Primary effusion lymphoma associated with type-8 human herpes virus infection

Primary Effusion Lymphoma is an unusual entity and it has been described as a subset associated with human herpes virus 8 infection in homosexual males with AIDS. Its inclusion as a new entity in the Revised European-American Lymphoma Classification has been recommended. The case in which it is presented is a 47-year-old man, diagnosed with AIDS two years ago, who came with Kaposi's sarcoma. Nowadays, he has a right pleural effusion and a thoracentesis has been carried out. We obtain 10 ml of haemorrhagic fluid which is processed by standard methods. The morphologic study reveals a non-Hodgkin's lymphoma of high-grade. The immunophenotypic study shows a lymphoid neoplasm of indeterminate lineage and high proliferation index. It confirms the HHV-8 in the neoplastic cells by PCR. The diagnosis is a non-Hodgkin's lymphoma of high-grade compatible with Primary Effusion Lymphoma.     

Novel association of haemophagocytic syndrome with Kaposi's sarcoma-associated herpesvirus-related primary effusion lymphoma

Haemophagocytic syndrome (HPS) is a fulminant, often fatal, systemic illness that occurs in association with infection and malignancy. We provide the first report of HPS that heralded a primary effusion lymphoma (PEL), a rare neoplasm linked to Kaposi's sarcoma-associated herpesvirus. The patient was a 38-year-old man with acquired immunodeficiency syndrome who presented with fever, sweats, lymphadenopathy, splenomegaly and refractory anaemia. Examination of the spleen demonstrated haemophagocytosis; analysis of ascites revealed PEL. Treatment with chemotherapy and ganciclovir resulted in complete remission of both conditions. This case illustrates the diagnostic challenges posed by HPS and supports the trial of antiviral agents in combination with chemotherapy in patients with PEL.     

Kaposi's sarcoma-associated herpesvirus-infected primary effusion lymphoma has a plasma cell gene expression profile

Kaposi's sarcoma-associated herpesvirus is associated with three human tumors: Kaposi's sarcoma, and the B cell lymphomas, plasmablastic lymphoma associated with multicentric Castleman's disease, and primary effusion lymphoma (PEL). Epstein-Barr virus, the closest human relative of Kaposi's sarcoma-associated herpesvirus, mimics host B cell signaling pathways to direct B cell development toward a memory B cell phenotype. Epstein-Barr virus-associated B cell tumors are presumed to arise as a consequence of this virus-mediated B cell activation. The stage of B cell development represented by PEL, how this stage relates to tumor pathology, and how this information may be used to treat the disease are largely unknown. In this study we used gene expression profiling to order a range of B cell tumors by stage of development. PEL gene expression closely resembles that of malignant plasma cells, including the low expression of mature B cell genes. The unfolded protein response is partially activated in PEL, but is fully activated in plasma cell tumors, linking endoplasmic reticulum stress to plasma cell development through XBP-1. PEL cells can be defined by the overexpression of genes involved in inflammation, cell adhesion, and invasion, which may be responsible for their presentation in body cavities. Similar to malignant plasma cells, all PEL samples tested express the vitamin D receptor and are sensitive to the vitamin D analogue drug EB 1089 (Seocalcitol).     

Hepatosplenic T-cell lymphoma: a distinct clinicopathologic entity of cytotoxic gamma delta T-cell origin

We identified eight cases of T-cell lymphoma with evidence of a gamma delta phenotype over a 13-year period. Seven of these cases conformed to a distinct clinicopathologic entity of hepatosplenic gamma delta T- cell lymphoma. Nearly all of these patients were young adult males (five of seven), with a median age at presentation of 20 years. They presented with marked hepatosplenomegaly, without lymphadenopathy or significant peripheral blood lymphocytosis. Thrombocytopenia was seen in all patients, and five of seven were mildly anemic. The clinical course was aggressive, and despite multiagent chemotherapy, the median survival duration was less than 1 year. The morphologic findings were uniform; a monomorphic population of medium-sized lymphoid cells with moderately clumped chromatin and a rim of pale cytoplasm infiltrated the sinusoids of the spleen, liver, and bone marrow. The cells had a characteristic immunophenotype: CD2+, CD3+, CD4-, CD5-, CD7+, CD16+, CD57-, CD25-, T-cell receptor (TCR)delta +, beta F1-. CD8 was positive in four of seven cases tested, and CD56 was positive in five of six. All cases expressed the cytotoxic granule-associated protein, TIA1, but perforin was detected in only one case. All cases with assessable DNA had a TCR gamma gene rearrangement, and lacked Epstein-Barr virus sequences. Isochromosome 7q was identified in two cases with cytogenetic information. The one case of cutaneous gamma delta T-cell lymphoma differed in its clinical manifestations, histologic appearance, and immunophenotype. We conclude that hepatosplenic gamma delta T-cell lymphoma is a distinct clinicopathologic entity derived from cytotoxic gamma delta T cells, and should be distinguished from other lymphomas of T-cell and natural-killer cell (NK)-like T-cell derivation.     

Convoluted lymphocytic lymphoma in adults: a clinicopathologic entity

Twelve adults had a distinct clinicopathologic type of malignant lymphoma that closely resembles the mediastinal lymphomas of childhood. Nine patients presented with mediastinal masses, and seven had symptoms related to intrathoracic compression. Seven patients presented with or developed leukemia, and in four of these patients the central nervous system (CNS) became involved. Structurally, the tumor cells had a distinctive stippled chromatin pattern, in addition to the characteristic nuclear convolutions. Tumor cells from five patients were studied immunologically, and, in each case, the tumor cells formed rosettes with sheep erythrocytes. The response to combination chemotherapy was rapid and dramatic, but usually transient, with relapse in the CNS or previously involved sites. The above data strongly suggest that these cases represent a distinct clinicopathologic entity that should be treated similarly to childhood leukemia and lymphoma, with intensive multiple agent induction, CNS prophylaxis, possibly radiation therapy to initially involved sites, and prolonged maintenance.     

Establishment and characterization of a Kaposi's sarcoma-associated herpesvirus- and Epstein-Barr virus-negative malignant lymphoma cell line (OHK) with primary effusion lymphoma immunophenotype

A novel cell line, designated OHK, was established from ascites of a 59-year-old Japanese woman with diffuse large B-cell lymphoma showing a peculiar serosal tropism, as seen in primary effusion lymphomas (PEL). OHK exhibited a large pleomorphic morphology with irregular nuclei and distinct nucleoli, and included immunoblastic and Reed-Sternberg-like giant cells. On ultrastructural examination, rich intermediate filaments, and well-developed Golgi apparati and rough endoplasmic reticulum, were seen. Immunophenotypically, OHK lacked T and B cell-associated antigens, and had CD10, CD30, CD33 and CD138 antigens. Although OHK cells did not express immunoglobulin (Ig) protein, Southern blot analysis demonstrated clonal rearrangements of Ig heavy and light chain genes. These observations suggest that OHK cells are derived from preterminally differentiated B cells, and that they have features of PEL. Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus were not detected. OHK displayed hyperploid karyotypes with multiple structural abnormalities, and produced some cytokines such as macrophage-colony-stimulating factor (M-CSF), granulocyte-CSF, interleukin 6 and transforming growth factor beta 1. In particular, vascular endothelial growth factor (VEGF), whose stimulation of vascular permeability is thought to be critical to the pathogenesis of PEL, was also produced in large quantities. These results indicate that OHK may be a useful tool for the investigation of PEL.     

Primary gastric lymphoma: a clinicopathologic study

BACKGROUND/AIMS: This study aims to define the clinicopathologic criteria of primary gastric lymphoma in view of MALT concept and to present the outcome after different treatment modalities. METHODOLOGY: Seventy-six cases of primary gastric lymphoma treated between January 1980 and December 2001 were reviewed. All tissue specimens (endoscopic or surgically resected) were re-examined. Tumors were staged according to Ann Arbor staging system and the Musshoff modification (IE in 30.3%, IIE in 39.4% and IIIE in 30.3%). Sixty patients underwent gastrectomy (partial or total) with postoperative chemotherapy for 32 patients. Sixteen patients were treated by chemotherapy only. The mean follow-up period was 15 years (range, 6 months to 21 years). RESULTS: Primary gastric lymphoma represented 69.1% of cases of gastrointestinal lymphoma and 16.2% of all gastric malignancy. The mean age was 45 years and male to female ratio was 2.3:1. Epigastric pain was the commonest symptom (in 88.2%). Ulcer-like lesions were the commonest (65.8%) and the most commonly involved site was the lower third (48.7%). The resectability rate was 80%. The operative mortality rate was 2.7%. Another 2 cases died after partial gastrectomy and chemotherapy. Four cases in the chemotherapy group (25%) died. Tumor recurrence occurred in 4 cases (out of 32) after gastrectomy and chemotherapy (12.5%), 2 of them died and 2 were cured by chemotherapy. The mean overall survival was 18.49 years, survival was 20.28 years after gastrectomy, 15.48 years after gastrectomy with chemotherapy and 5.76 years after chemotherapy (p=0.0056). CONCLUSIONS: Primary gastric lymphoma is not an uncommon tumor. Gastritis-like lesions are rare. If the tumor is resectable, gastrectomy will provide the most accurate means of diagnosis, staging and locoregional control of the disease.     

Primary pulmonary Hodgkin's disease: a distinct entity

A 30-year-old lady presented with fever, dry cough and weight loss for the preceding five months. Radiological investigations revealed a solitary nodular lesion in the lingula of the left lung. Guided fine needle aspiration cytology failed to yield any diagnostic material. Bronchoscopic cytology was also not contributory. As a last resort open lung biopsy was done and a diagnosis of Hodgkin's disease was made. Hilar and pre aortic lymph node biopsies showed only reactive change. The final diagnosis was primary pulmonary Hodgkin's disease.     

Kaposi's sarcoma-associated herpesvirus (KSHV or HHV8) in primary effusion lymphoma: ultrastructural demonstration of herpesvirus in lymphoma cells

Recent molecular evidence suggests an association with a new herpesvirus, Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8), and primary effusion lymphomas (PELs). PELs have a characteristic morphology, phenotype, and clinical presentation, with malignant effusions in the absence of a contiguous solid tumor mass. We have established a cell line (KS-1) from a KSHV-positive human immunodeficiency virus (HIV)-negative patient with pleural cavity-based lymphoma that was passaged into triple-immunodeficient BNX mice. In contrast to cell lines from body cavity-based lymphomas derived from HIV-positive individuals that contain both KSHV and Epstein Barr viral genome, these cells contain only KSHV, allowing for uncontaminated virologic studies. Ultrastructural examination identified malignant cells with features of late differentiating B cells (immunoblasts). Cells with viral cytopathic effect contained typical 110-nm intranuclear herpesvirus nucleocapsids and complete cytoplasmic virions, confirming the association of PEL with KSHV.     

Eosinophilia-myalgia syndrome. Recognition of a distinct clinicopathologic entity

The eosinophilia-myalgia syndrome is a newly described disorder related to the ingestion of L-tryptophan-containing products. Its presentation may mimic other disorders characterized by eosinophilia and muscle pain and/or weakness, but can be differentiated by certain characteristic laboratory and pathologic findings. We report two such cases, describe their features, and review similar syndromes.     

Healthcare associated infective endocarditis: a distinct entity

The terms hospital- and community-acquired infections do not cover any longer the full spectrum of acquisition of infection. Consequently, the term healthcare associated infection (HCA) has been recently introduced. In order to examine the applicability of 'HCA infection' to patients with infective endocarditis (IE), 125 episodes of culture-positive IE were categorized into 3 groups of acquisition. 14 (11%) of 125 episodes were defined as hospital acquired (HA) IE (onset of more than 72 h after admission), 52 (42%) as HCA (IE on admission in patients with significant previous healthcare contact), and 59 (47%) as community acquired (CA) (IE on admission in people without recent healthcare contact). 41 (77%) of the 53 causative agents in the HCA IE group were typical nosocomial pathogens, whereas these types of pathogens constituted only 22% (14/64) of the microorganisms in the group of CA IE (p<0.0001). Mortality in the HA and HCA groups combined was significantly higher than that in the CA group (19/62, 31%, vs 6/59, 10%, p=0.01). HCA IE should be recognized as a distinct category that constitutes a large proportion of all cases of IE. HCA IE is significantly different from CA IE and, therefore, may require a different therapeutic approach.     

Primary effusion lymphoma with B-cell phenotype

We describe here a case of primary effusion lymphoma that occurred in a 78-year-old woman. She was successively treated with prednisolone but died 15 months after the diagnosis of primary effusion lymphoma. The immunohistochemistry revealed the neoplastic cells to be CD19(+), CD20(+), CD21(+), Sm-Ig(+), and HLA-DR(+). This patient exhibited clonal IgH and clonal kappa light chain gene rearrangement, indicating a B-cell origin. The present case was distinguished from the majority cases of HHV-8-positive primary effusion lymphoma. Here we present clinical details of response to therapy in this case.     

Primary autoimmune myelofibrosis: definition of a distinct clinicopathologic syndrome

Myelofibrosis is characterized by reticulin fibrosis of the bone marrow with resulting features of myelophthisis. Besides hematopoietic malignancies and other neoplasms involving the bone marrow, myelofibrosis has been described in association with autoimmune disorders, especially systemic lupus erythematosus. We describe the clinicopathologic features of a primary form of autoimmune myelofibrosis (AIMF) in patients who do not have systemic lupus erythematosus or another well-defined autoimmune syndrome. Absence of marked splenomegaly, peripheral blood cytopenias with mild teardrop poikilocytosis and leukoerythroblastosis, bone marrow lymphoid aggregates, and presence of autoantibodies are some of the salient features of primary AIMF. AIMF should especially be differentiated from chronic idiopathic myelofibrosis, a neoplastic myeloproliferative disease. Primary AIMF appears to have an excellent prognosis, with all patients reported in this series responding to a short course of corticosteroid therapy.     

Atypical carcinoid of the lung. A distinct clinicopathologic entity

Eleven cases of atypical carcinoid (AC) of the lung were identified during an eight-year period. Their clinical features and treatment responses were contrasted with our experience at Vanderbilt with small cell lung cancer (SCLC) and a literature review of typical bronchial carcinoids (TC). Clinically, there were no features to distinguish AC from TC except for age at diagnosis (59 vs 49 years). Atypical carcinoid was similar to SCLC with respect to many clinical features, although female sex, absence of smoking history and localized disease at presentation were more common in AC. Pathologically, these tumors were distinguished by cellular atypia, necrosis, architectural disorder, or increased mitotic rate in the presence of a recognizable carcinoid pattern. Immunoperoxidase staining revealed no difference between AC and TC or SCLC. Atypical carcinoid of the lung represents a distinct clinicopathologic disease.