Intravascular Lymphoma Research Articles

Rehabilitation Course and Management of Intravascular Lymphoma Presenting as Recurrent Strokes: A Case Report

Background and Purpose: Intravascular lymphoma (IVL) is characterized by the proliferation of lymphoma cells within small blood vessels. Diagnosis of IVL is difficult, and neurologic manifestations of the disease are common. Currently, there is little information related to the clinical course and rehabilitation of patients with IVL. This case report describes the presentation and treatment of an individual with IVL presenting as recurrent strokes. Case Description: A 53-year-old man was admitted for treatment of bilateral multifocal infarcts in cerebral watershed areas. Initial assessments indicated that he required minimal assistance for functional activities, and he was discharged home with outpatient services. He was readmitted 7 days later with worsening confusion, left hemiparesis, and deteriorating functional mobility. Rehabilitation team concerns related to the patient's progressive functional decline led to additional testing, resulting in a diagnosis of IVL. Outcomes: The patient initially required relatively little assistance with most functional activities, scoring 23 to 24/24 and 21/24 on the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility and Daily Activity Scales, respectively, 46/56 on the Berg Balance Scale (BBS), and 19/30 on the Montreal Cognitive Assessment (MoCA). He was subsequently readmitted and demonstrated a rapid functional decline, as evidenced by AM-PAC and BBS scores of 7/24 and 6/56, respectively. Discussion: This patient presented with neurological deficits and an initial diagnosis of bilateral multifocal infarcts. Documentation of his progressive functional decline and decreasing AM-PAC and BBS scores facilitated interdisciplinary communication and led to additional diagnostic testing, resulting in a final diagnosis of IVL and appropriate medical intervention.

PET/CT imaging of renal intravascular large B-cell lymphoma.

PET/CT imaging of renal intravascular large B-cell lymphoma.

Early Diagnosis of Intravascular Large B-Cell Lymphoma by Random Skin Biopsy.

IntroductionDelayed diagnosis of intravascular large B-cell lymphoma (IVLBCL) is associated with a poor prognosis, making early diagnosis and treatment essential. However, early diagnosis remains challenging.Case descriptionHere we present the case of a 75-year-old man with fever of unknown origin, in whom random skin biopsy (RSB) allowed early diagnosis of IVLBCL.DiscussionThe usefulness of RSB, which involves incisional skin biopsies of three or more sites that contain subcutaneous fatty tissue, such as the thighs, abdomen and upper arms, has been debated. In cases of suspected IVLBCL, RSB is less invasive than a biopsy of the internal organs.ConclusionWe suggest that combining RSB with bone marrow examination may facilitate the diagnosis of IVLBCL.LEARNING POINTSDelayed diagnosis of intravascular large B-cell lymphoma (IVLBCL) is associated with a poor prognosis, but early diagnosis is difficult due to its diverse, non-specific presentation.This case report illustrates the value of random skin biopsy in the early diagnosis of IVLBCL in a man with fever of unknown origin and haematological abnormalities without lymphadenopathy, splenomegaly or bone marrow abnormalities.The diagnostic accuracy of random skin biopsy depends on several factors, including the location and number of sites biopsied, and the depth and width of the biopsy.

Intravascular large B-cell lymphoma with hot lung sign diagnosed by transbronchial lung cryobiopsy.

Intravascular large B-cell lymphoma with hot lung sign diagnosed by transbronchial lung cryobiopsy.

Clinical characteristics, prognostic indicators, and survival outcomes in intravascular lymphoma: Mayo Clinic experience (2003-2018).

Intravascular lymphoma (IVL) is a rare extranodal non‐Hodgkin lymphoma. We performed a retrospective analysis of 55 IVL patients who were treated at our institution 2003–2018. Median age at diagnosis was 68 years, and 64% were males. The most frequent presenting symptoms were skin rash 43% and weight loss 30%. MRI brain on IVL patients with CNS involvement (CNS‐IVL) showed multifocal involvement in 76% (13/17). 89% (17/19) of non‐CNS‐IVL patients with abnormal FDG‐PET had biopsy of an avid lesion resulting in definitive diagnosis. The top diagnostic biopsy site was the bone marrow (45%). 56% had multiorgan involvement. Based on CNS involvement, 36.5% (20/55) had CNS‐IVL and 63.5% (35/55) had non‐CNS‐IVL. CNS‐IVL group consists of clinically isolated CNS involvement (CNS‐only IVL) (22%;12/55) and mixed clinical CNS and peripheral site involvement (M‐IVL) (14.5%; 8/55). Non‐CNS‐IVL group consists of clinically isolated skin involvement (skin‐only IVL) (9%; 5/55) and peripheral IVL with or without skin involvement (P‐IVL); (54.5%; 30/55). Skin involvement was predominantly in the lower extremities. Pathologically, 89% (48/54) were B‐cell IVL. Rituximab + high‐dose methotrexate‐based regimen were used in 75% (12/16) of CNS‐IVL patients and RCHOP in 60% (17/28) of non‐CNS‐IVL patients. Estimated 5‐year progression free survival (PFS) and overall survival (OS) for the entire cohort were 38.6% and 52%, respectively. Skin‐only IVL was associated with excellent survival. Platelet count <150x109/L, age > 60Y, and treatment without Rituximab were poor prognostic factors. Further research is necessary to identify novel therapies.

A rare case report of Intravascular Diffuse Large B cell Lymphoma presenting as subcutaneous nodules

Intravascular diffuse large B-cell lymphoma is a rare entity where the large lymphoma cells are seen within the vessels. The difficulty is in its diagnosis, as it can have varied presentations affecting multiple systems. Here, we present the case report of a woman with intravascular diffuse large B-cell lymphoma who presented with subcutaneous nodules.

Current Trends in the Surgical Management of Intramedullary Tumors: A Multicenter Study of 1,033 Patients by the Neurospinal Society of Japan.

ObjectiveWe performed a retrospective observational study to demonstrate the surgical risks and long-term prognoses of intramedullary tumors in Japan using a multicenter registry authorized by the Neurospinal Society of Japan. MethodsData from 1,033 consecutive patients with intramedullary tumors, treated between 2009 and 2020, were collected from 58 centers. Patients with spinal lipomas or myxopapillary ependymomas were excluded. Patient characteristics, clinical presentations, imaging characteristics, treatments, and outcomes were analyzed. The modified McCormick scale was used to classify functional status. Survival was described using Kaplan-Meier curves, and multivariable logistic regression analyses were performed. ResultsThe mean age of the patients was 48.4 years. Data of 361 ependymomas, 196 hemangioblastomas, 168 astrocytic tumors, 160 cavernous malformations, and the remaining 126 cases including subependymomas, metastases, schwannomas, capillary hemangiomas, and intravascular B-cell lymphomas were analyzed. Twenty-two patients were undiagnosed. The mean follow-up duration was 46.1 ± 38.5 months. Gross total tumor removal was achieved in 672 tumors (65.1%). On the modified McCormick scale, 234 patients (22.7%) had worse postoperative grades at the time of discharge. However, neurological status gradually improved. At 6 months postoperatively, 251 (27.5%), 500 (54.9%), and 160 patients (17.6%) had improved, unchanged, and worsened grades, respectively. Preoperative functional status, gross total tumor removal, and histopathological type were significantly associated with mortality and functional outcomes. ConclusionOur findings demonstrate better postoperative functional outcomes in patients with fewer preoperative neurological deficits. Degree of resection, postoperative treatments, and prognoses are closely related to the histology of intramedullary tumors.

Syndrome of inappropriate secretion of antidiuretic hormone as an initial sign of primary central nervous system lymphomas in the hypothalamus.

Primary central nervous system lymphoma (PCNSL) rarely originates in the hypothalamus. Hypothalamic PCNSL can present with various symptoms specific to dysfunction of the hypothalamus, including consciousness disturbance, cognitive impairment, hypopituitarism, and diabetes insipidus (DI). However, it remains unclear whether syndrome of inappropriate secretion of antidiuretic hormone (SIADH) can present as an initial sign of hypothalamic PCNSL. Ninety-nine patients with PCNSL were diagnosed between January 2006 and December 2020 at our institutes. The initial symptoms and signs, hypothalamic-pituitary functions, serum sodium (Na) value, Karnofsky Performance Status (KPS) score on admission, and duration from onset to diagnosis were retrospectively investigated from the medical charts. Eight and 91 patients had hypothalamic PCNSL (hypothalamic group) and PCNSL located in other regions (control group), respectively. Patients' pathological diagnoses were diffuse large B-cell lymphoma (97 patients) and intravascular lymphoma (two patients). Six patients presented with hyponatremia derived from SIADH or suspected SIADH, and one presented with DI. Statistically significant differences between the hypothalamic and control groups were detected only in the preoperative serum Na values and KPS scores. SIADH can be an initial presentation of hypothalamic PCNSL. Early detection of hypothalamic PCNSL from SIADH may lead to proper management and improved prognosis.

P.109 Isolated central nervous system lymphoma in the inpatient setting: a case series

Background: Isolated central nervous system lymphomas (CNS-L) has non-specific clinical presentations causing delays in diagnosis and treatment. This retrospective case series aims to characterize these challenges in the inpatient setting. Methods: Chart review of biopsy-proven CNS-L cases (n=10) presenting to Vancouver General Hospital from 2018-2020: diffuse (8/10) and intravascular (2/10) large B-cell lymphomas were included. Results: Median age was 69 years (31-83); 50% were female; 9/10 immunocompetent, 1/10 had well-controlled HIV. Neurologic symptoms at presentation: ataxia (7/10), paresis (4/10), dysphagia (4/10), dysarthria (2/10), and cognitive decline (4/10). Median time from symptom onset to admission with paresis, ataxia, dysphagia, or dysarthria was 3 days (1-14), compared to 84 days (28-384) with transient/vague symptoms. Median time from admission to biopsy was 25 days (5-148). 4/10 received steroid prior to biopsy. 1/10 had solitary lesion on MRI, 8/10 had ≥2 lesions. Diagnosed on lumbar puncture (0/10), skin biopsy (1/10), vitreous biopsy (1/10), brain biopsy (8/10), autopsy (1/10). 4/10 survived, 6/10 died; median time from admission to mortality was 133 days (61-342). Conclusions: Many factors lead to delays in diagnosis and treatment of CNS-L, including non-specific clinical presentations and time to brain biopsy for definitive diagnosis. Earlier recognition and reducing biopsy delays may help achieve earlier diagnosis.

Primary Cutaneous B-Cell Lymphoma: An Update on Pathologic and Molecular Features

Primary cutaneous B-cell lymphomas (PCBCLs) account for 25% of all primary cutaneous lymphomas. Three major types are currently recognized by the WHO classification: primary cutaneous marginal zone B-cell lymphoma (PCMZL), primary cutaneous follicle centre lymphoma (PCFCL) (both considered indolent lymphomas) and primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT), which is, instead, a very aggressive disease. Nowadays, the PCBCL’s category also includes some rare entities such as intravascular B-cell lymphoma (IVBL) and the EBV+ mucocutaneous ulcer (EBVMCU). Furthermore, controversies still exist concerning the category of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL), because some cases may present with clinical and histological features between PCFCL and PCDLBCL-LT. Therefore, some authors proposed introducing another category called PCDLBCL, not otherwise specified (NOS). Regardless, PCBCLs exhibit distinct features and differ in prognosis and treatment from their nodal/systemic counterparts. Therefore, clinicopathologic analysis is a key diagnostic element in the work-up of these lymphomas.

Clinical presentation, outcome, and prognostic markers in patients with intravascular large B-cell lymphoma, a lymphoma study association (LYSA) retrospective study.

BackgroundIntravascular large B‐cell lymphoma (lVLBCL) is a very rare type of large B‐cell lymphoma.MethodsWe conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers.ResultsSixty‐five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23–92). Thirty‐four patients (64%) had an IPI score >3 and 40 patients (67%) had a performance status ≥2. The most frequent extra‐nodal locations were bone marrow (n = 34; 52%), central nervous system (n = 25; 39%), and skin (n = 21; 33%). Nodal involvement and endocrine system were observed in 34% (n = 22) and 18% (n = 12) of all cases, respectively. Twenty‐six patients (41%) had macrophage activation syndrome. Tumor cells were frequently CD5 positive (52%) with a non‐germinal center origin (86%). BCL2 was expressed in 87% of all samples analyzed (n = 20) and 43% of patients had a MYC/BCL2 double expression. Fifty‐six patients were treated with a regimen of chemotherapy containing rituximab, among whom 73% reached complete remission. The median progression‐free survival (PFS) and median overall survival (OS) were 29.4 months and 63.8 months, respectively. History of autoimmune disorder (Hazard ratio [HR] 3.3 [1.4–7.8]; p < 0.01), nodal involvement (HR 2.6 [1.4–5.1]; p < 0.01), lack of anthracycline (HR 0.1 [0–0.4] for use; p < 0.001), or no intensification at first‐line regimen (p = 0.02) were associated with worse PFS. High‐dose methotrexate use was not associated with better PFS or OS.ConclusionsOur study highlights the aggressive clinical picture of IVLBCL, in particular the frequency of macrophage activation syndrome, and the need for new therapies despite a response to R‐CHOP‐like regimen similar to non‐intravascular diffuse large B‐cell lymphomas.

Hypopituitarism caused by intravascular large B cell lymphoma (IVLBCL)

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Cerebral Gnathostomiasis: An Unusual Course of Recurrent Hemorrhagic Stroke.

Cerebral Gnathostomiasis: An Unusual Course of Recurrent Hemorrhagic Stroke.

Intravascular Large B-Cell Lymphoma: A Review with a Focus on the Prognostic Value of Skin Involvement.

Intravascular large B-cell lymphoma (IVLBCL) is an aggressive Non-Hodgkin lymphoma (NHL) characterised by the presence of neoplastic lymphoid cells within small- and medium-sized blood vessels. According to the clinical presentation, the current WHO classification distinguishes the ‘classic’ (formerly ‘Western’) from a hemophagocytic syndrome-associated (formerly ‘Asian’) variant. A third ‘cutaneous’ variant has been proposed, characterised by a good prognosis and unique clinical features. While laboratory findings can hint at diagnosis, symptoms are rather nonspecific, and deep skin biopsy supported by further measures such as bone marrow aspiration and positron emission tomography-computed tomography scanning is needed to make a definite diagnosis. Treatment is comprised of anthracycline-based chemotherapy supplemented with rituximab and central nervous system prophylaxis. While there are various prognostic models for NHL, only one is specific to IVLBCL, which does not sufficiently represent some patient groups, especially regarding the lack of differentiation within the patient collective with skin involvement. This underlines the necessity for the establishment of further prognostic models in particular for IVLBCL patients with cutaneous manifestations.

The Relevance of Skin Biopsies in General Internal Medicine: Facts and Myths.

IntroductionNon-dermatology medical specialties may refer patients for skin biopsies, searching for a particular diagnosis. However, the diagnostic impact of the skin biopsy is not clearly established. This article aims to assess the indications for, and evaluate the clinical relevance of, skin biopsies in non-dermatology medical specialties.MethodsA questionnaire was sent to 23 non-dermatology specialty departments in a university medical center, requesting a list of indications for skin biopsies, as well as to 10 staff dermatologists to collect the indications of skin biopsies requested by non-dermatology specialties. Once the indications were collected, a literature search was performed to evaluate their clinical value and relevance.ResultsEleven non-dermatology specialties provided a list of skin biopsy indications, to which staff dermatologists added seven more indications. A literature search revealed evidence-based medicine data for six diseases, that is, amyloidosis, peripheral autonomic neuropathy, Sneddon’s syndrome, intravascular lymphoma, sarcoidosis, and chronic graft-versus-host disease. Results were questionable concerning infectious endocarditis, acute graft-versus-host-disease, and the lupus band test. Skin biopsy were not evidenced as useful for the diagnosis of calciphylaxis, systemic scleroderma, Behçet’s disease, or hypermobile Ehlers–Danlos syndrome. For the diagnosis of Alport’s syndrome, pseudoxanthoma elasticum, and vascular Ehlers–Danlos syndrome, skin biopsy is currently outperformed by genetic analyses. For diagnoses such as Henoch–Schönlein purpura and Sjögren’s syndrome, skin biopsy represents an additional item among other diagnostic criteria.ConclusionThe usefulness of skin biopsy as requested by non-dermatology specialties is only evidenced for amyloidosis, peripheral autonomic neuropathy, Sneddon’s syndrome, intravascular lymphoma, sarcoidosis, chronic graft-versus-host-disease, Henoch–Schönlein purpura, and Sjögren’s syndrome.

Intramural Great Vessel Lymphoma in a Patient with Left Ventricular Assist Device

<h3>Introduction</h3> Intramural Great Vessel lymphoma (IMGVL) is an extremely rare lymphoma proliferating within the lumina of large vessels like Superior vena cava and Aorta. We present a case of an IMGVL presenting in a patient with a Left Ventricular Assist Device (LVAD). <h3>Case Report</h3> A 63-year-old male with ischemic cardiomyopathy and advanced systolic failure supported by an LVAD as a bridge to transplant, presented to the clinic complaining of claudication symptoms. He has known peripheral vascular disease and underwent Aortobifemoral stenting in the past. Coronary Tomography with Angiography (CTA) showed a large intraluminal thrombus above the iliac limbs with severe narrowing of the lumen thought to be flow-limiting (Figure 1). He underwent a mechanical thrombectomy. Intra-operatively, a large mural thrombus with near occlusion of the descending aorta was noted (Figure 2). Pathology revealed diffuse large B-cell lymphoma (DLBCL) with immunohistochemistry positive for BCL2, MYC, Ki-67 and CD20. EBV status was negative. A whole-body Positron Emission Tomography (PET) scan was negative for malignancy elsewhere. He was initiated on chemotherapy. <h3>Summary</h3> Primary IMGVL is a rare subtype of extranodal lymphoma with only 4 cases reported in literature. It is distinct from Intravascular Large B-cell Lymphoma (IVLBCL) which is limited to small vessels. Furthermore, only a single case of aortic IMGVL found on autopsy of an EBV positive patient, has been reported. DLBCL is known to be an aggressive subtype of lymphoma often requiring a combination of chemotherapy and immune therapy. Long term prognosis in our patient awaiting heart transplant is rather uncertain.

Intravascular large B-cell lymphoma associated with sudden stridor arising from thyroid mucormycosis and concomitant bacterial infection

Dear Editor, Mucormycosis is a life-threatening fungal infection that mainly affects immunocompromised patients. It typically has low prevalence, but fatality rate is as high as 50%. We present a patient with intravascular lymphoma with secondary bacterial infection and invasive mucormycosis involving the thyroid gland, who experienced good outcomes following surgical decompression and prolonged intravenous antibiotics.

Clinical impact of central nervous system-directed therapies on intravascular large B-cell lymphoma: A single institution's experience.

Intravascular large B‐cell lymphoma (IVLBCL) is a rare subtype of B‐cell lymphoma characterized by aggressive disease progression with a high incidence of central nervous system (CNS) involvement. We retrospectively analyzed 16 patients with de novo IVLBCL treated at our hospital between 2004 and 2018 with either standard therapy plus CNS‐directed therapy or standard therapy alone. CNS‐directed therapy was associated with a significantly better 2‐year CNS‐free survival (100% vs. 63%, p = 0.0191), despite no significant effects on progression‐free or overall survival. Further studies should assess CNS‐focused treatment in patients with IVLBCL with or without primary CNS involvement.

Immunohistochemistry of the oncofetal protein IMP3 is helpful in the diagnosis of intravascular large B-cell lymphoma using skin biopsy.

The oncofetal protein insulin-like growth factor 2 mRNA binding protein-3 (IMP3) is expressed in various cancers. In this study, we examined the diagnostic utility of IMP3 immunohistochemistry in the context of intravascular large B-cell lymphoma (IVL). We obtained 25 skin biopsy (SB) specimens diagnosed as IVL and nine IVL-negative SB specimens from 27 IVL patients. Additionally, 27 negative SB specimens from 26 non-IVL patients were obtained from our pathology archives. We performed IMP3 immunohistochemistry on these 61 SB specimens, considering IMP3 expression in any mononuclear cell as positive. In selected cases, triple immunostaining for IMP3, PAX5, and CD34 was performed to analyze the origin and location of IMP3-positive cells. IMP3 was expressed in most intravascular lymphoma cells in all the 25 SB specimens diagnosed as IVL. Furthermore, our evaluation revealed the presence of intravascular IMP3-positive B-cells in five of the nine negative SB specimens from IVL patients; however, this was not observed in the 27 SB specimens from non-IVL patients. IMP3 was expressed in most IVL cells, and IMP3 immunohistochemistry could serve as a sensitive diagnostic aid for detecting IVL cells in SB.

Intravascular Large B-Cell Lymphoma

Intravascular large B-cell lymphoma (IVLBCL) is a rare hematopathologic entity, posing both a clinical and histologic challenge for diagnosis. Numerous pitfalls can hinder making the diagnosis. To summarize recent developments in literature pertaining to IVLBCL and point out key pitfalls pathologists should be prepared to encounter. Literature review via PubMed search and hospital (Darnall Medical Library) resources. The 3 primary pitfalls of IVLBCL include masking of IVLBCL, mimicry by IVLBCL, and mimicry of IVLBCL. These scenarios illustrate the importance of histologic pattern recognition and subsequent usage of immunohistochemistry, especially in context of a clinical history that may be noncharacteristic.