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Mucosa-Associated Lymphoid Tissue Lymphoma of the Labial Minor Salivary Glands: Case Report
J Oral Med Pain 2024;49:22-27
Published online March 30, 2024;  https://doi.org/10.14476/jomp.2024.49.1.22
© 2024 Korean Academy of Orofacial Pain and Oral Medicine

Jung Eun Lee1│Dawool Han2│Hyun Sil Kim2│Chena Lee3│YounJung Park4│Jeong-Seung Kwon4

1Yonsei First TMJ Clinic, Seoul, Korea
2Department of Oral Pathology, Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, Korea
3Department of Oral and Maxillofacial Radiology, Dental Hospital of Yonsei University College of Dentistry, Seoul, Korea
4Department of Orofacial Pain and Oral Medicine, Dental Hospital of Yonsei University College of Dentistry, Seoul, Korea
Correspondence to: Jeong-Seung Kwon
Department of Orofacial Pain and Oral Medicine, Dental Hospital of Yonsei University College of Dentistry, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea
E-mail: jskwon@yuhs.ac
https://orcid.org/0000-0003-4584-7355
Received November 13, 2023; Revised December 6, 2023; Accepted December 29, 2023.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
A 74-year-old female presented with a complaint of dry mouth, continuous spontaneous burning sensation in the tongue, and asymptomatic submucosal soft tissue mass on both sides of the lower labial mucosa. She refused to undergo total excision of the mass due to concern about the possibility of complications such as nerve damage because of the large size of the mass. As her clinical features and magnetic resonance imaging indicated the possibility of Sjögren’s syndrome, a biopsy of the minor salivary gland of the right lower lip was performed. Consequently, she was diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. Although the patient had typical signs and symptoms of Sjögren’s syndrome, the histopathological result of MALT lymphoma made it impossible to determine whether the patient had a history of Sjögren’s syndrome. For patients with risk factors for MALT lymphoma, such as Sjögren’s syndrome, a biopsy of the labial minor salivary gland with immunohistochemical staining can be helpful in the diagnosis of not only Sjögren’s syndrome but also MALT lymphoma.
Keywords : B-cell; Immunohistochemistry; Lymphoma; Marginal zone; Salivary gland diseases; Sjögren’s syndrome
INTRODUCTION

Mucosa-associated lymphoid tissue (MALT) lymphoma is a subtype of marginal zone B-cell lymphoma that was first discovered by Isaacson and Wright in 1983 [1]. MALT lymphoma is a low-grade lymphoma that tends to remain localized and accounts for approximately 8% of malignant lymphomas. It can progress into diffuse large B-cell lymphoma, which can metastasize into other organs. Although MALT lymphoma mostly occurs in the gastrointestinal tract, the salivary glands are among the nongastric sites frequently affected by it. Salivary gland MALT lymphoma is a rare disease, with an incidence of only 0.086 cases per 100,000 people; this number includes all types of salivary gland MALT lymphoma, most of which occur unilaterally in the parotid gland [2], making MALT lymphoma in the minor salivary gland even more exceptional.

The prevalence of salivary gland MALT lymphoma is significantly higher in female. The reason for this sex-related difference is unclear, but it might be associated with the higher prevalence of Sjögren’s syndrome in female [3]. Factors underlying MALT lymphoma differ depending on the affected site. Gastric and splenic MALT lymphomas are associated with chronic inflammation caused by Helicobacter pylori and the hepatitis C virus, respectively, whereas salivary gland and thyroid MALT lymphomas are relatively frequent complications of autoimmune diseases such as Sjögren’s syndrome and Hashimoto’s thyroiditis [4]. Salivary gland MALT lymphoma is more common in patients with Sjögren’s syndrome. Furthermore, patients with Sjögren’s syndrome have a 44-fold higher risk of developing non-Hodgkin’s lymphoma, with MALT lymphoma accounting for 46%–56% of malignant lymphoma cases in these patients. Factors such as lymphadenopathy, splenomegaly, and persistent enlargement of the parotid gland increase the probability of developing lymphoma in patients with Sjögren’s syndrome [5].

This report presents a rare case of MALT lymphoma that developed in the minor salivary glands of the lower lip.

The study protocol was approved by the Institutional Review Board of Yonsei University Dental Hospital (IRB no. 2020-0008-002) with the written informed consent.

CASE REPORT

A 74-year-old female visited the Department of Orofacial Pain and Oral Medicine of Yonsei University Dental Hospital (Seoul, Korea) with a complaint of dry mouth and continuous spontaneous burning sensation in the tongue. These symptoms had been present for 5 months, and tongue pain increased during stimulation by spicy, hot, or salty food. In addition, the patient complained of asymptomatic submucosal soft tissue masses on both sides of the lower labial mucosa. She had no other medical history, except for rhinitis, and was not taking any medication. Sialometry performed at her initial visit to the clinic revealed a whole unstimulated salivary flow rate of 0.097 mL/min and a stimulated salivary flow rate with a gum base of 0.458 mL/min, indicating the presence of remarkable hyposalivation. The mass in the lower lip clinically resembled a mucocele with soft tissue consistency and a size of 2×1 cm2 (Fig. 1).


Blood tests revealed an elevated erythrocyte sedimentation rate (44 mm/h). Due to the presence of ocular dryness, laboratory tests for autoantibodies associated with Sjögren’s syndrome were conducted, which yielded negative results for anti-Ro/SSA and anti-La/SSB antibodies but positive results for antinuclear antibodies (titer=1:160), with a speckled pattern. The patient was prescribed saliva substitutes, an antifungal agent (Diflucan®), and sodium lauryl sulfate-free toothpaste, which relieved her dry mouth symptoms and tongue pain. As the patient had experienced repetitive trauma to the soft tissue mass on her right lower lip, an excisional biopsy of the mass was recommended. However, she refused to undergo total excision of the mass because of concern about the possibility of complications such as nerve damage due to the large size of the mass. During follow-up, the patient complained of lethargy, cutaneous pain upon touching, arthralgia, swelling of the ankle, pruritus, and eye discomfort (i.e., visual field defect and swelling). She also found a lump around her left parotid gland 2 months after her initial visit.

Magnetic resonance imaging (MRI) with gadolinium enhancement (3.0 –T; Pioneer, GE Healthcare) was performed (Fig. 2), which showed heterogeneous signal changes in both parotid glands. The imaging features in MR sialography—severe punctate or globular cavitation dispersed within both parenchyma of the parotid glands—were also highly suggestive of Sjögren’s syndrome. As the patient had dental prostheses on both posterior teeth, the lower lip mass could not be identified on MRI due to the presence of imaging artifacts.


Because the patient’s clinical features and MRI indicated the possibility of Sjögren’s syndrome, a biopsy of the minor salivary gland of the right lower lip was performed. Histopathological examination of the minor salivary glands showed dense and diffuse lymphocytic infiltration (Fig. 3A, B). Islands of lymphocyte-infiltrated glands and ducts as well as lymphoepithelial lesions were found within the tumor (Fig. 3C). The infiltrated lymphoid cells were mainly monotonous, comprising small- to medium-sized marginal zone cells with abundant cytoplasm and inconspicuous nucleoli. Furthermore, there were small numbers of various types of B-cell differentiation, including plasmacytic differentiated cells, centroblast-like cells, and immunoblast-like cells (Fig. 3D).


Immunohistochemical staining showed that the infiltrated lymphocytes were predominantly CD20-positive B cells (Fig. 4B) along with very few scattered reactive CD3-positive T cells (Fig. 4C), confirming a pathological diagnosis of B-cell MALT lymphoma. A few scattered clusters of CD10-positive lymphocytes were also seen, but they lacked well-structured germinal centers, which shows that the reactive germinal centers were infiltrated by the tumor cells and hence the tumor was not a follicular lymphoma (Fig. 4D). Staining of lambda and kappa light chains revealed lambda light-chain restriction in plasma cells (Fig. 4E, F). Comprehensive assessment of the clinical and pathological findings led to the final diagnosis of extranodal marginal zone B-cell lymphoma.


After the diagnosis, the patient was referred to a hematologist. Contrast-enhanced computed tomography (CT) showed a prominent increase in the size of both parotid glands compared with that observed on MRI performed 2 months previously. Swelling of both lacrimal glands was also noted. Both the parotid and lacrimal glands as well as the lower lip lesion exhibited high fluorodeoxyglucose uptake in combined positron emission tomography and CT (Fig. 5). The doctors recommended chemotherapy. However, the patient decided not to undergo active treatment for MALT lymphoma.

DISCUSSION

MALT lymphoma is known to be a low-grade and frequently localized lymphoma; it also has a good prognosis. However, in some cases, MALT lymphoma can occur at multiple sites or progress into diffuse large B-cell lymphoma, making early diagnosis of the disease crucial. Oral involvement of MALT lymphoma can be easily confused with other types of oral soft tissue diseases such as mucoceles owing to its low incidence rate. In the present case, MRI of both parotid glands revealed a punctate acinar cavity, which can also be observed in patients with Sjögren’s syndrome. However, the presence of the mucosal soft tissue mass played a pivotal role in the differential diagnosis of MALT lymphoma. Furthermore, CT images obtained at the 2-month follow-up revealed a significant increase in the volume of the glands. Sjögren’s syndrome causes gradual regression of gland volume and fatty atrophy rather than volume increases [6], and hence, this change in the imaging findings indicated a high probability of a tumorous lymphoma.

According to Zhang et al. [7], MALT lymphoma mostly occurs in the oromaxillofacial region, with 90% of patients showing only local progressive swelling. Therefore, a biopsy of an intraoral mass on the lip or palate should be performed to diagnose MALT lymphoma in cases accompanied by cervical lymphadenopathy, salivary gland swelling, or symptoms suggestive of Sjögren’s syndrome. In the present case report, although the patient had typical signs and symptoms of Sjögren’s syndrome on MRI imaging, the histopathological result of MALT lymphoma made it impossible to determine whether the patient had a history of Sjögren’s syndrome. Several patients with symptoms suggestive of Sjögren’s syndrome (e.g., long-term xerostomia or chronic parotitis) exhibited no remarkable swelling or mass on the salivary glands before a biopsy of the labial minor salivary gland was performed to diagnose Sjögren’s syndrome [8,9]. For patients who have risk factors for MALT lymphoma, such as autoimmune diseases (e.g., Sjögren’s syndrome, rheumatoid arthritis, and systemic lupus erythematosus), performing a biopsy of the labial minor salivary gland with immunohistochemical staining can be helpful in the diagnosis of not only Sjögren’s syndrome but also MALT lymphoma when an intraoral mass is not present.

CONFLICTS OF INTEREST

No potential conflicts of interest relevant to this article were reported.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article because no new data were created or analyzed in this study.

AUTHOR CONTRIBUTIONS

Conceptualization: JEL, JSK. Data curation: JEL. Visualization: JEL, DH, CL. Writing - original draft: JEL. Writing - review & editing: HSK, CL, YP, JSK.

Figures
Fig. 1. Intraoral photographs showing an asymptomatic submucosal soft tissue mass on both sides of the lower labial mucosa.
Fig. 2. Magnetic resonance imaging (MRI) of the patient. T2-weighted (A) and T1-weighted (B) MRI images of the patient showing heterogeneous signal changes in both parotid glands. Magnetic resonance sialography (C) reveals punctate acinar fillings dispersed within the parenchyma of both parotid glands.
Fig. 3. Histopathological examinations of a biopsy specimen of the labial minor salivary gland, with hematoxylin and eosin staining. (A, B) Diffuse dense lymphocytic infiltration was seen throughout the minor salivary glands. Remnants of the salivary gland architecture and cells (arrows) were observed (magnifications: A, ×40; B, ×200). (C) Monotonous lymphocytes infiltrated the glandular epithelium, which are typical features of lymphoepithelial lesions (arrows; magnification ×400). (D) The infiltrated lymphocytes were mainly small- to medium-sized monocytoid or centrocyte-like cells characterized by cleaved shape, abundant cytoplasm, and inconspicuous nucleoli. There were also a few lymphocytes with centroblast-like, immunoblast-like, and plasma cell-like features (magnification ×400).
Fig. 4. Immunohistochemical staining of the biopsy specimen (magnification ×200). (A) Representative hematoxylin and eosin-stained image of the lesion. (B) The infiltrated lymphoid cells were diffusely positive for CD20, suggesting a tumor originating from B cells. (C) A few scattered lymphoid cells were positive for CD3 (a T-cell marker) and were considered to be reactive lymphocytes. (D) A few clustered cells were positive for CD10 in a structural destructed pattern, indicating that the reactive germinal centers were heavily infiltrated by tumor cells. (E, F) The tumor cells showed lambda light-chain restriction (E) and were minimally stained for kappa light chain (F).
Fig. 5. (A) Computed tomography (CT) with contrast medium shows increased size of both parotid glands (arrows). (B) Swelling of the lacrimal gland was also noted (arrow heads). (C-E) Increased fluorodeoxyglucose uptake is evident in both the parotid and lacrimal glands in combined positron-emission tomography and CT images, as well as in the lower lip lesion (asterisks).
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