Oral and Maxillofacial Surgery Cases 3 (2017) 70e75

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Oral and Maxillofacial Surgery Cases

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Case Report

MALT Lymphoma occurring in the maxillofacial region: A

review of the literature and case report
Francisco Merino*, Cristina Va

zquez Martinez, Ignacio Zubillaga,


Gregorio Sanchez Aniceto, Claudio Ballestín
Hospital Universitario 12 de Octubre, Madrid, Spain

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: Mucosa-associated lymphoid tissue (MALT) lymphoma is a non-Hodgkin

Received 8 March 2017
Lymphoma (NHL) localized all along the aerodigestive tract. The aim of this report is to
Received in revised form 23 May 2017
present the case of a patient with MALT lymphoma in soft palate treated in our
Accepted 12 June 2017
Available online 14 June 2017 department.
Case report: Case of a 26-year-old female who visited our department. She presented a
Keywords: tumor in soft palate that she reported a year ago. A biopsy was performed with the
MALT Lymphoma diagnosis of a Low-B-grade MALT lymphoma type. Due to the low initial stage of the lesion
Oral malignant neoplasm the haematologist decided to start monotherapy with Rituximab. The therapy was changed
Rituximab to R-Bendamustine. At present and after two years since diagnosed (May, 2015eFebruary,
2017), the patient is disease-free.
Discussion: The MALT lymphoma constitute 8% of the NHL. Progression to aggressive
lymphoma is rare, occurring in under 10% of cases. Tumors are sensitive to radiotherapy
and local treatment, both options can be followed by a prolonged disease-free period.
The optimal treatment of MALT Lymphoma has not been agreed yet.
Conclusion: MALT lymphoma is a rare disease in maxillofacial area, with tendency to
remain in the original location for long periods. The optimal treatment of MALT Lymphoma
has not been agreed yet. Due to persistent disease and concomitant Sjo€ gren’s syndrome, in
our case it was agreed that combination of Rituximab with other chemotherapy agents was
indicated, with a good response.
© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

1. Introduction

Mucosa-associated lymphoid tissue (MALT) lymphoma is a non-Hodgkin Lymphoma (NHL) localized all along the aero-
digestive tract [1]. Specifically, these are clusters of lymphocytes found throughout the mucosal tissue. MALT Lymphomas or
MALTomas represent 5e10% of all NHLs. MALT are low-grade B-cell tumors that involve any mucosal site and are promoted by
local inflammatory processes or autoimmune disease. The most important feature is the marginal zone growth pattern and
the presence of lymphoepithelial lesions [2].

* Corresponding author.
E-mail address: fmerinodomingo@gmail.com (F. Merino).

http://dx.doi.org/10.1016/j.omsc.2017.06.001
2214-5419/© 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/).
 F. Merino et al. / Oral and Maxillofacial Surgery Cases 3 (2017) 70e75 71

About 48% of NHLs are located in extranodal regions, such as salivary glands and the oral cavity. The most common
extranodal lymphoma is MALT gastric lymphoma secondary to Helicobacter pylori infection and the second one is located in
salivary glands associated to Sjo €gren’s syndrome. Almost half of the patients with salivary gland lymphomas have clinical or
radiological evidence of Sjo € gren syndrome [3].
In the maxillofacial region, lymphomas represent 3e5% of all oral malignant neoplasms, which are the third most common
group following squamous cell carcinoma and salivary gland neoplasms. MALT lymphomas have an indolent behavior and
tend to remain localized. However, 25% of them disseminate to multiple sites. The aim of this report is to present the case of a
patient with MALT lymphoma in soft palate treated in our department.

2. Presentation of case

We report a case of a 26-year-old female who visited our department in June, 2015. She presented a tumor in soft palate
that she reported a year ago. Two years before, she had been treated for sialolithiasis in the right parotid and submaxilar
glands in another center.
The size of the soft palate bulk didn’t suffer any modification throughout the day or while eating. In fact, she didn’t refer
any local or systemic symptoms. As previous diseases, when she was 13-years old she was diagnosed with Sjo € gren’s syndrome
and had been followed by a Rheumatologist since then.
The patient presented bilateral upper palpebral ptosis and an increased size of right parotid gland (Fig. 1). Physical ex-
amination confirmed a fixed mass of elastic consistency and 3  2 cm in size on soft palate without bleeding or ulceration
(Fig. 2) The rest of physical examination had no relevant findings.
A biopsy of the mass was performed. The Pathologist reported a “diffuse infiltration by medium-size lymphocytes,
lymphoepithelial lesions and growth centers” (Fig. 3) consistent with the diagnosis of a Low-B-grade MALT Lymphoma type.
Inmunohistochemistry was positive for Bcl-2, CD20 and CD79a antigens and negative for CD3 and CD5 (Fig. 4). Proliferative
index (MIB-1) was 30%. The body-CT-scan, showed no systemic abnormalities. Locally, it was described an anomalous pa-
renchyma of both submandibular glands and enlarged parotid glands with microcalcifications and cysts inside in congruency
with Sjo€ gren's Syndrome. The mass on soft palate was circumscribed to mucous membrane without affecting the bone.
A gastroscopy and bone marrow aspirate dismissed the possibility of distance dissemination. According to the modifi-
cation of the scale of Ann Arbor by Lugano, stage I was compatible with the initial diagnosis.
The patient was referred to the Hematology Department in order to begin systemic treatment. Secondary to the low initial
stage of the lesion, they decided to start monotherapy with Rituximab [4,5].
After 1 month of therapy and four cycles of rituximab, the patient was remitted again to our department to evaluate the
lesion in the soft palate. The lesion had significantly decreased in size after chemotherapy with rituximab so we decided
watchful-waiting (Figs. 5e6). After 2 months, the lesion didn’t disappear so we decided to rebiopsy it.
The Pathologist reported the lesion as persistent low-grade MALT lymphoma. Subsequently, the haematologist changed
the therapy to R-Bendamustine. The patient received 8 cycles in total. A control head and neck PET- CT scan was performed in
12 weeks after end of Chemotherapy and no remaining disease was found (Fig. 7).
At present and after two years since diagnosed (May, 2015eFebruary, 2017), the patient is disease-free.

Fig. 1. Upper palpebral ptosis and increased size of right parotid space.
72 F. Merino et al. / Oral and Maxillofacial Surgery Cases 3 (2017) 70e75

Fig. 2. Mass of elastic consistency on soft palate.

Fig. 3. Soft palate mucosa with diffuse infiltration by medium-size lymphocytes, lymphoepithelial lesions and growth centers. HE 40-1000.

Fig. 4. Proliferative cells were positive for CD20 (A), Bcl-2 (B) and CD79a (C). Inmunohistochemistry was negative for CD3, CD43, CD10, BCL-6, CD5, D1 cyclin and
CD23. Techniques for CD38, lambda y kappa were negative as well. Proliferative index (MIB-1) was 30% (D).
 F. Merino et al. / Oral and Maxillofacial Surgery Cases 3 (2017) 70e75 73

Fig. 5. Decreased size of right parotid space after rituximab therapy.

3. Discussion

NHL represent only 3.5% of the malignant pathology in the oral cavity. The most frequent is B-cell lymphoma, followed by
the T-cell and natural killer lymphoma. NHL of the oral cavity and oropharynx represent 13% of their extranodal location,
approximately 70% of them located in the tonsils. MALT Lymphoma is included within the marginal zone lymphomas. These
are non-Hodgkin’s lymphomas of B cells, whose evolution is possible commitment to lymph nodes and other organs. There
are three types of marginal zone lymphomas, and they all have a similar immune characteristics: positive for B cell markers
(CD 19, 20 CD and CD 22) and negative for CD5 and CD10, CD23. According to the REAL/WHO (World Health Organization)
classification includes:

 Splenic Marginal Zone Lymphoma

 Extranodal Marginal Zone B cell Lymphoma of mucosa associated lymphoid tissue (MALT).
 Nodal Marginal Zone Lymphoma

Initially Isaacson and Wright described MALT Lymphoma in 1983 as a pseudo-lymphoma secondary to their tendency to
remain in the original location for long periods of time. The European and American society officially recognized it in 1994 [6].
Currently it is considered a B-cell neoplasia that presents a high rate of local recurrence and potential to become a high-grade
B-cell lymphoma. While the marginal zone B-cell lymphoma and splenic lymphomas are rare, representing less than 2% of the
NHL, the MALT lymphoma is more common, constituting 8% of the NHL. MALT Lymphoma was originally identified in the
gastrointestinal tract, as a low-grade indolent lymphoma. It was subsequently defined in other mucosal and non-mucosal
organs, including lung, salivary gland, conjunctiva, tear gland, thyroid, breast, timo, orbit and skin.
Approximately 6% of the NHL that affect the Waldeyer ring are MALT lymphomas of the palatine tonsil. Salivary glands
MALT lymphomas are very rare in the literature; its emergence is reduced to small series of clinical cases without a protocoled
treatment. The largest series of cases described includes 63 patients [2]. In these cases, the prognosis of MALT Lymphoma
doesn’t impress to be worse, even when they have disseminated extranodal disease, as in the bone marrow, spleen and liver.
74 F. Merino et al. / Oral and Maxillofacial Surgery Cases 3 (2017) 70e75

Fig. 6. Persistent lesion on soft palate.

Fig. 7. Absence of lesion absence after second line of chemotherapy.

MALT Lymphoma mainly affects adults over 60, with a slight predominance in females. Clinical signs and symptoms are
mainly related to the location of the tumor. They often remain located for an extended period, with a reported 5-years overall
survival between 86% and 95%, without significant difference in clinical course between localized and disseminated disease
[7]. Recurrences may involve extranodal or nodal sites. Progression to aggressive lymphoma is rare, occurring in under 10% of
cases. Tumors are sensitive to radiotherapy and local treatment, both options can be followed by a prolonged disease-free
period.
It is postulated as a hypothesis that the origin of this Lymphoma comes from memory centers in B-lymphocytes with the
capacity to differentiate into marginal cells and plasma cells [8]. They have described four translocations associated with this
lymphoma:

 t(11; 18) (q21; q21)

 t(14; 18) (q32; q21)
 t(1; 14) (p22; q32)
 t(3; 14) (p13; q32)

There is increasing evidence that marginal zone lymphomas may be associated with inflammatory chronic episodes,
usually secondary to autoimmune or bacterial stimuli. The classic example is the association of H. Pylori with chronic gastritis
and gastric MALT Lymphoma. One of the mechanisms suggested for marginal zone lymphomas is the accumulation and
proliferation of B and T antigen-dependent cells secondary to chronic inflammation. Development of NHL is the most serious
 F. Merino et al. / Oral and Maxillofacial Surgery Cases 3 (2017) 70e75 75

complication of Sjogren’s syndrome. Different histological subtypes of NHL have been described associated with this syn-
drome, most frequently the MALT lymphoma. Tonami et al. [9] estimated the prevalence of both entities in 5.8%. Harris [10]
reported that lymphoepithelial sialadenitis is associated with the development of malignant lymphoma, 80% of which are
MALT subtype.
The most frequent clinical symptom is local swelling with or without ulceration. Underlying bone may be affected, showed
as radiolucent areas in radiographic studies. Differential diagnosis with squamous cell carcinoma and other histological
malignancies must be considered [11].
The optimal treatment of MALT Lymphoma of salivary glands has not been agreed yet, so according to the NCCN (National
Compressive Cancer Network) guidelines the treatment is guided by the staging of the lymphoma. The stadiums are
determined by the modification of the scale of Ann Arbor by Lugano.
Limited stages (stage I and II) include those patients who suffers a unique extralymphatic location or in which a lymph
node affected by continuity an organ or extralymphatic tissue. Loco regional radiotherapy is the main therapeutic option for
these stadiums (dose of 25e30 Gy). We used surgery with a diagnostic purpose, although it can also play an important role in
the treatment in areas with no indication of radiation therapy (e.g. Lung). Other options in selected cases are treatment with
Rituximab or clinical control.
Advanced stages (stage III and IV) include those patients with extranodal involvement and nodal involvement of other
organs or tissues. In these patient treatment is not clearly defined because of its low incidence, therefore they are usually
treated in a similar way to the follicular lymphomas with advanced stage, including immunotherapy with monoclonal an-
tibodies directed to CD20 (Rituximab e.g.) with or without adjuvant chemotherapy.
Surgery has played an important role (particularly in patients with Parotid location), but due to her loss of volume, and the
possible comorbid conditions is not considered the initial treatment option. Locoregional radiation therapy is an option that
results in less morbidity and has similar cure rates as surgery in early stages.
The use of anti-CD20 antibodies (Rituximab) has proved to be an effective option for the treatment of low-grade lym-
phomas. There are controversies regarding its efficacy for glandular lymphomas associated with Sjo € gren’s syndrome, and it is
considered that its combination with other chemotherapy agents is indicated as in our case [3e5].

4. Conclusion

MALT lymphoma is a rare disease, with a tendency to remain in the original location for long periods. It is suspected that it
may arise due to chronic inflammatory processes such as sialadenitis and Sjogren syndrome. The optimal treatment of MALT
Lymphoma has not been agreed yet, in the literature the use Rituximab has proved to be an effective option for the treatment
of low-grade lymphomas. Owing to persistent disease and concomitant Sjo €gren’s syndrome, in our case it was agreed that its
combination with other chemotherapy agents was indicated, with a good response.

Conflict of interest statement

There is no Conflict of Interest.

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