Transformation of t(14;18)-negative follicular lymphoma to plasmablastic lymphoma: a case report with analysis of genetic evolution.

BACKGROUND: Follicular lymphoma (FL) is characterized by t(14;18)(q32;q21) involving the IGH and BCL2 genes. However, 10-15% of FLs lack the BCL2 rearrangement. These BCL2-rearrangement-negative FLs are clinically, pathologically, and genetically heterogeneous. The biological behavior and histological transformation of such FLs are not adequately characterized. Here, we report the first case of t(14;18)-negative FL that rapidly progressed to plasmablastic lymphoma (PBL). CASE PRESENTATION: A previously healthy 51-year-old man presented with leg swelling. Computed tomography (CT) showed enlarged lymph nodes (LNs) throughout the body, including both inguinal areas. Needle biopsy of an inguinal LN suggested low-grade B-cell non-Hodgkin lymphoma. Excisional biopsy of a neck LN showed proliferation of centrocytic and centroblastic cells with follicular and diffuse growth patterns. Immunohistochemical analysis showed that the cells were positive for CD20, BCL6, CD10, and CD23. BCL2 staining was negative in the follicles and weak to moderately positive in the interfollicular areas. BCL2 fluorescence in situ hybridization result was negative. Targeted next-generation sequencing (NGS) revealed mutations in the TNFRSF14, CREBBP, STAT6, BCL6, CD79B, CD79A, and KLHL6 genes, without evidence of BCL2 or BCL6 rearrangement. The pathologic and genetic features were consistent with t(14;18)-negative FL. Two months after one cycle of bendamustine and rituximab chemotherapy, the patient developed left flank pain. Positron emission tomography/CT showed new development of a large hypermetabolic mass in the retroperitoneum. Needle biopsy of the retroperitoneal mass demonstrated diffuse proliferation of large plasmablastic cells, which were negative for the B-cell markers, BCL2, BCL6, and CD10; they were positive for MUM-1, CD138, CD38, and C-MYC. The pathologic findings were consistent with PBL. The clonal relationship between the initial FL and subsequent PBL was analyzed via targeted NGS. The tumors shared the same CREBBP, STAT6, BCL6, and CD79B mutations, strongly suggesting that the PBL had transformed from a FL clone. The PBL also harbored BRAF V600E mutation and IGH::MYC fusion in addition to IGH::IRF4 fusion. CONCLUSIONS: We propose that transformation or divergent clonal evolution of FL into PBL can occur when relevant genetic mutations are present. This study broadens the spectrum of histological transformation of t(14;18)-negative FL and emphasizes its biological and clinical heterogeneity.

Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management.

DISEASE OVERVIEW: Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals. DIAGNOSIS: The diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. RISK STRATIFICATION: Age ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival. MANAGEMENT: Combination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

[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).

Plasmablastic lymphoma: current knowledge and future directions.

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin lymphoma associated with HIV infection and immunodeficiency. However, PBL can also be seen immunocompetent individuals in recent studies. PBL was characterized by distinct clinical and pathological features, such as plasmablastic morphology and universal expression of plasma cell markers. The clinicopathologic features were different between HIV-negative and HIV-positive patients. Gene expression analysis identified the unique molecular feature in PBL, including frequent c-MYC rearrangement and downregulation of BCR signaling pathway. Despite the recent advances in the treatment of PBL, the prognosis of PBL patients remains dismal. The objectives of this review are to summarize the current knowledge on the epidemiology, molecular profiles, clinical and pathological features, differential diagnosis, treatment strategies, prognostic factors, and potential novel therapeutic approaches in PBL patients.

Plasmablastic transformation of a double hit follicular lymphoma: An emerging entity.

ABSTRACT: Plasmablastic transformation of follicular lymphoma is very rare and has been reported in only 5 cases till date. We report a case of simultaneous identification of extranodal, soft tissue plasmablastic lymphoma in the ankle and bone marrow involvement by follicular lymphoma. This unusual case presentation is a challenge for the treating physician with the patient becoming resistant to chemotherapy and succumbing to the disease within a few months of diagnosis. These cases are known to have an aggressive clinical course with very poor prognosis and survival rate of less than 6 months. This report broadens the spectrum of morphological transformation of follicular lymphoma and it may represent a new category of high-grade transformation of follicular lymphoma.

Oral Plasmablastic Lymphoma: A Rare Manifestation of HIV-Related Neoplasm-A Brief Clinical Study.

Plasmablastic lymphoma (PBL) is an uncommon and aggressive large B-cell lymphoma commonly diagnosed in human immunodeficiency virus-positive patients. Though the oral cavity is a common site for PBL, this condition is not commonly reported in the literature as an oral manifestation. Most oral PBLs presented as an asymptomatic swelling, frequently associated with ulcerations and bleeding. No standard treatment is yet advocated for oral PBL. Five-year survival rate was recorded not more than 33.5%. This presentation emphasizes on oral manifestation of plasmablastic lymphoma (PBL) as a rare entity, which was provisionally diagnosed for carcinoma (CA) oral cavity. A simple presentation of ulcerated growth in the upper jaw was excised for histopathologic evaluation. Subsequently, it turned out to be a rare oral manifestation of HIV-related lymphoma. It is imperative to understand simple oral presentation as a manifestation of an underlying systemic condition. With this interest, this case presentation is published with a literature review.

Epidemiologic Characteristics, Treatment Patterns, and Survival Analysis of Plasmablastic Lymphoma in the United States: A SEER and NCDB Analysis.

BACKGROUND: Plasmablastic Lymphoma (PBL) is a rare aggressive B-cell lymphoma that primarily affects immunocompromised individuals, including those living with HIV. Historically, survival estimates are dismal and range from 8 to 15 months. We aimed to evaluate epidemiologic characteristics, treatment patterns and survival trends on a national scale. PATIENTS AND METHODS: Patients diagnosed with PBL from 2010 to 2020 were identified in the National Cancer Database (NCDB) and in the Surveillance, Epidemiology, and End Results (SEER) program. Incidence rates were calculated using SEER. Demographic features, treatment characteristics, and overall survival (OS) were identified using the NCDB. RESULTS: We identified 1153 patients in the SEER database and 1822 patients in the NCDB. The incidence of PBL is 0.07 cases per 100,000 US population per year. PBL is more common in males (77%), and white patients (77%), with 50% of cases in patients with HIV. Patients who were treated with multiagent chemotherapy had a median OS of 58.6 months. On multivariate Cox regression, we found that HIV status did not have a significant impact on OS. Factors associated with worse OS included advancing age and stage. CONCLUSION: We present the largest study to date on PBL. Among treated patients, we described a median OS of 58.6 months, greatly improved from previously reported estimates. We found that HIV status did not have a significant impact on OS. While OS remains poor, therapeutic advances over the last decade are promising and highlight the need for continued clinical advances aimed at improving therapeutic options for this rare lymphoma.

FLI-1 is expressed in a wide variety of hematolymphoid neoplasms: a special concern in the differential diagnosis.

Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing's sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing's sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.

Clinicopathological and genetic landscape of plasmablastic lymphoma in Taiwan.

Plasmablastic lymphoma (PBL) is an aggressive large B-cell lymphoma with a terminal B-cell differentiation phenotype and is frequently associated with immunodeficiency. We aimed to investigate the clinicopathological and immunophenotypic features, genetic alterations, and mutational landscape of PBL in Taiwan. We retrospectively recruited 26 cases. Five (5/18; 28%) patients were HIV-positive and 21 (81%) presented extranodally. There were two morphological groups: one with purely monomorphic large cells (85%) and the other comprising large cells admixed with plasmacytic cells (15%). Phenotypically, the tumors expressed MYC (8/10; 80%), CD138 (20/26; 77%), and MUM1 (20/20; 100%), but not CD20 (n = 26; 0%). Fourteen (54%) cases were positive for EBV by in situ hybridization; the EBV-positive cases were more frequently HIV infected (p = 0.036), with extranodal presentation (p = 0.012) and CD79a expression (p = 0.012), but less frequent light chain restriction (p = 0.029). Using fluorescence in situ hybridization, we identified 13q14 deletion, MYC rearrangement, and CCND1 rearrangement in 74%, 30%, and 5% cases, respectively, without any cases having rearranged BCL6 or IGH::FGFR3 fusion. In the 15 cases with adequate tissue for whole exome sequencing, the most frequent recurrent mutations were STAT3 (40%), NRAS (27%), and KRAS (20%). In conclusion, most PBL cases in Taiwan were HIV-unrelated. Around half of the cases were positive for EBV, with distinct clinicopathological features. Deletion of chromosome 13q14 was frequent. The PBL cases in Taiwan showed recurrent mutations involving JAK-STAT, RAS-MAPK, epigenetic regulation, and NOTCH signaling pathways, findings similar to that from the West.

Exploration and analysis of differentially expressed genes in Epstein–Barr virus negative and positive plasmablastic lymphoma

Objectives Plasmablastic lymphoma (PBL) is a subtype of diffuse large B-cell lymphoma (DLBCL) often associated with Epstein–Barr virus (EBV) infection. Despite recent advances in treatment, PBL still has a poor prognosis. EBV is listed as one of the human tumor viruses that may cause cancer, and is closely related to the occurrence of some nasopharyngeal carcinoma (NPC), lymphoma and 10% of gastric cancer (GC). It is very important to explore the differentially expressed genes (DEGs) between EBV-positive and EBV-negative PBL. Through bioinformatics analysis of DEGs between EBV-positive PBL and EBV-negative PBL, we gain a deeper understanding of the pathogenesis of EBV-positive PBL. Methods We selected the GSE102203 data set, and screened the DEGs between EBV-positive PBL and EBV-negative PBL. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied. The protein–protein interaction (PPI) network was constructed, and screened for the hub genes. Finally, Gene Set Enrichment Analysis (GSEA) was performed. Results In EBV-positive PBL, the immune-related pathway is upregulated and Cluster of differentiation 27 (CD27) and programmed cell death-ligand 1 (PD-L1) are hub genes. Conclusions In EBV-positive PBL, EBV may affect tumorigenesis through activation of immune-related pathways and upregulation of CD27, PD-L1. Immune checkpoint blockers of CD70/CD27 and programmed cell death 1 (PD-1)/PD-L1 pathways may be one of the effective strategies for the treatment of EBV-positive PBL (AU)

Overall survival in Chilean patients with lymphoma and human immunodeficiency virus: A retrospective cohort study

ABSTRACT Introduction: People living with human immunodeficiency virus (PLWH) still face high morbidity and mortality resulting from lymphoma. Aim: To describe a population of PLWH and lymphoma in a Chilean public hospital and compare the overall survival (OS) with a previously reported cohort from the same institution. Methods: Retrospective single-center cohort study. All the patients diagnosed between 2010 and 2017 were included. Demographic and clinical variables were obtained from medical records. The overall survival (OS) was estimated in treated patients from diagnosis until death or October 2020. The OS was then compared with a cohort of patients diagnosed between 1992 and 2008. Main Results: Eighty-four patients were included. The most common histological types were Burkitt's lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), Hodgkin's lymphoma (HL) and plasmablastic lymphoma (PBL) at 31%, 27%, 21% and 14%, respectively. The three-year OS for the whole cohort of BL, DLBCL, HL and PBL was 58.9%, 65.2%, 47.4%, 76.4% and 50%, respectively. Compared to the cohort of 1992 to 2008, a global increase in the OS was found after excluding HL and adjusting for age and clinical stage (HR 0.38, p = 0.002). However, when the main types were analyzed individually, the increase in the OS was statistically significant only in DLBCL (HR 0.29, p = 0.007). Most patients with DLBCL received CHOP chemotherapy, as in the previous cohort. Conclusion: The OS has improved in this population, despite no major changes in chemotherapy regimens, mainly due to the universal access to antiretroviral therapy.

Anal canal lymphoma: Case report and literature review / Linfoma de canal anal, reporte de caso y revisión de la literatura

Abstract Introduction: Primary tumors of the anal canal other than carcinomas are rare entities; among them, anal canal lymphomas are extremely unusual and pose both a diagnostic and therapeutic challenge for the coloproctologist. Case presentation: A male patient with positive human immunodeficiency virus (HIV) with proctalgia and mass sensation at the perianal level. A concentric thickening of the walls of the lower rectum was documented by magnetic resonance imaging, with colonoscopy and biopsies with histopathology compatible with plasmablastic lymphoma. Therefore, a diverting colostomy was performed and, subsequently, the hematology service indicated chemotherapy with the EPOCH scheme. Discussion: Lymphoma of the anus represents 0.2 % of anorectal tumors, most of these are non-Hodgkin's lymphomas; Hodgkin's disease at the anorectal level is even rarer. The population with the highest risk of this entity is HIV-positive patients, such as the patient in this case, although other associated factors are described in the literature.

Resumen Introducción: los tumores primarios del canal anal diferentes a carcinomas son entidades poco frecuentes; dentro de estos, los linfomas del canal anal son extremadamente raros y generan un reto tanto diagnóstico como terapéutico para el coloproctólogo. Presentación de caso: se presenta a continuación un caso clínico de un paciente con virus de inmunodeficiencia humana (VIH) positivo con proctalgia y sensación de masa a nivel perianal, se documentó por resonancia magnética un engrosamiento concéntrico de las paredes del recto inferior, con realización de colonoscopia y biopsias con histopatología compatible con linfoma plasmablástico, por lo que se realizó una colostomía derivativa y, posteriormente, se indicó por el servicio de hematología una quimioterapia con esquema EPOCH. Discusión: el linfoma de ano representa el 0,2 % de los tumores anorrectales, la mayoría de estos corresponde a linfomas no Hodgkin, y es aún más rara la enfermedad de Hodgkin a nivel anorrectal. La población con mayor riesgo de presentar esta entidad es los pacientes con VIH positivo, como el paciente descrito en el caso, aunque existen otros factores asociados descritos en la literatura.

Newest Reaserch Advance in treatment of Plasmablastic lymphoma--Review / 中国实验血液学杂志

Plasmablastic lymphoma(PBL) shows a low incidence and poor prognosis, moreover, there is no standard treatment regimen for PBL. The treatment effect and value of CHOP regimen and radiotherapy are limited. Some studies showed that intensive chemotherapy alone or its combination with proteasome inhibitors or immune regulator can improve the overall survival of patients with PBL, which can be used as the first-line therapy for PBL patients. CAR-T and immunocheckpoint inhibitors showed treatment effect for the patients with refractory and relapsed plasmablastic lymphoma. The clinical value of potential targets in treating tumour worth to be studied further.

Revisión sistemática del linfoma plasmablástico intraoral en paciente con virus de la inmunodeficiencia humana. A propósito de un caso / Intraoral plasmablastic lymphoma in a patient with human immunodeficiency virus. A case report and systematic review

Los linfomas son los tumores no epiteliales malignos más frecuente en la cavidad oral y región maxilofacial. El riesgo de los pacientes con VIH de presentar esta enfermedad es 200 veces mayor en comparación con la población general. El linfoma plasmablástico es una neoplasia agresiva poco frecuente. La clasificación del 2008 de la OMS lo define como una proliferación difusa de células grandes neoplásicas semejantes a inmunoblastos B con inmunofenotipo de células plasmáticas, con la mayoría de los casos asociados a pacientes con VIH. El propósito de este artículo es presentar una revisión sistemática de esta enfermedad junto a un caso clínico de difícil diagnóstico por su expresión clínica, en el que el estudio histopatológico fue determinante

Lynphomas are the most common malignant non-epithelial tumours in the oral cavity and maxilofacial región. The risk of HIV patients presenting with this condition is 200 times more compared to the general population. Plasmablastic lymphoma is a rare aggresive neoplasm. The WHO 2008 classification defines it as a diffuse proliferation of large neoplastic cells, such as B immunoblasts with plasma inmunophenotype cells, with most cases being associated with HIV patients. The purpose of this article is to present a systematic review of this pathology together with a case of difficult diagnosis due to its clinical expression, and in which the histopathology study was decisive