[Plasmablastic lymphoma presenting with plasmacytosis and polyclonal hypergammopathy].

A 72-year-old woman presented with generalized lymphadenopathies and plasmacytosis accompanied by polyclonal hypergammopathy. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG accumulation in the systemic lymph nodes, spleen, and multiple bones. Human immunodeficiency virus antibody was negative. Lymph node histologic findings showed a monotonous population of plasma cells with a starry-sky appearance. The cells were positive for CD19, λ, and Epstein-Barr virus-encoded RNA, and negative for CD20 and CD56. The MIB-1 index was 80%. A diagnosis of plasmablastic lymphoma with plasmacytosis and polyclonal hypergammopathy was made, and complete metabolic response was achieved after six cycles of dose-adjusted-EPOCH therapy (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin).

Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.

Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.

Identification of Potential Therapeutic Targets for Plasmablastic Lymphoma Through Gene Expression Analysis: Insights into RAS and Wnt Signaling Pathways.

Plasmablastic lymphoma (PBL) is a rare and aggressive B-cell lymphoma with overlapping characteristics with diffuse large B-cell lymphoma (DLBCL) and multiple myeloma. Hyperactive Wnt signaling derails homeostasis and promotes oncogenesis and chemoresistance in DLBCL and multiple myeloma. Evidence suggests active cross-talk between the Wnt and RAS pathways impacting metastasis in solid cancers in which combined targeted therapies show effective results. Recent genomic studies in PBL demonstrated a high frequency of mutations linked with the RAS signaling pathway. However, the role of RAS and Wnt signaling pathway molecule expression in PBL remained unknown. We examined the expression of Wnt and RAS pathway-related genes in a well-curated cohort of PBL. Because activated B cells are considered immediate precursors of plasmablasts in B cell development, we compared this data with activated B-cell type DLBCL (ABC-DLBCL) patients, employing NanoString transcriptome analysis (770 genes). Hierarchical clustering revealed distinctive differential gene expression between PBL and ABC-DLBCL. Gene set enrichment analysis labeled the RAS signaling pathway as the most enriched (37 genes) in PBL, including upregulating critical genes, such as NRAS, RAF1, SHC1, and SOS1. Wnt pathway genes were also enriched (n = 22) by gene set enrichment analysis. Molecules linked with Wnt signaling activation, such as ligands or targets (FZD3, FZD7, c-MYC, WNT5A, WNT5B, and WNT10B), were elevated in PBL. Our data also showed that, unlike ABC-DLBCL, the deranged Wnt signaling activity in PBL was not linked with hyperactive nuclear factor κB and B-cell receptor signaling. In divergence, Wnt signaling inhibitors (CXXC4, SFRP2, and DKK1) also showed overexpression in PBL. The high expression of RAS signaling molecules reported may indicate linkage with gain-in-function RAS mutations. In addition, high expression of Wnt and RAS signaling molecules may pave pathways to explore benefiting from combined targeted therapies, as reported in solid cancer, to improve prognosis in PBL patients.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

From the archives of MD Anderson Cancer Center: Plasmablastic lymphoma presenting as a kidney mass in an immunocompetent patient: Case report and literature review.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare, aggressive large B-cell lymphoma with plasmablastic or immunoblastic morphology and a terminally differentiated B-cell immunophenotype. PBL often presents at extranodal sites, commonly the oral cavity of immunocompromised patients with human immunodeficiency virus (HIV) and/or Epstein-Barr virus (EBV) infection. Cases of PBL arising outside the oral cavity in previously healthy immunocompetent patients are rare. CASE REPORT: We report a 65-year-old HIV- and EBV-negative man who presented with abdominal pain, fatigue, and vomiting. Imaging studies showed a 30 × 18 cm bulky lobulated mass located within the left kidney with surrounding para-aortic lymphadenopathy. Serum and urine protein electrophoresis revealed a monoclonal gammopathy of IgA lambda type. Biopsy of the mass showed PBL. Bone marrow lumbar puncture evaluations also showed evidence of PBL. The patient was treated with chemotherapy and radiation with initial improvement; however, he died 14 months after initial diagnosis. CONCLUSIONS: Based on our literature review, this case of PBL is one of the few reported to present as a kidney mass in immunocompetent, HIV- and EBV-negative patient. Distinguishing PBL from plasma cell myeloma (PCM) can be challenging. Knowledge of clinical features including presence of CRAB (hypercalcemia, renal failure, anemia, bone lesions) or bone marrow infiltration by mature clonal plasma cells is helpful to establish a diagnosis of PCM. Genetic features of PCM (typical translocations or mutations) also can be helpful in distinguishing plasmablastic transformation of PCM and from PBL. The case we report also highlights the need for more studies to identify specific immunohistochemical and molecular markers to improve PBL diagnosis in immunocompetent patients.

Primary plasmablastic lymphoma of the gastrointestinal tract: A series of 13 HIV-negative cases and a review of literature.

CONTEXT: Primary gastrointestinal plasmablastic lymphoma (GI-PBL) is a rare variant of diffuse B-cell lymphoma with an aggressive clinical course. PBL was initially reported among HIV-positive patients; however, subsequent studies have shown that it also occurs among HIV-negative patients. Its clinical characteristics remain poorly understood. This study aims to retrospectively analyze the clinicopathological findings of primary GI-PBLs in HIV-negative patients. DESIGN: Primary HIV-negative GI-PBL cases from 2008 to 2022 were reviewed. Clinicopathologic features and outcomes were analyzed. RESULTS: The cohort of 13 patients had a male-to-female ratio of 9:1 (3 patients' genders not available), with an average age of 61 (range, 30-92) years. The most involved location was the colon (n = 7 [53.8 %]), followed by the small bowel (n = 3 [23.1 %]), stomach (n = 2 [15.4 %]), rectum (n = 1 [7.7 %]), and anus (n = 1 [7.7 %]). Most patients (n = 10 [77 %]) showed isolated GI tract involvement. Eight patients had chronic inflammatory and/or immunocompromised status, including 4 with inflammatory bowel disease (all of whom underwent treatment), 3 with post-organ transplant status, and 1 with irritable bowel syndrome. All cases exhibited cytokeratin-/CD20-/PAX-5-/CD138+ and/or MUM1+ immunophenotype. Based on available data, 8 of 11 (72.7 %) patients had Epstein-Barr virus reactivation. Among 11 patients with follow-up data, the mean follow-up duration was 13.5 (range, 3-40) months; at the end of follow-up, 45.5 % of patients (5 of 11 patients) showed complete remission after chemotherapy. CONCLUSION: Primary HIV-negative GI-PBL occurs predominantly in the colon of relatively elderly males with immunosuppression. Its clinical course can be heterogenous, presenting a comorbidity with inflammatory bowel disease or post-organ transplantation status.

[Plasmablastic lymphoma presenting clinical symptoms similar to plasmablastic myeloma].

A 75-year-old man developed multiple head masses as well as a compression fracture. His blood test revealed elevated immunoglobulin G (IgG) protein levels, and immunofixation electrophoresis revealed the presence of monoclonal IgGκ. Furthermore, positron emission tomography/computed tomography revealed multiple bone lesions, although bone marrow examination revealed only 1.2% of plasma cells. Biopsy of a head mass led to the diagnosis of plasmablastic lymphoma (PBL), an aggressive B-cell lymphoma with plasma cell phenotypes but no B-cell antigen expression. Because the tumor cells have plasmablastic morphologies, it is difficult to distinguish PBL from plasmablastic myeloma, which is a subtype of multiple myeloma. Both diseases have similar immunophenotypes and clinical courses. In this case, PBL was finally diagnosed based on Epstein-Barr virus positivity, and the patient made a complete recovery after treatment with DA-EPOCH.

Clinicopathological characteristics and long-term outcomes of plasmablastic lymphoma in British Columbia.

Plasmablastic lymphoma (PBL) is an aggressive and rare subtype of non-Hodgkin lymphoma with no standard-of-care therapy. We reviewed all patients diagnosed with histologically confirmed PBL in British Columbia, Canada between 1997 and 2019. Overall, 42 patients were identified, including 15 (36%) positive for HIV and nine (21%) on chronic immunosuppression. Curative-intent treatment consisting primarily of cyclophosphamide, doxorubicin, vincristine and prednisone was administered to 31 patients, of which 74% achieved response, however 61% relapsed after a median of 7.5 months. At a median follow-up of eight years for the whole cohort, five-year progression-free survival (PFS) and overall survival (OS) were 18% [95% confidence interval (CI): 6%, 30%] and 22% (95% CI: 8%, 36%) with median eight and 15 months respectively. There were no differences in relapse rate (p = 0.962), PFS (p = 0.228) or OS (p = 0.340) according to immune status. For those treated with curative intent, five-year PFS and OS were 24% (95% CI: 8%, 40%) and 31% (95% CI: 13%, 49%) with median 18 and 27 months respectively. In this population-based cohort of PBL patients spanning 20 years, survival outcomes were poor. Ultimately, further research is needed to develop more effective treatment strategies and to improve survival for patients.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

HIV-associated plasmablastic lymphoma: A single-centre 12-year experience in Kwa-Zulu Natal, South Africa.

OBJECTIVE: To describe the clinical profile and outcome of patients with HIV-associated plasmablastic lymphoma (PBL) treated with cyclophosphamide, doxorubicin, oncovin, prednisone (CHOP) chemotherapy in a tertiary hospital in KwaZulu-Natal, South Africa. METHODS: This 12-year retrospective clinical chart review, from 2006 to 2018, of patients with PBL treated with CHOP chemotherapy describes their clinical presentation, complete response (CR), progression-free survival (PFS) and disease-free survival (DFS). Response to salvage chemotherapy was also assessed, as was the overall survival (OS). RESULTS: Of 26 patients included in the study, PBL was the presenting manifestation of underlying HIV infection in 58% (n = 15). The median age was 35 years (range 13-49), and 62% (n = 16) were males. The median CD4 count was 285 cells/µL (range 45-863). All patients had extranodal disease, with 4% having bone marrow involvement (n = 1) and > 60% presenting with advanced stage and high-risk PBL. Central nervous system (CNS) involvement was present in 15% (n = 4). A CR was attained in 46% (n = 12). The median DFS was 23.5 months (range 5-91 months), with an overall 2-year survival of 42% (n = 11). CONCLUSIONS: Patients with PBL had a low CR with CHOP chemotherapy and poor OS. Use of alternative chemotherapy regimens needs to be investigated to optimally manage this aggressive lymphoma. The surprisingly low incidence of marrow involvement is the focus of ongoing local research.

Oral versus extra-oral plasmablastic lymphoma: A comparative analysis of 101 cases.

AIMS: Originally described exclusively orally in HIV-infected patients, plasmablastic lymphoma (PBL) is increasingly described extra orally and in non-HIV-infected persons. The study comparatively analysed the clinico-pathologic features of oral PBLs (n = 55) to previously published extra-oral PBLs (n = 45 + 1) diagnosed over a seven-year period at the same institution in an HIV prevalent setting in South Africa in order to clarify any distinction between oral and extra-oral PBLs. METHODS AND RESULTS: Tumours were assessed histologically and immunohistochemically with CD45 (LCA), CD3, CD20, CD79a, PAX5, CD138, MUM1, BLIMP1, VS38c, Ki-67, BCL6 and CD10 using standard protocols. Age ranged from 22 to 76 years (oral) and 9 and 59 years (extra-oral). Most PBL patients were HIV positive [oral (84%); extra-oral (65%)]. Male:female ratio was 2.7:1 for oral and 1.4:1 for extra-oral PBLs. Favoured oral and extra-oral sites were the maxilla and anus. PBLs displayed an indistinguishable immunohistochemical profile with unusually high CD45 expression (oral: 98%, extra-oral: 84%). EBV assessed by chromogenic in situ hybridisation (ISH) showed positivity in all oral PBLs and 95% extra-oral PBLs. MYC rearrangements (fluorescence ISH MYC break-apart probe) were similar in all the PBLs. CONCLUSIONS: Extra-oral PBL is identical to its oral counterpart in gender and age distribution, HIV status, morphological appearances, immunophenotypic profile and EBV association. PBL should be regarded as the same tumour irrespective of oral or extra-oral site of origin.

Primary adrenal plasmablastic lymphoma presenting as lymphomatous meningitis - A diagnostic perplexity.

A rare presentation of primary plasmablastic lymphoma (PBL) of the adrenal gland, as lymphomatous meningitis in a patient living with HIV.

[Long-term complete remission of HIV-negative primary testicular plasmablastic lymphoma treated with bortezomib in combination with EPOCH].

Plasmablastic lymphoma (PBL) is a rare variant of diffuse large B-cell lymphoma that is frequently associated with HIV infection or other immunodeficiencies. We present a case of HIV-negative primary testicular PBL with long-term complete remission (CR) and successful treatment with bortezomib in combination with EPOCH (V-EPOCH). Because of rapidly increasing right testicular swelling, an 86-year-old man without immunodeficiencies was admitted to our hospital. Following that, a right high orchiectomy was performed. Histopathological and immunohistochemical analyses revealed diffuse infiltration of plasmablastic lymphocytes, which were positive for CD38, CD138, CD56, MUM1, lambda, EBER, and MYC respectively, but negative for CD20. The MIB-1 index was 90%. FDG abnormal uptake was discovered on PET/CT at systemic lymph nodes. There was no abnormal cell infiltration in either the bone marrow or cerebral spinal fluid. He was diagnosed with PBL, clinical-stage IIIE-A, IPI high-intermediate risk. He achieved durable CR more than 30 months after the diagnosis after six courses of V-EPOCH, followed by intrathecal prophylaxis (IT) and adjuvant radiation therapy (total 30 Gy). Although PBL shows an aggressive clinical course and poor prognosis, adequate therapeutic approaches for PBL have not been established due to the rarity of this disease. According to our findings, V-EPOCH combined with IT and adjuvant radiotherapy appeared to be feasible and effective as a frontline treatment for elderly patients with primary testicular PBL.

[HIV-negative plasmablastic lymphoma sustaining long-term response after autologous peripheral blood stem cell transplantation].

The patient is a 34-year-old HIV antibody-negative female with normal immunocompetence. The patient was referred to the hospital of the current study due to diarrhea and abdominal pain, which developed in May 2014. On conducting computed tomography (CT), remarkable wall thickening was noted in the terminal ilium over the ascending colon, suggesting a malignant tumor. However, making a definite diagnosis by lower gastrointestinal endoscopic biopsy and left hemicolectomy was not possible. The dense proliferation of plasma cell-like cells and plasmablasts was noted; CD20, CD19, CD79a, CD3, CD4, and Epstein-Barr virus-encoded miRNAs (EBER) were negative and CD138 was positive on immunostaining. Based on the aforementioned data, the patient was diagnosed with plasmablastic lymphoma (PBL). High-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (PBSCT) was performed in the first remission period after the completion of four cycles of hyper CVAD/MTX-AraC alternating therapy. Remission was confirmed by FDG-PET/CT 3 months after autologous PBSCT. No signs of recurrence have been observed in 6 years after the transplantation. Although no standard treatment for PBL has been established, autologous peripheral blood stem cell transplantation combined with high-dose chemotherapy during the first remission period may be a beneficial treatment option.

Plasmablastic lymphoma in Johannesburg, South Africa, in the era of widescale antiretroviral therapy use.

OBJECTIVES: Plasmablastic lymphoma (PBL) is a clinically aggressive lymphoma which has a predilection for extranodal sites and is frequently HIV-associated. The incidence of non-Hodgkin lymphoma is thought to be reduced by widescale antiretroviral therapy (ART) coverage, but the literature is sparse as regards the impact of ART on the incidence of PBL and its outcomes in South Africa (SA). This study aimed to compare factors of interest in cases of PBL diagnosed before and after the widespread availability of ART in Johannesburg, SA. METHODS: All cases of PBL diagnosed in the state sector hospitals of Johannesburg in 2007 and 2017 (before and after the widespread availability of ART, respectively) were extracted from the laboratory information system, and factors of interest compared. RESULTS: The majority (> 95%) of cases of PBL were seen among people with HIV infection (PWH) at both time-points, and the proportion of patients on ART and with virological suppression (VS) increased significantly in 2017. However, the number of cases of PBL did not differ significantly between the two years assessed, comprising 46/397 (11.6%) and 53/582 (9.6%) of all lymphomas in 2007 and 2017, respectively (P = 0.23). Ongoing risk for PBL among PWH with virological control and immunological recovery was evident in 2017, as 18.9% of the patients had both VS and CD4 counts > 200 cells/µL at diagnosis. Inferior survival times were associated with elevated lactate dehydrogenase (LDH) levels and Epstein Barr virus (EBV) negativity, but were not influenced by the presence of AIDS, ART or VS. EBV negativity was significantly associated with VS, and appeared to flag a particularly aggressive form of the disease. CONCLUSIONS: Widescale ART coverage has not reduced the incidence of PBL in Johannesburg, and an ongoing risk for this disease among PWH with adequate virological control and immunological recovery persists.

MYC status in HIV-associated plasmablastic lymphoma: dual-colour CISH, FISH and immunohistochemistry.

AIMS: We utilised chromogenic and fluorescence in-situ hybridisation (CISH and FISH) to evaluate MYC gene copy numbers and rearrangements within HIV-associated plasmablastic lymphomas (PBLs). Thereafter, clinicopathological features were explored retrospectively. METHODS AND RESULTS: Sixty-seven (n = 67) patients were included and the HIV seropositive status was confirmed in 98% (63 of 64) with a median viral load of 55 587 (IQR 273 582) copies/ml and median CD4 count of 170 (IQR 249) cells/µl. The mean age was 41 ± 10.1 years and females comprised 54%. PBL was documented predominantly at extra-oronasal topographic regions. Starry-sky (SS) appearance was evident in 33% in association with monomorphic morphology (P-value 0.02). c-MYC protein was expressed in 81% and latent EBV infection was detected in 90%. EBER ISH-positive status and MYC rearrangement occurred in 67% of HIV PBL. MYC aberrations included MYC rearrangement (70%), low-level increase in MYC gene copy numbers (43%), concurrent MYC rearrangement and increased MYC gene copy numbers (49%) as well as low-level chromosome 8 polysomy (6%). MYC aberrations in HIV PBLs were significantly associated with SS appearance (P -0.01), monomorphic morphology (P - 0.03), c-MYC protein expression ≥40% (P - 0.03) and mortality (P - 0.03). There was advanced stage (Ann Arbor III/IV) at presentation (77%) and the median overall survival for HIV PBL was 75 days (95% CI 14-136). CONCLUSION: Majority of the HIV-associated PBL tumours harbour MYC aberrations. Due to the persistently inferior survival outcome of HIV-associated PBL in the era of antiviral treatment, targeted and/or intensified therapy of oncogenic MYC may need to be explored in future.

Cytokeratin expression in plasmablastic lymphoma - a possible diagnostic pitfall in the routine work-up of tumours.

AIMS: Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoma that frequently arises at extranodal sites in the setting of immunosuppression. The diagnosis of PBL is complex, owing to a frequent solid or cohesive growth pattern, and an often unusual immunophenotype. Several case reports have described cytokeratin (CK) expression in PBL, introducing a diagnostic pitfall. The aim of this study was to determine the frequency of CK expression in PBL in the largest series available to date. METHODS AND RESULTS: By using immunohistochemistry in a cohort of 72 PBLs, we identified CK8/18 positivity in 11 of 72 cases (15%) and AE1/3 positivity in six of 65 cases (9%), clearly contrasting with a control series of non-PBL aggressive B-cell lymphomas (one of 96 diffuse large B-cell lymphomas), as well as with data in the literature describing only occasional CK expression in haematological neoplasms. CONCLUSIONS: Our data indicate CK expression in a substantial number (15%) of PBLs. In view of the particular morphological features of PBL and its frequent negativity for the common leukocyte antigen and B-cell markers, this feature represents a pitfall in the routine diagnostic work-up of PBL, and requires more extensive immunohistochemical and molecular characterisation of cases entering the differential diagnosis.

Oral plasmablastic lymphoma: A clinicopathological study of 113 cases.

BACKGROUND: Plasmablastic lymphoma (PBL) is an aggressive neoplasm that commonly develops in HIV-positive patients, usually affecting the oral cavity. EBV is present in the majority of cases, therefore, playing an important role in the pathogenesis of this neoplasm. METHODS: PBL diagnosed from 2000 to 2020 were retrieved from the archives of the Department of Oral Pathology and Oral Biology at the University of Pretoria, South Africa. The patients' clinical information including gender, age, tumour location and HIV status was obtained from the original histopathology request forms. A morphological description was assessed using H&E-stained slides, with diagnoses confirmed by immunohistochemistry, and EBV detection performed via in situ hybridisation. RESULTS: During the 20 years period investigated, 113 PBL were found. Males outnumbered females (M:F ratio of 3:1), with a median age of 41 years (range 8-62). The gingiva (50 cases or 44.2%) and the palate (23 cases or 20.4%) were the most affected sites. All cases with available information were HIV positive. The tumours were composed of a diffuse proliferation of immunoblasts or plasmablasts in all cases. A starry-sky pattern, tissue necrosis, cellular pleomorphism and mitotic figures were common microscopic findings. IHC for CD3 and CD20 were negative in all cases, while positivity for CD38, CD138 and MUM1 was observed in 70.2%, 79.2% and 98.9%, respectively. EBV was present in 100% of the cases. CONCLUSION: PBL is a frequent diagnosis in South Africa, due to the country's HIV burden, where it usually affects the oral cavity and is always associated with EBV infection.

High incidence of MYC rearrangement in human immunodeficiency virus-positive plasmablastic lymphoma.

AIMS: MYC rearrangements are the main cytogenetic alterations in plasmablastic lymphoma (PBL). We aimed to investigate the relationship between MYC rearrangement and the clinicopathological features of PBL. METHODS AND RESULTS: MYC rearrangements assessed in 13 unpublished single-centre PBL cases, and an additional 85 cases from the literature, with reported MYC rearrangement information individualised by patient, were reviewed. In Asia, PBL was much less commonly diagnosed in human immunodeficiency virus (HIV)-positive patients (27% versus 84%, P = 0.000), with older age (median age at diagnosis: 52 years versus 44 years, P = 0.046) and a lower EBV infection rate (56.8% versus 81.8%, P = 0.049), than in non-Asian regions. Overall, MYC rearrangements were identified in 44 of 98 (44.9%) PBL cases, and IGH was the partner in almost all available cases (30/31, 96.8%), as confirmed with a MYC-IGH fusion probe. The MYC rearrangement rate in HIV-positive cases (33/55, 60.0%) was significantly higher than that in HIV-negative cases (11/38, 28.9%, P = 0.003). Patients with MYC rearrangement showed a trend towards an inferior median survival time (9.6 months versus 15.7 months, P = 0.122) and 2-year overall survival (17% versus 32%, P = 0.238). CONCLUSIONS: MYC rearrangement was frequently identified in PBL patients, and IGH was the partner gene in an overwhelming majority of MYC rearrangements. In addition, the MYC rearrangement rate was significantly higher in HIV-positive PBL patients than that in HIV-negative patients. MYC rearrangement may play an important role in the pathogenesis of HIV-positive PBL, but further studies are required to understand the underlying mechanisms.

Extraoral plasmablastic lymphomas in a high human immunodeficiency virus endemic area.

AIMS: Plasmablastic lymphoma (PBL) occurs mainly in immunocompromised individuals, usually secondary to human immunodeficiency virus (HIV) infection. It classically occurs intraorally, but has been described in extraoral locations. The aim of this study was to define the immunophenotype and Epstein-Barr virus (EBV) status in a large single-centre cohort of extraoral PBL (EPBL) in South Africa, a high-prevalence HIV setting. METHODS AND RESULTS: This retrospective study of 45 EPBLs included patients' age, gender, race, HIV status, and site. Cases were reviewed histologically, and classified morphologically as pure plasmablastic or plasmablastic with plasmacytic differentiation, and assessed immunohistochemically with antibodies against CD45, CD20, CD79a, PAX5, CD138, MUM1/IRF4, BLIMP1, VS38c, Ki67, bcl-6, CD10, cyclin D1, and human herpesvirus-8, by the use of standard automated procedures. EBV was assessed by the use of chromogenic in-situ hybridisation. Tumours were assessed with a fluorescence in-situ hybridisation (FISH) MYC break-apart probe. Twenty-seven PBLs showed pure plasmablastic morphology, and 18 showed plasmacytic differentiation. The male/female ratio was 1.5:1. The anus was the favoured extraoral site (31.1%), followed by lymph nodes (15.6%). All 29 patients with known HIV status were HIV-positive. The immunohistochemical profile recapitulated that reported for oral PBLs and EPBLs in HIV-positive and HIV-negative patients. EBV was positive in 92.5% of PBLs. FISH analysis showed MYC rearrangement in 48% of cases. CONCLUSION: This study showed a strong association of EPBLs with HIV and EBV infection, similarly to the previously described oral PBL. The strong EBV association together with other clinicopathological parameters and an immunohistochemical profile that includes CD45, CD20, MUM1/IRF4, CD138 and Ki67 may be used in distinguishing PBL from diffuse large B-cell lymphoma and plasma cell myeloma.