Analysis of CXCL9 and CXCR3 expression in a case of intravascular large B-cell lymphoma

Intravascular Lymphoma: Case Series and Review of the Literature.

Intravascular lymphoma is a rare disease characterized by the proliferation of neoplastic monuclear cells within the lumens of small blood vessels. The neoplastic cells are usually of B-cell origin, and rarely of T-cell or histiocytic origin. Although this clinicopathological entity of lymphoma has not been listed in general pathological classifications such as REAL classification or the Working Formulation, it is recently in the WHO classification scheme, which is essentially an updated REAL scheme, and the EORTC classification scheme. In this report, a 62-year-old woman with intravascular large B-cell lymphoma was observed by clinical, histopathological, immunohistochemical and molecular methods. A 62-year-old woman presented with large erythematous macules on the bilateral thighs and lower legs. The lesions were accompanied with hard, tender, intradermal or subcutaneous nodules mimicking erythema nodosum. Histopathological examination in the first biopsy revealed non-specific panniculitis compatible with erythema nodosum. The second biopsy revealed emboli of atypical lymphocytes within many of the dilated and proliferated vessels in the deep dermis and subcutaneous tissue. These cells were positive for L-26 and kappa light chain, and negative for lambda light chain, factor VIII-related antigen, CD30, CD34, CD68 and UCHL-1. These findings confirmed the diagnosis of intravascular large B-cell lymphoma. A laboratory examination showed a high level of LDH and abnormal cells in the bone marrow. An MRI of the brain and computed tomographic (CT) scans of the chest and abdomen revealed no evidence of malignancy. Before the treatment, the size of the nodules decreased spontaneously by about 50% in one month and significantly in two months. Although combination chemotherapy, which consisted of CHOP, brought her partial remission, she experienced neurological symptoms 6 months after the initial treatment and died of brain metastasis 9 months after the treatment. This is a unique case for two following reasons: 1) the first biopsy revealed non-specific findings compatible with erythema nodosum; and 2) before the treatment, the nodules regressed spontaneously. Dermatologists should take multiple skin biopsies for EN lesions with the non-specific histopathological findings not to refute the existence of this disease.

A CASE OF DISSEMINATED INTRAVASCULAR LYMPHOMA PRESENTING AS SEPSIS WITH MULTIORGAN FAILURE

Intravascular lymphoma (IVL) is a rare and fatal disease, typically of B-cell origin. Most of the reported cases have been for primary IVL, and only a minority of cases are of recurrent IVL. In addition, recurrent IVL occurring after treatment of anaplastic large T-cell lymphoma (ALCL) by contrast is extraordinarily rare. In this article, we present 3 cases of recurrent cutaneous IVL (2 men and 1 woman) and compare these with 1 case of primary IVL. The patients ranged in age from 56 to 73 years and were encountered in the routine dermatopathology and consultative practices of one of the authors. In 2 of the cases, the patients had intravascular cutaneous ALCL. In regard to the remaining 2 patients, 1 patient had a recurrent intravascular cutaneous follicular lymphoma in the context of a history of diffuse large B-cell lymphoma. The fourth patient had a primary intravascular ALCL because there was no antecedent history. In all cases, the skin biopsies showed large aggregates of atypical cells within the blood vessels. Phenotypic studies revealed variable staining results with CD29 and CD54 in cases of recurrent IVL compared with those of primary IVL. Recurrent cutaneous IVL represents a somewhat heterogeneous group of lymphoproliferative disorders with a distinct variant being in the context of intravascular ALCL; the mechanisms of intravascular localization in recurrent IVL are likely different from those of primary IVL.

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in the various organs (Swerdlow et al, 2008). Because of its rarity and its variety of the clinical presentations, the definite diagnosis of IVLBCL often requires long time with repeated applications of biopsy on the various organs. Bone marrow is demonstrated to be one of the affected organs (Masaki et al, 2009) and a diagnostic site in IVLBCL (Murase et al, 2007). However, the detection of lymphoma cells within the lumina of small vessels and/or sinuses in the bone marrow biopsy specimen is not necessarily guaranteed because, at least in part, the quantity of specimen yield by a single painful procedure is not large. We show characteristic morphology of IVLBCL cells in the May-Grünwald Giemsa (MG)-stained bone marrow smear preparation, which could be one of the useful features for the diagnosis of IVLBCL. From February 2006 through April 2010, 11 patients were clinically diagnosed as having intravascular lymphoma in our institute. In the retrospective analysis, five out of the 11 patients fulfilled the following presentations for the definite diagnosis of IVLBCL: (i) the proposed clinical diagnostic criteria for IVLBCL (Masaki et al, 2009), (ii) the characteristic accumulation of 18[F]-fluorodeoxyglucose (FDG) in the positron emission tomography (PET)/computed tomography (CT) (Miura & Tsudo, 2010) and (iii) the existence of atypical lymphoid cells within the lumina of small vessels in the biopsy specimens (Asada et al, 2007). In the examination of MG-stained bone marrow smear preparation, four out of the five patients presented with an involvement of IVLBCL cells (Table I). Among the four patients, the IVLBCL cells demonstrated similar unique morphological features in the three patients (Fig 1, Case #2, #3 and #5). The IVLBCL cells are large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Fig 1, Case #2 and #5). May-Grünwald Giemsa (MG)-stained bone marrow smear preparation of three intravascular large B-cell lymphoma (IVLBCL) patients. (Case #2) 64-year-old man. (Case #3) 74-year-old woman. (Case #5) 57-year-old woman. All three patients fulfilled the proposed clinical diagnostic criteria of IVLBCL, showed the characteristic features in 18[F]-PET/CT examination and existence of atypical lymphoma cells within the lumina of small vessels in the random skin biopsy specimens. The IVLBCL cells demonstrated a similar unique morphological feature in all three patients showing large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Case #2 and #5). Bone marrow is one of the initial sites of histological examination for the diagnosis of lymphoma. Biopsy specimen of bone marrow is reported to be useful for the diagnosis of IVLBCL (Masaki et al, 2009). In our retrospective analysis, however, the existence of lymphoma cells within the lumina of small vessels and/or sinuses in the hematoxyline-eosin (HE)-stained bone marrow biopsy specimen was confirmed in none of the patients with definite diagnosis of IVLBCL (Table I). Regarding the discrepancy between the previous reports and our results, we would speculate that there are methodological differences in detection of lymphoma cells such as the quantity of biopsy specimen yield, the number of biopsy specimen sections reviewed and the use of immunohistochemical analysis. On the other hand, the preparation of MG-stained smear of bone marrow aspirate is a relatively uniform procedure. In our analysis, the involvement of IVLBCL cells in the bone marrow smear was observed in four out of the five patients in which multiple accumulations of FDG in the bones were confirmed in the PET/CT examination (Table I). Three out of the four patients presented with IVLBCL cells with a similar unique characteristic morphology in the MG-stained bone marrow smear preparation (Fig 1). We would like to suggest that lymphoma cells shown here are one of the patterns of IVLBCL cells and that further investigations including 18[F]-FDG-PET/CT and/or random skin biopsy should be applied actively to make an early diagnosis of IVLBCL for such patients.

Interleukin-18 and Soluble Interleukin-2 Receptor Are Useful Markers for Enhanced Diagnosis of Intravascular Lymphoma

Use of Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma

We retrospectively evaluated the diagnosis and clinical courses of 8 patients with intravascular large B-cell lymphoma (IVL) diagnosed while they were alive. The median age was 67 years old (range 54 to 82). Most complaints at diagnosis were fever or dyspnea. All patients were in clinical stage IV with B symptoms and 4 patients showed performance status 4. The diagnosis of IVL was confirmed by biopsy specimens from the bone marrow in 4, lung in 2, muscle, adrenal gland, and lymph node in 1 case, respectively. Initial bone marrow involvement was found in 6 patients. Chemotherapy was performed in 7 patients. Rituximab was added to chemotherapy in 5 patients. Though 5 patients are alive at the median follow up of 12.3 months, only 1 patient is in remission. Four of 5 patients treated with Rituximab relapsed. In suspicious cases, it is important to bear IVL in mind and examine bone marrow biopsies for an early diagnosis. In addition, it is suggested that Rituximab may play only a temporary role in the treatment of IVL.

Intravascular large B-cell lymphoma is characterized by clusters of large neoplastic B cells within small blood vessels, most commonly in the dermis and subcutis. There is no nodal or parenchymal involvement until late in the disease, and its endothelial tropism is responsible for the variable clinical features. We report the case of a 51 year-old man who presented with fever, altered mental status, generalized edema, and profound telangiectasia. The diagnosis was made by a skin biopsy from the right thigh. Histology revealed ectatic vessels in the superficial dermis and large atypical lymphoid cells filling the small blood vessels in the deep dermis. Immunohistochemical staining showed strongly positive results for CD45 and CD79a. This was a rare case of intravascular large B-cell lymphoma with generalized edema and telangiectasia as the only cutaneous manifestation.

Intravascular lymphoma (IVL) is a rare form of non-Hodgkin's lymphoma that is characterized by the preferential growth of malignant lymphocytes within blood vessels. Pulmonary presentation of IVL is uncommon, and only a few cases have been reported in Korea. Here, we report on a 59-year-old woman with relapsed intravascular large B-cell lymphoma in the lungs. She had been treated with 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP) combination chemotherapy for intravascular large B-cell lymphoma in the nasal cavity, and was followed up regularly with no evidence of disease recurrence. About 1 year later, her chest computed tomography showed extensive ground-glass opacity, suggesting interstitial lung disease and, interestingly, diffuse pulmonary fluorodeoxyglucose (FDG) uptake was observed in positron emission tomography (PET). We performed bronchoscopy, bronchoalveolar lavage, and transbronchial lung biopsy. Pathology revealed relapsed intravascular large B-cell lymphoma in the lungs, and she commenced ifosfamide, methotrexate, etoposide, prednisolone (IMVP-16/PD) salvage chemotherapy. After 3 cycles of chemotherapy, PET showed no abnormal FDG uptake. We suggest that a primary or relapsed pulmonary IVL should be considered in the differential diagnosis of unexplained interstitial lung disease and that PET appears be useful in evaluating pulmonary IVL. (

Intravascular large B cell lymphoma is a rare subtype of diffuse large B cell lymphoma. Abnormal proliferation of intravascular lymphoma cells is its pathological feature with aggressive clinical behavior such as easy invasive feature, rapid disease progression, poor prognosis and low survival rate. We review the progress in recent research on classification, diagnosis, treatment and prognosis of intravascular large B cell lymphoma. Key words: Intravascular large B cell lymphoma; Diagnosis; Therapy; Prognosis

Intravascular Large B-Cell Lymphoma (IVLBCL): A Study of 12 Cases with Special Emphasis on High Density Lipoprotein Cholesterol (HDL-C) Preceding Diagnosis

We report a 35-year-old Japanese woman with intravascular large B-cell lymphoma diagnosed by percutaneous renal biopsy. The patient was referred to our institution for further examination of fever of unknown origin. She had renal dysfunction with a creatinine clearance of 44.1 mL/min, and daily urinary excretion of 0.22 g of protein and 21.5 mg of beta 2 microglobulin. Computed tomography showed markedly enlarged kidneys bilaterally. Percutaneous renal biopsy showed that an island-like atypical lymphoid cell accumulation was encircled with the peritubular capillary walls in many areas of the tubulo-interstitium, resulting in marked destruction of tubular structure. However, almost all the glomeruli were intact. Immunohistochemical analysis confirmed the diagnosis of intravascular large B-cell lymphoma. Shortly after diagnosis, she was treated with rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisolone, and her renal function and size improved. Renal involvement by lymphoma has been classified into two categories: intraglomerular intravascular lymphoma and tubulointerstitial diffuse invasion type that is distinct from intravascular lymphoma. For the latter cases with renal dysfunction and marked bilateral nephromegaly but without proteinuria, intravascular lymphoma within intra-peritublar capillaries should be considered as a possible diagnosis.

Intravascular large B-cell lymphoma (IVLBCL) is characterized by clinical presentations described as B symptoms, consisting of fever, night sweats, and weight loss. Intravascular lymphomas are more frequently diagnosed in elderly patients and are challenging to diagnose because of their nonspecific clinical presentation. Malignant lymphomas are recognized as the leading cause of fever of unknown origin. Although random skin biopsy is useful for diagnosing intravascular lymphomas, no standardized method for random skin biopsy has been established. Methods to avoid unnecessary skin biopsies and improve diagnostic accuracy have been investigated previously. Here, we report a case of a man in his seventies with intravascular large B-cell lymphoma diagnosed by skin biopsy targeting senile hemangiomas. The combination of random skin and targeted biopsies of skin lesions such as senile hemangiomas may help avoid the diagnostic invasiveness caused by unnecessary biopsies and improve the diagnostic accuracy for intravascular lymphomas.

Spinal cord lesions are observed in 40% of all central nervous system lesions in intravascular large B-cell lymphoma (IVLBCL). However, because IVLBCL is a very rare disease, its clinical features are not well defined, which may delay appropriate diagnosis and treatment, whilst the acute to subacute course of brain lesions in patients with IVLBCL is well established. Therefore, this study aimed to clarify the clinical features of spinal cord lesions in patients with IVLBCL. The medical records of patients with IVLBCL admitted to our hospital between 2010 and 2020 were searched. The inclusion criteria were preceding neurological symptoms without non-neurological symptoms and pathologically confirmed IVLBCL in various organs. Clinical features of spinal cord involvement in patients with IVLBCL were assessed and distinguished from those of brain involvement. Sixteen consecutive patients with IVLBCL were divided into two groups: six patients with spinal involvement (spinal cord type) and 10 patients with brain involvement (brain type). In the spinal cord type, four patients had chronic progression and two had subacute progression. Acute progression (0% vs. 80.0%) and sudden onset (0% vs. 50.0%) occurred significantly less frequently in the spinal cord than in the brain. All spinal cord lesions involved the conus medullaris. Spinal cord involvement in IVLBCL has a predominantly chronic progressive course that is exclusive to brain involvement. Conus medullaris lesions are suggestive of IVLBCL and are useful for early and accurate diagnosis and treatment.