Plasmablastic Lymphoma in a Human Immunodeficiency Virus-positive Child With a Suspicion of Concomitant Primary Immunodeficiency Disorder.

Plasmablastic lymphoma (PBL) occurs in the setting of immunodeficiency, in association with human immunodeficiency virus (HIV) infection, in elderly patients, and in the posttransplantation state. It is exceptionally rare in children. PBL is an aggressive lymphoma with a poor prognosis. We present a case of pediatric PBL in an HIV-positive child with suspicion of a concomitant underlying immune deficiency state other than HIV. A 7-year-old girl presented to the pediatric emergency department with complaints of fever and painful swelling on the left side of her face for 15 days, associated with headache, snoring, and difficulty in breathing. She had a history of watery diarrhea, oral thrush, recurrent fever, and hospitalizations for skin infections since the age of 1 year. Histopathological findings were consistent with PBL. Her HIV RNA polymerase chain reaction was positive. She was offered chemotherapy based on the FAB/LMB 96 protocol. This case demonstrates an aggressive presentation of a rare entity, HIV-associated PBL, in a child, with underlying immunodeficiency and highlights the issues which caused a significant challenge in making the diagnosis. The presence of HIV infection and contradicting other immunologic investigations posed a dilemma in establishing an association of PBL in this child. The outcome of patients with this tumor is associated with high mortality.

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.

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.

[Endoscopic mucosal resection of localized plasmablastic lymphoma with early rectal cancer:a rare case report and literature review].

A 79-year-old male with a positive fecal occult blood test result underwent total colonoscopy, which revealed a 15-mm-semipedunculated polyp in the rectum. The polyp appeared to be an adenoma using narrow-band imaging observation in magnifying endoscopy, although a 3mm reddish segment with a different surface structure was identified adjacent to the base of the polyp. En-bloc endoscopic mucosal resection (EMR) was performed. From the pathological evaluation using the specimen, the polyp was mainly a tubular adenoma with an adenocarcinoma component within the lesion. Additionally, a tiny plasmablastic lymphoma (PBL) component, which was positive for CD45, CD79a, CD30, CD38, MUM1, and lambda light chain;negative for CD3, CD5, CD20, CD56, CD138, cyclin D1, PAX5, IgG, IgA, IgM, IgE, HHV8, and kappa light chain, coexisted near the stalk. The proliferation index using Ki-67 immunohistochemistry was approximately 80%. Furthermore, Epstein-Barr virus-encoded RNAs were identified in in-situ hybridization, although the human immunodeficiency virus was not detected. The patient received contrast-enhanced computed tomography (CT) and positron emission tomography-CT (PET-CT) follow-ups after treatment without recurrence for two years. This is the first report of gastrointestinal PBL that could be treated using EMR.

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.

An Endotracheal Plasmablastic Lymphoma.

We describe an exceptionally rare case of a male patient with newly diagnosed advanced human immunodeficiency virus (HIV) infection, who presented with a plasmablastic lymphoma involving the right maxillary alveolar ridge with associated cervical lymphadenopathy. On a staging positron emission tomography computed tomography (PET-CT) scan, he was incidentally found to have an endotracheal tumour involving the anterolateral aspect of the mid-trachea. The tumour appeared to be well-vascularised at bronchoscopy and was confirmed as well-differentiated plasmablastic lymphoma. Plasmablastic lymphoma is a rare form of non-Hodgkin lymphoma and is associated with HIV. Tracheal involvement to the extent seen in our patient is exceptionally rare, and, to the best of our knowledge, has never been described.

Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1.

Plasmablastic lymphoma is an uncommon aggressive non-Hodgkin B-cell lymphoma type defined as a high-grade large B-cell neoplasm with plasma cell phenotype. Genetic alterations in MYC have been found in a proportion (~60%) of plasmablastic lymphoma cases and lead to MYC-protein overexpression. Here, we performed a genetic and expression profile of 36 plasmablastic lymphoma cases and demonstrate that MYC overexpression is not restricted to MYC-translocated (46%) or MYC-amplified cases (11%). Furthermore, we demonstrate that recurrent somatic mutations in PRDM1 are found in 50% of plasmablastic lymphoma cases (8 of 16 cases evaluated). These mutations target critical functional domains (PR motif, proline rich domain, acidic region, and DNA-binding Zn-finger domain) involved in the regulation of different targets such as MYC. Furthermore, these mutations are found frequently in association with MYC translocations (5 out of 9, 56% of cases with MYC translocations were PRDM1-mutated), but not restricted to those cases, and lead to expression of an impaired PRDM1/Blimp1α protein. Our data suggest that PRDM1 mutations in plasmablastic lymphoma do not impair terminal B-cell differentiation, but contribute to the oncogenicity of MYC, usually disregulated by MYC translocation or MYC amplification. In conclusion, aberrant coexpression of MYC and PRDM1/Blimp1α owing to genetic changes is responsible for the phenotype of plasmablastic lymphoma cases.

Vulvar and gastric involvement in plasmablastic lymphoma.

Plasmablastic lymphoma is highly malignant and invasive. It is most commonly found in gastrointestinal tract and is strongly asso- ciated with human immunodeficiency virus (HIV). The authors report a case of a 37-year-old HIV-positive African American woman with a vulvar mass diagnosed as plasmablastic lymphoma. Involvement of the upper gastrointestinal tract had been detected by endoscopic biopsy, suggesting that any patient diagnosed with plasmablastic lymphoma in unusual locations should be investigated for primary lesions in the gastrointestinal tract.

Primary Maxillary Sinus Plasmablastic Lymphoma in HIV/AIDS.

Classically, the HIV/AIDS-related lymphomas are of the B cell type and involve the central nervous system and the abdominal cavity. Primary maxillary sinus lymphoma is rare. Plasmablastic lymphoma (PBL) is an aggressive form of non-Hodgkinvs lymphoma, and is extremely rare. Here we present a case of plasmablastic lymphoma with primary site being maxillary sinus, a rare location.

Plasmablastic lymphoma: an atypical cutaneous presentation of a rare entity.

Plasmablastic lymphoma is a very rare B-cell lymphoma typically associated with immunosuppression: It occurs primarily in the oral cavity, although some cases were reported in other organs and tissues.To date, only 10 cases of primary cutaneous plasmablastic lymphoma have been described. Clinically, primary cutaneous plasmablastic lymphoma presents as non-specific cutaneous lesions (purple nodules, erythematous infiltrated plaques). In previously described cases, as in this case, histology and immunohistochemistry are required to make the diagnosis. Owing to the rarity of this entity, there is no established therapy, which makes its management an individualized, patient-based decision.

Case report: Lymphoma in a nasopharyngeal branchial cleft cyst.

OBJECTIVE: Nasopharyngeal branchial cleft cysts are rare, and only case reports have been published. We present a patient whose nasopharyngeal cyst contained a malignant lymphoma, and we review previous reports of this condition. METHODS: Case report with a relevant literature review. RESULTS: Sixteen case reports of nasopharyngeal branchial cleft cysts in 24 patients were included. The average age was 36 years; most cysts were on one side. Five patients underwent aspiration, 18 underwent surgery. The cyst wall was lined by stratified squamous epithelium in seven patients and by ciliated colomunar epithelium in 14. All previous cysts showed benign pathology. Our case is the first report of a malignant disease hidden in a nasopharyngeal branchial cleft cyst. CONCLUSIONS: To our knowledge, malignant lymphoma in a nasopharyngeal branchial cleft cyst has not been reported previously. Nevertheless, the possibility of this finding should be kept in mind when evaluating patients with nasopharyngeal cystic lesions.

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.

Duodenal plasmablastic lymphoma in an human immunodeficency virus-negative patient: a case report.

BACKGROUND: Plasmablastic lymphoma is a rare type of non-Hodgkin lymphoma that generally presents an aggressive clinical course. It is strongly associated with human immunodeficency virus (HIV) infection, and the most common site of involvement is the oral cavity. Although extraoral PBL has been reported in several places, small intestine involvement is extremely rare. CASE PRESENTATION: Here, we describe an exceptionally rare case of a 24-year-old immunocompetent Asian Male patient with newly diagnosed plasmablastic lymphoma of the duodenum. The patient was admitted to our oncology facility due to the patient's clinical course, which included persistent vomiting, hematemesis, weight loss, and generalized weakness. Computed tomography of the abdomen (triphasic) of the patient showed thickness at the 2nd part of the duodenum measuring 2.6 cm in width and 16 cm in length blocking the pancreatic and common bile ducts by entering the second section of the duodenum. The biopsy specimen's pathological investigation indicated abnormal cells with plasmacytoid characteristics and a high proliferation index. The diagnosis of PBL was confirmed by immunohistochemical profiling. Supportive therapies like blood transfusions, antacids, and antiemetics were started to manage the patient's symptoms. Palliative radiation was also anticipated for the lesion site. CONCLUSIONS: Duodenal involvement to the extent seen in our patient is exceptionally rare and, to the best of our knowledge, has hardly been described. The main goal of the article is to review the literature and report a case.

Epstein-Barr virus-positive mucocutaneous ulcer, plasmablastic type, associated with nodal CD4+ angioimmunoblastic T-cell lymphoma and generalised pruritus: a self-limiting lymphoproliferative disorder resembling cutaneous plasmablastic lymphoma.

A woman in her 80s reported of generalised pruritus, which was treated with phototherapy and steroid administration. Two months after onset, lymph node biopsy revealed CD4+ angioimmunoblastic T-cell lymphoma with systemic superficial nodal involvement. Intractable prurigo was judged as T-cell lymphoma related. After effective chemotherapy (7 months later), skin nodules appeared multifocally, including on the lip, thumb and lower leg. The biopsied infiltrative lesion on the right lower leg microscopically revealed subcutaneous growth of atypical plasmablasts with nearly 100% Ki-67 labelling and Epstein-Barr virus (EBV)-encoded small nuclear RNA positivity. Plasmablastic lymphoma (CD45/CD19/CD38/CD138/MUM1+, CD20/CD79a/PAX5-) was suspected. Immunoglobulin light-chain restriction and nuclear expression of c-myc protein were undetectable, and the ulcers were spontaneously epithelialised by the cessation of steroid administration. After 10 months, non-progressive prurigos persisted on the extremities, but without regrowth of nodal T-cell lymphoma and cutaneous lymphoproliferative lesion. Reactive nature of the EBV-induced mucocutaneous plasmablastic growth (EBV-positive mucocutaneous ulcer, plasmablastic type) is discussed.

HIV-related plasmablastic lymphoma causing extensive bone destruction in the mandible.

Plasmablastic lymphoma (PBL) is a rare subtype of large B-cell lymphoma commonly associated with HIV infection. HIV-related PBL has a dismal prognosis. The aggressive clinical course of the disease may lead to the development of rapid-growing swellings, like several benign and malignant conditions. Herein, we reported the case of a 38-year-old woman with a painful swelling in the mandible initially diagnosed as an abscess derived from a tooth extraction. Intraoral examination revealed a painful swelling with reddish, white and purplish areas in the posterior region of the mandible without signs of infection. Imaging exams showed an extensive bone destruction in the left mandibular body. Histopathological examination revealed a high proliferation of plasmacytoid cells with nuclear hyperchromatism. Tumor cells were negative for CD20, and positive for Ki-67, CD138, IgG and lambda chain. The diagnosis of oral PBL was defined and serological test showed positivity for HIV. Eight months after starting treatment, the patient died due to complications of cancer treatment. Lymphoproliferative malignancies related to HIV infection should be included in the differential diagnosis of rapid-growing swellings in the oral cavity.

Integrative genomic and transcriptomic analysis in plasmablastic lymphoma identifies disruption of key regulatory pathways.

Plasmablastic lymphoma (PBL) represents a clinically heterogeneous subtype of aggressive B-cell non-Hodgkin lymphoma. Targeted-sequencing studies and a single-center whole-exome sequencing (WES) study in HIV-positive patients recently revealed several genes associated with PBL pathogenesis; however, the global mutational landscape and transcriptional profile of PBL remain elusive. To inform on disease-associated mutational drivers, mutational patterns, and perturbed pathways in HIV-positive and HIV-negative PBL, we performed WES and transcriptome sequencing (RNA-sequencing) of 33 PBL tumors. Integrative analysis of somatic mutations and gene expression profiles was performed to acquire insights into the divergent genotype-phenotype correlation in Epstein-Barr virus-positive (EBV+) and EBV- PBL. We describe a significant accumulation of mutations in the JAK signal transducer and transcription activator (OSMR, STAT3, PIM1, and SOCS1), as well as receptor tyrosine-kinase RAS (ERBB3, NRAS, PDGFRB, and NTRK) pathways. We provide further evidence of frequent perturbances of NF-κB signaling (NFKB2 and BTK). Induced pathways, identified by RNA-sequencing, closely resemble the mutational profile regarding alterations accentuated in interleukin-6/JAK/STAT signaling, NF-κB activity, and MYC signaling. Moreover, class I major histocompatibility complex-mediated antigen processing and cell cycle regulation were significantly affected by EBV status. An almost exclusive upregulation of phosphatidylinositol 3-kinase/AKT/mTOR signaling in EBV+ PBL and a significantly induced expression of NTRK3 in concert with recurrent oncogenic mutations in EBV- PBL hint at a specific therapeutically targetable mechanism in PBL subgroups. Our characterization of a mutational and transcriptomic landscape in PBL, distinct from that of diffuse large B-cell lymphoma and multiple myeloma, substantiates the pathobiological independence of PBL in the spectrum of B-cell malignancies and thereby refines the taxonomy for aggressive lymphomas.

A Rare Case of Plasmablastic Lymphoma in a Patient with HIV and SARS-CoV-2 Infections.

Lesions commonly associated with HIV infection include oral candidiasis, herpes simplex infection, oral Kaposi's sarcoma, hairy leukoplakia, periodontal diseases (linear gingival erythema and necrotizing ulcerative periodontitis), xerostomia, human papillomavirus-associated warts, aphthous ulcers, non-Hodgkin's lymphoma, histoplasmosis, carcinoma, exfoliative cheilitis, and HIV salivary gland disease. Non-Hodgkin's lymphoma (NHL) is the most common cancer in people living with HIV (PLWH), and the incidence is increased for aggressive B-cell NHL. Plasmablastic lymphoma (PbL) is a rare and aggressive B-cell malignancy that is often unresponsive to chemotherapy and usually has a poor prognosis. We hereby present the case of a patient with a recent history of COVID-19 infection who was diagnosed with HIV and NHL, with manifestations in the oral cavity and a favorable evolution after the introduction of antiviral therapy, specific chemotherapy, and radiotherapy. Dental expertise is necessary for the appropriate management of oral manifestations of HIV infection or AIDS, and lymphoma should be included in the differential diagnosis of any oral lesions.