If the current HAART regimen caused no toxicity, less than 10% of naïve patients discontinue their first HAART regimen because of failure after 1 year from starting therapy.

Combination CHT-RT is superior to RT alone. Patients treated with primary CHT containing HD-MTX exhibited improved survival. In these patients, the addition of HD-cytarabine was associated with a better survival, whereas intrathecal CHT was not correlated to outcome. RT may be unnecessary in patients achieving complete remission after receiving HD-MTX-based primary CHT.

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PEL is a rare HIV-associated NHL type occurring as a late manifestation of HIV infection with a poor clinical outcome and a shorter overall survival compared with CBCL patients.

Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).

Primary effusions presenting as the sole lymphoma localization are also known as body-cavity-based-lymphoma (BCBL), and have been shown to carry Kaposi's sarcoma herpesvirus (KSHV) DNA sequences. The aim of this study was a comparative analysis of the clinical, pathologic and molecular features of BCBL and lymphomatous effusions secondary to tissue-based lymphomas occurring both in the general population and in HIV-1-infected individuals. All the lymphomatous effusion samples (seven AIDS-related and nine AIDS-unrelated) were subjected to an identical multiparameter investigation, including collection of clinical data, analysis of morphology and immunophenotype, as well as the study of viral sequences and genetic lesions. In six cases defined as BCBL (four AIDS-related and two AIDS-unrelated), the patients exhibited exclusive or predominant involvement of the body cavities. BCBL tended to display indeterminate phenotypes (4/6), whereas all AIDS-related and AIDS-unrelated lymphomatous effusions secondary to tissue-based lymphomas consistently expressed B-cell phenotype. Detection of KSHV DNA sequences was restricted to cases of BCBL (3/4 AIDS-related and 1/2 AIDS-unrelated), whereas EBV association (3/4) and expression of EBV-encoded antigens (LMP-1, 2/3; EBNA-2, 1/3) were confined to the AIDS-related BCBL. Overall, our results confirm that both AIDS-related and AIDS-unrelated BCBL preferentially associate with peculiar clinical, immunophenotypic and molecular features among lymphomatous effusions and therefore should be singled out as a specific clinico-pathologic entity.

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IntroductionMantle cell lymphoma (MCL) is a distinct B-cell non-Hodgkin lymphoma whose normal counterpart is likely represented by pre-germinal center, naive B cells that populates the mantle zone of lymph nodes. 1 MCL is characterized by advanced stage at presentation, frequent extranodal localization, and aggressive clinical behavior, with poor response to conventional therapeutic regimens and a very unfavorable prognosis, even when the disease is treated with high-dose therapy and autologous bone marrow transplantation. 1 More than 95% of MCLs show the t(11;14) (q13;q32) translocation, which results in a juxtaposition of the CCND1 gene locus to the immunoglobulin heavy chain promoter and the subsequent cyclin D1 overexpression, 1,2 leading to the deregulation of the cyclin D/Rb pathway. Cyclin D1 deregulation, however, is not sufficient for lymphomagenesis; cooperation with microenvironmental stimuli, such as IL-4, IL-10, and CD40 activation, as well as additional genetic changes, are probably required to induce and sustain the transformed phenotype of mantle cells. Indeed, defects involving inhibitors of G 1 cell-cycle progression, such as p53, p27 Kip1 , p16 INK4a , and p15 INK4 , may also occur in MCL. 3,4 More recently, gene-expression profiling and proteomic studies demonstrated that MCL cells carry a profound deregulation of multiple genes and pathways that are involved in the control of cell growth and survival. 5,6 Despite these advances, however, only limited information is available on the mechanisms responsible for the constitutive activation of critical signaling pathways and their functional significance. Elucidation of these issues is of particular relevance to identify and exploit tumor-specific molecular signatures for new treatment strategies.Among the signaling pathways that may be deregulated in MCL cells, the phosphatidyl-inositol-3 kinase (PI3-K)/Akt pathway has recently attracted great interest as a possible therapeutic target. The PI3-K pathway is activated by a wide range of tyrosine kinase growth factor receptors and is the major activator of Akt, a serine/threonine protein kinase that modulates the function of a variety of downstream substrates involved in the regulation of cell-cycle progression, differentiation, transcription, translation, cell survival, and angiogenesis. Activation of PI3-K generates the membrane lipid phosphatidylinositol-trisphosphate (PIP3), which favors the recruitment of Akt to the plasma membrane, where the Akt kinase is activated upon phosphorylation by 3-phosphoinositide-dependent protein kinase-1 (PDK-1). Akt activation is counteracted by PTEN, a lipid phosphatase that dephosphorylates PIP3, whose expression is lost in a variety of tumor cells. 7 Moreover, recent evidence also indicates that PTEN can be inactivated by phosphorylation of serine 380/threonine 382/383 on its carboxy-terminal regulatory domain. [8][9][10] Nevertheless, the role of phosphorylated PTEN in human tumors has been poorly investigated so far. Submitted July 26, 2007; accepted Marc...