Hemorrhagic Presentation in Primary Central Nervous System Lymphoma: A Case Study.

BACKGROUND Primary central nervous system diffuse large B-cell lymphoma (DLBCL) is an extremely aggressive brain disease that rarely affects immunocompetent non-elderly patients, particularly with hemorrhagic presentation. Brain magnetic resonance imaging (MRI) plays an important role in the diagnosis of this entity, which typically demonstrates restricted diffusion and a T2 hypointense appearance, suggesting hypercellularity. CASE REPORT A 44-year-old man came to the emergency department with a persistent and treatment-resistant bilateral frontal headache that had been bothering him for the past 3 weeks. Upon conducting a neurological assessment, the patient displayed temporal disorientation and incoherent speech, but without any observable motor deficits. A non-contrast enhanced brain computed tomography scan was carried out, revealing a hyperattenuating, space-occupying lesion and hemorrhage in the left hemisphere of the brain. Subsequently, brain MRI demonstrated hypointense signal on T2-weighted images, restricted diffusion, and homogeneous lesional contrast enhancement, suggesting a very cellular expansive lesion with hemorrhage. To establish a definitive diagnosis, a brain biopsy was undertaken, confirming the presence of DLBCL of the primary central nervous system (germinal center phenotype). CONCLUSIONS Hemorrhagic presentation of primary central nervous system DLBCL occurs very rarely, particularly in non-elderly immunocompetent patients. Brain MRI plays an important role in the diagnosis of this entity, which allows differentiation from high-grade glial or other lesions that present more frequently with hemorrhage. Therefore, it is crucial to suspect lymphoma before surgical intervention for appropriate patient management.

Gastrosplenic fistula due to splenic lymphoma: two case reports and review of the literature.

BACKGROUND: Gastrosplenic fistula is a rare and potentially fatal complication of various conditions. Lymphoma is the most common cause. It can occur spontaneously or after chemotherapy. Gastrosplenic fistula diagnosis can be confused with a splenic abscess because of the presence of air into the mass. The computed tomography identification of the fistulous tract is the key to a right diagnosis. Treatment modalities include surgical resection, chemotherapy, or a combination of both. CASE PRESENTATION: Here we report two patients with gastrosplenic fistula due to diffuse large B cell lymphoma. The first patient was a 54-year-old Caucasian woman with an enormous primary splenic diffuse large B cell lymphoma leading to the development of a spontaneous fistula in the stomach. The second patient was a 48-year-old Caucasian male patient with an enormous splenic diffuse large B cell lymphoma complicated by fistula after chemotherapy. Both patients died of septic shock several days after surgery. CONCLUSION: Gastrosplenic fistula is a rare complication with a poor-prognosis, for which surgery is currently the preferred treatment.

[Diffuse large B-cell lymphoma concurrent with Kaposi's sarcoma in the same lymph node in a human immunodeficiency virus-negative patient].

An 80-year-old Japanese man presented with systemic lymphadenopathy, including the para-aortic area and left inguinal nodes, which was diagnosed as diffuse large B-cell lymphoma (DLBCL) and human herpesvirus (HHV) 8-positive/HIV-negative Kaposi's sarcoma (KS). Immunohistochemical examination revealed that the lymphoma cells were negative for HHV-8. The patient received combined chemotherapy with rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone for six cycles and achieved complete remission. In the literature, five cases of simultaneous appearance of malignant lymphoma and KS in the same lymph node have been reported, but DLBCL as a histological subtype has not yet been reported.

Paraneoplastic gastrointestinal dysmotility due to non-Hodgkin diffuse large B cell lymphoma: a case report.

Paraneoplastic gastrointestinal dysmotility is a rare entity which occurs in association with malignancy. We present the second case associated with lymphoma, characterised by generalised gastrointestinal dysmotility with constipation, malnutrition, weight loss, and capsule endoscope retention. This case highlights the importance of maintaining a high index of suspicion for malignancy in patients with unexplained gastrointestinal dysmotility.

[Spontaneous regression of HIV-associated EBV-positive mucocutaneous ulcer due to immune reconstruction with antiretroviral therapy].

A 24-year-old man was found to have an ileocecal ulcer by colonoscopy. A pathological diagnosis of diffuse large B-cell lymphoma (DLBCL) with diffuse positive reaction of Epstein-Barr encoding region (EBER) by in situ hybridization was made based on analysis of the specimen. Acquired immunodeficiency syndrome (AIDS) complicated by pneumocystis jirovecii pneumonia was also diagnosed. As no other significant lymphomatous lesions were identified by further examination, a clinical diagnosis of EBV-positive mucocutaneous ulcer (EBVMCU) was made. Rather than performing systemic chemotherapy, the lesion was closely monitored and antiretroviral therapy (ART) for AIDS was started with the hope of treating the lesion through immune reconstitution. The lesion had completely disappeared by day 79 after starting ART, and has not recurred for over 3 years. EBVMCU is known to develop secondary to various immunosuppressive states including AIDS. Here we report a rare case of EBVMCU detected at diagnosis of AIDS that entered complete remission after immune reconstitution by ART.

Kaposi sarcoma herpesvirus/human herpesvirus 8-positive diffuse large B-cell lymphoma characterized by malignant ascites: A case report.

Herein, we report a rare case of Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8)-positive diffuse large B-cell lymphoma (DLBCL), which is characterized by malignant ascites and complex karyotypes. A 72-year-old male patient who tested negative for human immunodeficiency virus presented with thrombocytopenia and lymphadenopathies. He was diagnosed with KSHV/HHV8-associated multicentric Castleman disease (MCD). After three years, he developed progressive lymphadenopathies and massive ascites. The lymphoma cells in the ascitic fluid presented with characteristic immunophenotype and monoclonality, which support the diagnosis of KSHV/HHV8-positive DLBCL. Lymphadenopathies and massive splenomegaly are common manifestations of KSHV/HHV8-positive DLBCL. Nevertheless, peritoneal involvement, as observed in this case, is a rare presentation. This emphasizes the diagnostic complexities of KSHV/HHV8-associated lymphoproliferative disorders. Within the context of preexisting KSHV/HHV8-associated multicentric Castleman disease, the differential diagnosis of this disorder can be challenging.

Analysis of Notch1 protein expression in methotrexate-associated lymphoproliferative disorders.

Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a lymphoproliferative disorder in patients treated with MTX. The mechanism of pathogenesis is still elusive, but it is thought to be a complex interplay of factors, such as underlying autoimmune disease activity, MTX use, Epstein-Barr virus infection, and aging. The NOTCH genes encode receptors for a signaling pathway that regulates various fundamental cellular processes, such as proliferation and differentiation during embryonic development. Mutations of NOTCH1 have been reported in B-cell tumors, including chronic lymphocytic leukemia/lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). Recently, it has also been reported that NOTCH1 mutations are found in post-transplant lymphoproliferative disorders, and in CD20-positive cells in angioimmunoblastic T-cell lymphoma, which might be associated with lymphomagenesis in immunodeficiency. In this study, to investigate the association of NOTCH1 in the pathogenesis of MTX-LPD, we evaluated protein expression of Notch1 in nuclei immunohistochemically in MTX-LPD cases [histologically DLBCL-type (n = 24) and classical Hodgkin lymphoma (CHL)-type (n = 24)] and de novo lymphoma cases [DLBCL (n = 19) and CHL (n = 15)]. The results showed that among MTX-LPD cases, the expression of Notch1 protein was significantly higher in the DLBCL type than in the CHL type (P < 0.001). In addition, among DLBCL morphology cases, expression of Notch1 tended to be higher in MTX-LPD than in the de novo group; however this difference was not significant (P = 0.0605). The results showed that NOTCH1 may be involved in the proliferation and tumorigenesis of B cells under the use of MTX. Further research, including genetic studies, is necessary.

Skeletal muscle index impacts the treatment outcome of elderly patients with diffuse large B cell lymphoma.

Sarcopenia is a crucial factor in the physical fitness of elderly individuals. This study investigated the prognostic values of multiple parameters of sarcopenia in association with established prognostic factors in elderly Japanese patients with diffuse large B cell lymphoma (DLBCL). As candidate indicators for sarcopenia, the skeletal muscle index (SMI) (cm2 /m2 ), the psoas muscle index, the erector spinae muscle index, the visceral fat index, the subcutaneous fat index, and the visceral to subcutaneous fat area ratio at the third lumbar level were assessed by computed tomography at their initial diagnosis in 102 patients with DLBCL over 75 years old those were diagnosed and treated in our institute from 2007 to 2020. The primary endpoint was overall survival (OS), and the secondary endpoint was progression-free survival (PFS). The median age of patients analyzed was 80 years at diagnosis. The sex-specific cut-offs for the indices adopted two approaches: (i) the historical cut-off values established in the previous study for healthy Japanese individuals (Hamaguchi Y. J Cachexia Sarcopenia Muscle. 2018), and (ii) each sex-specific lowest quartile in our cohort. As the results, SMI evaluated by the historical cut-off and sex-specific lowest quartile was identified as the most influential independent prognostic factor for both OS and PFS among various parameters for sarcopenia. Furthermore, we developed an elderly sarcopenia prognostic index (ESPI). ESPI, which combines SMI evaluated by the historical cut-off and LDH > ULN, demonstrated statistically significant prognostic impacts on OS and PFS. Moreover, compared to the R-IPI, ESPI showed the ability to identify intermediate-risk groups and indicated a trend toward improved predictive accuracy. Our study revealed that SMI is the most appropriate assessment method for evaluating sarcopenia and the critical prognostic factor in OS and PFS of elderly patients with DLBCL.

Irreversible Intrathecal Chemotherapy-induced Myelopathy in a Patient with Diffuse Large B-cell Lymphoma.

Intrathecal chemotherapy is often administered for prophylaxis and treatment of central nervous system involvement in hematological malignancies. However, it may rarely cause neurotoxicity as a side effect. We herein report a 74-year-old woman with diffuse large B-cell lymphoma including a spinal lesion. She received systemic and intrathecal chemotherapy. After five doses of intrathecal chemotherapy, she developed intrathecal chemotherapy-induced myelopathy. Intrathecal treatment was discontinued, and she was administered vitamin B12 and folic acid, along with steroid pulses. However, her symptoms did not improve. Intrathecal chemotherapy-induced myelopathy is rare, but may be irreversible; therefore, clinicians should be aware of this potential complication.

Cardiac Tamponade as an Initial Manifestation of Diffuse Large B-cell Lymphoma One Year after IgG4-related Disease in Remission.

A 65-year-old man with multiple lymphadenopathies was diagnosed with IgG4-related disease (IgG4-RD) based on findings of a cervical lymph node biopsy and an elevated serum IgG4 level. Treatment was initiated after the onset of autoimmune pancreatitis, and he achieved remission. He developed diffuse large B-cell lymphoma one year later. Pericardial involvement of lymphoma resulted in cardiac tamponade, and he died before histopathological confirmation of lymphoma was made due to a lethal arrhythmia caused by massive involvement of lymphoma into the myocardium. Because patients with IgG4-RD might have an increased risk of malignant diseases, including lymphoma, histopathological examinations should be considered at any time during the course of IgG4-RD.

An extranodal Richter's syndrome presenting with cardiac diffuse large B-cell lymphoma: a case report.

BACKGROUND: Richter's syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves lymph nodes and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose. CASE PRESENTATION: A 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm × 37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma. CONCLUSIONS: We present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

Hypopharyngeal Diffuse Large B-Cell Lymphoma in a 74-Year-Old Man Presenting with Dysphagia: A Case Report.

BACKGROUND Malignant lymphomas can occur at various sites. Hypopharyngeal tumors are at risk for airway obstruction and require rapid diagnosis and treatment. Most hypopharyngeal malignancies are squamous cell carcinomas; other tumors are rare. To date, only a few cases of malignant hypopharyngeal lymphoma have been reported, and its specific characteristics are unknown. Herein, we report a case of right hypopharyngeal diffuse large B-cell lymphoma (DLBCL) in a 74-year-old man with dysphagia. CASE REPORT A 74-year-old man presented to our hospital with dysphagia. He had no relevant medical history. Endoscopic examination revealed a right hypopharyngeal tumor. The surface of the tumor was smooth, with no evidence of hemorrhage. Computed tomography revealed a 40-mm mass located in the hypopharynx. We performed a tracheotomy and biopsy of the tumor. Histopathological examination revealed a diffuse proliferation of large atypical B cells with negative staining for Epstein-Barr virus by in situ hybridization. Immunohistochemical staining was positive for CD20 but negative for CD3 and CD10. The patient was administered chemotherapy. The tumor reduced in size, and the patient recovered completely. During the two-year follow up, no recurrence of cancer was observed. CONCLUSIONS Although most hypopharyngeal tumors are squamous cell carcinomas (SCCs), the possibility of other types of tumors should also be considered. Malignant lymphoma of the hypopharynx is rare, and more cases need to be studied and reported in the future.

Primary adrenal diffuse large B cell Lymphoma with Tumor thrombus in central adrenal vein: a case report and literature review.

BACKGROUND: Primary adrenal lymphoma (PAL) is a rare disease confined wholly or chiefly to extramural involvement. Tumor thrombus in the central adrenal vein, renal vein, and inferior vena cava has been reported in adrenal pheochromocytoma, adrenocortical carcinoma, adrenal metastasis carcinoma, and adrenal leiomyosarcoma. Primary adrenal diffuse large B cell lymphoma with tumor thrombus in the central adrenal vein has rarely been reported in the current study. ( We searched in PubMed, Web of Science databases, Embase, and Medline in the English language from 1970 to December 2022. The keywords used were "Primary adrenal lymphoma " and " tumor thrombus".) CASE PRESENTATION: In this report, we discuss the case of a 57-year-old woman who complained of abdominal discomfort following cold stimulation, low back pain, anorexia, fatigue, and weight loss for 1 year. Contrast-enhanced spiral computed tomography (CT) showed mild-to-moderate enhancement of the bilateral masses and central adrenal vein tumor thrombus. After an exhaustive study, the patient was diagnosed with primary adrenal diffuse large B-cell lymphoma. In the diagnosis of PAL, the possibility of a tumor embolism in the central adrenal vein, renal vein, or inferior vena cava should be considered, although this is rare.

Profiling risk factors for separation of infection complications in patients with gastrointestinal and nodal diffuse large B-cell lymphoma.

OBJECTIVE: To identify risk factors for infection complications in patients with gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) and nodal DLBCL (N-DLBCL) during treatment, respectively. METHODS: Total 51 GI-DLBCL patients and 80 N-DLBCL patients were included after retrieving clinical data from a single medical center in the past ten years. Logistic regression analysis was utilized to analyze patients' data, including baseline demographics, treatments and laboratory values, to determine independent risk factors of infection in these patients. RESULTS: Total 28 of 51 patients (54.9%) in the GI-DLBCL group and 52 of 80 patients (65%) in the N-DLBCL group were observed infection events during treatment. A multivariate logistic regression model revealed that Ann-arbor stage IV (P = 0.034; odds ratio [OR]: 10.635; 95% confidence interval [CI]: 1.152-142.712), extra-nodal lesions ≥ 2 (P = 0.041; OR: 23.116; 95%CI: 1.144-466.949) and high serum lactate dehydrogenase (LDH) at the time of diagnosis (LDH > 252U/L; P = 0.033; OR: 6.058; 95%CI: 1.159-31.659) were independent risk factors for the development of infection in patients with GI-DLBCL after systemic treatment. In the N-DLBCL group, high serum C-reactive protein (CRP) (P = 0.027; OR: 1.104; 95%CI: 1.011-1.204) and a low platelet count (P = 0.041; OR: 0.991; 95%CI: 0.982-1.000) at routine blood tests just before infection occurred were identified as significant risk factors related to infection events during treatment. CONCLUSIONS: Discordant independent risk factors induced infection may be present during the treatment in patients with GI-DLBCL and N-DLBCL. Close monitoring these risk factors is likely an effective strategy to prevent microbial infections in these patients.

Diffuse Large B-Cell lymphoma Misdiagnosed as a Hematoma: Case Report.

Background: Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, often presents diagnostic challenges due to its diverse clinical presentation. We present a case of DLBCL that was initially misdiagnosed as a hematoma, highlighting the importance of considering malignancy when faced with unresponsive soft tissue swelling. Methods: A 76-year-old man presented to the emergency department with right periorbital swelling and ecchymosis following a traumatic injury. Despite ongoing anticoagulant therapy (warfarin) for atrial fibrillation, the symptoms persisted. A CT scan of the facial bones revealed a large, irregular, homogeneous mass. Initially, the clinical history and radiologic findings suggested an extraconal hematoma. As a result, an incision and drainage procedure was performed, and the old blood was evacuated. However, the patient's symptoms continued to worsen. A follow-up CT scan showed enlargement of the lesion, prompting a surgical excisional biopsy. Results: Pathologic examination of the excised mass revealed a diffuse infiltrate of lymphocytes surrounding the tissue, confirming the diagnosis of diffuse large B-cell lymphoma (DLBCL). The patient was subsequently referred to hematology for further management. Conclusions: Although rare, DLBCL is associated with a challenging prognosis. This case highlights the diagnostic complexities that can arise, particularly when factors such as prior injury and anticoagulant therapy confound the clinical picture. The initial misclassification of the condition as a hematoma led to a delay in diagnosis and the subsequent initiation of treatment. Therefore, it is imperative to remain vigilant and consider malignancy as a potential underlying cause of unresponsive soft tissue swelling. Timely recognition and accurate diagnosis are paramount to improving patient outcomes in DLBCL, an aggressive lymphoma with a diverse clinical presentation.

An Elusive Diagnosis: Diffuse Large B-Cell Lymphoma Masquerading as Acute Liver Failure with Persistent Lactic Acidosis.

BACKGROUND Acute liver failure (ALF) associated with malignant lymphoma is a rare condition with non-specific clinical and radiological features. Here, we describe an unusual case of ALF due to DLBCL with an image negative on presentation posing diagnostic difficulty. CASE REPORT A 74-year-old man was admitted to our hospital with abdominal pain. Radiological and laboratory investigations revealed lymphadenopathy with mildly elevated transaminitis and alkaline phosphates levels. A right upper-quadrant ultrasound showed heterogeneous hepatic parenchyma. Eight days later, he had worsening abdominal pain. He was found to have altered mental status and asterixis. His liver function was worsened with ALT 101, AST 328, lactic acid 4.2, total bilirubin 2.5, INR 6.35, and ammonia level 117 µmol/L. He continued to deteriorate with worsening lactic acidosis, coagulopathy, severe anemia, elevated liver enzymes, and thrombocytopenia. Unfortunately, the patient died of multi-organ failure on the 14th day of hospitalization. The autopsy findings revealed DLBCL involving multiple organs, including the liver, lung, bone marrow, and multiple lymph nodes. Despite an extensive diagnostic workup, an underlying diagnosis was unable to be established antemortem. CONCLUSIONS We describe a case of ALF linked to DLBCL discovered at autopsy. The non-specific clinical and radiological features of this condition make diagnosis challenging, and the prognosis is often poor. Further research and awareness are needed to improve the early detection and management of ALF associated with malignant lymphoma. By expanding the literature on this topic, we aim to improve outcomes and optimize patient care in similar clinical scenarios.