Mucosa‑associated lymphoid tissue in the central nervous system presenting as meningioma: A case report
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- Published online on: May 12, 2023 https://doi.org/10.3892/ol.2023.13863
- Article Number: 277
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Copyright: © Ren et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Abstract
Introduction
Primary central nervous system lymphoma (PCNSL) is an extranodal non-Hodgkin lymphoma that primarily affects the brain parenchyma, eyes, cranial nerve and meninges. It is an extremely rare occurrence, accounting for <3% of intracranial tumors in the US (1,2). PCNSL is primarily composed of diffuse large B-cell lymphomas of the activated B-cell subtype (3,4), with a small percentage of these lymphomas being marginal zone B-cell lymphoma (MZBL). MZBL also includes extranodal MZL of mucosa-associated lymphoid tissue (MALT) lymphoma, nodal MZL and splenic MZL (5). MALT lymphoma was initially thought to arise from gastrointestinal lymphoma, which is the most common site; however, it can also occur in other sites, such as the lungs, head and neck, skin, thyroid and breast (5,6). Meningioma, a common tumor of the central nervous system, is easy to diagnose because of its unique imaging features, such as the dural tail sign (7). MALT lymphoma involving meningeal tissue is uncommon and can be easily confused with meningiomas clinically. In the present report, the patient had similar imaging manifestations with meningioma, but was finally diagnosed with MALT lymphoma based on pathologic findings (Fig. 1). MALT lymphoma is rare in clinical practice, therefore, the mechanism and treatments were investigated.
Case report
A 59-year-old female with a history of hypertension, but no other significant medical and surgical history, presented to The Affiliated Huai'an No. 1 People's Hospital of Nanjing Medical University (Huai'an, China) with a 3-day history of dizziness accompanied by bilateral leg weakness after an epileptic seizure with no apparent cause in November 2015. No abnormalities were found after neurological examination or routine laboratory tests. Cranial computerized tomography (CT) revealed a mass lesion in the left temporal lobe surrounded by an edema lesion (Fig. 2A). Enhanced magnetic resonance imaging (MRI) showed a relatively homogeneous enhancing mass measuring 18×43 mm with a dural tail sign under the left frontal-parietal medial plate, which is a typical imaging manifestation of meningioma (Fig. 2B and C). Based on this information, a diagnosis of meningioma was made on November 11, 2015. The patient subsequently underwent a gross total resection of the tumor. Intraoperatively, a dark red-white 4×5×3 cm-sized tumor based on the dura mater was observed, along with invasion and adhesion of adjacent brain tissue.
For H&E staining, surgical specimens were fixed in 10% neutral formalin at room temperature for 24–48 h, and paraffin-embedded sections were produced (4 µm), stained with H&E at room temperature for 5 min and analyzed under a light microscope. Histological assessment of the tumor revealed a diffuse infiltration containing uniformly sized lymphocytes with atypia (Fig. 3A), consistent with a lymphoma diagnosis, as opposed to a meningioma diagnosis. Generally, most meningiomas are benign, and atypia is rare. The meningothelial meningioma, the most common subtype, is composed of polygonal, ill-defined, arachnoid epithelial cells variable in size, with abundant cytoplasm and large nuclei. The characteristic structure of meningiomas is the arrangement of cells in concentric circles of different sizes, with small blood vessels; the vessel walls can exhibit hyalinization, calcification or psammoma bodies.
Subsequently, H&E staining and immunohistochemistry was performed on the patient's tumor tissues. The primary antibodies used included anti-CD2, anti-CD3, anti-CD5, anti-CD10, anti-CD20, anti-CD21, anti-CD23, anti-CD43, anti-CD68, anti-CD79a, anti-Bcl-2, anti-Bcl-6, anti-MPO, anti-Cyclin D1 and anti-Ki-67 Immunohistochemical findings were as follows: CD20+++; CD79a+++; CD21+, CD23 follicle+; Ki-67+ 5%; BCL-2++++; CD10+10%; CD3+, CD5+, CD43 T-cell+; Cyclin D1−; MPO−; CD68−; and CD10+10% (Fig. 3B shows representative staining for CD20). The characteristics of small B-cell malignant lymphoma were consistent with extranodal MZBL of the MALT type.
Based on the immunohistochemical findings and histological assessment, it was recommended the patient receive chemotherapy or radiation therapy; however, the patients' economic situation led to her decision to be discharged from hospital. Patient follow-up after discharge from hospital continued via telephone and the internet (messaging) for 2 years, during which time the patient experienced no discomfort such as dizziness, headache and weakness. After this 2-year period, the patient began experiencing these symptoms; however, no abnormalities were found upon examination. Unfortunately, a cranial enhancing CT performed in November 2021 revealed a mass lesion in the left temporal lobe, along with left frontotemporal lobe and basal ganglia edema, which could not rule out postoperative recurrence; however, the patient opted out of treatment. The patient developed slurred speech accompanied by intermittent nausea, vomiting, headache and dizziness after 2 months, prompting her to re-evaluate treatment. Given the possibility of lymphoma recurrence, an MRI in January 2022 was performed and subsequently revealed abnormal enhancement of the left frontotemporal lobe along with surrounding edema and multiple enhancements of the intracranial meninges (Fig. 3C-E). Furthermore, a PET-CT scan showed multiple metastases throughout the patient's body. The patient was transferred to the oncology department for antitumor therapy after discharge.
Discussion
Primary central nervous system lymphomas are predominantly aggressive diffuse high-grade B-cell lymphomas of the large B-cell type. MALT lymphomas arise from B-cells in the MALT marginal area and are also known as extranodal marginal area B-cell lymphoma. The majority of MALT lymphomas occur in middle-aged women, and symptoms include epilepsy, headache and visual disturbance (8). The cytologic composition can vary, including small lymphocytic, plasmacytoid and marginal zone type cells; these may have reactive follicles, numerous transformed lymphocytes, plasma cells and other inflammatory cells (9).
Currently, there are a few widely accepted mechanisms for the formation of MALT lymphomas. In embryology, meningothelial cells are concentrated in the arachnoid membrane and dural venous sinuses, similar to epithelial cells in other sites where MALT lymphoma develops (4,10) In addition, dural-based MALT may be caused by the implantation metastasis of undiagnosed or disappearing MALT lymphoma at the meninges (11). Furthermore, the role of chronic inflammatory disease, including hepatitis C (12) and Helicobacter pylori-associated gastritis cannot be ruled out (8,9,12,13). Additionally, autoimmune diseases have been reported to be associated with MALT lymphoma, such as Grave's disease (14), Sjögren syndrome (8,14), scleroderma (14) and Hashimoto thyroiditis (9,13). Furthermore, IgG4 expression has been linked to primary intracranial MZBLs (15,16); Venkataraman et al (15) demonstrated this association through a series of retrospective analyses. A number of cases from the literature have been collated to further understand the characteristics of MALT lymphomas (Table I). Historically, the majority of cases occur in middle-aged women who primarily present with headaches and seizures, yet other manifestations can include hearing impairment, numbness, visual impairment and dysphasia, depending on the location of the tumor.
Table I.Summary of patient characteristics with intracranial extranodal marginal zone B-cell lymphomas. |
Clinically, the differential diagnosis of lymphoma is important; however, due to the dural tail sign, it can be difficult to distinguish it from meningioma based solely on imaging and clinical manifestations. Small lymphocytic lymphoma, chronic lymphocytic leukemia (CLL), lymphoplasmacytic lymphoma (LPL) are other potential diagnoses that require further histological and immunophenotypic analysis for confirmation. Notably, MALT lymphomas express CD20, CD79a and CD38, which can also be seen in LPL (Table II). In addition, CLL expresses CD5 and CD23. In the present case, a 59-year-old woman presented with dizziness and bilateral leg weakness. Immunophenotypically, the patients' lymphoid cells were positive for CD20, CD79a, CD21, CD23, BCL-2, CD3, CD5 and CD43, but were negative for Cylin D1, MPO and CD68. Although the immunohistochemical findings were similar to follicular lymphomas, the cells of follicular lymphoma grew nodular and formed obvious follicular structures at low magnification, which were not observed in the pathological findings of this tumor. Although the specific type of lymphoma cannot be confirmed, MALT lymphoma is more likely based on clinical symptoms, imaging and immunohistochemistry. However, it is unfortunate that genetic analysis of the lesion was not performed to verify and validate the diagnosis and treatments. Additional detection of MYD88, IgM and BRAF would aid in differentiating between LPL/Waldenstrom's macroglobulinemia, hairy-cell leukemia and MALT, increasing the accuracy of diagnosis.
In conclusion, MALT lymphomas are often confused with meningioma owing to similarities in imaging and clinical manifestations; thus, clinicians should not jump to conclusions when presented with images that resemble meningiomas, especially containing the dural tail sign. MALT lymphomas are generally indolent, localized lesions that can be cured through surgical resection and radiotherapy. Current evidence suggests that radiotherapy is the most commonly used treatment, and the extent of the dural lesions and leptomeningeal involvement determine the radiation field. As molecular genetic changes are tightly associated with classification, prognosis and treatment of tumors, additional detection of mutated genes is recommended, so as to more effectively treat diseases.
Acknowledgements
Not applicable.
Funding
The study was supported by the Key Science and Technology Project of Jiangsu Commission of Health (grant. no. ZD2021051).
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Authors' contributions
JBR, LYC, SXL and JHR confirm the authenticity of all the raw data. Study conception and design was performed by LSD and JBR. Material preparation and data collection were taken by LYC. Analysis and interpretation of data was performed by SXL. Follow-up of the patients was performed by JHR. All authors contributed to manuscript writing. All authors read and approved the final version of the manuscript.
Ethics approval and consent to participate
The report has obtained approval from the Ethics Committee and Institutional Review Board of Huai'an First People's Hospital (Huai'an, China; approval number: KY-2023-035-01).
Patient consent for publication
Written informed consent was obtained from the patient for the publication of the case details and any associated images.
Competing interests
The authors declare that they have no competing interests.
Glossary
Abbreviations
Abbreviations:
CLL |
chronic lymphocytic leukemia |
CT |
computerized tomography |
LPL |
lymphoplasmacytic lymphoma |
MALT |
mucosa-associated lymphoid tissue |
MPO |
myeloperoxidase |
MRI |
magnetic resonance imaging |
MZBL |
marginal zone B-cell lymphoma |
PCNSL |
primary central nervous system lymphoma |
PET-CT |
positron emission tomography computerized tomography |
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