of progressive dementia and cumulative motoric dysfunction. The autopsy disclosed pure intravascular malignant lymphoid aggregates (LCA, CD 20, Bcl 2-positive) in the brain and kidney of both patients. In the patients with the longer disease period, a dissemination to lung was also found. Definitive diagnosis was issued as a B cell type of angiotropic lymphoma. Skin, lymph nodes, spleen, and bone marrow were not affected in any case. The clinical differential diagnosis algorithm did not involve this rare etiology in these particular uncommon neurologic cases and even brain biopsy performed in both women did not recognize the substantiality of the disease.     

Intravascular lymphomatosis with bone marrow involvement.

We describe the case of a 56-year-old man who presented with numbness and tingling of the extremities, weakness, and fatigue. Laboratory findings included anemia and thrombocytopenia. A diagnosis of intravascular lymphomatosis was established when liver, omentum, and bone marrow samples were examined. A review of the literature reveals that most cases of intravascular lymphomatosis have cytopenias, mainly anemia and thrombocytopenia, but bone marrow involvement is rare. In our case, a subtle neoplastic infiltrate in the marrow sinusoids was highlighted with a B-cell marker. While immunohistochemical analysis was not performed in most reported cases in the literature, our studies suggest that a systematic search in bone marrow of cases of intravascular lymphomatosis may reveal unsuspected neoplastic cells. We conclude that bone marrow involvement in intravascular lymphomatosis appears to be rare, has subtle features, and is difficult to diagnose if unsuspected and not searched for.     

Detection of circulating tumor cells in a patient with intravascular lymphomatosis: A case study examined by the cytology method

Detection of circulating tumor cells in a patient with Intravascular lymphomatosis (IVL) of the lung is reported. Peripheral blood ceils were suspended in an isotonic sodium chloride solution, and red blood cells were lysed. The suspension was smeared on glass slides, fixed In 95% ethanol solution and stained using the Papanicolaou method. At the diagnosis of IVL, approximately 65 tumor cells were detected in one smear preparation, which contained about 8 × 10⁵ nucleated cells. However, tumor cells disappeared from peripheral blood when those in the lung were eliminated by multiagent chemotherapy. Cytology examination of peripheral blood cells may be of assistance in the early diagnosis of IVL and In the assessment of therapeutic intervention.     

淋巴结血管内T细胞淋巴瘤1例报道及文献复习

目的　探讨血管内淋巴瘤 (IVL)的临床病理特征。方法　对 1例腹股沟淋巴结IVL临床、病理组织学及免疫表型进行观察分析并复习文献。结果　男性 31岁 ,不明原因高热伴消瘦 5 0天 ,右腹股沟直径 1cm淋巴结 1枚 ,B超示肝脏轻度增大 ,血LDH明显升高伴ESR及转氨酶轻度升高 ,外周血WBC 3 3× 10 7/L ,骨髓像、多种病原及各肿瘤相关抗原检测均无异常。病理活检 :腹股沟淋巴结大部分破坏 ,代之以大量扩张的中小血管 ,腔内充满大量异型淋巴样细胞 ,局部伴管壁、管周浸润并累及结外脂肪组织。瘤细胞免疫表型CD4 5、CD4 5RO、CD3阳性 ,CK、CD6 8、CD79α、CD2 0均阴性 ,血管壁及内皮细胞CD31、CD34阳性。行CHOP化疗后症状缓解 ,现仍在随访中。结论　IVL是一罕见的非霍奇金淋巴瘤 ,好发于中枢神经系统及皮肤 ,其他部位少见 ,绝大数为B细胞型 ,T型罕见 ,以浅表淋巴结活检确诊者尚无报道。临床表现有一定提示性 ,确诊靠组织病理学检查 ,部分病例对化疗敏感 ,但多数病例预后差     

Intravascular malignant lymphomatosis: a case of T-cell lymphoma probably associated with human T-cell lymphotropic virus

Intravascular malignant lymphomatosis (IML) is an unusual condition characterized by proliferation of lymphoma cells exclusively within the blood vessels. Most of the cases reported are of B-cell origin. We report a rare case of T-cell IML probably associated with human T-lymphotropic virus (HTLV-1) infection. The present case suggests that T-cell lymphoma and HTLV-1-associated lymphoma occasionally represent a form of intravascular proliferation.     

Angiotropic lymphoma: report of a case with histiocytic features.

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.     

Primary hepatic lymphoma presenting as intravascular lymphomatosis

A case of primary hepatic lymphoma presenting as intravascular lymphomatosis was diagnosed in a 69-year-old woman who presented with symptoms related to the digestive tract. These symptoms were followed by neurologic disorders, including disturbance of sensation and mentality, and pathologic reflexes suggestive of a broad intracerebral lesion. Computed tomography of the brain showed an ill-defined, low-density area in the bilateral parietotemporal lobes. Autopsy revealed a well-circumscribed hepatic tumor, 6 cm in diameter, and scattered hemorrhagic foci in the cerebral cortexes. Microscopically, the hepatic tumor was a diffuse lymphoma, large cell, of the B-cell type. The small vessels of the brain were found to be packed with lymphoma cells, having caused the florid neurologic manifestations.     

Intravascular large B-cell lymphoma presenting as cutaneous panniculitis

In this report the case of intravascular large B-cell lymphoma (angiotropic lymphoma, intravascular angioendotheliomatosis, malignant endotheliomatosis) with panniculitis features is present. The diagnosis was based on finding of typical CD20 positive tumorous cells within capillaries, veins, and small arteries in the biopsy of subcutaneous adipose tissue. An accurate and early diagnosis together with combined chemotherapy resulted in good response and remission of the disease.     

Neoplastic angioendotheliomatosis: immunopathologic and morphologic evidence for intravascular malignant lymphomatosis

Neoplastic angioendotheliomatosis (NAE) is a rare entity characterized by multifocal, intravascular proliferation of large pleomorphic cells within small vessels of most organs, with a particular affinity for the central nervous system. Clinically, patients with NAE present with focal neurologic signs and a progressive decline in mental status, followed by death in a few months. The histogenesis of NAE is controversial but has been previously thought to represent a malignant proliferation of endothelial cells. Three autopsy cases with clinical and histologic features of NAE were investigated by electron microscopic, standard histochemical, and immunohistochemical technics that included the use of three panleukocyte monoclonal antibodies (PLA), the endothelial-cell-specific reagents, FVIII-RAG anti-sera and Ulex europaeus agglutinin (UEA), and muramidase. The NAE cells in all three cases were stained positively by the PLA, whereas the adjacent endothelial cells and not the NAE cells were stained by FVIII-RAG and UEA. Muramidase by immunoperoxidase technic and nonspecific esterase (chloracetate) were not present in NAE cells. These results indicate that NAE is a leukocyte-derived neoplasm and not a malignant endothelial cell neoplasm. Based on these findings and on a review of the literature, it is proposed that NAE represents intravascular malignant lymphomatosis (IML). IML appears to be a primary manifestation and/or a major secondary form of disseminated malignant lymphoma. This would explain the spectrum of findings in previously reported cases.     

Intravascular large cell lymphoma: diagnosis on renal biopsy.

The case is reported of a woman aged 60 yrs who presented with systemic symptoms and who was found to have proteinuria of 3.5 g per day. A renal biopsy revealed numerous neoplastic cells filling many of the glomerular capillary lumina. Immunoperoxidase stains revealed that the phenotype of the malignant cells was LCA+, L26+, MB2+, UCHL1-, CD43-, CAM5.2- and S100-, indicating that they were of lymphoid origin and B-cell lineage. The diagnosis of intravascular large cell lymphoma was therefore made. Remission was induced by chemotherapy with CAVP (cyclophosphamide, adriamycin, vincristine and prednisone). A subsequent relapse was treated with cyclophosphamide, VP16 and prednisone, and again remission occurred. This is the first case known to the authors in which the diagnosis of intravascular large cell lymphoma was made on renal biopsy. We confirm the experience of others that chemotherapy with regimens utilized in other varieties of large cell lymphoma may also be appropriate for this unusual neoplasm.