Search

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of B-cell lymphoma, characterized by lymphoma cell proliferation within small blood vessels. We herein describe a rare case with long spinal cord lesions caused by venous congestive myelopathy associated with IVLBCL. An 81-year-old man presented with paraplegia of the lower limbs and sensory disturbances. Magnetic resonance imaging revealed intramedullary longitudinal T2-hyperintensity lesions in the thoracic cords. The patient died three months after disease onset, and a neuropathological analysis revealed predominantly atypical B-lymphocytes located sparsely in the veins of the spinal cord. IVLBCL should be considered in the differential diagnoses of long spinal cord lesions.

Chae Hong Lim,1 Sang Eun Yoon,2 Won Seog Kim,2 Kyung-Han Lee,3,4 Seok Jin Kim2,4 1Department of Nuclear Medicine, Soonchunhyang University College of Medicine, Seoul, Korea; 2Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 3Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, KoreaCorrespondence: Seok Jin KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-1766Fax +82-2-3410-1754Email kstwoh@skku.eduKyung-Han LeeDepartment of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, KoreaTel +82-2-3410-2630Fax + 82-2-3410-2638Email khnm.lee@samsung.comPurpose: The clinical value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in intravascular large B-cell lymphoma (IVLBCL) is unknown. This study investigated the association between PET/CT features and prognosis in IVLBCL patients.Patients and Methods: Subjects were 30 newly diagnosed Asian variant IVLBCL patients at a single institution. Baseline PET/CT was analyzed for the distribution and intensity of FDG lesions, and PET/CT pattern groups were compared for the outcome.Results: Eight patients had hypermetabolic lymph node (LN) lesions (Nodal group). The remaining 22 patients with extranodal (EN) involvement were categorized into Deauville score 3– 4 (EN/DS3-4; n = 14) and DS5 groups (EN/DS5; n = 8). First-line therapy resulted in a complete or partial response in 75.0%, 64.3%, and 100% of the respective groups. Treatment-related deaths occurred in one nodal group and three EN/DS3-4 group cases, but none among the EN/DS5 group. During 56 months of follow-up, disease progression or relapse occurred in five, four, and one case of respective groups. Cancer-related death occurred more frequently in the Nodal (n = 6) and EN/DS3-4 groups (n = 7) than the EN/DS5 group (n = 1; P = 0.041). Nodal and EN/DS3-4 groups had worse 5-year event-free survival (EFS; 25.0% and 49.0%, respectively, P = 0.010 and 0.076) and overall survival (OS; 33.3% and 48.2%, P = 0.010 and 0.068) compared to the EN/DS5 group (87.5% EFS and 87.5% OS).Conclusion: In patients with Asian variant IVLBCL, the distribution and intensity of FDG uptake lesions on PET/CT can be useful for predicting treatment outcomes and survival.Keywords: intravascular lymphoma, 18F-fluorodeoxyglucose, PET/CT, prognosis

Intravascular large B-cell lymphoma (IVLBCL) is a very rare subtype of malignant lymphoma that is difficult to diagnose. Cases of myocardial infarction caused by IVLBCL are even rarer. Herein, we report a case presenting with heart failure and delayed enhancement in the hypokinetic cardiac septum on contrast-enhanced cardiac magnetic resonance imaging. Myocardial biopsy showed large B-cell lymphoma cells in the microvessels within the myocardium. To the best of our knowledge, this is the first report of imaging findings of cardiac involvement in IVLBCL.

Pseudolymphomatous infiltrates associated with angiosarcoma are a rarely reported phenomenon. Recognition of this reactive process is critical to making an accurate diagnosis, both in diagnosing the angiosarcoma and in avoiding an incorrect diagnosis of lymphoma. Here, we present a novel histopathologic pattern, angiosarcoma with a prominently intravascular atypical lymphoid component, mimicking intravascular T-cell lymphoma. Interestingly, serial biopsies in this case revealed a progressive increase in lymphocyte density and intravascular component over time. Despite prior reports of improved progression-free survival and overall survival of patients with pseudolymphomatous angiosarcoma, this patient showed rapid disease progression.

Intravascular large B-cell lymphoma (IVLBCL) is defined by the World Health Organization (WHO) Classification as one type of extranodal large B-cell lymphoma and it is characterized by the selective growth of lymphoma cells within blood vessels with minimal extravascular invasion. According to the criteria, however, several reported cases of IVLBCL with significant extravascular invasion cannot be classified as IVLBCL. The purpose of the present study was to assess the clinicopathological significance of the WHO criteria for IVLBCL. We characterized clinical, histopathological, and immunohistochemical features of 11 patients with extranodal diffuse large B-cell lymphoma (DLBCL) with significant intravascular invasion (DLBCL-IV), and statistically compared their features with those of 11 patients with IVLBCL and 15 patients with extranodal DLBCL with virtually no intravascular invasion (DLBCL-noIV). When compared with the DLBCL-noIV group, the DLBCL-IV group was characterized by significantly higher rates of splenomegaly, hemophagocytosis, advanced stage disease, and CD5 expression; higher average platelet count, serum lactate dehydrogenase level, and serum ferritin level. Progression-free survival was significantly shorter in the DLBCL-IV group than the DLBCL-noIV group. In contrast, there were no significant differences in clinicopathological features between the DLBCL-IV and the IVLBCL groups. Our study suggests that DLBCL-IV should be regarded as IVLBCL-related.

One of the rare variants of extranodal large B-cell lymphoma is intravascular large B-cell lymphoma (IVLBCL). Characteristics of IVLBCL include intraluminal selective proliferation of atypical lymphoid cells in small to medium-sized vessels. The etiologic of IVLBCL is unknown, but due to the growth pattern of this tumor, it is speculated that IVLBCL is caused by a defect in homing receptor of tumor cells. IVLBCL can involve any organ but central nervous system, lungs, and skin are the most involved sites. IVLBCL does not usually involve lymph nodes. IVLBCL mainly occurs in the middle aged to elderly population with a slight male predominance. Generally, IVLBCL is aggressive and rapidly fatal if left untreated. We here reported two cases of IVLBCL who succumbed to the disease at initial phase of treatment to emphasize the difficulty in diagnosis of IVLBCL due to its exclusive intravascular growth pattern and fulminant clinical course.

Background Intravascular lymphoma (IVL) is a rare subtype of lymphoma involving the growth of lymphoma cells within the vessel lumina without lymphadenopathy. Because of various modes of presentation and its rarity, IVL is often diagnosed postmortem. Herein, we report a case of intravascular B-cell lymphoma with hypopituitarism, an extremely rare complication, that was successfully treated with chemotherapy. Case summary An 80-year-old Japanese woman presented with a 7-mo history of a tingling sensation in the lower limbs. She also presented with various other symptoms such as pancytopenia, high fever daily, and unconsciousness with hypoglycemia. Although the doctor who previously treated her diagnosed hypoglycemia as being due to hypopituitarism, the cause of the other symptoms remained uncertain despite a 7-mo evaluation period. We performed bone marrow aspiration to evaluate pancytopenia and found that she had hemophagocytic lymphohistiocytosis (HLH). On the basis of a random skin biopsy for assessing the cause of HLH, she was diagnosed with intravascular B-cell lymphoma. HLH and hypopituitarism were considered secondary to IVL. All her clinical findings matched the presentations of IVL. She was immediately treated with chemotherapy and achieved complete response. She was relapse free two years after treatment. Conclusion IVL should be included in the differential diagnosis of hypopituitarism, which although life-threatening, is treatable through prompt diagnosis and appropriate chemotherapy.

Background and aims - Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports - Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion - Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.

Background Intravascular large B-cell lymphoma (IVLBCL) is a rare and aggressive subtype of non-Hodgkin lymphoma with a varied presentation and no pathognomonic findings. Early diagnosis is critical to altering the disease course as early treatment with chemoimmunotherapy is required to prevent a rapidly fatal outcome. Strategies including improved awareness of this clinical entity through publication of cases with unique presentations are essential to prompt consideration of IVLBCL early in the disease workup. Here, we present a case of IVLBCL presenting with altered mental status and systemic organ dysfunction. Case summary A 61-year-old male patient presented with flu-like symptoms and a high fever. He experienced rapid clinical deterioration with liver, kidney failure, and shock despite rapid antibiotic administration and supportive care. A broad infectious workup was negative. Intracranial imaging revealed nonspecific changes to the corpus callosum suspicious for vasculitis. Renal biopsy was non-diagnostic. After further progression of his symptoms, the family elected to withdraw care and the patient died shortly thereafter. Post-mortem analysis revealed clear multi-organ involvement by IVLBCL, prompting re-examination of the ante-mortem renal biopsy that also identified IVLBCL involvement. Conclusion IVLBCL is a rare disease. Communication with specialties and early biopsy is critical to establishing the diagnosis and initiating therapy.

We present the first report of two rare yet remarkably similar autopsy cases of Kaposi sarcoma (KS) and intravascular human herpesvirus 8 (HHV8) positive lymphoproliferative disorder in renal transplant patients. It is well established that HHV8 infection causes Kaposi sarcoma (KS). More recently, it is recognized that HHV8 is also related to several lymphoproliferative conditions. These are poorly characterized and often difficult to diagnose. In both cases described herein, the diagnoses of multifocal hepatic KS and intravascular HHV8 positive (EBV negative) systemic diffuse large B-cell lymphoma, NOS were made at autopsy. Given the findings we describe in cases with fatal outcomes, we discuss the implications of HHV8 screening in solid allograft recipients.

Intravascular large B-cell lymphoma is a rare malignancy characterized by the presence of lymphoma cells within the lumen of blood vessels. The annual incidence of cases is fewer than 0.5 cases per 1,000,000. It usually affects the elderly with an average age of diagnosis around 70 years. Due to the absence of lymphoma cells in the peripheral smear and lymphadenopathy, it is difficult to diagnose these cases. Although the central nervous system and skin are the commonly involved organs, they can involve any organ system. Prompt diagnosis and initiation of treatment are very crucial as it carries a high mortality. We describe two patients who presented with constitutional symptoms and fever of unknown origin, later diagnosed as intravascular large B- cell lymphoma. The diagnosis was difficult in both cases as the presenting symptoms were atypical. One of the patients was diagnosed at autopsy. The delay in diagnosis often leads to fatal outcomes as the disease is very aggressive. A high degree of clinical suspicion is the key to prompt diagnosis and improved outcomes.

Intravascular B‐cell Lymphoma is a rare lymphoproliferative disorder with a none specific clinical presentation. The association of cutaneous telangiectasia‐like lesions and elevated inflammatory markers should be guaranteed a skin biopsy.

Intravascular lymphoma is a rare type of lymphoma with some fundamental differences compared to other types of non–Hodgkin lymphoma in general. Its clinical manifestations vary greatly and depend on the affected organs. There is no pathognomonic signs of intravascular lymphoma, either in clinical, laboratory or radiological findings. This case is challenging to detect and often misdiagnosed because it does not show symptoms that are commonly found in other types of lymphoma, such as mass or nodules formation. The treatment is relatively similar to other lymphoma in general, but the prognosis is worse because it was mostly diagnosed in the advanced stage. These specific conditions become the main reason to separate this case as a special entity of lymphoma.

Intravascular lymphoma (IVL) is a rare subtype of extranodal lymphomas that is characterized by the selective growth of neoplastic cells within the lumen of small vessels. Authors document the case of an unexpected death caused by an undiagnosed intravascular large B-cell lymphoma with multi-organ involvement, which had initially manifested as an infection and then as an unclarified central nervous system pathology. Histological examination showed a diffuse intravascular large B-cell brain lymphoma with prominent cerebral involvement. The relevance of the case report reveals the importance of an autopsy of an extremely rare and threatening pathology that in most cases is diagnosed only postmortem. As a result, the role of the forensic pathologist becomes particularly important. When specifically performing an in-depth autopsy evaluation with a specific histologic analysis, it is possible to identify the intravascular lymphoma and declare a more accurate cause of death.

Oral Medicine Department of Diagnosis and Surgery Araraquara Dental School Universidade Estadual Paulista (UNESP)

Resume Introduction Le lymphome intravasculaire a grandes cellules B (LIVB) est une hemopathie rare de diagnostic difficile. La biopsie cutanee en peau saine pourrait etre utile pour en faire le diagnostic. Nous rapportons un cas de LIVB diagnostique grâce a cet examen, et proposons une revue de la litterature afin d’en preciser la sensibilite. Observation Une femme de 67 ans etait hospitalisee pour fievre prolongee inexpliquee (FPI) et alteration de l’etat general. Le bilan biologique montrait un syndrome inflammatoire, une elevation des LDH superieure a 2000 UI/L, une cytolyse hepatique et un abaissement du temps de prothrombine a 47 %. Les prelevements infectieux et les examens d’imagerie eliminaient une etiologie infectieuse ou inflammatoire, ainsi qu’une neoplasie solide. Une biopsie cutanee en peau saine permettait de retenir le diagnostic de LIVB. Discussion Ce cas clinique illustre l’interet de la biopsie cutanee en peau saine pour le diagnostic de LIVB chez les patients hospitalises pour FPI. A partir d’une revue systematique de la litterature dans PubMed/Medline, nous avons inclus huit series d’au moins trois patients evaluant l’interet de la biopsie cutanee en peau saine pour le diagnostic de LIVB. La sensibilite pour le diagnostic variait de 67 % a 100 %, avec une sensibilite de 100 % dans quatre des huit etudes. Le detail des sites de biopsie etait disponible dans trois etudes et la sensibilite etait globalement similaire entre la cuisse, l’abdomen et les bras. Conclusion La biopsie cutanee en peau saine realisee sur au moins deux sites est un examen sensible et peu invasif pour le diagnostic precoce de LIVB.

Intravascular large B-cell lymphoma (IVLBCL) is a unique type of extranodal lymphoma characterized by selective growth of tumor cells in small vessels without lymphadenopathy. Greater understanding of the molecular pathogenesis of IVLBCL is hampered by the paucity of lymphoma cells in biopsy specimens, creating a limitation in obtaining sufficient tumor materials. To uncover the genetic landscape of IVLBCL, we performed whole-exome sequencing (WES) of 21 patients with IVLBCL using plasma-derived cell-free DNA (cfDNA) (n = 18), patient-derived xenograft tumors (n = 4), and tumor DNA from bone marrow (BM) mononuclear cells (n = 2). The concentration of cfDNA in IVLBCL was significantly higher than that in diffuse large B-cell lymphoma (DLBCL) (P < .0001) and healthy donors (P = .0053), allowing us to perform WES; most mutations detected in BM tumor DNA were successfully captured in cfDNA and xenograft. IVLBCL showed a high frequency of genetic lesions characteristic of activated B-cell–type DLBCL, with the former showing conspicuously higher frequencies (compared with nodal DLBCL) of mutations in MYD88 (57%), CD79B (67%), SETD1B (57%), and HLA-B (57%). We also found that 8 IVLBCL (38%) harbored rearrangements of programmed cell death 1 ligand 1 and 2 (PD-L1/PD-L2) involving the 3′ untranslated region; such rearrangements are implicated in immune evasion via PD-L1/PD-L2 overexpression. Our data demonstrate the utility of cfDNA and imply important roles for immune evasion in IVLBCL pathogenesis and PD-1/PD-L1/PD-L2 blockade in therapeutics for IVLBCL.

Livedo reticularis (LR) is a net-like cyanotic skin pattern resulting from cutaneous blood flow disturbance associated with several medical conditions. The authors present a case of a 77-year-old woman with a history of asthenia over one year, admitted to the hospital with sepsis by pneumonia. During her hospitalization, she developed a livedoid rash, and skin biopsy revealed infiltrates of atypical mononuclear cells causing capillary lumen obstruction. Intravascular large B-cell lymphoma was suspected and confirmed by bone marrow study. This case highlights the importance of being aware of different medical conditions associated with LR and the atypical presentation of a lymphoproliferative disorder.

Diffuse Large B-Cell Lymphoma is characterized by the infiltration of small vessels by lymphoid cells. These cells are not seen in the systemic circulation. Depending on the involvement location, it may present with different clinics such as central nervous system and skin involvement. Therefore, diagnosis may delay. Diagnosis is based on pathology. Herein we present a rare patient who initially presented with cellulitis and was ultimately diagnosed with Intravascular Large B Cell Lymphoma. With this case, we aim that lymphoma infiltration should be considered in skin lesions that are difficult to diagnose.

A 67-year-old man had a sudden onset of headache and aphasia, evolving to spontaneous improvement. A few months later, he developed dysarthria and left hemiparesis. Brain MRI showed several punctate lesions with perilesional edema, perivascular enhancement and restricted diffusion on DWI (). PET-CT demonstrated mild uptake (). Anatomopathological and immunohistochemical analysis were compatible with intravascular large B-cell lymphoma (IVL) (). Treatment with R-CHOP and intrathecal methotrexate was established, with favorable response due to high tumor sensitivity. Approximately half of IVL [...]

Intravascular large B-cell lymphoma is a rare type of non-Hodgkin lymphoma characterized by intravascular proliferation of clonal lymphocytes within the lumen of small vessels, which is often fatal. Diffuse FDG uptake in the lung without clear/evident CT findings, "hot lung," is quasi-pathognomonic for lung intravascular large B-cell lymphoma. In this report, we present the case of a 43-year-old man who was diagnosed as having intravascular lymphoma thanks to this rare finding.

This case series examines susceptibility-weighted imaging in patients who had intravascular lymphoma of the central nervous system.

Intravaskulare B‑Zell-Lymphome (IVL) sind seltene Neoplasien, die in jedem Alter auftreten konnen (Durchschnittsalter ca. 62–63 Jahre). Etwa die Halfte der Falle ist mit dem Epstein-Barr-Virus assoziiert. Die haufigsten Manifestationen finden sich im Gehirn, in der Haut und im Knochenmark. Die Diagnostik wird dadurch erschwert, dass die klinische Prasentation und die Laborwerte unspezifisch sind und die FACS(fluorescence-activated cell sorting)- und Klonalitatsanalysen aus dem peripheren Blut sowie die radiologischen Befunde nicht diagnostisch sein konnen. Die sensitivste und spezifischste diagnostische Methode ist die histopathologische und immunhistochemische Evaluation einer Gewebebiopsie. Wegen der Seltenheit dieser Krankheit gibt es nur wenige Erkenntnisse zu Therapie und Prognose, wobei die Therapie sich weitgehend an aggressiven Nicht-IVL-Lymphomen orientiert. Die Prognose ist schlecht (medianes Uberleben nach Diagnose etwa ein Jahr).

Intravascular lymphoma (IVL) has been characterized in many case reports by multiple white matter lesions reflecting ischemic changes. In contrast, there are very few case reports of cerebral or cerebellar hemorrhage resulting from IVL. A 56-year-old woman was referred to our department with two-week history of headache, nausea, and poor appetite. Gadolinium (Gd)-enhanced magnetic resonance imaging (MRI) showed dilated veins on the cerebellar surface. No ischemic lesions were detected on diffusion-weighted images. Three days after admission, the patient had a large cerebellar hemorrhage, prompting emergency surgery. Unfortunately, the patient died on the 11th postoperative day. Massive CD20-positive lymphoma cells were recognized in the cerebellar veins, but not in the arteries or the parenchyma of the brain. This is the rare case report of a cerebellar hemorrhage complication from IVL that might have been caused by venous congestion. The dilated veins on the cerebellar surface recognized from the Gd-enhanced T1-weighted images were specific clues in this case.

Case Presentation: The patient is a 60 year old male with a past medical history of celiac disease, paroxysmal Afib, iron deficiency, and CAD who presented with lightheadedness, dizziness, and fatigue. Notable workup revealed that the patient had Afib with RVR, a TSH of 0.189, Free t4 0.51an LDH of 2726, hemoglobin of 8.7, AST of 155, ALT of 19, WBC of 4.5, and serum iron of 20. The patient’s cardizem dose was adjusted and repeat transthoracic echocardiogram was unremarkable compared to history. The patient presented again with complaints of abdominal distension, postural dizziness, occasional night sweats, and fevers. Repeat workups revealed pancytopenia, proteinuria, hypotension, and anasarca most pronounced in the lower extremity and scrotum. Ultimately, a kidney biopsy revealed an intravascular B cell non-Hodgkin lymphoma (IVBCL). Notable repeat labs include a CRP of 44 and a failed ACTH stimulation test. A brain MRI revealed a 6mm pituitary microadenoma. The patient placed on an R-CHOP regiment and is scheduled for repeat MRI to rule out pituitary involvement. Discussion: IVBCL’s are a rare form of diffuse B cell lymphoma and remain a diagnostic challenge due to the variety of involved systems including skin, CNS, and endocrine. IVBCL is also known to not produce a mass or lymphadenopathy. Celiac disease is a known risk factor for non-Hodgkin’s lymphoma. A literature search reveals a few case reports with common themes of increased LDH and inflammatory markers, anemia, and hepatic and renal dysfunction. Postural hypotension can also be a presenting symptom due to IVBCL’s ability to infiltrate neurovascular tissue to cause autonomic neuropathy. However, in this case, the patient’s history of primary adrenal insufficiency makes this unlikely. Hypothyroidism secondary to pituitary and thyroid involvement was suspected due to TSH level suppressed enough for central hypothyroidism. Repeated MRI showed resolution of Pituitary Microadenoma post Chemo therapy. Sylvain Raoul Simeni Njonnou, Bruno Couturier, Yannick Gombeir, Sylvain Verbanck, France Devuyst, Georges El Hachem, Ivan Theate, Anne-Laure Trepant, Virginie De Wilde, Frédéric-Alain Vandergheynst, “Pituitary Gland and Neurological Involvement in a Case of Hemophagocytic Syndrome Revealing an Intravascular Large B-Cell Lymphoma”, Case Reports in Hematology, vol. 2019, 6 pages, 2019. https://doi.org/10.1155/2019/9625075 Catassi C, Fabiani E, Corrao G, et al. Risk of Non-Hodgkin Lymphoma in Celiac Disease. JAMA. 2002;287(11):1413 Khan MS, McCubbin M, Nand S. Intravascular Large B-Cell Lymphoma: A Difficult Diagnostic Challenge. J Investig Med High Impact Case Rep. 2014 Mar 6;2(1):2324709614526702. Pearce C, Hope S, Butchart J. Intravascular lymphoma presenting with postural hypotension. BMJ Case Rep. Published 2018 Jan 29.

Introduction: Intravascular lymphoma (IVL) is an extra nodal non-Hodgkin lymphoma with tropism for vascular endothelium. It is characterized by growth of large cells within the lumen of small to medium sized blood vessels. Central nervous system (CNS) and skin are predominantly involved. This report represents a retrospective single-institution review of IVL. Methods: We identified patients (pts) with IVL evaluated at Mayo Clinic Cancer Center between January 2003 and December 2018. Demographic, clinical, radiologic, pathologic, and therapeutic data were extracted. Statistical analysis of overall survival (OS) and progression free survival (PFS)] was performed using Kaplan-Meier method. Results: Total number of pts was 55; 22% (12/55) had CNS-only IVL, 14.5% (8/55) had CNS and non-CNS IVL, and 63.6% (35/55) had non-CNS IVL. Eighty seven percent (47/54) pts were B cell type, 11% (6/54) were T cell type, one pt had NK cell type IVL and another was unknown. Four pts were diagnosed by autopsy. Median age at diagnosis was 68 years (range, 40-85). Sixty-four percent were males. ECOG performance status was The median follow-up time from diagnosis was 63 months [CI 95%, 9-NR], and 47% (26/55) were alive. The most common diagnostic biopsy sites were bone marrow (BM) 45% (25/55), skin 25% (14/55), and brain 29% (16/55). Twenty-nine patients had a PET scan. Seventy nine percent (23/29) had abnormal PET findings, with mean SUV of 8.6 (range 2.5-19.1). Of the 35 pts with non-CNS IVL, 76% (16/21) had abnormal PET; furthermore, the diagnosis was made with biopsies of the following sites: bone marrow 54% (19/35), skin 40% (14/35), lung 14% (5/35), liver 5.7% (2/35), spleen 2.8% (1/35), and omentum 2.8% (1/35). Forty-six percent (13/28) received CNS prophylaxis and ten percent (3/55) had relapse in CNS. Two out of the three pts who had CNS relapse had received CNS prophylaxis. The median time to CNS relapse in non-CNS IVL was 9 months. The most common first-line regimen was high-dose methotrexate+ rituximab containing regimen 62% (10/16) in IVL with CNS involvement and RCHOP (60%) (17/28) in non-CNS IVL. Seventeen percent of (8/48) pts received autologous stem cell transplant (ASCT) and 63% (5/8) pts were transplanted in first complete remission (CR1), and 3 pts after the first relapse. Median OS (mOS) for the whole cohort was 57 months, [CI 95%, 9-NR], and median PFS was 7 months [CI 95%, 2-NR]. There was no significant difference in mOS between groups; CNS-only IVL- 9 months (CI 95%, 1-NR), non-CNS IVL -62 months (CI 95%, 20-NR) vs combined CNS and non-CNS IVL- 4 months (CI 95%, 3-NR). mOS for those who received ASCT in CR1 was not reached (CI 95%, 10-NR) vs 51 months in non-transplant group (CI 95%, 3-NR) p=0.24. In pts with non-CNS IVL, there was no significant difference in mOS between CNS prophylaxis subgroup (NR: CI 95%, 57-NR) vs no-CNS prophylaxis subgroup (20 months: CI 95%, 0-NR), p=0.12. In those with CNS IVL mOS for early diagnosis (0-30 days from symptom onset to diagnosis was NR (CI 95%, 3-NR) vs mOS for late diagnosis (>30 days {31-14,440})-5months (CI 95% 1-NR), p=0.29]. Conclusion: 1. BM was most frequently involved in our patients. We suggest that BM biopsy should be part of diagnostic testing when IVL is suspected. 2. Most cases are of B-cell linage, consistent with reported literature. All non-B cell cases were in non-CNS locations. 3. PET scans were abnormal in more than 70% of cases indicating that this imaging modality is vital in the diagnosis due to odd location and small size of lesions. 4.Overall prognosis in the literature was poor with most patients surviving 5. CNS involvement had an overall trend towards poor prognosis; however, those diagnosed early had better outcomes; this did not reach statistical significance due to small sample size. 6. mOS was not reached for those transplanted CR1. There was a trend towards a better survival associated with CNS prophylaxis versus no prophylaxis in non-CNS IVL. 7. We suggest that CNS-centric therapeutic approach and intensive consolidation with ASCT should be considered in managing IVL. Figure 1 Figure 1. Disclosures Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Incyte: Other: Scientific Advisory Board; Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Ansell: Bristol Myers Squibb, ADC Therapeutics, Seattle Genetics, Regeneron, Affimed, AI Therapeutics, Pfizer, Trillium and Takeda: Research Funding. Tun: Mundipharma, Celgene, BMS, Acrotech, TG therapeutics, Curis, DTRM: Research Funding; Gossamer Bio, Acrotech: Consultancy.

Background/Aims: This study examined the role of random normal skin biopsy in the diagnosis of intravascular lymphoma (IVL) in adult Western patients with clinically diagnosed hemophagocytic lymphohistiocytosis (HLH). Methods: In a retrospective chart review study, we analyzed a total of 59 skin biopsies that were performed to diagnose IVL in 21 adult patients with HLH seen at Stanford Hospital between 2004 and 2016. Results: Out of the 59 skin biopsies, 42 were taken from clinically normal-appearing skin and 17 from clinically abnormal-appearing skin. None of the 59 biopsies revealed a diagnosis of primary or metastatic malignancy, regardless of the malignancy history, clinical presentation, and biopsy and histopathologic characteristics. A review of 8 positive IVL cases at Stanford Hospital including 1 case associated with HLH showed 1 positive diagnosis by a targeted skin biopsy and other positive diagnoses by bone marrow (n = 4), lung (n = 2), brain (n = 2), muscle (n = 1), and nerve (n = 1). Conclusion: Random skin biopsies have a limited role in diagnosing IVL in adult patients with HLH, in the setting of a single academic institution in the USA. A review of the literature emphasizes the role of a full body skin exam with a selective skin biopsy in these patients.

An 87-year-old woman presented with a 3-month history of fever, edema of the lower legs, and gait disturbance. A laboratory examination revealed high serum levels of myeloperoxidase-specific antineutrophil cytoplasmic antibody (MPO-ANCA). Although microscopic polyangiitis was initially suspected and treated, the patient subsequently developed transient hemiparesis and disturbed consciousness. Brain magnetic resonance imaging/angiography revealed infarct-like lesions, pachymeningeal involvement, and diffuse cerebral vasoconstriction. A random skin biopsy confirmed the histological diagnosis of intravascular lymphoma. Diffuse cerebral vasoconstriction and a high serum MPO-ANCA level have rarely been reported in patients with intravascular lymphoma. Endothelial damage due to immune-mediated mechanisms, tumor derived factors, or the direct interaction of lymphoma cells with endothelial cells may commonly predispose patients to both cerebral vasoconstriction and the development of ANCAs.

We herein report the case of a 52-year-old woman who consulted us because of a 2-month history of a fever, anorexia and weight loss. A physical examination was unremarkable. The blood count showed mild anemia and lymphopenia, and lactate dehydrogenase was elevated. Creatinine clearance was normal and proteinuria was undetectable. CT showed enlarged kidneys. A bone marrow biopsy was normal. PET-CT showed an intense uptake of 18fluorodeoxyglucose in both kidneys. A kidney biopsy provided the diagnosis of intravascular large B-cell lymphoma (IVLBCL). Kidney-limited IVLBCL without an impairment in the renal function or proteinuria has not been described. We analyzed the 38 published cases of IVLBCL involving the kidney to describe the main features of this entity.

Primary superior vena cava lymphoma originating from the endothelium of a large vein is very rare. A 70-year-old man was admitted to the hospital; computed tomography showed a tumor limited to the inside of the superior vena cava, completely occluding the vessel. A transjugular biopsy confirmed the diagnosis of diffuse large B-cell lymphoma, which was diffusely positive for CD30. Rituximab monotherapy followed by five courses of R-CHOP chemotherapy induced a complete remission. There was no recurrence after two years. The pathophysiology of lymphoma derived from large vessels may be different from intravascular large B-cell lymphoma, which usually involves small vessels.