Plasmablastic lymphoma of the sphenoid bone in an immunocompetent patient: A diagnostic challenge

Abstract

Plasmablastic lymphoma is a rare type of highly aggressive B-cell non-Hodgkin lymphoma that usually occurs in immunocompromised patients and involves chiefly extra-nodal sites such as the oral cavity, jaw, gastrointestinal tract, soft tissue, bone, and skin. People above the age of 50 years are more commonly affected, with male predominance having a survival rate of 8 to 15 months. Here, we describe the case of a 48-year-old man who had an isolated plasmablastic lymphoma of the right sphenoid bone without any immunodeficiency. Plasmablastic lymphoma in immunocompetent patients at rare sites is a diagnostic challenge for both clinicians and pathologists because of vague clinical and histomorphology findings. This rare case report reemphasizes the utility of complete assimilation of clinical, histopathological, and immunohistochemical findings in such rare cases.

INTRODUCTION

Plasmablastic lymphoma (PBL) is classified as a subtype of B-cell non-Hodgkin’s lymphoma (NHL) that develops after the differentiation of activated B-cell lymphocytes into plasmablasts. The tumor cell subsequently loses its B-cell immunophenotype, giving rise to morphology and immunohistochemical expression that mimic plasmablasts.^[1] PBL is more common among immunocompromised groups, especially those positive for the human immunodeficiency virus (HIV), accounting for 69% of cases compared to 20.6% of HIV-negative individuals.^[2,3] PBL primarily affects extra-nodal sites such as the oral cavity, gastrointestinal tract, soft tissue, bone, and skin.^[4,5] In HIV-negative individuals, it affects the sinuses and nasal cavity.^[6] To date, only a handful of PBL cases have been documented in the sinuses of immunocompetent patients, and none have been discussed in relation to the sphenoid bone.^[7,8] Plasmablastic lymphoma exhibits diverse clinical, histological, and immunophenotypic characteristics, posing a diagnostic quandary for both clinicians and pathologists.^[9] In this case study, we have described a case of PBL in an immunocompetent patient that was centered in the right sphenoid bone and extended to the clivus and base of the skull.

CASE REPORT

A 48-year-old male presented to the neurosurgery department of our institute with chief complaints of on/off nasal bleeding and decreased vision in the right eye from the last two months associated with on/off a headache. For that, he took multiple courses of analgesics and oral antibiotics, but there was no improvement in symptoms. No documented history of fever, weight loss, or immunodeficiency was noted. A noncontrast magnetic resonance imaging (MRI) scan of the brain revealed an irregular, heterogeneous, expansile, and infiltrative mass centered in the body of the sphenoid bone. Involvement of the clivus, the base of the skull, and posterior ethmoidal air cells were also noted [Figure 1]. The MRI findings were suggestive of a neoplastic etiology, likely clival chordoma, non-Hodgkin’s lymphoma, or squamous cell carcinoma. Routine blood tests were conducted, and the results were within normal limits. A test for HIV by antigen immunoassay was also performed and reported as negative. The endoscopically guided biopsy was performed on the central lesion. The hematoxylin–eosin (H-E)-stained section of biopsy tissue revealed sheets of large cells displaying anisokaryotic hyperchromatic nuclei, coarse chromatin, and a moderate amount of cytoplasm. Intervening areas also showed foci of necrosis and cell debris [Figure 2a and b]. On the basis of histomorphology, the differential diagnosis of NHL, Ewing’s sarcoma, rhabdomyosarcoma, and undifferentiated epithelial malignancy was kept, and an immunohistochemistry panel was applied accordingly. On immunohistochemistry, the tumor cells showed positive expression for MUM-1 and CD138. The Ki-67 proliferation index was remarkably high (85%). No expression was noted for CD3, CD20, PAX-5, CD10, Bcl-6, CK, vimentin, myogenin, or CD99 [Figure 3a-d]. Based on histomorphology and immunochemistry, a diagnosis of PBL was made. A bone marrow examination was performed, which showed normal hematopoiesis. No increased plasma cells were noted in bone marrow aspirate smears or biopsy. An amalgamation of chemotherapy [etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride (EPOCH)] was given to the patient as primary treatment with radiotherapy at the local site. However, after one cycle of chemotherapy, the patient succumbed to his illness.

Figure 1: Noncontrast MRI scan of the brain revealed an irregular heterogeneous, expansile, and infiltrative mass centered in the body of sphenoid bone involving the clivus and the base of skull

Figure 2: Photomicrograph of hematoxylin–eosin (H-E)-stained sections of the plasmablastic lymphoma. (a) Tumor cells disposed in sheets (x4). (b) Tumor cells displaying anisokaryotic hyperchromatic nuclei and a moderate amount of cytoplasm (x40)

Figure 3: Photomicrograph of immunohistochemistry in plasmablastic lymphoma. (a) MUM1 displaying nuclear positive expression in tumor cells. (b) Membranous positive expression of CD138 in tumor cells. (c) Ki-67 proliferation index (85%). (d) Negative expression for CD3 (x40)

DISCUSSION

PBL is an uncommon malignant neoplasm with a wide spectrum of clinical and pathologic presentations. The literature lacks substantial knowledge regarding its clinical behavior and immunopathological characteristics because of its low prevalence.

Regarding clinical presentation, it has been noted that the sinuses, nasal, and oral cavities are the most frequently affected locations in non-HIV patients; however, it has also been noted in other sites, such as the gastrointestinal system, soft tissue, bone, and skin.^[5,10] A significant percentage of the reported cases of PBL in HIV-negative patients are shown to have immunosuppression. According to a systematic review conducted on HIV-negative patients with PBL, it was found that 58% of the cases were positive for Epstein–Barr virus (EBV). The review concluded that EBV may have a significant involvement in the development of PBL in HIV-negative patients. In addition, immunosuppression subsequent to post-transplantation, immune-related illness, and present or prior cancer all played a role in the development of PBL in 21% of the cases reported.^[10] In contrast, there were no factors of immunosuppression noted in the present case. Thus, it suggests that PBL in immunocompetent individuals may be caused by reasons other than HIV or immunosuppression.

The diagnosis of PBL in an immunocompetent patient is a challenge and requires a high level of clinical suspicion, imaging, histomorphological examination, and careful application of a battery of immunohistochemical markers. A heterogeneous histomorphological picture is seen in cases of PBL in an immunocompetent patient, varying from the diffuse and cohesive proliferation of neoplastic cells mimicking immunoblasts to cells with plasmacytic differentiation. The immunohistochemical markers for PBL have a peculiar pattern and display terminal differentiation of B-lymphocytes with plasma cell markers such as MUM1, CD138, and CD38. PBL is negative or weakly positive for CD20 and PAX-5. The Ki-67 proliferation index is generally very high (>90%).^[4,11] In a few cases, differentiation between plasmablastic plasma cell myeloma and PBL is not possible. In such cases, a clinical correlation with bone marrow analysis is the primary requirement for pathologists. The presence of end-organ damage, myeloma-defining events, and positive marrow findings for myeloma support the diagnosis of plasmablastic plasma cell myeloma over PBL.^[12]

The standard combination of chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) does not respond adequately in PBL. According to the National Comprehensive Cancer Network (NCCN) guidelines, the recommended chemotherapy regimen for PBL is etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride (EPOCH). PBL has a poor prognosis and worse clinical behavior. The clinical course of PBL is very assertive with a very poor prognosis despite the best treatment. The survival is fitfully ranging from 8 to 15 months.^[13]

CONCLUSION

The clinical and histomorphological findings are usually vague in cases of PBL, and hence, the diagnosis of this rare entity is very difficult without complete assimilation of clinical, histopathological, and immunohistochemical findings. The definitive diagnosis of PBL is necessary for its fortunate management, which leads to a better prognosis.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.