Lumina Of Vessels Research Articles

LR11 Is a Potential Serum and Histological Biomarker for Intravascular Large B-Cell Lymphoma

Abstract 5104 Introduction:Intravascular large B-cell lymphoma (IVLBCL) is a rare disease entity of malignant lymphoma, characterized by the selective growth of lymphoma cells within the lumina of vessels in various organs. Although recent reports showed that prompt and accurate diagnosis lead to better outcomes, absence of typical clinical manifestations and its aggressive behavior frequently makes it difficult. LR11 (also called SorLA or SORL1) is a type I membrane protein, from which a soluble form (sLR11) is released by proteolytic shedding. sLR11 is originally known to be a biomarker of carotid intima-media thickness. We have recently found that LR11 is expressed on human leukemia cell lines, and sLR11 is released in its culture medium. Serum sLR11 levels are significantly elevated in patient serum samples with acute leukemia and B cell lymphomas, and are associated with tumor burden and bone marrow invasion. Based on these findings, we hypothesized that LR11 may be also expressed and released from IVLBCL cells; therefore we evaluated its clinical importance in IVLBCL. Materials and methods:Serum samples and paraffin embedded tumor specimens were obtained from 6 patients who were histologically diagnosed as IVLBCL from 2009 to 2012. Specimens were subjected to immunostaining using anti-LR11 antibody, and serum sLR11 levels were measured by ELISA method. Patient laboratory and clinical data were collected retrospectively. Also, serum samples from 75 healthy volunteers, and 10 patients with collagen diseases presenting similar clinical manifestations as IVLBCL were analyzed. Results:Tissue samples of IVLBCL were obtained by bone marrow biopsy (N=2), transbronchial lung biopsy (N=2), and random skin biopsy (N=2). Biopsy specimens showed that cytoplasm of IVLBCL cells were specifically immunoreacted against the anti-LR11 antibody (Figure 1). Median serum sLR11 level of IVLBCL patients was 86. 0 ng/ml (mean ± SD: 201. 8 ± 260. 0 ng/ml), which was significantly elevated than those of healthy volunteers (median: 8. 4 ng/ml, mean±SD: 8. 8 ± 1. 8 ng/ml, p<0. 0001) and patients with collagen diseases (median: 14. 4 ng/ml, mean ± SD: 15. 9 ± 5. 9 ng/ml, p<0. 0001). Paired sample analysis showed that elevated sLR11 levels at disease diagnosis were decreased to normal range when disease remission was achieved (median: 13. 3 ng/ml, mean ± SD: 11. 0 ± 3. 3 ng/ml). Conclusions:We have identified LR11 as a novel molecule which was proven to be expressed in IVLBCL cells and circulated in patients' serum. LR11 immunostaining clearly highlights the tumor cells and sLR11 enables to distinguish IVLBCL from other differential diagnosis by serum evaluation. These findings suggest that LR11 is a useful diagnostic tool for IVLBCL, and serum sLR11 is a sensitive biomarker for diagnosis and disease monitoring of this challenging disease. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Dating of snow avalanches by means of wound‐induced vessel anomalies in sub‐arctic Betula pubescens

Dendrogeomorphic research has long relied on scarred trees to reconstruct the frequency of mass‐movement processes. Injuries have mostly been dated macroscopically by counting the tree rings formed after wounding. Tree‐ring anatomical anomalies induced by cambial injury, in contrast, have only recently been recognized as proxy records of past events. We investigated 12 sub‐arctic downy birch (Betula pubescens Ehrh.) trees scarred by snow avalanches in Norway and Iceland. Earlywood vessel lumina were measured for each tree in the xylem tissue bordering the scars. Seven successive rings were examined, namely two control rings laid down prior to wounding and five rings in the wound xylem. We provide evidence that snow‐avalanche‐induced wounding resulted in atypically narrow earlywood vessels over at least two years. Our data demonstrate that wound‐associated vessel anomalies represent tangible markers of mass‐movement processes, and as such make a viable tool for reconstructing past events. Similar dendrogeomorphic studies based on tree‐ring anatomy can be readily conducted with other mass‐movement processes, as well as with other broad‐leaved tree species. Ultimately, this new approach will foster increment coring over more invasive sampling techniques.

Intravascular B-cell lymphoma presenting as retiform purpura

To the Editor: Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal lymphoma characterized by proliferation of neoplastic lymphocytes within the lumina of blood vessels. We report a case of IVLBCL presenting as retiform purpura with painful ulcerations on the lower extremities.

Clinical and pathological analysis of six cases of eruptive microvenular hemangioma

Objective To analyze the clinical and histopathologic features of eruptive microvenular hemangioma (EMVH). Methods The clinical and histological findings in six patients with EMVH were retrospectively reviewed.Results The patients were young or middle-aged,with a median age of onset of 34 years.The ratio of males to females was 1 ∶ 1.Clinically,all the patients experienced a sudden development of widespread,asymptomatic,brunneus,flat-topped papules and plaques measuring from 0.1 to 2.0 cm in diameter.Histopathologic examination revealed a poorly circumscribed proliferation of small,irregularly branched,thin-walled blood vessels haphazardly arranged between collagen fiber bundles in the dermis.The lumina of the blood vessels were often collapsed.There was no cellular atypia or mitosis.A variable degree of sclerosis was noted in the surrounding stroma.Immunobistochemical study revealed that the endothelial cells stained positive for CD34,CD31,and factor Ⅷ-related antigen.Conclusions The diagnosis of EMVH is proposed,and awareness of this disease may benefit its early diagnosis and avoidance of unnecessary treatment. Key words: Eruptive microvenular hemangioma; Skin manifestations; Pathologic processes

Blood Vessel Adaptation with Fluctuations in Capillary Flow Distribution

Throughout the life of animals and human beings, blood vessel systems are continuously adapting their structures – the diameter of vessel lumina, the thickness of vessel walls, and the number of micro-vessels – to meet the changing metabolic demand of the tissue. The competition between an ever decreasing tendency of luminal diameters and an increasing stimulus from the wall shear stress plays a key role in the adaptation of luminal diameters. However, it has been shown in previous studies that the adaptation dynamics based only on these two effects is unstable. In this work, we propose a minimal adaptation model of vessel luminal diameters, in which we take into account the effects of metabolic flow regulation in addition to wall shear stresses and the decreasing tendency of luminal diameters. In particular, we study the role, in the adaptation process, of fluctuations in capillary flow distribution which is an important means of metabolic flow regulation. The fluctuation in the flow of a capillary group is idealized as a switch between two states, i.e., an open-state and a close-state. Using this model, we show that the adaptation of blood vessel system driven by wall shear stress can be efficiently stabilized when the open time ratio responds sensitively to capillary flows. As micro-vessel rarefaction is observed in our simulations with a uniformly decreased open time ratio of capillary flows, our results point to a possible origin of micro-vessel rarefaction, which is believed to induce hypertension.

Intravascular large B cell lymphoma presenting as anasarca: an unusual presentation of a rare lymphoma

Dear Editor, An 82-year-old male presented with progressive generalized edema over a month without associated fever, angina, dyspnea, rash, lymphadenopathy, and neurological or gastrointestinal symptoms. He was found to be profoundly hypotensive requiring vasopressor support. Initial blood work revealed severe hypoalbuminemia of 1.6 g/dL and a markedly elevated LDH of 1891 U/L. Complete blood count revealed normocytic anemia with hemoglobin of 9.8 g/dL and normal platelet and leukocyte count. Peripheral smear showed no abnormal cells. Liver function tests, urinalysis, chest X-ray, and echocardiogram were unremarkable. Random skin biopsies were subsequently performed revealing intravascular infiltration of CD5and CD20-positive malignant cells compatible with intravascular B cell lymphoma (IVLBCL; Fig. 1). IVLBCL is a rare malignancy with estimated incidence of less than one per million per year [1]. It was first described as endothelial cell tumor [2]. Subsequent immunohistochemical studies confirmed its lymphoidal nature [3]. In 2008, WHO classified IVLBCL as a subtype of extranodal diffuse large B cell lymphoma characterized by limited proliferation of lymphoma cell within lumina of small blood vessels [4]. Diagnosis of IVLBCL can be challenging given its bewildering presentation. Virtually, any organ can be affected as a result of small vessel occlusion. Fever, night sweat, and weight loss are the most common presentation. In western countries, these constitutional symptoms are frequently accompanied by neurological and cutaneous symptoms, whereas hemophagocytic syndrome is more predominant in Asian population [1, 5]. Anarsarca is an unusual initial presentation and was found in less than 5 % in one case series [5]. Biopsy is mandatory for the diagnosis. Involved tissues demonstrate large lymphoid cells with prominent nucleoli and frequent mitotic figures in the capillaries and venules. B cell-associated antigens, particularly CD20, CD5, and CD10, are typically positive. Selection of organ for biopsy should be guided by patient's manifestation as identification of tumor cells is relatively easy when an affected organ is biopsied [6]. In case of no apparent specific organ involvement, as seen in our patient, random skin biopsy from normal-appearing skin is an alternative diagnostic approach with a high sensitivity of 83.3 % [7]. Prognosis of a patient with IVLBCL is unfavorable although recent retrospective studies suggest more promising outcome with the use of rituximab in conjunction with anthracycline-based chemotherapy [1, 8]. Our patient, with unstable hemodynamics despite of vigorous resuscitation, was not a suitable candidate for instituting chemotherapy. Unfortunately, his clinical course deteriorated and he passed away after a week of hospitalization.

Defining an adequate sample of earlywood vessels for retrospective injury detection in diffuse-porous species.

Vessels of broad-leaved trees have been analyzed to study how trees deal with various environmental factors. Cambial injury, in particular, has been reported to induce the formation of narrower conduits. Yet, little or no effort has been devoted to the elaboration of vessel sampling strategies for retrospective injury detection based on vessel lumen size reduction. To fill this methodological gap, four wounded individuals each of grey alder (Alnus incana (L.) Moench) and downy birch (Betula pubescens Ehrh.) were harvested in an avalanche path. Earlywood vessel lumina were measured and compared for each tree between the injury ring built during the growing season following wounding and the control ring laid down the previous year. Measurements were performed along a 10 mm wide radial strip, located directly next to the injury. Specifically, this study aimed at (i) investigating the intra-annual duration and local extension of vessel narrowing close to the wound margin and (ii) identifying an adequate sample of earlywood vessels (number and intra-ring location of cells) attesting to cambial injury. Based on the results of this study, we recommend analyzing at least 30 vessels in each ring. Within the 10 mm wide segment of the injury ring, wound-induced reduction in vessel lumen size did not fade with increasing radial and tangential distances, but we nevertheless advise favoring early earlywood vessels located closest to the injury. These findings, derived from two species widespread across subarctic, mountainous, and temperate regions, will assist retrospective injury detection in Alnus, Betula, and other diffuse-porous species as well as future related research on hydraulic implications after wounding.

Cauda equina syndrome secondary to intravascular lymphoma

Intravascular lymphoma (IVL) is an extranodal B-cell lymphoma that involves the lumina of small and medium size vessels.1 Neurologic presentations are varied and include encephalopathy, myelopathy, and polyradiculoneuropathy, among other features.1,2 Cauda equina syndrome (CES) with IVL has been identified late, either at autopsy or after complications such as flaccid paraplegia.2⇓–4 Early diagnosis and treatment before disease dissemination is difficult but increases progression-free survival and remission.1 We describe a patient with isolated CES and subtle non-nodular MRI nerve root enhancement, who was identified to harbor IVL by cauda equina biopsy. A 70-year-old man presented with a 4-week history of perineal, patchy lower limb numbness and urinary retention. Neurologic examination disclosed absent ankle reflexes and sensory alterations in the back of his thighs and perineal region in an S2-S5 distribution. He had an absent anal wink. Normal investigations included complete blood count, electrolytes, creatinine, urea, thyroid-stimulating hormone, B12, hepatic enzymes, serology for hepatitis B and C and HIV 1 and 2, and paraneoplastic antibodies. Lactate dehydrogenase was elevated (460 U/L: normal 100–235). Serum protein electrophoresis identified an immunoglobulin G (IgG) κ monoclonal protein (1.3 g/L). CSF had an …

A unifying diagnosis for pancytopenia, fever, hypoglycemia, and lactic acidosis

A unifying diagnosis for pancytopenia, fever, hypoglycemia, and lactic acidosis

Sellar and Parasellar Intravascular Lymphoma Mimicking Pituitary Apoplexy

Intravascular lymphoma (IVL) is a rare subtype of large-cell non-Hodgkin lymphoma, characterized by proliferation of lymphoma cells within the lumina of small vessels. There are no previously reported cases of IVL involving the pituitary gland presenting with neuro-ophthalmic findings. A 68-year-old female presented with headache, right third nerve palsy, and Horner syndrome. MRI showed a 1.4-cm sellar mass consistent with a pituitary macroadenoma. Two weeks later, despite treatment with dexamethasone, the patient developed complete bilateral ophthalmoplegia and ptosis. Repeat MRI showed invasion of the clivus and cavernous sinuses, and a transsphenoidal pituitary biopsy was undertaken. The preliminary histopathology was consistent with bland pituitary apoplexy, but subsequent examination of an incidentally biopsied nasal polyp revealed endovascular malignant lymphoid cells that, on further scrutiny, were also present in the pituitary tissue. The diagnosis of IVL was confirmed, and the patient had an excellent clinical and radiological response to cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab (CHOP-R) chemotherapy. IVL may involve the pituitary gland, causing sellar mass effect, cavernous sinus infiltration, and pituitary ischemia, mimicking pituitary apoplexy with neuro-ophthalmic features. It can be effectively treated with CHOP-R chemotherapy.

Linfoma intravascular de células B grandes: hallazgos clínicos y morfológicos en un caso con desenlace fatal

Intravascular large B cell lymphoma is a rare subtype of large cell lymphoma that is characterized by the proliferation of lymphoid cells within the lumina of small blood vessels. We report a 61-year-old male presenting paresis of both lower limbs, confusion and a history of weight loss. Magnetic resonance and CAT imaging studies showed multiple images of brain and cerebellar infarctions. Twenty days after admission, the patient died and the postmortem study demonstrated a multisystem intravascular large B cell lymphoma.

Optical Coherence Tomography-Derived Anatomical Criteria for Functionally Significant Coronary Stenosis Assessed by Fractional Flow Reserve

For the identification of functionally significant coronary artery disease, there have not been any dedicated optical coherence tomography (OCT) studies reported previously, although OCT can clearly detect coronary vessel lumina at higher resolution than intravascular ultrasound (IVUS). OCT and fractional flow reserve (FFR) measurements were performed in 62 intermediate coronary lesions in 59 patients. FFR was calculated as the ratio of distal coronary pressure divided by proximal coronary pressure during maximal hyperemia. FFR <0.75 was used as the threshold for diagnosing functionally significant stenosis. Minimal lumen area (MLA), minimal lumen diameter (MLD) and percent lumen area stenosis were measured by OCT. FFR values correlated significantly with OCT-derived MLA (r=0.75, P<0.01), MLD (r=0.76, P<0.01) and percent lumen area stenosis (r=-0.77, P<0.01). Receiver-operating characteristic curve suggested an OCT-derived MLA <1.91 mm(2) (sensitivity 93.5%, specificity 77.4%), MLD <1.35 mm (sensitivity 90.3%, specificity 80.6%) and percent lumen area stenosis >70.0% (sensitivity 96.8%, specificity 83.9%) as the best cutoff values for a FFR <0.75. Anatomical measurements of coronary stenosis obtained by OCT show significant correlation with FFR. OCT has the potential to predict functionally significant stenosis, although the present OCT-derived parameters were smaller than those reported in previous IVUS studies.

ANATOMIA DA MADEIRA DE Toona ciliata CARACTERÍSTICAS DAS FIBRAS PARA PRODUÇÃO DE PAPEL

A madeira de cedro-australiano, plantado no Brasil visando à produção de serrados, foi caracterizada anatomicamente, avaliando-se os elementos constituintes no sentido medula–casca, além das relações entre as dimensões das fibras, índices indicadores da qualidade da polpa celulósica a ser produzida. Foram utilizados discos retirados do diâmetro à altura do peito (DAP) de cinco árvores com 18 anos de idade. A madeira apresenta cerne e alburno distintos, anéis de crescimento distintos a olho nu, textura fina a média, com brilho e grã regular. O diâmetro tangencial dos poros e a largura dos raios aumentaram no sentido medula casca, ao contrário do número de poros por milímetro quadrado e a quantidade de raios por milímetro, que diminuíram. Os valores médios do comprimento dos elementos de vaso, das fibras, a largura da fibra e o diâmetro do lume aumentaram no sentido medula–casca, sendo que a espessura da parede teve uma pequena variação, mas não significativa estatisticamente. Os valores obtidos para os índices indicativos da qualidade da polpa celulósica não sugerem a madeira de Toona ciliata M. Roem para a produção de papel do tipo embalagem.Palavras chave: Cedro-australiano; características anatômicas; polpa celulósica. AbstractToona ciliate wood anatomy and fiber characteristics for paper production. The Australian cedar wood, planted in Brazil to aim at saw wood production, was anatomically characterized, evaluating the constituent elements variation from pith to bark, as well the relationship between fiber dimensions, index indicating the quality of cellulose produced. Were obtained discs at breast high (DBH) of five trees with 18 years old. The wood has heartwood and sapwood distinct, growth rings distinct without lens, fine to medium texture, with brightness and straight grain. Tangential diameter of vessel lumina and ray width increased from pith to bark; unlike vessels per square millimeter and rays per millimeter that decreased. The mean values of vessel element length, fiber length, fiber width, lumen diameter increased from pith to bark, and fiber wall thickness had a little variation, but not statistically significant. The obtained values for quality pulp indicative index don’t suggest Toona ciliata M. Roem wood for package paper production. Keywords: Australian cedar; anatomic characteristic; cellulose pulp.

Salt stress induces the formation of a novel type of ‘pressure wood’ in two Populus species

• Salinity causes osmotic stress and limits biomass production of plants. The goal of this study was to investigate mechanisms underlying hydraulic adaptation to salinity. • Anatomical, ecophysiological and transcriptional responses to salinity were investigated in the xylem of a salt-sensitive (Populus × canescens) and a salt-tolerant species (Populus euphratica). • Moderate salt stress, which suppressed but did not abolish photosynthesis and radial growth in P. × canescens, resulted in hydraulic adaptation by increased vessel frequencies and decreased vessel lumina. Transcript abundances of a suite of genes (FLA, COB-like, BAM, XET, etc.) previously shown to be activated during tension wood formation, were collectively suppressed in developing xylem, whereas those for stress and defense-related genes increased. A subset of cell wall-related genes was also suppressed in salt-exposed P. euphratica, although this species largely excluded sodium and showed no anatomical alterations. Salt exposure influenced cell wall composition involving increases in the lignin : carbohydrate ratio in both species. • In conclusion, hydraulic stress adaptation involves cell wall modifications reciprocal to tension wood formation that result in the formation of a novel type of reaction wood in upright stems named 'pressure wood'. Our data suggest that transcriptional co-regulation of a core set of genes determines reaction wood composition.

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

Abstract 5221 Background:Intravascular large B-cell lymphoma (IVLBCL) is a rare entity characterized by growth of neoplastic lymphocytes in the lumina of small blood vessels. Hallmarks of the disease include poor performance status, elevated lactate dehydrogenase levels, anemia, B symptoms and variable clinical presentation. In this study, we conducted a retrospective analysis of all identified cases of intravascular lymphoma that presented within a large integrated healthcare delivery system, reviewing clinical presentation, laboratory findings, pathological features and outcomes. Methods:Kaiser Permanente Northern California (KPNC) provides care to approximately 3.2 million members and maintains centralized database of all hospital and ambulatory visits, laboratory, pathology, radiology, and pharmacy records. We utilized electronic pathology record databases to identify all cases of intravascular lymphoma, defined by the World Health Organization from January 1995 - July 2010 using the following search terms: intravascular lymphoma, intravascular B-cell lymphoma, intravascular T-cell lymphoma, intra vascular lymphoma, malignant angioendotheliomatosis, and angiotropic large-cell lymphoma. Results:Twelve cases of IVLBCL were identified. Median age was 70 years, female to male ratio of 2 to 1. 50% were diagnosed in vivo. The median time of diagnosis from onset of symptoms was 1.5 months. Four patients underwent multiple biopsies prior to diagnosis. Of the six patients with in vivo diagnosis, three were made by bone marrow biopsy, one by small bowel resection, one by muscle biopsy, and one by abdominal fat pad biopsy.At the time of diagnosis, ten (83%) patients had B symptoms and seven (58%) patients had ECOG≥4. Other common organ systems involved on presentation included neurological (58%) and gastrointestinal symptoms or hepatic involvement (58%).Increased serum lactate dehydrogenase was seen in 92% of patients, anemia in 92% of patients and thrombocytopenia in 75% of patients. Elevated erythrocyte sedimentation rate seen in 67% of patients and elevated C-reactive protein in 58% of patients.Extremely low subnormal high density lipoprotein cholesterol level (HDL-C) was present in 10 of 11 patients with measured lipoprotein profiles. The median HDL-C was 22 mg/dl (range <4–56 mg/dl). Levels of low density lipoprotein cholesterol, total cholesterol and triglyceride levels were all within the normal range (median 61 mg/dl, 117 mg/dl and 230 mg/dl respectively).All patients had biopsy proven involvement of at least one organ. Four patients had complete autopsy. The sites of disease involvement included bone (4), gastrointestinal tract (4), renal (4), lymph node (3), spleen (3), central nervous system (2), liver (2), peripheral blood (1), hemophagocytosis syndrome (1).Four patients received chemotherapy. CHOP (1), R-CHOP (3). Overall survival was 8 days (CHOP); 38 days to >5 years (R-CHOP). The one patient in our cohort who achieved complete remission had localized bowel IVLBCL, treated with resection and three cycles of R-CHOP. Conclusions:Our cases represent a population-based ascertainment of IVLBCL within a large unselected clinic population. The clinical presentation and organ system involvement is variable. The disease is aggressive with poor outcomes. The unique finding in our series was the low HDL-C prior to diagnosis of IVLBCL. HDL-C may represent a possible preclinical indicator of this rare lymphoma. Disclosures:No relevant conflicts of interest to declare.

Intravascular B-cell lymphoma with hypercalcemia as the initial presentation

Intravascular B-cell lymphoma (IVLBCL) is a rare subtype of extranodal diffuse large B-cell lymphoma, which is characterized by the growth of lymphoma cells within blood vessel lumina without nodular lesions, and which predominantly affects elderly patients. IVLBCL is characterized by B-symptoms and a variety of systemic symptoms due to focal obstruction of blood flow, but may be difficult to diagnose due to its peculiar intravascular localization and the lack of nodular lesions. While hypercalcemia is one of the complications of various types of cancerous diseases, it has rarely been reported as the first presentation of IVLBCL. In this report, we present the case of a 71-year-old male with IVLBCL who showed hypercalcemia accompanied by elevation of serum parathyroid hormone-related protein (PTH-rP) as the initial presentation. Interestingly, immunohistochemical staining revealed that the intravascular lymphoma cells expressed high levels of PTHrP. Six courses of immunochemotherapy, consisting of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), and two courses of high-dose methotrexate induced complete remission (CR) and retained CR for 4months. We also reviewed other IVBCL cases in which hypercalcemia was the initial presentation. We suggest that IVLBCL, although rare, should be considered as a possible causative in hypercalcemia of unknown underlying disease.

Serial renal biopsy findings in a case of POEMS syndrome with recurrent acute renal failure

This report describes a patient presenting with recurrent acute renal failure occurring in the course of POEMS syndrome, a multisystem disease associated with plasma cell dyscrasia. Several combined immunosuppression therapies failed to resolve recurrent acute renal failure; autologous peripheral blood stem cell transplantation was therefore applied. A renal biopsy was performed on each of four occasions when he developed renal dysfunction. The renal biopsy showed typical renal histology of POEMS, membranoproliferative glomerulonephritis-like lesions and narrowing of vessel lumina of various sizes caused by endothelial injury, which progressed to glomerulosclerosis and vessel occlusion. Recurrent acute renal failure might be caused by ischemia due to arterial occlusion. Serum levels of vascular epithelial growth factor (VEGF), which is considered to be a causative factor of endothelial lesions in POEMS syndrome, were not elevated throughout the course of this case.

Proliferation of CD8-Positive T Cells in Blood Vessels of Rat Renal Allografts

It is still disputed in which anatomical compartments of allograft recipients T-cells proliferate. After experimental renal transplantation, host monocytes and lymphocytes accumulate in the lumina of graft blood vessels. In this study, we test the hypothesis that T lymphocytes proliferate in the vascular bed of the graft. Kidneys were transplanted in the Dark Agouti to Lewis rat strain combination, an established experimental model for acute rejection. Isogeneic transplantation was performed as a control. Cells in the S-phase of mitosis were detected in situ three days posttransplantation by pulse-labeling with BrdU and by immunohistochemical detection of the proliferating cell nuclear antigen (PCNA). More than 20% of all T-cells in the lumina of allograft blood vessels incorporated BrdU and approximately 30% of them expressed PCNA. In the blood vessels of isografts as well as in other organs of allograft recipients, only few BrdU(+) cells were detected. A majority of the BrdU(+) cells in graft blood vessels expressed CD8. In conclusion, we demonstrate that CD8(+) T lymphocytes proliferate in the lumina of the blood vessels of renal allografts during the onset of acute rejection.

Isolated intraorbital intravascular large B-cell lymphoma: a case report

Intravascular large B-cell lymphoma is a rare B-cell lymphoma subtype characterized by tumor cells found exclusively within vascular lumina. We report the case of an 88-year-old woman who initially presented with pain, swelling, and loss of vision in her left eye. A left orbital mass was revealed by computed tomography, and a biopsy was performed. On histologic examination, large atypical lymphoid cells were present in blood vessel lumina of the intraorbital adipose tissue. No tumor cells were seen in the surrounding tissue. By immunohistochemistry, the tumor cells were positive for CD20, BCL-2, Bcl-6, and CD5; they were negative for CD10 and cyclin D1. Ki-67 revealed a proliferation rate of approximately 80–90%, and CD31 highlighted the vascular endothelium. These findings confirmed the diagnosis of intravascular large B-cell lymphoma. Results of bone marrow and cerebrospinal fluid examinations were negative for involvement, and there was no radiographic evidence of systemic disease. The patient received systemic treatment with etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab in addition to intrathecal methotrexate. The patient had resolution of her intraorbital mass. While it is understood that this disease can involve any organ, only very rarely does intravascular large B-cell lymphoma present with primary ophthalmologic symptoms. Additionally, this patient’s disease initially appeared to be isolated, with no skin manifestations or other systemic involvement. To our knowledge, this is the first reported case in which this disease manifested as an isolated intraorbital mass without detectable involvement of any other organ.

High frequency of neurolymphomatosis as a relapse disease of intravascular large B‐cell lymphoma

Intravascular large B-cell lymphoma (IVL) is characterized by lymphoma cell proliferation in the lumina of small vessels in various organs. A high incidence of neurologic symptoms associated with the central nervous system has been reported, but peripheral nerve involvement (neurolymphomatosis [NL]) rarely has been described. The medical records from patients who were diagnosed with IVL over the past 4 years were reviewed. A diagnosis of NL was made based on the combination of neurologic symptoms and their correspondence with imaging studies, such as magnetic resonance imaging (MRI), (18) F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography (PET/CT), and/or the histologic confirmation of lymphoma cells within the peripheral nerves, nerve root/plexuses, or cranial nerves. Four patients with NL were identified among 11 patients who had IVL. All cases of NL occurred as relapsed disease during or shortly after the completion of chemotherapy. Although MRI studies of the brains and whole spines revealed nerve infiltration by gadolinium enhancement in 2 patients, the technology was not sensitive enough to detect such infiltration in the remaining 2 patients. In contrast, FDG-PET/CT studies successfully revealed cranial or peripheral nerve lesions in all 4 patients and was useful for evaluating therapeutic response. Patients received treatment with high-dose methotrexate with or without other systemic chemotherapy, which achieved varied success. Further studies will be needed to determine the optimal treatment. Considering the rarity of IVL and NL, the current observations suggested that IVL may have a predilection not only for the vessels but also for both the central and peripheral nervous systems.