Primary Effusion Lymphoma Presenting Research Articles

A CASE OF EXTRACAVITARY PRIMARY EFFUSION LYMPHOMA

SESSION TITLE: Medical Student/Resident Disorders of the Mediastinum Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Among HIV related malignancies, primary effusion lymphoma (PEL) is uncommon and represents 1-4% of HIV-associated lymphomas.1 PEL is associated with HHV-8 & EBV, and is monotypic B-cell lymphoma. Despite similar demographic and epidemiologic risk factors, PEL has a distinct genetic and histopathologic profile compared to other HIV-associated non-Hodgkin’s lymphomas (NHL). The classic presentation of PEL is characterized by liquid accumulation of malignant cells associated with serosal surfaces without a localized mass or solid tissue infiltration.1 However, about 1/3 of PEL are extracavitary, and form solid tumors with or without effusions. These mass lesions are often found in the GI tract, spleen, or lymph nodes.2 This can pose a diagnostic challenge, as extracavitary PEL can be mistaken for more common HIV associated lymphomas such as Burkitt’s or DLBCL. CASE PRESENTATION: 41-year-old man presented to clinic with a history of well-controlled HIV on HART therapy, and a complex oncologic history including high grade NHL (likely Burkitt’s lymphoma) diagnosed 17 years prior. His initial course was complicated by CNS involvement, treated with 6 cycles of R-EPOCH, radiation and intra-thecal chemotherapy. He relapsed and underwent autologous stem cell transplant in 2005 with complete remission. Surveillance PET/CT in 2019 demonstrated a 1-cm right-sided lower paratracheal lymph node with mild FDG avidity. The patient endorsed some night sweats but was otherwise asymptomatic. EBUS TBNA confirmed extracavitary primary effusion lymphoma. Immunostains demonstrated lymphoma cells positive for HHV and EBV. Bone marrow biopsy was negative. Notably, this extracavitary PEL was thought to be a second primary malignancy, and not relapse of his prior NHL DISCUSSION: Although relapse of this patient’s prior NHL would be the most expected diagnosis, this case demonstrates two distinct HIV-associated primary lymphomas. Bronchoscopic sampling was critical for pathologic differentiation of these two conditions. The patient’s age, gender, HIV status, and immunohistochemical profile are in line with prior reports,. However, this case is especially unique in that other cases have typically occurred in patients more immunosuppressed than ours. In one of the largest case studies performed, the median CD4 count was 200 and 65% had a history of an AIDS defining condition.2 Other complications of HHV-8 such as Kaposi’s Sarcoma or Multicenter Castleman’s Disease are also common in patients with PEL.2 However prior lymphomas such as Burkitt’s or DLBCL have not been reported as preceding PEL. CONCLUSIONS: This case highlights the spectrum of NHL that can occur in HIV patients, and the importance of appropriate tissue acquisition for clarifying the diagnosis which may be accomplished bronchoscopically. Reference #1: Chen, Y.-B., Rahemtullah, A. and Hochberg, E. (2007), Primary Effusion Lymphoma. The Oncol, 12: 569-576. doi:10.1634/theoncologist.12-5-569 Reference #2: Guillet, S., Gérard, L., Meignin, V., Agbalika, F., Cuccini, W., Denis, B., Katlama, C., Galicier, L. and Oksenhendler, E. (2016), Classic and extracavitary primary effusion lymphoma in 51 HIV-infected patients from a single institution. Am. J. Hematol., 91: 233-237. doi:10.1002/ajh.24251 Reference #3: Chadburn A, Hyjek E, Mathew S, et al. KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma. Am J Surg Pathol 2004;28:1401–1416. DISCLOSURES: Speaker/Speaker's Bureau relationship with Boehringer-Ingelheim Pharmaceuticals Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Vapotherm, Inc Please note: $5001 - $20000 Added 04/07/2020 by Jaime Betancourt, source=Web Response, value=Honoraria No relevant relationships by Gwenyth Day, source=Web Response No relevant relationships by Kevin Eng, source=Web Response No relevant relationships by Katy Lawson, source=Web Response

WHERE ARE THE EFFUSIONS?

SESSION TITLE: Fellows Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Primary effusion lymphoma (PEL) is a rare and aggressive subset of B-cell lymphoma that is commonly associated with immune deficiencies such as HIV/AIDS and organ transplant. It commonly manifests as a serous effusion in either pleural, pericardial or peritoneal spaces, and is associated with human herpesvirus-8 (HHV-8) or Epstein-Barr virus (EBV). One study showed that about one third of patients with the diagnosis of PEL did not have effusions; but were diagnosed by pathology of solid tumors. CASE PRESENTATION: A 58-year-old man with a multi-decade history of HIV infection was referred to the Emergency Department for anemia and low CD4 T cell count with elevated HIV viral load. He had a long history of HIV infection. Other medical problems include Kaposi sarcoma, hypertension, and spinal osteoarthritis. His physical exam was notable for pre-auricular and inguinal lymphadenopathy. Initial laboratory evaluation included anemia, leukocytosis with left shift, thrombocytopenia, elevated serum protein, low bicarbonate and elevated lactate. He was given fluid resuscitation, broad-spectrum antibiotics, and vasopressor support. Cerebrospinal fluid studies showed high total protein at 72, 88% lymphocytes. Continued evaluation of his lymphadenopathy, anemia and thrombocytopenia included detection of EBV and HHV-8. Excisional biopsy of left cervical lymph node showed clusters and sheets of large atypical cells with plasmablastic morphology admixed with small mature lymphocytes and plasma cells. The suspected diagnosis was primary effusion lymphoma without lymphomatous effusions. His course was complicated by respiratory insufficiency requiring non invasive ventilation in the setting of new bilateral ground glass opacities. He was treated for pneumonia with clinical improvement. He became altered on the medical floor, and a guardian was appointed for his medical decision making. In light of HIV-associated lymphoma with unclear benefit to aggressive chemotherapy, his guardian opted for comfort care and he was discharged to home hospice. DISCUSSION: We present a case of PEL presenting in a patient with long-standing HIV infection and history of Kaposi sarcoma. Despite the name, not all cases have lymphomatous effusions on presentation. PEL is uncommon, and available information is based on case series. The treatment of PEL involves multi-drug chemotherapy, including use of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and methotrexate. One case series of 28 patients treated for PEL with CHOP had median overall survival of 6.2 months . Another case series of 51 patients treated for PEL using CHOP-like regimen and the addition of methotrexate showed median overall survival 10.2 months . CONCLUSIONS: The prevalence of PEL is low; but should be considered in in patients with long standing HIV infection and Kaposi sarcoma. Reference #1: Guillet, S., Gérard, L., Meignin, V., Agbalika, F., Cuccini, W., Denis, B., Katlama, C., Galicier, L. and Oksenhendler, E. (2016), Classic and extracavitary primary effusion lymphoma in 51 HIV-infected patients from a single institution. Am. J. Hematol., 91: 233-237. doi:10.1002/ajh.24251 Reference #2: Kazuyuki Shimada, Fumihiko Hayakawa, Hitoshi Kiyoi; Biology and management of primary effusion lymphoma. Blood 2018; 132 (18): 1879–1888. doi: https://doi.org/10.1182/blood-2018-03-791426 Reference #3: Emmanuelle Boulanger, Laurence Gérard, Jean Gabarre, Jean-Michel Molina, Christophe Rapp, Jean-François Abino, Jacques Cadranel, Sylvie Chevret, and Eric Oksenhendler Prognostic Factors and Outcome of Human Herpesvirus 8–Associated Primary Effusion Lymphoma in Patients With AIDS (2005) Journal of Clinical Oncology 23:19, 4372-4380 DISCLOSURES: No relevant relationships by Saud Alrawaf, source=Web Response No relevant relationships by Benjamin DelPrete, source=Web Response No relevant relationships by Lisa Glass, source=Web Response No relevant relationships by Marwa Oudah, source=Web Response

Primary effusion lymphoma in a human immunodeficiency virus-negative patient with unexpected unusual complications: a case report

BackgroundPrimary effusion lymphoma is a rare, high-grade non-Hodgkin’s lymphoma that usually occurs in immunosuppressed or human immunodeficiency virus-positive individuals in advanced stages of the disease. However, primary effusion lymphoma occasionally affects immunocompetent patients who are infected with human herpes virus type 8 or Epstein-Barr virus. This disease manifests with liquid collections in cavities, producing constitutional symptoms; fever; weight loss; and symptoms related to extrinsic compression, such as dyspnea or abdominal discomfort. Diagnosis is confirmed with cytological or tissue evaluation showing large, multinucleated lymphoid cells with positive specific markers for the disease, such as CD45 and markers related to viral infections, when present. There is no standard treatment for primary effusion lymphoma, but several chemotherapy protocols are recommended, usually with poor results.Case presentationWe present a case of an adult human immunodeficiency virus-negative Hispanic origin woman with primary effusion lymphoma with pleuritic, pericardial, and peritoneal compromise who also had unusual complications during a diagnostic procedure: the accidental rupture of the left ventricle and the development of a secondary left ventricular pseudoaneurysm. We describe the clinical, radiological, and laboratory characteristics as well as the outcome of this case.ConclusionsPrimary effusion lymphoma is a very rare entity that represents 4% of non-Hodgkin’s lymphoma cases associated with human immunodeficiency virus and 0.1% to 1% of all lymphomas in patients with another type of immunodeficiency in regions where human herpes virus type 8 is not endemic. This reported case is an unusual presentation of primary effusion lymphoma because it occurred in an immunocompetent human immunodeficiency virus-negative adult woman without the presence of Kaposi’s sarcoma or Castleman’s disease and for whom the clinical course after chemotherapy was successful. However, the rupture of the free wall of the left ventricle is a very rare catastrophic event that usually occurs after myocardial infarction. Left ventricle free wall rupture rarely goes unnoticed, but when it occurs, it leads to the development of a ventricular pseudoaneurysm in which the rupture is contained by the pericardium with an organized thrombus and an adjacent hematoma.

Extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass

BackgroundPrimary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus 8 (HHV8). It has the highest incidence in HIV-positive individuals. It often presents as a malignant pleural, peritoneal and/or pericardial effusion without a detectable solid mass. Most cases are co-infected with Epstein–Barr virus (EBV). Rare cases of HHV8-positive lymphoma with features similar to PEL can present as tumor masses and are considered to represent an extracavitary or solid variant of PEL. We report a case of EBV negative, extracavitary/solid variant of primary effusion lymphoma presenting as a gastric mass. Case presentationA 48-year-old man was admitted to an outside hospital with abdominal pain and weight loss. At the outside hospital, he was found to be HIV positive and have a 3×2cm gastric mass. He was subsequently diagnosed with ALK negative anaplastic large cell lymphoma by gastric biopsy. The patient was referred to Harbor-UCLA Medical Center for further management. Review of the outside slides and additional stains performed at our hospital revealed sheets of large anaplastic lymphoma cells that were positive for CD30, CD138, MUM1 and HHV8, focally weakly positive for CD3, and negative for other T- and B-cell markers and EBER, consistent with extracavitary/solid variant of primary effusion lymphoma. Interestingly, for the first time, cyclin D1 positivity was also demonstrated in PEL. ConclusionPrimary effusion lymphoma, particularly the extracavitary/solid variant, is very rare, and the diagnosis can be challenging. In some cases, when CD30 is uniformly positive, this lymphoma can be misdiagnosed as ALK negative anaplastic large cell lymphoma. This lymphoma can also aberrantly express T-cell markers as seen in this case, making diagnosis even more difficult. Awareness of the existence and the features of solid variant PEL and assessment for HHV8 infection are essential for correct diagnosis.

Extracavitary primary effusion lymphoma: A case report from India

We present a case of extracavitary primary effusion lymphoma presenting, as jejunal polyps in a 38-year-old man. This is the first report of this entity from India. Although rare in our country, the diagnosis should be suspected in cases of CD20 negative large cell lymphoma with plasmablastic or immunoblastic differentiation in seropositive patients. Immunostaining for latency-associated nuclear antigen-1 and in situ hybridization for Epstein-Barr virus-associated RNA will confirm the diagnosis.

Extracavity primary effusion lymphoma presenting in a lymph node without lymphomatous effusions

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with human herpesvirus 8 (HHV8), which usually presents as a lymphomatous body cavity effusion. Rare cases of PEL are extracavitary and manifest as a solid tumor mass. Here we report an unusual case of extracavitary PEL (EPEL) involving lymph nodes with no evidence of a body cavity effusion. The neoplasm was comprised of large pleomorphic cells with prominent nucleoli and frequent mitotic figures that expressed HHV8, EBV, CD38 and CD30, but lacked all lineage-specific markers. The patient was found to be HIV positive after the diagnosis of EPEL. Antiretroviral therapy initially reduces tumor size, but the patient expired three months later due to multiple complications. PEL and EPEL are differing manifestations of a rare disease entity as defined by the World Health Organization 2008 classification. It is unknown why a small subset of these cases forms extracavitary masses with or without malignant effusions. Comparison with mouse xenograft models may provide unique insights into the pathogenesis of this disease for possible future studies.

Primary Effusion Lymphoma: Secretome Analysis Reveals Novel Candidate Biomarkers with Potential Pathogenetic Significance

Primary Effusion Lymphoma: Secretome Analysis Reveals Novel Candidate Biomarkers with Potential Pathogenetic Significance

Diagnosis and Management of Primary Effusion Lymphoma in the Immunocompetent and Immunocompromised Hosts

Primary effusion lymphoma (PEL) is an uncommon non-Hodgkin lymphoma associated with human herpes virus-8 (HHV-8) that grows mainly in serous body cavities. The most common presentation of PEL is that of a young immunocompromised male with shortness of breath, as the pleural cavity is most commonly affected. Diagnosis is primarily based on fluid cytology in which PEL cells display variable morphology and a null lymphocyte immunophenotype; however, evidence of HHV-8 infection within the neoplastic cell is essential. Patients have commonly been treated with systemic multidrug chemotherapy and antiretroviral therapy if they were HIV positive or were immunocompromised for other reasons. In the immunocompetent patient, there have been no agreed-upon pathways for management of this condition. Progression of disease is common and median survival is approximately 6 months. Novel intrapleural treatments with antiviral agents such as intracavity cidofovir have shown to be effective in controlling local disease, and ongoing clinical trials may provide some promise in the treatment for this condition.

A Computational Profiling of Changes in Gene Expression and Transcription Factors Induced by vFLIP K13 in Primary Effusion Lymphoma

Infection with Kaposi's sarcoma associated herpesvirus (KSHV) has been linked to the development of primary effusion lymphoma (PEL), a rare lymphoproliferative disorder that is characterized by loss of expression of most B cell markers and effusions in the body cavities. This unique clinical presentation of PEL has been attributed to their distinctive plasmablastic gene expression profile that shows overexpression of genes involved in inflammation, adhesion and invasion. KSHV-encoded latent protein vFLIP K13 has been previously shown to promote the survival and proliferation of PEL cells. In this study, we employed gene array analysis to characterize the effect of K13 on global gene expression in PEL-derived BCBL1 cells, which express negligible K13 endogenously. We demonstrate that K13 upregulates the expression of a number of NF-κB responsive genes involved in cytokine signaling, cell death, adhesion, inflammation and immune response, including two NF-κB subunits involved in the alternate NF-κB pathway, RELB and NFKB2. In contrast, CD19, a B cell marker, was one of the genes downregulated by K13. A comparison with K13-induced genes in human vascular endothelial cells revealed that although there was a considerable overlap among the genes induced by K13 in the two cell types, chemokines genes were preferentially induced in HUVEC with few exceptions, such as RANTES/CCL5, which was induced in both cell types. Functional studies confirmed that K13 activated the RANTES/CCL5 promoter through the NF-κB pathway. Taken collectively, our results suggest that K13 may contribute to the unique gene expression profile, immunophenotype and clinical presentation that are characteristics of KSHV-associated PEL.

Extracavitary Primary Effusion Lymphoma Presenting as Spontaneous Tumor Lysis Syndrome: A Case Report

Extracavitary Primary Effusion Lymphoma Presenting as Spontaneous Tumor Lysis Syndrome: A Case Report

Human herpesvirus 8‐associated lymphoma mimicking cutaneous anaplastic large T‐cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.

Understanding pathogenetic aspects and clinical presentation of primary effusion lymphoma through its derived cell lines

Primary effusion lymphoma (PEL) is a very rare subgroup of B-cell lymphomas presenting as pleural, peritoneal and pericardial neoplastic effusions in the absence of a solid tumor mass or recognizable nodal involvement. There is strong evidence that Kaposi's sarcoma-associated herpesvirus (KSHV) is a causal agent of PEL. PEL tumor cells are latently infected by KSHV with consistent expression of several viral proteins and microRNAs that can affect cellular proliferation, differentiation and survival. The most relevant data on pathogenesis and biology of KSHV have been provided by studies on PEL-derived cell lines. Fourteen continuous cell lines have been established from the malignant effusions of patients with AIDS-associated and non-AIDS-associated PEL. These KSHV+ EBV+/- cell lines are well characterized, authenticated and mostly available from public biological resource centers. The PEL cell lines display unique features and are clearly distinct from other lymphoma cell lines. PEL cell lines represent an indispensable tool for the understanding of KSHV biology and its impact on the clinical manifestation of PEL. Studies on PEL cell lines have shown that a number of viral genes, expressed during latency or lytic life cycle, have effects on cell binding, proliferation, angiogenesis and inflammation. Also, PEL cell lines are important model systems for the study of the disorder of PEL including the lack of invasive or destructive growth patterns and the peculiar propensity of PEL to involve body cavity surfaces.

Primary effusion lymphoma presenting as Richter’s syndrome

Primary effusion lymphoma presenting as Richter’s syndrome

Primary Effusion Lymphoma in an Hiv-Negative Patient with No Serologic Evidence of Kaposi's Sarcoma Virus

Primary effusion lymphoma (PEL) is a newly described high-grade B cell lymphoma which develops in association with Kaposi's sarcoma-associated herpesvirus (KSV) in human immunodeficiency virus (HIV)-infected individuals. We hereby describe a very unusual presentation of PEL that developed in the abdominal cavity of an HIV negative, KSV negative patient with a 1-year history of refractory ascites due to alcohol-related liver cirrhosis. Possible factors aiding lymphomagenesis in the cirrhotic state are discussed.