The pathological diagnosis of the mass was extranodal marginal zone B-cell lymphoma of the accessory parotid gland. Torso positron emission tomography–computed tomography (PET-CT) was conducted for tumor staging and evaluation of lymphomatous involvement of other organs. In addition to the left accessory parotid gland, focal hypermetabolic lesions were identified in both lacrimal glands and in the right retropharyngeal space, a finding suggestive of lymphomatous involvement (Fig. 5A–C). The subsequent bone marrow section biopsy did not reveal bone marrow involvement. The patient's laboratory values were as follows: white blood cell count of 4000 × 103/μL, hemoglobin level of 14.5 g/dL, platelet count of 290 × 103/μL, and lactate dehydrogenase (LDH) level of 368 IU/L, all of which were within normal limits. Considering the multisite involvement and the staging of the primary lesion (stage IIE), we planned to provide immunochemotherapy rather than surgery or radiotherapy. The patient was then transferred to the Department of Hematology to undergo therapy. She has received 6 cycles of rituximab with cyclophosphamide, vincristine, and prednisone (R-CVP) chemotherapy. After 6-month follow-up, enhanced CT demonstrated complete remission. There was no adverse effect and now she is currently under periodic follow-up.
We obtained the patient's medical records and reviewed the relevant literature. Informed written consent was obtained from the patient for publication of this case report and accompanying images. This study was approved by the Chonnam National University Hospital Institutional Review Board (IRB No. CNUH-2019-041).
According to the World Health Organization classification, malignant lymphoma can be divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). MALT lymphoma is a form of NHL. While HL usually arises from the inguinal, axillary, and cervical nodes, NHL occurs at extranodal sites.
MALT lymphoma most frequently occurs in the gastric mucosa, but can also develop in the gastrointestinal tract, lung, breast, lacrimal glands, and salivary glands. Possible causes include Helicobacter pylori-associated chronic gastritis, gastrointestinal bacterial infections, pulmonary bacterial infections, autoimmune diseases (e.g., Sjogren's syndrome and Hashimoto thyroiditis), and hepatitis C viral infection.[2,6] Such conditions of chronic inflammation induce proliferation of lymphoid tissue, leading to the development of MALT lymphoma.[1,3,9] In our case report, the patient had a history of an autoimmune disease (i.e., MG) and thymectomy. This history of chronic inflammation is thought to have induced lymphoid tissue proliferation, leading to the development of lymphoma.
The accessory parotid gland is a variation of the anteriorly extended parotid gland. This gland may be either continuous with or separated from the main parotid gland. Among the tumors that may arise in the parotid gland, NHL only accounts for 1% to 4%,[1,4] with subtypes including follicular lymphoma, diffuse large B-cell lymphoma, and MALT lymphoma. Of these subtypes, development of MALT lymphoma in the parotid gland is rare[1,5]; further, its development in the accessory parotid gland is especially rare, and such cases have scarcely been reported.
Imaging studies using ultrasonography, CT, and PET-CT must be performed to diagnose MALT lymphoma. However, there are limitations to these tests; therefore, pathological findings are necessary for a precise diagnosis. A simple diagnostic method to obtain pathological findings is fine needle aspiration biopsy.[4,5,12] On cytology, MALT lymphoma is positive for CD20 and CD79a, and negative for CD5, CD10, and cyclin D1.[5,6]
The treatment for nongastric MALT lymphoma varies according to its stage. According to the Ann Arbor staging system, stage I indicates involvement of a single lymph node region (I) or a single organ (IE). Stage II indicates involvement of 2 or more lymph node regions (II) or extranodal organs (IIE) on the same side of the diaphragm. Stage III indicates involvement of 2 or more lymph node regions above and below the diaphragm, and stage IV indicates widespread disease with or without lymph node involvement. According to the National Comprehensive Cancer Network guidelines, radiotherapy must be initially considered in stage I and II tumors,[7,12] and rituximab may be used in certain cases. If the tumor is located in the lung, breast, thyroid, or colon, surgery and additional radiotherapy may be considered. The treatment for stage III and IV tumors may be either chemotherapy or radiotherapy or even observation in certain cases. Periodic follow-up is necessary after treatment, and radiotherapy is considered in cases of local recurrence. Systemic recurrence can be treated with rituximab or in accordance with the treatment algorithm of marginal zone lymphoma. In addition to the tumor stage, the patient's overall health and age must be considered when determining the treatment method. In our case report, the patient was found to show localized lymphomatous involvement in the lacrimal gland and the retropharyngeal space, consistent with stage IIE. Although radiotherapy is the preferred treatment for stage IIE tumors, the patient was treated with immunochemotherapy using an R-CVP regimen due to the wide range of the lesion sites. Rituximab, a monoclonal anti-CD20 antibody, is effective in the treatment of B-cell lymphoma in combination with conventional chemotherapy including cyclophosphamide, vincristine, and prednisone.[13–15]
However, when evaluating patients who present with a cheek mass, physicians generally do not consider the possibility of a lymphoma. Because it is extremely difficult to distinguish lymphomas from other masses based on clinical and radiological features, they are often missed and are treated with surgical procedures, such as simple excision or parotidectomy. In such cases, if the intraoperative frozen biopsy reveals malignant and lymphoid tissue, superficial parotidectomy or total parotidectomy is recommended depending on the location of the mass. Adjuvant radiotherapy is also effective.[1,12] Further, PET-CT must be performed to evaluate lymphomatous involvement at other sites.
The complications of MALT lymphoma include local or distant organ involvement, central nervous system involvement, loss of organ function, weakened immune system, and intestinal obstruction. Additionally, the chemotherapy-related complications include dizziness, vomiting, and hair loss. The prevalence rate of dissemination at diagnosis of MALT lymphoma has been reported to be approximately 34%. The recurrence rate is approximately 48%. Furthermore, the 5-year overall survival rates of stage I/II and stage III/IV MALT lymphoma are approximately 94% and 69%, respectively. MALT lymphoma tends to remain localized for a long period and has a low tendency for systemic dissemination, although systemic dissemination can occur in some cases due to delayed diagnosis or treatment. Dissemination to the lymph nodes or bone marrow decreases the overall survival rate, which is why early diagnosis and treatment of MALT lymphoma are clinically important.
Generally, it has been reported that patients with a poor performance status score experience more adverse effects and have a lower survival rate. Additionally, abnormal LDH levels have been reported to be associated with a decreased therapeutic effect. Our patient had a performance status score of 0 and an LDH level of 368 IU/L; thus, we were able to expect good treatment outcomes and a favorable prognosis.
Our study has a few limitations. Several previous studies have investigated the relationship between MG and thymic MALT lymphoma,[2,18,19] as well as the relationship between thymectomy and the development of T-cell lymphoma in patients with MG.[9,20] However, in our case, MALT lymphoma (a form of B-cell lymphoma) developed in the accessory parotid gland after thymectomy for MG treatment, and the relationship between these 2 events was not investigated. Future prospective studies are necessary to identify any such associations.
Physicians should be aware that MALT lymphoma can also occur in the accessory parotid gland and that the choice of radiotherapy, chemotherapy, or surgery depends on accurate staging of the tumor. Therefore, when patients present with a cheek mass, careful history-taking and proper imaging workup are essential for its diagnosis. In addition, preoperative fine needle aspiration biopsy or intraoperative frozen biopsy should be performed if there is any suspicion of malignancy for the cheek mass.
Conceptualization: Jae Ha Hwang.
Data curation: Dong Wan Kim.
Formal analysis: Dong Wan Kim.
Resources: Jae Ha Hwang.
Supervision: Kwang Seog Kim, Sam Yong Lee.
Writing – original draft: Jae Ha Hwang.
Writing – review & editing: Jae Ha Hwang.
Jae Ha Hwang orcid: 0000-0001-6992-8067.
. Aydin S, Demir MG, Barişik NÖ. Extranodal marginal zone lymphoma of the parotid gland. J Maxillofac Oral Surg 2016;15(Suppl 2):346–50.
. Fukui T, Okazaki K, Tamaki H, et al. Immunogenetic analysis of gastric MALT lymphoma-like lesions induced by Helicobacter pylori
infection in neonatally thymectomized mice. Lab Invest 2004;84:485.
. Bende RJ, van Maldegem F, van Noesel CJ. Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas. Haematologica 2009;94:1109–23.
. Lee HG, Lee JY, Song JM. Malignant lymphoma on parotid gland: a clinical case. J Korean Assoc Oral Maxillofac Surg 2017;43:138–43.
. Mezei T, Mocan S, Ormenisan A, et al. The value of fine needle aspiration cytology in the clinical management of rare salivary gland tumors. J Appl Oral Sci 2018;26:e20170267.
. Urano M, Kiriyama Y, Abe M, et al. A case of mucosa-associated lymphoid tissue (MALT) lymphoma arising in the accessory parotid gland. Oral Med Pathol 2007;12:19–22.
. Kalra B, Kingsley PA, Negi P, et al. Bilateral parotid MALToma: a sure shot for radiation. Blood Res 2015;50:262–4.
. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016;127:2375–90.
. Sauce D, Larsen M, Fastenackels S, et al. Evidence of premature immune aging in patients thymectomized during early childhood. J Clin Invest 2009;119:3070–8.
. Aydin Y, Ulas AB, Mutlu V, et al. Thymectomy
in myasthenia gravis
. Eurasian J Med 2017;49:48–52.
. Ahn D, Yeo CK, Han SY, Kim JK. The accessory parotid gland and facial process of the parotid gland on computed tomography. PLoS One 2017;12:e0184633.
. Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN Guidelines Insights: B-Cell Lymphomas, Version 3.2019: Featured Updates to the NCCN Guidelines. J Natl Compr Canc Netw 2019;17:650–61.
. Marcus R, Imrie K, Belch A, Smith P. CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005;105:1417–23.
. Dotan E, Aggarwal C, Smith MR. Impact of rituximab (Rituxan) on the treatment of B-cell non-Hodgkin's lymphoma. P T 2010;35:148–57.
. Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance. Blood 2016;127:2082–92.
. Arcaini L, Burcheri S, Rossi A, et al. Nongastric marginal-zone B-cell MALT lymphoma: prognostic value of disease dissemination. Oncologist 2006;11:285–91.
. Raderer M, Streubel B, Woehrer S, et al. High relapse rate in patients with MALT lymphoma warrants lifelong follow-up. Clin Cancer Res 2005;11:3349–52.
. Gabrielli GB, Codella O, Capra F, De Sandre G. Pulmonary mucosa-associated lymphoid tissue lymphoma
and myasthenia gravis
. A case report. Haematologica 1998;83:381–2.
. Ragheb S, Lisak RP. B-cell-activating factor and autoimmune myasthenia gravis
. Autoimmune Dis 2011;2011:939520.
. Ohara M, Ozaki K, Ohkubo T, et al. Myasthenia gravis
complicated with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), following thymectomy
and longstanding tacrolimus therapy. Intern Med 2018;57:601–4.
Keywords:Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.
mucosa-associated lymphoid tissue lymphoma; myasthenia gravis; non-Hodgkin lymphoma; salivary gland neoplasm; thymectomy