Remission of an HHV8-related extracavitary primary effusion lymphoma in an HIV-positive patient during antiretroviral treatment containing dolutegravir.

BACKGROUND: Human herpes virus 8 (HHV8) is the causative agent of Kaposi's sarcoma and has been associated with an increasing number of hematologic diseases such as primary effusion lymphoma (PEL) (both classic and extracavitary form), multicentric Castleman disease and the germinotropic lymphoproliferative disorder. PEL is a rare B cell non-Hodgkin lymphoma that primarily affects immunocompromised patients; aggressive chemotherapy and antiretroviral therapy (ART) with protease inhibitors have been used, with poor results. We present a case of extracavitary PEL in an HIV-infected patient, regressed after ART initiation. CASE PRESENTATION: A 42-year-old male was admitted to the emergency room because of several months of malaise, fever and progressive deterioration of the general conditions. On physical examination soft non-painful subcutaneous masses were palpable at retronuchal, retroauricolar and thoracic regions. HIV serology resulted positive: HIV plasma viremia was 782,270 copies/mL, CD4 103 cells/mL. The excision of one of the masses, metabolically active at a positron emission tomography (PET-CT) scan, revealed an HHV8-related extracavitary PEL. HHV8 plasma viremia was 44,826 copies/mL. ART with tenofovir alafenamide/emtricitabine/dolutegravir was started together with ganciclovir for cytomegalovirus chorioretinitis. The progressive disappearance of the masses was seen after 6 weeks of ART, and a PET-CT scan resulted completely negative at 3 months. After 19 months of ART the patient was in remission of PEL, HIV viremia was undetectable (< 20 copies/mL), CD4 count was 766 cells/mL and HHV8 viremia was undetectable. CONCLUSIONS: In this clinical case, the complete regression of PEL has been achieved after the immune recovery, as a consequence of ART introduction, without chemotherapy. It cannot be excluded that ganciclovir, used for the treatment of CMV chorioretinitis, may have contributed to the control of HHV8 replication. Whether to try or not a conservative approach in HIV-infected PEL patients must be carefully evaluated, considering the patient's characteristics and the prognostic factors.

Brentuximab vedotin as frontline treatment for HIV-related extracavitary primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare and aggressive herpesvirus-8 (HHV-8) driven B cell non-Hodgkin's lymphoma (NHL) that is usually associated with human immunodeficiency virus (HIV) infection, and has a poor prognosis. PEL is comprised of two clinically distinct but pathologically similar variants: classic and extracavitary PEL. Based on retrospective series, treatment options include combined antiretroviral therapy (cART) in conjunction with chemotherapy regimens used in other forms of NHLs. Treatment outcomes with this approach are usually dismal and there is no standard of care. We present a case of a patient with HIV associated CD30+ extracavitary PEL unfit for multi-agent chemotherapy, who achieved a durable complete response with single agent brentuximab-vedotin and cART.

A case of Epstein-Barr virus-negative human immunodeficiency virus-related primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare subtype of large B-cell lymphoma associated with human herpesvirus-8. Most cases are co-infected with Epstein-Barr virus (EBV). The prognosis of PEL is extremely poor and no optimal treatment regimen has been established. We report a case of EBV-negative PEL in a 49-year-old human immunodeficiency virus-positive man, presenting with massive bilateral pleural effusion.

Lymphoproliferative Disorders of the Lung.

This review aims to describe some of the most frequent lymphoproliferative disorders arising from the lung: pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma, lymphomatoid granulomatosis (LG), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and nodular lymphoid hyperplasia (NLH). Primary pulmonary lymphoma is defined as a clonal lymphoproliferative disorder affecting one or both lungs, without extrapulmonary involvement 3 months after diagnosis, and includes pulmonary MALT lymphoma and LG. MALT lymphoma is the most common pulmonary lymphoma. The disease is slow growing, most often asymptomatic, and revealed by chronic alveolar opacity on radiography. The diagnosis should involve minimally invasive techniques, and the prognosis is typically excellent. LG is a rare B-cell lymphoma driven by Epstein-Barr virus infection. The disease may mimic pulmonary vasculitis, often revealed by systemic signs. The diagnosis usually requires surgical lung biopsy. Its evolution is unpredictable, but median survival is poor and chemotherapy is usually proposed. MCD and PEL are both driven by Human herpesvirus 8 infection. Patients with MCD present with fever and lymphadenopathy associated with interstitial lung disease. PEL provokes a febrile, lymphocytic-exudative pleural effusion, without any pleural mass on CT. Specific chemotherapy is urgent for both MCD and PEL. NLH is a benign lymphoproliferative disorder of the lung that is usually asymptomatic and revealed by a single nodular opacity. The prognosis is good, without recurrence after surgical resection.

[Human herpesvirus 8-negative primary effusion lymphoma-like lymphoma with t(8;14)(q24;q32)].

Primary effusion lymphoma (PEL) is a large B-cell lymphoma proliferating only in the body cavity effusion. It often occurs in advanced AIDS patients and is associated with human herpesvirus 8 (HHV-8). On the other hand, HHV-8 negative effusion lymphoma, which is different from PEL in many ways, has also been reported and is referred to as HHV8-unrelated PEL-like lymphoma. This lymphoma is very rare and its clinical characteristics have not yet been fully clarified. We therefore report an HIV seronegative elderly patient with HHV8-unrelated PEL-like lymphoma. An 89-year-old woman was admitted to our hospital due to general fatigue and dyspnea. The patient presented with left pleural effusion in the absence of lymphadenopathy and tumor masses. The pathological examination of the pleural effusion showed proliferation of atypical large lymphoid cells, which were positive for CD19, CD20, CD10, CD38, CD7, BCL2 and BCL6 but negative for CD5, CD30, MUM1, surface immunoglobulin, HHV-8 and EBV. Cytogenetic analysis showed a complex karyotype including t(8;14)(q24;q32). The pleural effusion decreased in response to monotherapy with oral low-dose etoposide, but recurrence was detected 7 months later. Rituximab was transiently effective for the recurrent pleural effusion, but the patient died of lymphoma exacerbation 13 months after the diagnosis.

HIV-associated primary effusion lymphoma presenting as a paracardial mass.

Primary effusion lymphoma (PEL), a rare type of non-Hodgkin's lymphoma, is an AIDS-defining illness and always associated with human herpesvirus 8 (HHV-8). Classic presentations involve the pleural, pericardial or peritoneal cavities. Infrequently, extracavitary solid tumours develop. Treatment of PEL requires chemotherapy and highly active antiretroviral therapy (HAART). We report a case of a 46-year-old man, who presented with right-sided chest pain, dyspnoea and night sweats. Evaluation revealed decreased breath sounds and dullness to percussion on the right side of the chest. Imaging demonstrated a 6.1 cm×6.3 cm right paracardial mass and right-sided pleural effusion. Pleural fluid was HHV-8 positive. The patient was diagnosed with PEL with extracavitary involvement and treated with chemotherapy and concurrent HAART. This case is the first reported case of extracavitary paracardial involvement and adds new insight to the accepted treatment for PEL with extracavitary lesions.

Primary effusion lymphoma-like lymphoma in a patient with inflammatory bowel disease.

A 77-year-old man with inflammatory bowel disease (IBD) and who was treated with anti-tumor necrosis factor (TNF), 6-mercaptopurine and corticosteroids, presented with primary effusion lymphoma-like lymphoma (PEL-like lymphoma) with massive ascites. The patient's clinical course was complicated by acute renal insufficiency and hypotension, which led to death within 2 wk. In general, patients with IBD may have an increased risk for development of lymphoma, which is frequently associated with immunosuppressive and/or anti-TNF antibody therapies. PEL is a rare subset of lymphoma localized to serous body cavities, lacks tumor mass or nodal involvement, and is associated with infection by human herpes virus 8 (HHV-8). Primary neoplastic effusion may also be present in patients with large B-cell lymphoma without evidence of human immunodeficiency virus or HHV-8 infections. This type of lymphoma is classified as PEL-like lymphoma. Both PEL and PEL-like lymphoma types have been reported in patients undergoing immunosuppressive therapy, but to the best of our knowledge, the case described herein represents the first PEL-like lymphoma occurring in a patient with IBD.

Hepatitis C-related primary effusion lymphoma of the pleura and peritoneum, imaged with F-18 FDG PET/CT.

Primary Effusion Lymphoma (PEL) is a rare form of Non-Hodgkin lymphoma that involves serous body cavities (pleural, pericardial, or peritoneal) with lymphomatous effusions in the absence of lymphadenopathy or organomegaly. Although it was seen mostly in HIV-positive patients, it has recently been reported in HIV-negative patients with chronic Hepatitis B or C infections. PEL is associated with human herpes virus type-8 infection, often presents with rapidly progressive effusions and generally has a poor prognosis. This is a case of a 65-year-old HIV-negative man with Hepatitis C cirrhosis, who presented with abdominal pain. An F-18 FDG PET/CT showed marked ascites and pleural effusions with increased F-18 FDG uptake in the pleura and peritoneum on the left side. Analysis of the cells in the peritoneal fluid revealed a human herpes virus 8-positive PEL of the peritoneum. As a result the patient was no longer considered a liver transplant candidate and died 2 weeks after the diagnosis.

Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: report of a rare case and review of the literature.

A rare case of human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma: a report and review of the literature. APMIS 2009; 117:222-29. Primary effusion lymphoma (PEL) is a very rare type of lymphoma usually confined to the body cavities predominantly in immunosuppressed patients infected with human herpes virus 8 (HHV-8). The new term for HHV-8 independent PEL is HHV8-unrelated PEL-like lymphoma. We describe an 89-year-old human immunodeficiency virus (HIV)-negative male patient with HHV8-unrelated PEL-like lymphoma in the pleura. No hepatosplenomegaly or lymphadenopathy was detected. Chest radiography and computed tomography revealed right pleural effusion, but no evidence of tumor mass or lymph node enlargement. Cytological analysis of the pleural effusion revealed a high-grade lymphoma with round nuclei, prominent nucleoli and abundant cytoplasm with immunophenotypes positive for CD45, CD30, CD38, CD7 and CD71. Because of the advanced age, no chemotherapy was given. Effusion resolved spontaneously. One year after the diagnosis, a new pleural effusion developed at the left side. Following thoracentesis and pleurodesis, the patient remained in complete remission for 40 months. To date, 30 cases of HHV8-unrelated PEL-like lymphoma/HIV negative have been reported in the literature. The outcome of the HHV8-unrelated PEL-like lymphoma patients who were HIV negative seems to be better than HIV- and HHV-8-positive PEL.

[Prolonged survival in a patient with human herpesvirus-8-negative primary effusion lymphoma after combination chemotherapy with rituximab].

Primary effusion lymphoma (PEL) is a unique clinicopathological entity usually associated with human herpesvirus-8 (HHV-8) infection. It occurs almost exclusively in human immunodeficiency virus (HIV) -infected individuals. We presented a rare case of HIV-negative PEL in an elderly HHV-8-negative patient who developed cardiac tamponade due to pericardial effusion. The patient was treated with rituximab and cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). This disease generally has a poor prognosis; however, this patient achieved complete remission and remains without signs of disease 30 months after the last treatment. Because most HIV-negative and HHV-8- negative PEL cases show pan-B-cell markers, there is considerable usage of rituximab, though its optimal usage for PEL is unclear. To the best of our knowledge, there have been five reported cases where rituximab treatment has been used against HIV-negative and HHV-8-negative PEL. The clinical courses of these cases were relatively good without specific adverse effects. HIV-negative and HHV-8-negative PEL appears to be a reasonably new clinicopathological entity. While further investigation will of course be needed, the use of rituximab is worth considering for treatment of such patients.