Plasmablastic lymphoma of the oral cavity: a rapidly progressive lymphoma associated with HIV infection

Plasmablastic lymphoma of the oral cavity is a form of non-Hodgkin lymphoma (NHL) and was first described in 1997. We describe a case of plasmablastic lymphoma in an HIV-infected patient who presented with an expanding oral lesion and symptoms of a toothache. We review all cases of plasmablastic lymphoma that have been reported in the literature. Plasmablastic lymphoma is strongly associated with immunodeficiency, and most particularly, with HIV infection. The pathophysiological origin of plasmablastic lymphoma has not been fully characterised, but the presence of Epstein-Barr virus (EBV) has often been documented in biopsy specimens, supporting a role for EBV in the pathogenesis of this lymphoma. The differential diagnosis for an expanding oral lesion includes both infectious and malignant processes. Biopsy is essential for making a correct and prompt diagnosis. Treatment usually involves chemotherapy, but antiretroviral therapy may also have an important role. Infectious disease clinicians should be aware of this newly described and increasingly encountered lymphoma, since it is prominently associated with immunosuppression and may be mistaken for other entities.     

Human immunodeficiency virus (HIV) associated non-Hodgkin's lymphomas in Denmark: report of three cases

High grade malignant non-Hodgkin's lymphoma (NHL) was the presenting manifestation of the acquired immunodeficiency syndrome (AIDS) in 3/81 reported cases of AIDS in Denmark (by April 2, 1986). Asymptomatic HIV infection, 1 and 5 yr prior to the onset of lymphoma, was documented in 2 cases. 1 patient became infected by Factor VIII treatment, 2 were male homosexuals. 2 patients had an uncommon tumour presentation in the oral cavity, 1 patient presented with an abdominal mass. The histologic subtypes were immunoblastic (2), and small noncleaved cell, Burkitt's (1). Helper/suppressor T-cell ratio was decreased at onset of lymphoma in 2 cases. All 3 patients have died, 4, 6, and 24 months after diagnosis of NHL. Only 1 patient died of NHL, 1 died of an unclassified pneumonia and the third developed progressing supranuclear HIV-associated polyneuropathy without evidence of CNS lymphoma. Thus, high grade malignant B-cell NHL is a regular initial manifestation of AIDS, and may develop after years of asymptomatic HIV infection.     

High incidence of Kaposi sarcoma-associated herpesvirus-related non-Hodgkin lymphoma in patients with HIV infection and multicentric Castleman disease

Multicentric Castleman disease (MCD) is a distinct type of lymphoproliferative disorder associated with inflammatory symptoms and interleukin 6 (IL-6) dysregulation. In the context of human immunodeficiency virus (HIV) infection, MCD is associated with Kaposi sarcoma-associated herpesvirus, also called human herpesvirus type 8 (KSHV/HHV8). Within a prospective cohort study on 60 HIV-infected patients with MCD, and a median follow-up period of 20 months, 14 patients developed KSHV/HHV8-associated non-Hodgkin lymphoma (NHL): 3 "classic" KSHV/HHV8(+) Epstein-Barr virus-positive (EBV(+)) primary effusion lymphoma (PEL), 5 KSHV/HHV8(+) EBV(-) visceral large cell NHL with a PEL-like phenotype, and 6 plasmablastic lymphoma/leukemia (3/3 KSHV/HHV8(+) EBV(-)). The NHL incidence observed in this cohort study (101/1000 patient-years) is about 15-fold what is expected in the general HIV(+) population. MCD-associated KSHV/HHV8(+) NHL fell into 2 groups, suggesting different pathogenesis. The plasmablastic NHL likely represents the expansion of plasmablastic microlymphoma from the MCD lesion and progression toward aggressive NHL. In contrast, the PEL and PEL-like NHL may implicate a different original infected cell whose growth is promoted by the cytokine-rich environment of the MCD lesions.     

HIV-associated lymphomas and gamma-herpesviruses

Among the most common HIV-associated lymphomas are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with immunoblastic-plasmacytoid differentiation (also involving the central nervous system). Lymphomas occurring specifically in HIV-positive patients include primary effusion lymphoma (PEL) and its solid variants, plasmablastic lymphoma of the oral cavity type and large B-cell lymphoma arising in Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease. These lymphomas together with BL and DLBCL with immunoblastic-plasmacytoid differentiation frequently carry EBV infection and display a phenotype related to plasma cells. EBV infection occurs at different rates in different lymphoma types, whereas KSHV is specifically associated with PEL, which usually occurs in the setting of profound immunosuppression. The current knowledge about HIV-associated lymphomas can be summarized in the following key points: (1) lymphomas specifically occurring in patients with HIV infection are closely linked to other viral diseases; (2) AIDS lymphomas fall in a spectrum of B-cell differentiation where those associated with EBV or KSHV commonly exhibit plasmablastic differentiation; and (3) prognosis for patients with lymphomas and concomitant HIV infection could be improved using better combined chemotherapy protocols incorporating anticancer treatments and antiretroviral drugs.     

HIV and plasmablastic lymphoma manifesting in sinus, testicles, and bones: a further expansion of the disease spectrum

Patients with HIV infection are at increased risk for B-cell neoplasms and plasma cell dyscrasias. Both B cell and plasma cell tumors tend to be intermediate or high grade and are frequently associated with Epstein-Barr virus. Patients with HIV infection are also at higher risk of acquiring plasmablastic lymphoma. Until this time, only sinus, oral gastrointestinal, and lung manifestation have been noted. In this report we describe a 41-year-old male with HIV infection who developed multiple pleomorphic, extramedullary plasmablastic lymphomas associated with Epstein-Barr virus. We review the clinical and immunological features of his malignancy and thereby expand the spectrum of disease to include additional sites (bones, testicles) not previously reported.     

A case of plasmablastic lymphoma of the liver without human immunodeficiency virus infection

Plasmablastic lymphoma(PBL)is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization.Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be observed at extra-oral sites in HIV-negative patients.Epstein-Barr virus(EBV)may be closely related the pathogenesis of PBL.PBL shows different clinicopathological characteristics between HIV-positive and-negative patients.Here,we report a case of PBL of the liver in a 79-yearold HIV-negative male.The patient died approximately1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass.Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs.The neoplastic cells were diffusely positive for CD30,EBV,Bob-1,and CD38.The autopsy findings suggested a diagnosis of PBL.To our knowledge,the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection.     

Regression of colonic low grade B cell lymphoma of the mucosa associated lymphoid tissue type after eradication of Helicobacter pylori

BACKGROUND: Lymphoma of the mucosa associated lymphoid tissue (MALT) arising in the stomach has been shown to be related to Helicobacter pylori infection, and total regression of gastric lymphoma after successful eradication of H pylori has consistently been reported. MALT-type lymphoma at other localisations, however, has to our knowledge not been linked to H pylori, and eradication of the bacteria has not been studied for management of such lymphomas. PATIENT/METHOD: A 67 year old man was diagnosed with MALT-type lymphoma simultaneously involving the stomach and the colon descendens. In addition to the presence of MALT-type lymphoma, H pylori associated chronic gastritis was diagnosed, and treatment with clarithromycin, metronidazole, and omeprazole was initiated, resulting in its successful eradication. RESULTS: Follow up performed four months later showed regression of the colonic manifestation, whereas the gastric lymphoma did not respond to antibiotic treatment, as assessed by regular follow up for 14 months, in spite of its restriction to mucosa and submucosa. The patient was therefore treated with oral cyclophosphamide (100 mg a day) resulting in partial remission after seven months of continuous treatment. Because of the presence of residual lymphoma, additional irradiation was performed, which led to complete remission of the gastric lymphoma. The patient remains in complete remission 40 months after diagnosis and 26 months after initiation of treatment. CONCLUSION: In the case of concurrent gastric and intestinal low grade MALT-type lymphoma, H pylori eradication may cause regression of the intestinal lesion.     

Unusual case of plasmablastic Non-Hodgkin’s lymphoma located in the liver. First case reported in an AIDS patient

Plasmablastic lymphoma is a rare and a relatively new entity that was first described in the jaws and the oral cavity of HIV-AIDS patients. We report a case of plasmablastic lymphoma involving the liver in an AIDS patient. Plasmablastic lymphoma is considered a diffuse large B-cell lymphoma with a unique phenotype and predilection for the oral cavity. The case presented had a unique hepatic lesion, localized in the left lobe of the liver. Diagnosis was confirmed by hepatic biopsy guided by Computerized Tomography scan and histopathology. The smears showed a dense infiltrate composed by atypical lymphocytes with numerous plasmocytes expressing the plasma cell markers MUM-1 and CD138 and negative for the B-cell markers CD3, CD20 and CD45. Immunohistochemical and in situ hibridization revealed the Epstein-Barr virus genome in the atypical cells. Polymerase chain reaction was negative for HHV-8 RNA.     

Plasmablastic Lymphoma of the Small Intestine in an HIV- and EBV-negative Patient

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.     

HIV-associated plasmablastic lymphoma: lessons learned from 112 published cases

Plasmablastic lymphoma (PBL) is a distinct subtype of non-Hodgkin B-cell lymphoma, originally described with a strong predilection to the oral cavity of human immunodeficiency virus (HIV)-infected individuals. Data regarding patient age and gender, HIV status, initiation of and response to highly active antiretroviral therapy (HAART), tumor extent, pathology, treatment, and outcome were extracted from 112 cases of PBL identified in the literature. The median age at presentation was 38 years with a male predominance of 7:1, and the median CD4+ count was 178 cells/mm(3). PBL presented on average 5 years after diagnosis of HIV. Common primary sites of presentation included the oral cavity, gastrointestinal tract, and lymph nodes. Most cases presented with either stage I or stage IV disease. There was a variable expression of B-cell markers in tumor cells, but plasma cell markers were expressed in all cases. EBV was detected in 74%. Chemotherapy was used to treat 55% patients and was combined with radiotherapy in 21% cases. Complete response was obtained in 66% of treated cases; the majority of these responses were seen after CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). The refractory/relapsed disease rate was 54%. Death occurred in 53% of patients, with a median overall survival of 15 months. Sex, CD4+ count, viral load, clinical stage, EBV status, primary site of involvement, and use of CHOP failed to show an association with survival. PBL is an aggressive B-cell lymphoma that presents in both oral and extra-oral sites of chronically HIV-infected immunosuppressed young men.     

Successful treatment of post-kala-azar dermal leishmaniasis (PKDL) in a HIV infected patient with multiple relapsing leishmaniasis from Western Europe

We present a 42-year-old man who was admitted with worsening of his general condition and facial skin lesions. He had previously been diagnosed with HIV infection and visceral leishmaniasis (VL). Diagnostic work-up revealed a new relapse of VL paralleled by the diagnosis of post-kala-azar dermal leishmaniasis (PKDL). The patient was treated with IV liposomal amphotericin B as well as sodium stibogluconate followed by oral hexadecylphosphocholine (miltefosine) over a period of 9 months. PKDL lesions began to disappear after 8 months of treatment. In addition, severe and relapsing VL so far remains in remission. This case demonstrates successful treatment of PKDL and relapsing VL in a Western European patient with HIV infection.     

Pulmonary non-Hodgkin's lymphoma in AIDS

Whereas extralymphatic involvement is common in lymphomas associated with HIV infection, there have been few reports of pulmonary lymphoma. In 648 cases of AIDS reported in Colorado, 40 have had non-Hodgkin's lymphoma. Of these, four have had documented pulmonary involvement and are reported in detail. Clinical manifestations were nonspecific and included fever, weight loss, generalized lymphadenopathy, dyspnea, chest pain and cough. Chest roentgenograms revealed multiple nodules or interstitial infiltrates. Transbronchial biopsy failed to establish the diagnosis in all cases. Three of four patients died four to five months after appearance of pulmonary nodules; one patient with stage IE disease showed slow radiographic progression over 16 months following radiation and chemotherapy and died 18 months after appearance of pulmonary nodules. Pulmonary involvement with lymphoma should be considered in patients with HIV infection, especially if multiple nodules are seen on chest roentgenograms.     

HIV-related non-Hodgkin's lymphoma among European AIDS patients

Abstract: The epidemiology of HIV associated non-Hodgkin's lymphoma (NHL) was investigated in 6550 European patients with AIDS. NHL was diagnosed in 3.5% of all patients at the time of the AIDS diagnosis. Although the probability of being diagnosed with NHL at AIDS diagnosis was significantly higher among intravenous drug users than among homosexual men, and was associated with increasing age, the observed incidences of NHL were more strikingly similar than any differences. The rate of developing NHL after a previous AIDS diagnosis was 2.4 per 100 patient years of follow-up, and remained constant during a 5-year follow-up period. While primary brain lymphomas comprised only 9% of NHL diagnosed at the time of AIDS, they comprised 38% of NHL diagnosed after AIDS (p<0.001). The prognosis for patients with NHL at AIDS diagnosis was poor with a median survival of 5 months. A diagnosis of primary brain lymphoma was uniformly associated with a poor outcome. It is concluded that the probability of developing NHL in late stage HIV infection is lower than previously anticipated from the results of small studies on patients receiving long-term anti-retroviral therapy.     

Regression of primary low-grade mucosa-associated lymphoid tissue lymphoma of duodenum after long-term treatment with clarithromycin

A 74-year-old woman was referred to our department because of epigastralgia. Endoscopic findings revealed yellowish bumpy mucosa from the bulbus to the second portion of the duodenum. The patient was admitted to our hospital for further examinations and treatment for this lesion. Endoscopic mucosal resection (EMR) was performed on part of the lesion to obtain the final diagnosis, and then mucosa-associated lymphoid tissue (MALT) lymphoma of the duodenum was diagnosed using this procedure. In this case, no evidence of Helicobacter pylori infection in the patient's stomach was detected by any of the diagnostic examinations used, such as the urea breath test, histological study, culture, and serological antibody. For this reason, the patient's duodenal MALT lymphoma was treated solely with long-term clarithromycin, which had an inhibitory action on lymphocyte activation. The lesion showed slight improved during the first 12 days of treatment, and complete regression was reached after 6 months of treatment. It is suggested that the long-term use of clarithromycin may be effective for diseases of the gastrointestinal tract associated with the lymphocyte proliferation.     

CD20‐positive plasmablastic lymphoma with excellent response to bortezomib combined with rituximab

As a distinct type of aggressive mature large B‐cell lymphoma, plasmablastic lymphoma (PBL) poses diagnostic and treatment challenges. PBL is distinguished from other B‐cell lymphomas by the presence of plasmacytic differentiation markers such as CD38, CD138, and MUM1. Clinically, PBLs from oral and extra‐oral sites are rapidly progressive tumors with frequent relapse after treatment with standard diffuse large B‐cell lymphoma regimens. Here, we report a near‐complete response of one patient with relapsed PBL following treatment with a non‐cytotoxic regimen containing bortezomib, rituximab, and dexamethasone.     

Combined chemotherapy including high-dose methotrexate in KSHV/HHV8-associated primary effusion lymphoma

Primary effusion lymphoma (PEL) is a rare KSHV/HHV8-associated high-grade non-Hodgkin's lymphoma (NHL) of B-cell origin, characterized by serous effusions in body cavities. Most patients are HIV-infected homosexual men with severe immunosuppression and other KSHV/HHV8-associated diseases such as Kaposi's sarcoma (KS). The prognosis is poor with a median survival of less than 6 months in most cohorts. The achievement of a sustained complete remission is rare. High-dose chemotherapy regimens are warranted to improve complete remission rate and survival. Seven patients with AIDS-associated PEL were treated with a combined chemotherapy including high-dose methotrexate followed by leucovorin rescue. In all cases, KSHV/HHV8 sequences were detected in the effusion samples using quantitative PCR assays. Five patients had a pre-existing KS, associated in three cases with multicentric Castleman's disease (MCD). Upon diagnosis, 6 patients received antiretroviral therapy, which was maintained during chemotherapy in 5 of them. At time of analysis, 3 out of 7 patients were in complete remission 18, 26, and 78 months after PEL diagnosis. Three patients died with a progressive PEL at 22, 67, and 153 days after diagnosis, and 1 patient died 9 months after PEL diagnosis with a MCD-associated plasmablastic NHL. Complete remission was obtained in 3 out of 7 patients treated for AIDS-associated PEL with combined chemotherapy containing high-dose methotrexate.     

Intestinal leishmaniasis and Sézary syndrome: endoscopic diagnosis

Sézary syndrome is a non-Hodgkin's lymphoma of cutaneous origin that provokes severe cellular immunosuppression leading to greater susceptibility to opportunistic infections. We present the case of a male patient with a diagnosis of Sézary syndrome complicated by visceral leishmaniasis and Mycobacterium avium complex coinfection, with intestinal involvement of both pathogens -an exceptional finding in the absence of HIV infection. The diagnosis was confirmed by bone marrow biopsy and oral endoscopy with intestinal biopsy. Because of the severity of the infection and the failure of conventional treatment, miltefosine, a new antiparasitic agent still under investigation, was administered with favorable response. However the patient developed fatal pneumonia.     

An unusual cause of pleural effusion

Primary effusion lymphoma (PEL) is a unique clinicopathological entity associated with human herpesvirus-8 (HHV-8) infection, occurring almost exclusively in human immunodeficiency virus (HIV)-infected individuals. We report a rare case of HHV-8-negative PEL in an HIV-negative elderly patient who presented with pleural effusion. The patient was treated with CHOP and Rituximab. As opposed to the general poor outcome of this disease, our patient achieved complete remission and is still without signs of disease 11 months after the last treatment.