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Differentiating HIV-associated non-Hodgkin's lymphomas with similar plasmacellular differentiation.


AIDS-related lymphomas (ARL) are divided by the World Health Organization (WHO) [1] into three main categories:

* Lymphomas also occurring in immunocompetent patients e.g. Burkitt's lymphoma and diffuse large B-cell lymphoma (DLBCL);

* Lymphomas occurring more specifically in HIV-infected patients e.g. primary efFusion lymphoma (PEL), plasmablastic lymphoma and lymphoma arising in HHV8-associated multicentric Castleman's disease;

* Lymphomas also occurring in other immunodeficiency states e.g. polymorphic B-cell lymphomas.

ARL display clinical, phenotypic and molecular heterogeneity [2-8]. However, many show evidence of similar plasmacellular differentiation [4,9]. ARL that take on a plasmacytoid appearance contain lymphoma cells with moderate amounts of basophilic cytoplasm, have eccentric nucleolated nuclei, and occasionally an identifiable perinuclear hof. Plasmacytoid lymphoma cells characteristically lose their B-cell (or T-cell) markers and acquire plasma cell markers. The ensuing difficulty in accurately diagnosing this group of similar ARL frequently translates into management difficulties. Moreover, because of these similarities there has been much confusion in the literature, especially with the emergence of new entities such as plasmablastic lymphoma, extracavitary (solid) variant of PEL, and polyclonal lymphoma [10, 11]. The new WHO classification (of tumours of haematopoietic and lymphoid tissues) divides DLBCL into: (a) those lymphomas not otherwise specified (NOS), such as immunoblastic lymphoma (IBL); (b) specific lymphoma subtypes, like primary DLBCL of the central nervous system (CNS); (c) other variant lymphomas with large B-cells, including plasmablastic lymphoma and PEL; and (d) borderline (unclassifiable) B-cell lymphoma cases, like those that have features intermediate between DLBCL and Burkitt's lymphoma (previously classified as Burkitt-like lymphoma) [12]. New concepts have also materialised, such as the development of microlymphomas from Castleman's disease into frank plasmablastic lymphomas. This article reviews the literature pertaining ro those ARL that share a common plasmacellular differentiation, and underscores the diagnostic clinicopathological features (Table 1) that can be used to help distinguish between them.


Plasma cells are a cellular product of the germinal centre cell reaction and central to humoral immunity. Plasma cells typically mature from antigen-stimulated naive B-cells (CD45+, CD20+) after passing through a germinal centre (Figure 1). When naive B-cells (BCL6-, MUM1-, CD 138-) enter the germinal centre, they become centroblasts (BCL6+, MUM1-, CD138-) that subsequently mature into centrocytes (BCL6+, MUM1-, CD138+) as they undergo immunoglobulin class switching, somatic hypermutation of the immunoglobulin variable genes and mutations of the proto-oncogene BCL6. B-cells that exit the germinal centre begin to differentiate into memory B-cells or plasma cells (BCL6-, MUM1+, CD138+). As BCL6 and PAX5 (master regulators of the germinal centre cell reaction and the B-cell transcriptional programmes, respectively) expression declines, the synthesis of other markers indicative of plasmacellular differentiation including multiple myeloma oncogene-1 (MUM1 or interferon regulatory Factor 4), VS38c, CD38 and CD138 (syndecan-1) increases [5], There is also a concomitant change from surface to cytoplasmic immunoglobulin expression, a reduction in CD45 (leukocyte common antigen or LCA) and CD20 expression in plasma cells. Various ARL may arise from transformed B-cells at the pre-germinal centre, follicular centre, or post-germinal centre stage during this differentiation process. The expression of BCL6, MUM1 and CD138 in these lymphomas corresponds to the stage from which they are thought to develop [13,14]. For example, Burkitt's lymphoma and DLBCL develop from follicular centre B-cells while plasmablastic lymphoma and most cases of PEL arise from post-germinal centre B-cells. Superimposed on this model are molecular events (e.g. MYC activation and p53 inactivation), aberrant somatic hypermutation resulting in mutations of one or more proto-oncogenes (e.g. c-MYC, PAX5, PIM1, RhoH/TTF) [15], and co-infection with Epstein--Barr virus (EBV) and human herpesvirus 8 (HHV8). Moreover, cytokines and highly active antiretroviral therapy (HAART) may further modify lymphomagenesis.



EBV and Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) are members of the gamma-herpes virus subfamily. As is the case with all herpesviruses, their life cycle includes both latent and lytic phases. Both viruses establish persistent latent infection in lymphocytes, which contributes to the transformation process, and helps drive cell proliferation and escape from immune attack [16-22]. Latency is characterised by persistence of the viral genome, restricted virus expression of latent gene products that alter cell growth and proliferation, and retained potential for reactivation to lytic replication. The percentage of ARL cases with these viral infections is variable (Table 1). The 172-kbp EBV genome encodes approximately 100 genes, 10 of which ale expressed during latency including six nuclear proteins (EBNAs 1, 2, 3A, 3B, 3C and LP), two latent membrane proteins (LMP1 and -2), and two EBV-encoded RNAs (EBERs 1 and 2). HHV8, a rhadinovirus, has a 165-kbp genome with more than 80 open reading frames. HHV8 genes encode numerous proteins that are homologous to cell-signalling and regulatory-pathway proteins, such as viral interleukin-6 (vIL-6) and D-type cyclin homologue (vcyc). While in latency, HHV8 exists as circular episomal DNA and expresses limited gene products, including LANA-1 (or LNA-1).


Burkitt's lymphoma accounts for up to 30% of HIV-associated lymphomas [10]. It typically develops in the setting of mild immunodeficiency (CD4+ T-cell count > 200 cells/[mm.sup.3]). HIV-positive persons may develop classical and less frequently atypical Burkitt's lymphoma, as well as Burkitt's lymphoma with plasmacytoid differentiation (Figure 2), which is relatively unique to patients with AIDS [1], Those Burkitt's lymphomas with predominantly plasmacytoid features account for up to two-thirds of ARL [1]. These lymphomas frequently involve the leptomeninges (Figure 3), bone marrow (Figure 4) and peripheral blood. In Africa, HIV-related Burkitt's lymphoma presents with usual facial as well as extrafacial (mainly lymphadenopathy) tumours [23]. A high proliferation index is typical, with >90% of cells staining positive for Ki-67 (Mib-1). Lymphoma cells are medium-sized, non-cleaved lymphocytes that have a deeply basophilic cytoplasm, lipid vacuoles and several nucleoli. In the plasmacytoid variant, lymphoma cells have a more basophilic cytoplasm with an eccentric nucleus and single central nucleolus. They are positive for B-cell-associated antigens (CD19, CD20), CD10 and BCL6, in keeping with a germinal centre stage of differentiation. Frequently, there is also CD38 coexpression [24] and monotypic cytoplasmic immunoglobulin present. Cases with absent immunoglobulins have been noted [25]. All cases have MYC activation and p53 inactivation. ebv genomes can be demonstrated in 30% of classical, 30-50% of atypical, and 50-70% of plasmacytoid Burkitt's lymphomas [26]. EBV protein LMP1 is not expressed in Burkitt's lymphoma, but EBNA-1, which is necessary for the replication and maintenance of the latent viral episomal DNA, is found consistently in Burkitt cells [27]. No association has been found between Burkitt's lymphoma and HHV8 by immunohistochemical analysis, in situ hybridisation and PCRm[28].





Morphological variants of DLBCL (NOS) include:

(a) centroblastic lymphomas (comprising centroblasts with several nuclear membrane-bound nucleoli);

(b) immunoblastic lymphomas (IBL) that, by convention, must contain at least 90% immunoblasts (which have single, central, prominent nucleoli); and (c) CD30+ LBCL with anaplastic features (or histology). Centroblastic lymphomas represent 25-30% of ARL, whereas IBL constitute 10% of ARL [26]. While IBL typically present with advanced HIV disease (CD4+ T-cell count <100 cells/[mm.sup.3]), centroblastic lymphomas may appear with less immunodeficiency. Primary DLBCL of the CNS associated with HIV infection is usually of the immunoblastic type. hiv-associated DLBCL tends to be high grade, with a high proliferation index (but <90%), and may be referred to by some as Burkitt-like lymphomas. Large areas of necrosis are often present. IBL is the variant that most commonly exhibits plasmacytoid features (Figure 5)- Surface and cytoplasmic immunoglobulin can be found in those cases with plasmacytoid features. While immunoblasts typically express pan-B-cell markers (CD20, CD22, CD79a), these markers may be lost in some lymphoma cells. Some cases may also coexpress BCL2, CD5, CD10 and CD30. Whereas rearrangements of BCL6 are detected in around 20% of centroblastic lymphomas, IBL are characterised by an absence of BCL6 rearrangements. EBV is positive in 30% of centroblastic lymphomas (LMP1 negative), but is associated with 90% of IBL (LMP1 positive) [26]. HHV8 has been shown to be associated with some (40%) cases of IBL in HIV-infected patients that lack effusions and do not have evidence of prior Castleman's disease [29-31]. Because these HHV8-bearing IBL cases sttongly resemble solid PEL and contain plasmablastic cells showing plasma cell differentiation, it is plausible that they may not be true IBL.



Plasmablastic lymphoma is a unique ARL that was first described in the jaws and oral cavity (Figure 6) of HIV-infected persons [32-35]- Since then, it has been reported to occur in several other extranodal sites such as the lung [36], mediastinum [37], oesophagus [38], anorectum [39,40], nose and paranasal sinuses [41], skin [42-44], orbit [45], testes and bone [46], breast [47], as well as within long-standing sacrococcygeal cysts [48] in HIV-positive individuals. Nodal involvement occurs but is uncommon [49]. Sinister presentations like spinal cord compression as a result of widespread lymphoma have been reported [50]. While this lymphoma arises mainly in adult HIV-infected males, rare cases involving children has been reported [51,52]. Reactive lymphoid infiltrates in HIV-positive individuals that mimic plasmablastic lymphoma have also been described [53]. Like Burkitt's lymphoma, plasmablastic lymphoma is a rapidly growing destructive tumour [54-56]. The proliferation index ranges from >60% to 95% [57]. They may also evolve into plasmablastic leukaemia in HIV-infected individuals [58]. Only a few cases have been reported with good outcomes after the use of HAART [37,52,59]. Microscopically, they consist of plasmablasts (Figure 7) that have abundant basophilic cytoplasm, eccentrically placed nuclei and occasional perinuclear clearing [60]. Tingible-body macrophages (akin to the 'starry sky' appearance seen with Burkitt's lymphoma) and mitotic figures indicative of a high-grade lymphoma are readily seen [39,61,62]. Based upon data from a recent review of 112 cases [52] of HIV-associated plasmablastic lymphomas, the median age at presentation appears to be 38 years with a male predominance of 7:1, with a median CD4 cell count of 178 cells/[mm.sup.3]. On average, plasmablastic lymphomas tend to present 5 years after the diagnosis of HIV [52]. Their occurrence following HAART-related immune reconstitution has also been documented [63].



Plasmablastic lymphoma has been subdivided into two morphological subgroups [64,65]: (a) plasmablastic lymphoma of the oral mucosa type that comprises a monomorphic population of plasmablasts/immunoblasts with no or minimal plasmacytic differentiation; and (b) plasmablastic lymphoma with plasmacytic differentiation that is composed predominantly of plasm ablasts/ immunoblasts, but in addition exhibits more differentiation with mature plasma cells. Plasmablastic lymphomas usually do not have a predominance of mature plasma cells, which helps to distinguish them from extramedullary plasmacytomas [66]. However, diagnostic difficulty may still arise with extramedullary plasmacytomas (Table 1), particularly those that exhibit anaplastic morphology as may occur in HIV-positive patients [67-69]. Unlike plasmacytoma, patients with plasmablastic lymphoma also do not usually have a serum monoclonal protein and tend to lack significant bone involvement. Compounding the problem, is the fact that plasmablastic lymphoma cells immunoreact only minimally or not at all with CD45 and/or CD20 and PAX5, but demonstrate strong immunoreactivity for the plasma cell markers (Figure 8) VS38c, CD38, IRF4/MUM1 or CD138 [49,70]. By comparison, IBL and Burkitt's lymphoma with plasmacytoid morphology will usually immunophenotype strongly as a B-cell lymphoma. A significant proportion (50-85%) of plasmablastic lymphomas may be immunoreactive for the B-cell marker CD79a [49]. Expression of CD56 may be seen in plasmablastic lymphomas with plasmacytic differentiation. EMA and CD30 are also frequendy positive. Like plasmacytomas, plasmablastic lymphomas may also have focal membranous staining for CD31, a member of the immunoglobulin supergene family of cell adhesion molecules. Cytoplasmic immunoglobulins (mainly IgG) are expressed in 50-70% of cases. It is easy to appreciate why AIDS-related plasmablastic lymphoma is so similar to plasma cell myeloma, given the fact that both neoplasms have virtually an identical tumour suppressor gene expression profde [71]. Recent studies have uncovered structural alterations of the MYC locus in up to 39% of plasmablastic lymphomas [72,73]. In most cases, these correspond to the t(8; 14) translocation, which together with CD10 immunoreactivity strongly mimics Burkitt's lymphoma [74].

Plasmablastic lymphoma differs from plasmacytoma In that EBV appears highly associated with plasmablastic lymphoma but is never detected in plasmacytoma or plasma cell myeloma. EBV EBER in situ hybridisation is positive in 60-75% of cases, but LMP1 and LMP2 are rarely expressed [49]. This is consistent with a restricted latency. The presence of HHV8 in plasmablastic lymphomas is controversial [4,52]. Early immunohistochemistry studies reported that these lymphomas were negative for HHV8 [75]. However, later studies using PCR-based methods showed that HIV-associated plasmablastic lymphomas might harbour HHV8 [76,77]. PCR is not informative about which, or how many, of the tumour cells contain the virus, and the possibility that a positive PCR result might be due to contaminating HHV8-infected non-tumour cells can not be formally excluded. This possibility is suggested by the inability of immunohistochemistry to detect HHV8 LNA in tumours that tested positive by PCR [76]. Not surprisingly, the presence of HHV8 in plasmablastic lymphomas has been disputed by others, based largely upon their findings that these lymphomas lack HHV8 by molecular (DNA-PCR) and immuno-histochemistry (for latency-associated nuclear antigen and viral interleukin-6) studies [78-80]. The demonstration of HHV8 infection by LNA immunohistochemistry in a plasmablastic lymphoma has been suggested by some authors to indicate rather, that it is a solid form of PEL [81], a viewpoint that we share. The association of plasmablastic lymphoma with HHV8 would certainly help explain why some of these lymphomas develop from HHV8-related Castleman's disease [82]. In such cases, HHV8-positive plasmablasts present in Castleman's disease have been shown to coalesce into microscopic aggregates and sheets (Figure 9). These collections of plasmablasts all have similar (lambda) light-chain restriction, and are referred to as microlymphomas [83]. Microlymphomas may arise within the mantle, and less often in the germinal centre of lymphoid follicles [84]. Large sheets of plasmablasts are thought to represent frank lymphoma. Of interest, the new WHO classification now includes large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease (also called HHV8-positive plasmablastic lymphoma) as a distinct entity [85]. This new lymphoma, already previously reported by others [86], corresponds to a naive IgM-producing plasma cell without Ig somatic hyper mutation. Patients with so-called HHV8-positive plasmablastic lymphoma present with profound immunodeficiency, enlarged lymph nodes, massive lymphadenopathy and concomitant Kaposi's sarcoma [85].



PEL is a rare lymphoma that represents approximately 4% of all ARL [1,10,87]. Because of the unique tropism it has for serous cavities of the body, PEL was formerly referred to as a body cavity-based lymphoma [88]. PEL was included as a distinct entity by the WHO in 2001. The classic variant of PEL is characterised by lymphomatous effusions of the pleural, peritoneal, and/or pericardial cavities (Figure 10). In these cases, there is, by definition, usually no tumour mass, lymphadenopathy or organomegaly [89]. Unusual sites of involvement may include the synovial joint and subarachnoid space [90]. While PEL tends to remain localised to the body cavity of origin, tissue extension into the pleura, lung, chest wall, peritoneum, omentum, and gastrointestinal tract may rarely occur. Nodal involvement is unusual [91]. PEL tends to occur as a late manifestation of HIV, which may partly explain why these lymphomas have such a dismal prognosis, often with a median survival of around 3-5 months [92]. Standard Ann Arbor staging for PEL is irrelevant, since all cases are stage IV by definition. Almost half of the patients also have Kaposi's sarcoma. PEL cells are usually large (Figure 11) with pleomorphic cytological features, ranging from immunoblast-like to anaplastic cells [93-94]. Even cells resembling Reed-Sternberg cells can be found in these lymphomas. PEL cells often appear more uniform in histological sections than in cytology specimens. Immunophenotypically, they are CD45 positive, exhibit an indeterminate phenotype (i.e. the majority of cases lack B- and T-cell associated antigens or have a null lymphocyte immunophenorype), have no cytoplasmic or surface immunoglobulin, are positive for CD30 (approximately 75% of cases) and coexpress the plasma cell antigens CD38 (Figure 12), CD138, VS38c and MUM1 [2,3,10]. PEL is of B-cell origin, which can be verified by the presence of clonal Ig gene rearrangements. Nevertheless, cases with an aberrant T-cell phenotype have been reported [95,96]. BCL6 is usually absent. Almost all PEL cells are HHV8 positive, and they are also frequently (-70%) co-infected with EBV (EBER positive, but LMP1 negative) [97-101]. PEL cells may contain 50-150 copies/cell of episomal HHV8 genomes [102]. HHV8, rather than EBV, is the driving force in these tumours. Rearrangement of the immunoglobulin heavy chain gene, and also occasionally the T-cell receptor gene, can be demonstrated. While gene expression profiling has shown PEL to express a gene profile distinct from other lymphomas, the expression of these genes is interestingly shared by multiple myeloma cell lines [103]. This may explain their common plasmacellular phenotype [4].



Solid (tissue-based) HHV8-positive lymphomas, also referred to as extracavitary PEL, are an uncommon lymphoma subtype seen primarily in HIV-positive individuals [104-106]. Solid PEL involves mainly extranodal solid tissues including the lower gastrointestinal tract, lung or skin, but may infrequently demonstrate nodal involvement [107-112]. Like other HHV8-associated lymphomas, solid PEL is often also associated with Kaposi's sarcoma or multicentric Castleman's disease. In rare cases, secondary distant (non-contiguous) lymphomatous effusions may develop [113]. Interestingly, patients who developed solid PEL appear to have a slighdy better survival (median 11 months) than those with classic PEL [106,114]. Apart from their clinical presentation, these lymphomas are virtually identical morphologically, immunophenotypically and genetically to classic PEL [106]. Gene expression profiling studies have also shown a similarity to classic PEL [111]. Solid PEL has a high mitotic rate and, like Burkitt's lymphoma, may be associated with a prominent 'starry-sky' pattern (Figure 13). PEL cells in the solid variant are often immunoblastic in appearance and express CD45, whereas only a subset are positive for B-cell markers and CD138. They seem to express B-cell associated antigens (25%) and immunoglobulin (25%) slightly more often than classic PEL cells (<5% and 15%, respectively) [106]. Lymphoma cells may also express CD30, epithelial membrane antigen (EMA) and HLA-DR. They are negative for CD10 and BCL6. Like classic PEL, extracavitary PEL is universally associated with HHV8. In most cases, they are also co-infected with EBV.





An AIDS-associated lymphoid proliferation ('polyclonal lymphoma') resembling post-transplant lymphoproliferative disorder (PTLD) has been described [115,116].These lymphomas represent less than 5% of ARL [l].They have been reported in lymph nodes and extranodal sites including the lung, parotid gland, perineum and skin [116]. Overall, afflicted patients generally appear to have less widespread disease than those who have systemic ARL. Like PTLD, these proliferations demonstrate a diffuse growth pattern and are composed of a polymorphous population of lymphocytes exhibiting a variable degree of plasmacellular differentiation. The infiltrates range from small cells with plasmacytoid features to immunoblasts with scattered large CD30+ bizarre cells. Admixed mature plasma cells and epithelioid histiocytes are frequently present. Most cases contain a polyclonal population of lymphoid cells together with a smaller subpopulation of monoclonal cells that may be hatd to identify. In these cases, PCR for clonality often reveals only a faint band representing the monoclonal subpopulation of lymphocytes 116]. Most of the cells express a B-cell marker (CD20), with a subset coexpressing kappa or lambda light chains. In addition, several cases are positive for both EBV and HHV8 [116 ]. Like PTLD, these lymphoid proliferations generally lack genetic lesions involving tumour suppressor genes or oncogenes. When clonal rearrangement and cytogenetic abnormalities (e.g. c-MYC, BCL6, and p53 gene mutations) arise, they are usually indicative of transformation to diffuse large B-cell lymphoma [3,116].


ARE encompass a heterogeneous group of lymphomas that, despite the diversification in clinical expression, exhibit similar plasmacellular differentiation. These plasmacytic lymphomas appear to represent the malignant counterpart of a B-cell that has reached a mature stage of development with a shift towards terminal plasma cell differentiation [117] They tend to be aggressive B-cell lymphomas that all display a marked propensity to involve extranodal sites. Most patients present with advanced clinical stage, bulky disease, markedly elevated LDH, and a high tumour burden. Investigations have shown that the underlying genotype in many of these lymphomas is shared by plasma cell myeloma [71,103]. These similarities make the diagnosis of these various entities challenging, which probably accounts for some of the confusion in terminology that exists in the literature [4]. A combination of clinical, morphological, immunophenotypic and molecular findings is often required to adequately differentiate between the various ARL that present with features of plasmacellular differentiation. Prior to making the diagnosis of plasmacytoma or immature plasma cell myeloma in the setting of HIV infection--two neoplasms that are relatively uncommon in HIV-infected patients compared to ARL--lymphomas with prominent plasmacytic differentiation must be excluded. Differentiation of these lymphomas may be regarded as an academic exercise by some, since they all behave aggressively and are currently treated in a similar way. Nevertheless, based upon the emerging literature, it appears that the biological behaviour, prognosis and treatment differ somewhat between these lymphomas. Moreover, a precise nosology of these diseases may be critical in the development and implementation of emerging targeted therapies. Recognition of these entities is particularly important when they lack lymphoid markers and express non-lymphoid markers such as EMA, because they can mimic other non-haematopoietic neoplasms (e.g. undifferentiated carcinoma). Finally, a significant number of these ARL are associated with co-infection by EBV and HHV8. In the presence of HIV-associated immunosuppression, proliferation of EBV- and HHV8-infected lymphocytes goes unchecked. The role of these viruses in lymphomagenesis may provide potential therapeutic targets [118-120]. Further research is still necessary, as we have yet to properly understand why these lymphomas, as a group, behave aggressively in some individuals but not in others [121], or why in some individuals they may even undergo regression [122,123]. Further clinical and experimental studies dealing with these ARL, including cell lines from these lymphomas, are needed that will hopefully shed more light on their pathogenesis and clinical management.



A. Carbone's work is supported by a grant from the Ministero della Salute (Rome, Italy) within the framework of the Progetto Integrato Oncologia-Advanced Molecular Diagnostics Project (RFPS-2006-2-342010.7, A.C.).


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(1) Department of Pathology, Baysrate Medical Center, Tufts School of Medicine, Springfield, USA

(2) Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA

(3) Department of Pathology and Laboratory Medicine, Istituto Nazionale Tumori, Milan, Italy

(4) Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA

Correspondence to; Liron Pantanowitz, Department of Pathology, Baystate Medical Center, 759 Chestnut Street, Springfield, MA, 01199, USA. (email:
Table 1: Comparison of AIDS-related lymphomas with plasmacellular
differentiation, Plasmacytoma is included for comparison purposes.
(Adapted from [4].)

 Plasmacytoid DLBCL immunoblastic
Lymphoma type Burkitt's lymphoma lymphoma

CD4 cell count Normal--low (>200) Very low (<100)

Common Mainly extranodal Nodal and extranodal
presentation (incl CNS)

Tumour cell size Intermediate Large

CD45 (LCA) Positive Positive

CD20 Positive Positive (may be lost)

BCL6 Positive Occasional positive

Other positive CD10 CD10
markers CD30
 CD5 rare

CD138 Negative Negative

CD38 Weak positive Negative

MUM1 Negative Occasional positive

Proliferation Very high (>90%) High (<90%)
index (Ki-67)

Paraprotein Absent Absent

EBV Positive (60%) Positive (100%)

HHV8 Negative Some positive

Genetic features MYC activation p53 mutation and MYC
 p53 inactivation rearrangement

Lymphoma type Plasmablastic lymphoma Classic PEL

CD4 cell count Low Very low (<100)

Common Nodal and extranodal Effusions

Tumour cell size Small--large Large

CD45 (LCA) Positive (may be lost) Positive

CD20 Positive (may be lost) Rare positive

BCL6 Rare positive Rare positive

Other positive CD10 CD30
markers CD31 CD71
 CD56 CD31

CD138 Positive Positive

CD38 Positive Positive

MUM1 Positive Positive

Proliferation High (75-95%) High (>80%)
index (Ki-67)

Paraprotein Absent Absent

EBV Positive (80%) Positive (90%)

HHV8 Controversial positive Positive

Genetic features MYC activation Rare chromosome
 p53 overexpression abnormalities

Lymphoma type Solid PEL Polyclonal lymphoma

CD4 cell count Low (<200) Low (<20O)

Common Extracavitary Nodal and extranodal

Tumour cell size Large Variable

CD45 (LCA) Positive Positive

CD20 Positive (may be lost) Positive

BCL6 Negative Rare positive

Other positive CD30 CD43
markers EMA

CD138 Positive Not reported

CD38 Positive Not reported

MUM1 Not reported Not reported

Prol iteration High Variable
index (Ki-67)

Paraprotein Absent Absent

EBV Positive (90%) Positive

HHV8 Positive Some positive

Genetic features Occasional p53 p53 mutation
 positive cells (minority)

Lymphoma type Plasmacytoma

CD4 cell count Normal--low

Common Bone (solitary) and
presentation extramedullary

Tumour cell size Small--intermediate

CD45 (LCA) Positive

CD20 Rare positive

BCL6 Negative

Other positive Rare CD10
markers CD31

CD138 Positive

CD38 Positive

MUM1 Positive

Proliferation Low
index (Ki-67)

Paraprotein Present (25%)

EBV Negative

HHV8 Controversial

Genetic features MUM1/IRF4

PEL, primary effusion lymphoma; LCA, leukocyte common antigen;
EMA, epithelial membrane antigen.
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Title Annotation:LEADING ARTICLE
Author:Pantanowitz, Liron; Pihan, German; Carbone, Antonino; Dezube, Bruce J.
Publication:Journal of HIV Therapy
Article Type:Report
Geographic Code:1USA
Date:Jun 1, 2009
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