Plasmablastic Lymphoma of Maxilla in an Immunocompetent Adult

Abstract

Plasmablastic lymphoma (PBL) is an aggressive non-Hodgkin's lymphoma often found in immunocompromised individuals, especially those with HIV. It features large neoplastic cells resembling plasmablasts and plasma cells, making it challenging to distinguish from plasma cell myeloma. PBL is difficult to diagnose, especially with small biopsies, and is associated with high relapse rates and mortality, even with treatment. A systematic diagnostic approach, including EBER status, helps confirm PBL. Awareness of its distinct features is vital for accurate diagnosis, particularly for dental professionals.

Introduction

Plasmablastic lymphoma (PBL), an aggressive variant of non-Hodgkin's lymphoma (NHL), commonly arising in immunocompromised patients and in those infected with human immunodeficiency virus (HIV). PBL is characterized by a diffuse proliferation of large neoplastic cells that resemble B cell immunoblasts or plasmablasts, often showing plasmacytic differentiation and a plasma cell immunophenotype. The diagnosis of PBL is often challenging in a small diminutive biopsy sample especially due to its distinct morphology and immunohistochemical profile, as it closely resembles plasma cell myeloma. Additionally, PBL presents a therapeutic challenge, with a clinical course marked by frequent relapses and a high mortality rate.

Case Report

A 57-year-old male presented to our facility with a one-month history of left-sided facial pain, which began gradually and progressed over time. He also reported a progressive swelling over his left cheek, along with generalized weakness and fatigue. The patient, known to have diabetes with moderate control on oral medications (HbA1c: 7.4%), underwent routine examinations, which were largely unremarkable except for an elevated serum globulin level of 2.8 g/dL. A whole-body PET-CT scan with contrast was performed, revealing a metabolically active soft tissue mass involving the left maxillary sinus, maxillary alveolus, and hard palate (Fig. 1a,b). Additionally, metabolically active lymphadenopathy was identified in left cervical nodes at levels Ib and II, alongside osteolytic lesions in the right humeral head, right femoral head, and L5 vertebra. Notably, a soft tissue mass adjacent to the L5 vertebra infiltrated the nearby psoas muscle and partially encased the common iliac vessels. To further evaluate, an incisional biopsy from the palate was conducted. Light microscopy revealed multiple tissue fragments with ulceration and underlying inflammatory granulation tissue characterized by small blood vessels with plump endothelial cells. This was surrounded by sheets of monomorphic plasmacytoid cells, morphologically resembling plasma cells (Fig. 2a-c). There was no evidence of dysplasia or any invasive carcinoma observed in the biopsy submitted. Based on these findings, a provisional diagnosis of plasma cell-rich lesion was made, and immunohistochemical (IHC) markers were applied to determine the final diagnosis. The IHC markers were observed as follows: CK was negative; CD3 and CD20 were negative; CD38, CD138, and MUM1 were positive; LCA showed heterogeneous weak positivity; CD56 and EBV were negative (Fig. 3a-e). Kappa and Lambda immunohistochemistry indicated Lambda light chain restriction, which was confirmed by paraffin immunofluorescence (IF) Kappa/Lambda staining (Fig. 3f,g). The Ki67 index was notably high, at 80–90% (Fig. 3h). Given these findings, plasmablastic plasmacytoma and plasmablastic lymphoma were considered as differential diagnoses. However, the presence of light chain restriction and the high Ki67 index supported a diagnosis of plasmablastic lymphoma over plasmacytoma. In light of these observations, a comprehensive evaluation for plasma cell dyscrasia was conducted. Beta-2-microglobulin was measured at 2.56 µg/mL. Serum protein electrophoresis (SPEP) revealed a 0.3 g/dL M-band in the early gamma globulin region. The free light chain ratio was 0.54, with kappa at 44 mg/L and lambda at 80.91 mg/L. A bone marrow assessment was also performed: aspiration showed cellular bone marrow with trilineage haematopoiesis and approximately 2% plasma cells, while biopsy findings showed cellular bone marrow with trilineage haematopoiesis and around 7–8% plasma cells. Thus, a final diagnosis of plasmablastic lymphoma was proffered.

Fig. 1.

a, b PET-CT scan image showing a metabolically active soft tissue mass involving the left maxillary sinus, maxillary alveolus, and hard palate

Fig. 2.

a-c Microphotographs showing tumor cells arranged sheets, individual malignant cells appearing monomorphic and plasmacytoid in appearance (HE 40x, 100x, 400x)

Fig. 3.

a LCA showing heterogeneous weak positivity (100x, inset 400x); b MUM1: positive (100x, inset 400x); (c) CD38: Positive in plasma cells (200x); d CD138: Positive in neoplastic plasma cells (100x, inset 400x); e Lambda: Positive (100x); f Kappa: Negative (100x); g CK: Negative; h Ki67 index: High 80–90% (100x)

Discussion

Plasmablastic lymphoma is included in the World Health Organization classification as a rare subtype of lymphoma described most frequently in HIV-infected patients and other immunosuppressed states [1]. This lymphoma is characterized by an unusual immunophenotype with negative CD20 (B cell-associated marker) and a predominant plasma cell differentiation, expressing markers, such as CD38, CD138 (plasma cell-associated antigens) and MUM1 protein. PBL immunophenotype is similar to myeloma; however, using genomic profiling, PBL seems closer to DLBCL. Recently Chang et al. studied genomic aberration pattern of PBL using array-based comparative genomic hybridization which appeared to be more similar to that of DLBCL than plasmacytoma [2]. Hence, even at genomic level PBL can be classified as a subtype of DLBCL.

In patients with AIDS, primary B cell lymphoma (PBL) most notably affects the oral cavity (21%), particularly the hard palate, gingiva, and jaw. Gingival involvement is a hallmark in HIV-positive individuals, while tongue involvement is more commonly observed in immunocompetent patients [3]. Within the oral cavity, PBL predominantly targets the hard palate. Plasmablastic lymphoma has also been linked to lymphoproliferative disorders, autoimmune diseases, immunosuppression, and cases following solid organ transplantation. Extranodal involvement is common in HIV-negative cases, occurring in 89% of patients. Extra oral sites include gastrointestinal tract (20%), soft tissues (17%), and bone marrow (15%). The present case showed both nodal and extra nodal involvement by plasmablastic lymphoma [4].

PBL is often diagnosed at an advanced stage, typically characterized by significantly elevated LDH levels and a high proliferation index (Ki67 > 80%), as observed in this case. Microscopically, PBL exhibits diverse histopathological features, with large cells resembling immunoblasts and plasmablasts. In some instances, a “starry sky” appearance is noted due to macrophages and apoptotic tumor cells. Plasmacytic differentiation can range from subtle to prominent, accompanied by a high mitotic and apoptotic index. Immunohistochemical analysis reveals unique features of PBL, including a lack of expression of mature B cell markers, such as CD20, CD45, and CD79a. Instead, markers of plasmacytic differentiation, such as CD138, CD38, and MUM1, are expressed. The proliferation index, measured by Ki67, typically exceeds 80%. Furthermore, in situ hybridization for EBER, associated with Epstein–Barr virus (EBV) infection, is positive in approximately 75% of cases [4]. These findings underscore the strong association between EBV and PBL, particularly in HIV-positive individuals. The immunosuppression caused by HIV promotes co-infection with oncogenic viruses like EBV, contributing to the poor prognosis of PBL in AIDS patients.

Although PBL was historically linked to HIV-positive individuals, its clinical spectrum has broadened to include HIV-negative patients, those with autoimmune disorders, organ or bone marrow transplants, or no prior history of chronic immunosuppression. Clinically, PBL often presents as a tumor mass in extranodal sites, with the head and neck region, particularly the oral cavity, being the most commonly affected. However, cases have also been reported in other organs. Diagnosing oral PBL can be particularly challenging, especially with limited biopsy samples. It must be carefully distinguished from histologically similar neoplasms, such as poorly differentiated oral carcinomas, anaplastic variants of diffuse large B cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK-positive DLBCL, and HHV8-positive large B cell lymphoma, Burkitt lymphoma with plasmablastic differentiation. These diagnostic complexities highlight the importance of thorough histopathological and immunohistochemical evaluation. Plasmablastic lymphoma (PBL) is distinct from plasma cell neoplasms, with one of its hallmark features being MYC overexpression. This may result from MYC translocations, gene amplifications, or constitutive activation of STAT3 [5]. Additionally, Epstein–Barr virus co-infection is a frequent characteristic of PBL, further distinguishing it from plasmablastic myeloma.

The prognosis for PBL is generally poor, influenced by several factors including immunosuppression, as seen in this case, advanced disease stages, EBV negativity, treatment resistance, and C-MYC mutations. The disease’s high relapse rate, often driven by severe immunosuppression in advanced HIV/AIDS and the inherent chemoresistance of PBL, contributes to its unfavorable outcomes. Lymphoma progression remains the leading cause of death in these patients. The treatment approach for PBL typically mirrors regimens used for other aggressive lymphomas, with CHOP or CHOP-like therapies being the most commonly employed options.

PBL is a rare and aggressive lymphoma with a dismal prognosis despite intensive chemotherapy regimens and virological suppression in the setting of HIV. Other aggressive lymphomas with plasmablastic morphology may lead to diagnostic dilemmas, however, a systematic laboratory diagnostic approach, including EBER status, typically clarifies the precise diagnosis of PBL. Awareness of this lymphoma variant and its distinct immunohistochemical profile is crucial for young dental surgeons and dental pathologists to ensure accurate diagnosis and prevent misdiagnosis.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations

Conflict of interest

The authors declare no conflicts of interest.

Consent of Participate

The authors certify that they have obtained the appropriate consent from the patient. The patient has given his consent for the images and other clinical information to be reported in the journal. The patient understands that the name and initials will not be published, and due efforts have been made to conceal the same.

Ethical Approval

For this case, formal consent from a local ethics committee is not required.