Extracavitary Primary Effusion Lymphoma Research Articles

Extracavitary primary effusion lymphoma: clinical, morphological, phenotypic and cytogenetic characterization using nuclei enrichment technique.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma, which typically manifests as malignant effusion in the body cavities. However, extracavitary solid variants are also described. The aim of this study was to investigate copy number aberrations in two cases of solid PEL at their first occurrences and relapse by applying a newly developed methodology of tumour nuclei enrichment. Using histological and genetic techniques, a novel protocol for tumour nuclei enrichment by flow sorting and array-comparative genomic hybridization, we characterized two cases of extracavitary PEL, one of which later relapsed as effusion. Both primary tumours were positive for HHV8 and EBV, confined to lymph nodes, and aberrantly expressed CD3, yet displaying clonal immunoglobulin gene rearrangements indicating B-cell origin. Cytogenetic characterization of primary tumours revealed modest number of aberrations, partially overlapping with previously reported affected loci. The effusional relapse in case 1 was cytogenetically related to the primary tumour but showed dramatic increase of chromosomal instability. We for the first time demonstrate a cytogenetic relationship between solid and effusional presentations of PEL. Moreover, we provide an indirect evidence of multiple malignant clones, which gave rise to clonally-related, yet karyotypically different relapsing lymphoma manifestations.

Current concepts in primary effusion lymphoma and other effusion-based lymphomas.

Primary effusion lymphoma (PEL) is a human herpes virus 8 (HHV8)-positive large B-cell neoplasm that presents as an effusion with no detectable tumor in individuals with human immunodeficiency virus infection or other immune deficiencies. PEL is an aggressive neoplasm with a poor prognosis. PEL cells show diverse morphologies, ranging from immunoblastic or plasmablastic to anaplastic. The immunophenotype of PEL is distinct, but its lineage can be misdiagnosed if not assessed thoroughly. PEL cells usually express CD45, lack B- and T-cell-associated antigens, and characteristically express lymphocyte activation antigens and plasma cell-associated antigens. Diagnosis of PEL often requires the demonstration of a B-cell genotype. HHV8 must be detected in cells to diagnose PEL. In most cases, PEL cells also harbor the Epstein-Barr virus (EBV) genome. Similar conditions associated with HHV8 but not effusion-based are called "extracavitary PELs." PELs should be differentiated from HHV8-negative, EBV-positive, body cavity-based lymphomas in patients with long-standing chronic inflammation; the latter can occur in tuberculous pleuritis, artificial pneumothorax, chronic liver disease and various other conditions. Despite their morphological similarity, these various lymphomas require different therapeutic strategies and have different prognostic implications. Correct diagnosis is essential to manage and predict the outcome of patients with PEL and related disorders.

Flip flop pattern of skeleton after treatment in a patient with Hodgkin's lymphoma

Extracavitary primary effusion lymphoma (ExPEL) is a rare, high-grade lymphoproliferative disorder that displays immunoblastic, plasmablastic, or anaplastic morphology. It usually lacks expression of B-cell and T-cell markers, but often expresses the plasma cell markers CD138 and MUM1, and the activation marker CD30, along with EMA. ExPEL, similar to classic PEL occurring as lymphomatous effusions in serous body cavities without an associated tumor mass, is consistently associated with human herpes virus-8 (HHV8) infection, while a majority of cases also exhibits Epstein–Barr virus (EBV) co-infection. Clinically, it is characterized by an almost exclusive male predominance (98% male), HIV-positivity (96% of patients are HIV +), acute presentation with B symptoms, and unfavorable overall survival (40% of patients die within 2 months). We report an asymptomatic HIV-negative female patient with incidentally found splenomegaly and extensive PET FDG-avid retroperitoneal, pelvic, and mediastinal lymphadenopathy. A core biopsy of her right pelvic lymph node showed aggregates of atypical cells with anaplastic features. Immunohistochemistry revealed that the neoplastic cells were positive for CD45, CD20, CD30, MUM1, CD138, EMA, CD3, HHV-8 and EBER. The diagnosis of ExPEL was established. Against medical advice and given the absence of significant symptoms, the patient refused to start treatment. Four months after the diagnosis, the patient remains asymptomatic, and follow-up CT scan demonstrates stability of her lymphadenopathy. We present here a case of ExPEL in which the patient's presentation defies the clinical norms, illustrating that ExPEL should also be included in the differential diagnosis of lymphomas occurring in asymptomatic HIV-negative patients.

Intracardiac extra-cavitary primary effusion lymphoma in an HIV-infected patient

Intracardiac extra-cavitary primary effusion lymphoma in an HIV-infected patient

Extracavitary/solid variant of primary effusion lymphoma

Primary effusion lymphoma (PEL) is a distinct clinicopathologic entity associated with human herpesvirus 8 (HHV8) infection that mostly affects patients with immunodeficiency. Primary effusion lymphoma usually presents as a malignant effusion involving the pleural, peritoneal, and/or pericardial cavities without a tumor mass. Rare cases of HHV8-positive lymphoma with features similar to PEL can present as tumor masses in the absence of cavity effusions and are considered to represent an extracavitary or solid variant of PEL. Here, we report 3 cases of extracavitary PEL arising in human immunodeficiency virus-infected men. Two patients had lymphadenopathy and underwent lymph node biopsy. One patient had a mass involving the ileum and ascending colon. In lymph nodes, the tumor was predominantly sinusoidal. The tumor involving the ileum and ascending colon presented as 2 masses, 12.5 × 10.6 × 2.6 cm in the colon and 3.6 × 2.7 × 1.9 cm in the ileum. In each case, the neoplasms were composed of large anaplastic cells, and 2 cases had "hallmark cells." Immunohistochemistry showed that all cases were positive for HHV8 and CD138. One case also expressed CD4 and CD30, and 1 case was positive for Epstein-Barr virus-encoded RNA. Evidence of B-cell differentiation was poorly developed in all tumors. These cases highlight the importance of assessing HHV8 in an anaplastic tumor that arises in a human immunodeficiency virus-positive patient and further contributes to the limited literature currently available for extracavitary 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

Complete Response to EPOCH in a Patient With HIV and Extracavitary Primary Effusion Lymphoma Involving the Colon: A Case Report and Review of Literature

Introduction Primary effusion lymphoma (PEL) is a rare malignancy that accounts for 5% of HIV-related non-Hodgkin lymphoma (NHL). It usually presents as a lymphomatous growth in liquid phase within various body cavities such as the pleural, pericardial, and peritoneal spaces. Although extracavitary tumors can occur in PEL, they do so rarely but may be histologically indistinguishable from PEL. PEL s also defined by the expression of Kaposi sarcoma–associated heresvirus (KSHV) (also known as human herpesvirus 8 [HHV8]) in

Primary Effusion Lymphoma/Extracavitary Effusion Lymphoma

Primary effusion lymphoma (PEL), and its solid counterpart, extracavitary PEL, is a rare, but unique, clinicopathologic entity, which is pathogenetically related to infection with the gamma herpesvirus, Kaposi sarcoma herpesvirus/human herpes virus 8. Although it occurs primarily in individuals positive for human immunodeficiency virus infection with low CD4 counts, it can develop in other patient populations as well. The tumor cells, which are morphologically pleomorphic, are usually positive for Epstein-Barr virus infection, classically lack expression of B- and T-cell–associated antigens, and are often positive for activation antigens such as CD30 and epithelial membrane antigen. Molecular studies show that they are of B-cell origin but usually lack structural alterations in oncogenes and tumor suppressor genes such as MYC. However, without attention to clinical history, careful examination of the cytomorphology and investigation for the presence of Kaposi sarcoma herpesvirus/human herpes virus 8, PEL/EC-PEL may be misdiagnosed or unrecognized. Here a case of PEL occurring in a patient positive for human immunodeficiency virus infection is described with a discussion of the pertinent cliniopathologic features of this unique entity.

Extracavitary primary effusion lymphoma in an HIV-positive patient with Kaposi sarcoma-associated

Extracavitary primary effusion lymphoma in an HIV-positive patient with Kaposi sarcoma-associated

Immunophenotypic analysis of the Kaposi sarcoma herpesvirus (KSHV; HHV‐8)‐infected B cells in HIV+ multicentric Castleman disease (MCD)

Kaposi sarcoma herpesvirus (KSHV) is aetiologically related to Kaposi sarcoma, classical and extracavitary primary effusion lymphoma (PEL; EC-PEL) and multicentric Castleman disease (MCD), entities preferentially occurring in HIV-infected individuals. Characterization of HIV-associated PELs/EC-PELs suggests that the KSHV-infected malignant cells originate from a pre-terminal stage of B-cell differentiation. However, only limited phenotypic studies have been performed on HIV+ MCD, including for PR domain containing 1 with zinc finger domain/B lymphocyte-induced maturation protein 1 (PRDM1/BLIMP1), a key regulator of terminal B-cell differentiation. The aim was to characterize KSHV-infected cells in 17 cases of HIV+ MCD. Double immunohistochemistry and immunohistochemistry-in situ hybridization were used to characterize the KSHV-infected cells in MCD; the results were compared with the phenotypic profiles of 39 PELs/EC-PELs and seven PEL cell lines. Whereas the immunophenotype of KSHV-infected cells in MCD and malignant KSHV+ PEL cells was similar (PAX5, Bcl-6-; PRDM1/BLIMP1, IRF4/MUM1+; Ki67+), the MCD KSHV-infected cells differed, as they expressed OCT2, cytoplasmic lambda immunoglobulin; variably expressed CD27; lacked CD138; and were Epstein-Barr virus negative. Although both PEL and MCD originate from KSHV-infected pre-terminally differentiated B cells, these findings, with previously reported genetic studies, indicate HIV+ MCD may arise from extrafollicular B cells, whereas PELs may originate from cells that have traversed the germinal centre.

Extracavitary Primary Effusion Lymphoma of the Anorectum

We report a case of an extracavitary primary effusion lymphoma occurring in the anorectum of a patient with advanced acquired immune deficiency syndrome. The morphology, null cell immunophenotype, and acquisition of plasma cell markers in this case are typical of the so-called solid variant of primary effusion lymphoma. Lymphoma cells in this case were shown to be co-infected with human herpesvirus- 8 and Epstein-Barr virus. Following combination chemotherapy and highly active antiretroviral therapy, this patient has remained in clinical remission for > 3.5 years. The purpose of this report is to add another case to the emerging literature regarding the heterogeneous category of extraserous human herpesvirus-8–associated lymphomas.

KSHV-positive solid lymphomas represent an extra-cavitary variant of primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a unique form of non-Hodgkin lymphoma (NHL) associated with Kaposi sarcoma-associated herpesvirus (KSHV; HHV-8) that displays a distinct constellation of clinical, morphologic, immunologic, and molecular characteristics. Rare KSHV-containing immunoblastic lymphomas occurring in solid tissues have been described. Whether they represent part of the spectrum of PEL has not been determined. The morphologic, immunophenotypic, and molecular features of KSHV-positive solid lymphomas occurring in 8 HIV+/AIDS patients were systematically investigated and compared with those of 29 similarly analyzed PELs. The 8 KSHV-positive solid lymphomas were virtually indistinguishable from the 29 PELs based on morphology (immunoblastic/anaplastic), immunophenotype (CD45 positive; T cell antigen negative; CD30, EMA, CD138 positive; CD10, CD15, BCL6 negative) and genotype (100% immunoglobulin genes rearranged; no identifiable abnormalities in C-MYC, BCL6, BCL1, BCL2; and uniformly EBV positive). The only identifiable phenotypic difference was that the KSHV-positive solid lymphomas appeared to express B cell-associated antigens (25%) and immunoglobulin (25%) slightly more often than the PELs (<5% and 15%, respectively; P = 0.11 and P = 0.08, respectively). The clinical presentation and course of the patients who develop KSHV-positive solid lymphomas were also similar, except for the lack of an effusion and somewhat better survival (median 11 months vs. 3 months). However, the 3 KSHV-positive solid lymphoma patients alive without disease 11, 25, and 44 months following initial presentation were recently diagnosed patients and, unlike the other patients with KSHV-positive solid lymphomas, received anti-retroviral therapy. These findings strongly suggest that these decidedly rare KSHV-positive solid lymphomas belong to the spectrum of PEL. Therefore, we propose that the KSHV-positive solid lymphomas be designated extra-cavitary PELs.