Roles of plasmablasts in IgG4-related disease and various immune-based diseases

IgG4-related disease(IgG4-RD) is a systemic fibroinflammatory disease with multiple organ disorders.Recently,in IgG4-RD,increased circulating plasmablasts have been found.The subsets of plasmablasts are negative for RP105(CD180).A large population of B cells lacking RP105(RP105-negative B cells) are found inpatients with active with systemic lupus erythematosus and other systemic autoimmune diseases,including dermatomyositis,and Sj?gren's syndrome.In other conditions,such as neuromyelitis optica,Kawasaki's disease,primary biliary cirrhosis and aging,RP105 expression on B cells and monocytes also alters.We review the basic science and clinical significance of RP105-negative B cells including plasmablasts in various immune-based diseases.RP105-negative B cells,especially plasmablasts,play crucial roles in both systemic and organ-specific autoimmune and inflammatory disorders.

Peripheral plasmablasts in anti-MuSK myasthenia gravis

As Hong and Sung[1] previously did, we read with great interest the study published by Guptill et al.[2] They reported that anti-muscle-specific kinase (MuSK) myasthenia gravis patients and healthy controls had similar percentages of peripheral plasmablasts.

Recent advances in the management of autoimmune pancreatitis in the era of artificial intelligence

Autoimmune pancreatitis(AIP)is a type of immune-mediated pancreatitis subdivided into two subtypes,type 1 and type 2 AIP.Furthermore,type 1 AIP is considered to be the pancreatic manifestation of the immunoglobulin G4(IgG4)-related disease.Nowadays,AIP is increasingly researched and recognized,although its diagnosis represents a challenge for several reasons:False positive ultrasound-guided cytological samples for a neoplastic process,difficult to interpret levels of IgG4,the absence of biological markers to diagnose type 2 AIP,and the challenging clinical identification of atypical forms.Furthermore,60%and 78%of type 1 and type 2 AIP,respectively,are retrospectively diagnosed on surgical specimens of resected pancreas for suspected cancer.As distinguishing AIP from pancreatic ductal adenocarcinoma can be challenging,obtaining a definitive diagnosis can therefore prove difficult,since endoscopic ultrasound fine-needle aspiration or biopsy of the pancreas are suboptimal.This paper focuses on recent innovations in the management of AIP with regard to the use of artificial intelligence,new serum markers,and new therapeutic approaches,while it also outlines the current management recommendations.A better knowledge of AIP can reduce the recourse to surgery and avoid its overuse,although such an approach requires close collaboration between gastroenterologists,surgeons and radiologists.Better knowledge on AIP and IgG4-related disease remains necessary to diagnose and manage patients.

Recent insights in the pathogenesis of post-transplantation lymphoproliferative disorders

Post-transplant lymphoproliferative disorder(PTLD) is an aggressive complication of solid organ and hematopoietic stem cell transplantation that arises in up to 20% of transplant recipients. Infection or reactivation of the Epstein-Barr virus(EBV), a ubiquitous human herpesvirus, in combination with chronic immunosuppression are considered as the main predisposing factors, however insight in PTLD biology is fragmentary. The study of PTLD is complicated by its morphological heterogeneity and the lack of prospective trials, which also impede treatment optimization. Furthermore, the broad spectrum of underlying disorders and the graft type represent important confounding factors. PTLD encompasses different malignant subtypes that resemble histologically similar lymphomas in the general population. Post-transplant diffuse large B-cell lymphoma(PT-DLBCL), Burkitt lymphoma(PTBL) and plasmablastic lymphoma(PT-PBL) occur most frequently. However, in many studies various EBV+ and EBV- PTLD subtypes are pooled, complicating the interpretation of the results. In this review, studies of the gene expression pattern, the microenvironment and the genetic profile of PT-DLBCL, PT-BL and PT-PBL are summarized to better understand the mechanisms underlying post-transplantation lymphomagenesis. Based on the available findings we propose stratification of PTLD according to the histological subtype and the EBV status to facilitate the interpretation of future studies and the establishment of clinical trials.

Plasmablastic lymphoma of the small intestine:Case report and literature review

Plasmablastic lymphoma(PBL) is a rare aggressive B-cell lymphoproliferative disorder,which has been characterized by the World Health Organization as a new entity.Although PBL is most commonly seen in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be seen in extraoral sites in immunocompromised patients who are HIV-negative.Here we present a rare case of PBL of the small intestine in a 55-year-old HIV-negative male.Histopathological examination of the excisional lesion showed a large cell lymphoma with plasmacytic differentiation diffusely infiltrating the small intestine and involving the surrounding organs.The neoplastic cells were diffusely positive for CD79a,CD138 and CD10 and partly positive for CD38 and epithelial membrane antigen.Approximately 80% of the tumor cells were positive for Ki-67.A monoclonal rearrangement of the kappa light chain gene was demonstrated.The patient died approximately 1.5 mo after diagnosis in spite of receiving two courses of the CHOP chemotherapy regimen.In a review of the literature,this is the first case report of PBL with initial presentation in the small intestine without HIV and Epstein-Barr virus infection,and a history of hepatitis B virus infection and radiotherapy probably led to the iatrogenic immunocompromised state.

AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: A diagnostic dilemma

Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis.

Duodenal localization of plasmablastic myeloma

Gastrointestinal involvement in plasma cell neoplasms,either as primary localizations(extramedullary plasma-cytomas) or as secondary involvement in systemic multiple myeloma, is a well-known event. Accurate histological examination is crucial in defining the diag-nosis. In this report, an uncommon case of duodenal localization of myeloma with plasmablastic features is described, with emphasis on the role of clinical data and findings from ancillary immunostaining techniques to avoid misdiagnosis.

Gastrointestinal bleeding as initial presentation of extramedullary plasma cell neoplasms: A case report and review of the literature

BACKGROUND Plasma-cell neoplasms rarely involve the gastrointestinal tract and manifest as gastrointestinal bleeding. Plasmablastic myeloma is an aggressive plasma cell neoplasm associated with poor outcomes. A small number of cases with gastrointestinal involvement is reported in the literature and therefore high index of suspicion is essential for avoiding delays in diagnosis and treatment.CASE SUMMARY Our aim is to present our experience of a 70-year-old patient with a secondary presentation of plasmablastic myeloma manifesting as unstable upper gastrointestinal bleeding and to review the literature with the view to consolidate and discuss information about diagnosis and management of this rare entity. In addition to our case, a literature search(Pub Med database) of case reports of extramedullary plasma cell neoplasms manifesting as upper gastrointestinal bleeding was performed. Twenty-seven cases of extramedullary plasmacytoma(EMP) involving the stomach and small bowel presenting with upper gastrointestinal bleeding were retrieved. The majority of patients were males(67%). The average age on diagnosis was 62.7 years. The most common site of presentation was the stomach(41%), followed by the duodenum(15%). The most common presenting complaint was melena(44%). In the majority of cases, the EMPs were a secondary manifestation(63%) at the background of multiple myeloma(26%), plasmablastic myeloma(7%) or high-grade plasma cell myeloma(4%). Oesophagogastroscopy was the main diagnostic modality and chemotherapy the preferred treatment option for secondary EMPs.CONCLUSION Despite their rare presentation, upper gastrointestinal EMPs should be considered in the differential diagnosis of patients with gastrointestinal bleeding especially in the presence of systemic haematological malignancy.

A case of plasmablastic lymphoma of the liver without human immunodeficiency virus infection

Plasmablastic lymphoma(PBL)is a very rare B-cell lymphoproliferative disorder was with an aggressive clinical behavior that recently characterized by the World Health Organization.Although PBL is most commonly observed in the oral cavity of human immunodeficiency virus(HIV)-positive patients,it can also be observed at extra-oral sites in HIV-negative patients.Epstein-Barr virus(EBV)may be closely related the pathogenesis of PBL.PBL shows different clinicopathological characteristics between HIV-positive and-negative patients.Here,we report a case of PBL of the liver in a 79-yearold HIV-negative male.The patient died approximately1.5 mo after examination and autopsy showed that the main lesion was a very large liver mass.Histopathological examination of the excised lesion showed large-cell lymphoma with plasmacytic differentiation diffusely infiltrating the liver and involving the surrounding organs.The neoplastic cells were diffusely positive for CD30,EBV,Bob-1,and CD38.The autopsy findings suggested a diagnosis of PBL.To our knowledge,the present case appears to be the first report of PBL with initial presentation of the liver in a patient without HIV infection.

Case of plasmablastic lymphoma of the sigmoid colon and literature review

Plasmablastic lymphoma(PBL) is a rare form of nonHodgkin's lymphoma that is associated with human immunodeficiency virus(HIV) infection. Although PBL is most commonly observed in the oral cavity of HIV-positive patients, it can also be observed at extra-oral sites in HIV-negative patients. This report represents an unusual case of HIV-negative PBL that occurred in the sigmoid colon. This patient had a history of systemic lupus erythematosus and an underlying immunosuppressive state from long term steroid therapy. The lymphoma cells were positive for CD138, kappa light chain restriction and Epstein-Barr virus and negative for CD20/L26, CD3, CD79 a, UCHL1(CD45RO) and cytokeratin(AE1/AE3). The patient died approximately 2 mo after the operation. In the present paper, we review cases of PBL of the colon in HIVnegative patients.

Manifestations of gastrointestinal plasmablastic lymphoma: A case series with literature review

Plasmablastic lymphoma (PBL) rarely occurs in the gastrointestinal (GI) tract with limited studies reported. We reviewed the clinical histories and pathology of four patients with GI PBL at our institute and similar case reports published in peer-reviewed journals. In our first case, a 40 year-old human immunodeficiency virus positive male presented with a hemorrhoid-like sensation, and was diagnosed with PBL via biopsy of a rectal mass. The second case involves a 65 year-old healthy male with bloody diarrhea who was found to have PBL in a resected sigmoid mass. The third patient was a 41 year-old male with a history of Crohn’s disease who presented with abdominal pain, diarrhea, and weight loss. A small intestinal mass (PBL) was removed. The fourth patient was a 65-year-old male who was found PBL after surgical resection of bowel for his florid Crohn’s disease. He later developed secondary acute myeloid leukemia. Clinical outcome was very poor in 3 out of 4 patients as reported in the literature. One patient survived chemotherapy followed by autologous transplant. The prototypical clinical presentation and variations of PBL can help create a more comprehensive differential diagnosis for GI tumors and establish an appropriate therapeutic guideline.

Pulmonary tuberculosis infection and CMV reactivation following daratumumab treatment in a patient with relapsed plasmablastic lymphoma

Plasmablastic lymphoma(PBL)is an aggressive lymphoma with limited treatment strategies.Tuberculosis(TB)infection poses a high risk for patients with hematologic malignancies,especially those treated with immune agents but were never reported postdaratumumab treatment.Herein,we reported a TB infection in a 57-year-old male diagnosed with HIV-negative PBL receiving daratumumab-based treatment,who showed atypical lung infection and yielded Mycobacterium tuberculosis and cytomegalovirus(CMV)in the bronchoalveolar lavage fluid.Anti-TB therapy was administered,and the following daratumumab treatment was complete with good tolerance.In this case,we demonstrated that TB infection might occur after daratumumab therapy,and adequate attention should be paid to atypical symptoms.

Angiogenesis and osteopontin expression in paraskeletal myeloma with plasmablastic morphology and aggressive clinical course:a report of two cases

Extramedullary disease(EMD)of multiple myeloma(MM)can present as paraskeletal(paraosseous)plasmocytoma(PP)that arise from skeletal focal lesions or extramedullary plasmacytomas(EMP)that derive from hematogenous spread.The pathogenetic mechanisms that distinguish classical MM,PP,and EMP are still insufficiently known,as are the therapies that would be effective in EMD.The aim of this study was to evaluate immunohistochemically the angiogenesis,determined as microvessel density(MVD)and osteopontin expression in PP,of two patients with MM of plasmablastic morphology and an aggressive course of disease.We found high levels of MVD and osteopontin expression in both cases of PP.The role of angiogenesis and osteopontin in EMD should be clarified in future investigations,especially since there are no satisfactory therapeutic protocols for this form of multiple myeloma,and both of these biological factors can be the potential targets of new therapies.