A Case of a Laryngeal MALT Lymphoma in a Patient with a History of Gastric MALT
We are reporting a case of a 62-year-old African American woman with a history of gastric MALT lymphoma successfully treated with radiation who presented with a laryngeal MALT lymphoma 4 years after her original diagnosis. She received definitive radiation with a complete response. The case presented is unique for the rare presentation of a MALT lymphoma in the larynx, especially in light of the patient’s previously treated gastric MALT lymphoma years ago.
Mucosa associated lymphoid tissue lymphomas, or MALT, are extranodal marginal zone B-cell lymphomas. While the most common anatomical location is the stomach, MALT lymphomas can also present in the lung, thyroid, breast, synovium, lacrimal and salivary glands, orbit, dura, skin, and soft tissues [1–13].
Laryngeal MALT lymphomas are exceedingly rare. Our search of the current literature revealed only 27 cases reported between 1990 and 2014 [14–16]. Caletti et al. previously reported a case of a patient with concomitant laryngeal MALT lymphoma and Helicobacter pylori (H. pylori) related gastric MALT lymphoma , but to our knowledge, a representation of a MALT lymphoma in the larynx following a gastric MALT lymphoma has never previously been described. Given the rarity of laryngeal MALT lymphomas, the risk factors, prognosis, and optimal management are not well defined.
2. A Case Report
In June 2010, a 62-year-old female presented to her gastroenterologist with intermittent epigastric pain for several months. Subsequent endoscopy revealed a gastric lesion. Immunohistochemistry was strongly positive for CD20 and negative for CD5, CD10, and BCL-6, confirming the diagnosis of MALT lymphoma. Testing was negative for H. pylori. Imaging with a PET/CT confirmed a malignancy confined to the stomach with no lymph node avidity or other evidence of disease. t(11;18) status was not performed at the time.
The patient received definitive radiation to her stomach, upper abdomen, and perigastric lymph nodes to a total dose of 3600 cGy at 180 cGy per fraction in 20 fractions over 3 weeks (Figure 1). The patient tolerated treatment well. The patient was followed with serial endoscopies and remained without evidence of disease.
Approximately 4 years following her initial diagnosis, she presented to her gastroenterologist complaining of one year of progressive difficulty breathing, dysphagia, odynophagia, and right ear fullness. Subsequent workup with esophagogastroduodenoscopy (EGD) revealed an exophytic, polypoid mass in the right false cord and pyriform sinus.
A fiberoptic examination confirmed a 3 cm mass arising from the right aryepiglottic fold obscuring view of the right vocal cord (Figure 2(a)). The left vocal cord was minimally visible upon phonation while the vallecula, epiglottis, and pharyngeal wall were spared. Partial involvement of the right pyriform sinus was again noted. PET/CT scan demonstrated avidity only within the laryngeal structures without any evidence of nodal involvement or distant disease (Figure 2(b)). The patient subsequently underwent biopsy of the right supraglottic lesion; pathology was consistent with MALT lymphoma (Figure 2(c)).
The patient received definitive radiation to 3000 cGy in 15 fractions to the larynx and hypopharynx (Figure 3). The patient tolerated the treatment well developing only mild odynophagia and hyperpigmentation of the skin without any breakdown.
At a follow-up visit 1 month after completing treatment, the patient’s odynophagia has resolved and she is tolerating a full PO diet. She has also had improvements in her voice. PET/CT performed 3 months after completing treatment demonstrated a complete resolution of the tumor subsequently (Figure 4), which was confirmed by fiberoptic examination.
Non-Hodgkin lymphomas (NHL) are tumors of the lymphoid tissues, derived from clonal expansion of B cells, T cells, natural killer (NK) cells, or their precursors. There are over 12 different types of NHL, including diffuse large B cell (31%), follicular (22%), and MALT lymphoma (5%) . MALT lymphomas are considered extranodal marginal zone B-cell lymphomas under the current world health organization classification system.
MALT lymphomas have been associated with immune system dysregulation from autoimmune disorders like Sjogren’s syndrome  or sustained immune stimulation from chronic infections with Chlamydia psittaci, Campylobacter jejuni, and Borrelia burgdorferi . In the stomach, they are most commonly associated with chronic infection with Helicobacter pylori [29, 30]. While information on a prognostic parameter such as LDH would be helpful, it was unavailable from an outside institution. Interestingly, our patient had neither a history of autoimmune disease nor an infection with the previously mentioned pathogens.
Radiation therapy represents a definitive treatment option for MALT lymphoma in patients with localized disease. For gastric MALT lymphomas, without t(11;18) status, antibiotics may not have been first line therapy. A radiotherapy regimen of 30 Gy in 20 fractions to the stomach and perigastric nodes has previously been reported with excellent clinical outcomes with high rates of pathological complete responses . In 2013, Zucca et al. presented the ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up, reporting excellent disease control with RT alone using moderate-dose involved-field radiotherapy using 24–30 Gy to the stomach and perigastric nodes given in 3 to 4 weeks . In its most recent guidelines released in 2014, the International Lymphoma Radiation Oncology Group reports its consensus on target definition and dose prescriptions for nodal non-Hodgkin lymphoma. There is a move away from previously applied extended-field and involved-field RT (IFRT) techniques that targeted nodal regions toward limiting the RT to smaller volumes based solely on detectable nodal involvement at presentation or involved-site RT (ISRT) as the clinical target volume . Both presentations of this patient were treated using 3D conformal IFRT technique in which the entire organ (larynx or stomach) was treated.
The presentation of laryngeal MALT lymphomas is exceedingly rare, with less than 30 previously reported cases in the literature. Of the previously reported cases, only 11 have involved the supraglottic larynx. These lymphomas are highly radiosensitive. For localized disease, radiotherapy is the most appropriate treatment for larynx preservation. Chemotherapy is reserved for recurrent or disseminated disease . The prognosis is generally favorable with some cases showing no evidence of disease up to 96 months after treatment (Table 1).
The larynx, which has little lymphoid tissue, may be involved secondarily in cases of disseminated malignant lymphoma; therefore clinical staging before and after treatment is necessary . When considering radiation as monotherapy, staging becomes of paramount importance. 18F-FDG PET/CT has been used for staging laryngeal MALT lymphomas and has provided a basis for both altering the therapeutic strategy and also evaluating the response to radiotherapy . However, despite being proven valuable in detecting sites of disease in some types of lymphomas, 18F-FDG PET/CT is not yet the standard method of staging and cannot substitute bone marrow examination. Biopsies from the ileum could add information as to the extent of this patient’s initial disease. It could also explain the fact that the lymphoma which was treated with local therapy relapsed in another extranodal site. The above could be also addressed after the representation and give important information for this case.
In conclusion, laryngeal MALT lymphomas represent rare clinical entities without any clear risk factors. For early stage disease, definitive radiation to a low dose represents an excellent treatment option with limited morbidity, excellent functional outcome, and durable disease control.
Conflict of Interests
The authors have no actual or potential conflict of interests.
M. F. Rosado, G. E. Byrne Jr., F. Ding et al., “Ocular adnexal lymphoma: a clinicopathologic study of a large cohort of patients with no evidence for an association with Chlamydia psittaci,” Blood, vol. 107, no. 2, pp. 467–472, 2006.View at: Publisher Site | Google Scholar
E. Zucca, A. Conconi, E. Pedrinis et al., “Nongastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue,” Blood, vol. 101, article 2489, 2003.View at: Publisher Site | Google Scholar
R. W. Tsang, M. K. Gospodarowicz, M. Pintilie et al., “Stage I and II malt lymphoma: results of treatment with radiotherapy,” International Journal of Radiation Oncology Biology Physics, vol. 50, no. 5, pp. 1258–1264, 2001.View at: Publisher Site | Google Scholar
F. M. Iwamoto, L. M. DeAngelis, and L. E. Abrey, “Primary dural lymphomas: a clinicopathologic study of treatment and outcome in eight patients,” Neurology, vol. 66, no. 11, pp. 1763–1765, 2006.View at: Publisher Site | Google Scholar
P. H. Tu, C. Giannini, A. R. Judkins et al., “Clinicopathologic and genetic profile of intracranial marginal zone lymphoma: a primary low-grade CNS lymphoma that mimics meningioma,” Journal of Clinical Oncology, vol. 23, no. 24, pp. 5718–5727, 2005.View at: Publisher Site | Google Scholar
A.-C. George, M. Ozsahin, R. Janzer et al., “Primary intracranial dural lymphoma of mucosa-associated lymphoid tissue (MALT) type: report of one case and review of the literature,” Bulletin du Cancer, vol. 92, no. 7, pp. E51–E56, 2005.View at: Google Scholar
J. S. Welsh, A. Howard, H. Y. Hong, D. Lucas, T. Ho, and D. J. Reding, “Synchronous bilateral breast mucosa-associated lymphoid tissue lymphomas addressed with primary radiation therapy,” American Journal of Clinical Oncology, vol. 29, no. 6, pp. 634–635, 2006.View at: Publisher Site | Google Scholar
J. I. Ikeda, E. Moni, A. Yamauchi et al., “Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type developing in gonarthritis deformans,” Journal of Clinical Oncology, vol. 25, no. 27, pp. 4310–4312, 2007.View at: Publisher Site | Google Scholar
O. Servitje, F. Gallardo, T. Estrach et al., “Primary cutaneous marginal zone B-cell lymphoma: a clinical, histopathological, immunophenotypic and molecular genetic study of 22 cases,” British Journal of Dermatology, vol. 147, no. 6, pp. 1147–1158, 2002.View at: Publisher Site | Google Scholar
J. A. Ferry, C. Y. Fung, L. Zukerberg et al., “Lymphoma of the ocular adnexa: a study of 353 cases,” The American Journal of Surgical Pathology, vol. 31, no. 2, pp. 170–184, 2007.View at: Publisher Site | Google Scholar
A. Stefanovic and I. S. Lossos, “Extranodal marginal zone lymphoma of the ocular adnexa,” Blood, vol. 114, no. 3, pp. 501–510, 2009.View at: Publisher Site | Google Scholar
M. Troch, M. Formanek, B. Streubel, L. Müllauer, A. Chott, and M. Raderer, “Clinicopathological aspects of mucosa-associated lymphoid tissue (MALT) lymphoma of the parotid gland: a retrospective single-center analysis of 28 cases,” Head & Neck, vol. 33, no. 6, pp. 763–767, 2011.View at: Publisher Site | Google Scholar
M. O. Khalil, L. M. Morton, S. S. Devesa et al., “Incidence of marginal zone lymphoma in the United States, 2001-2009 with a focus on primary anatomic site,” British Journal of Haematology, vol. 165, no. 1, pp. 67–77, 2014.View at: Publisher Site | Google Scholar
M. A. Tunio, M. AlAsiri, A. M. Maklad, and Y. Bayoumi, “Clinicopathological features and treatment outcomes of primary thyroid lymphomas in Saudi Arabia: a case series of seven patients,” Cancer Treatment Communications, vol. 1, no. 1, pp. 14–17, 2013.View at: Publisher Site | Google Scholar
K. Zhao, Y. Z. Luo, S. H. Zhou et al., “18F-fluorodeoxyglucose positron emission tomography/computed tomography findings in mucosa-associated lymphoid tissue lymphoma of the larynx: a case report and literature review,” Journal of International Medical Research, vol. 40, no. 3, pp. 1192–1206, 2012.View at: Publisher Site | Google Scholar
C. Bielinski, H. S. Luu, and T. Mau, “Mucosa-associated lymphoid tissue (MALT) lymphoma presenting as subglottic stenosis: single-agent treatment using rituximab,” Otolaryngology—Head and Neck Surgery, vol. 150, no. 2, pp. 334–335, 2014.View at: Publisher Site | Google Scholar
G. Caletti, T. Togliani, P. Fusaroli et al., “Consecutive regression of concurrent laryngeal and gastric MALT lymphoma after anti-Helicobacter pylori therapy,” Gastroenterology, vol. 124, no. 2, pp. 537–543, 2003.View at: Publisher Site | Google Scholar
K. Markou, J. Goudakos, J. Constantinidis, I. Kostopoulos, V. Vital, and A. Nikolaou, “Primary laryngeal lymphoma: report of 3 cases and review of the literature,” Head and Neck, vol. 32, no. 4, pp. 541–549, 2010.View at: Publisher Site | Google Scholar
N. Gonzàlez, B. Xicoy, A. Olivé, J. Jové, J.-M. Ribera, and E. Feliu, “Systemic lupus erythematosus in a patient with primary MALT lymphoma of the larynx,” Ear, Nose and Throat Journal, vol. 88, no. 8, pp. E4–E5, 2009.View at: Google Scholar
S. Arndt, H. Veelken, A. Schmitt-Gräff, A. Aschendorff, W. Maier, and B. Richter, “Multifocal extranodal mucosa-associated lymphoid tissue lymphoma affecting the larynx,” Annals of Otology, Rhinology and Laryngology, vol. 116, no. 4, pp. 257–261, 2007.View at: Publisher Site | Google Scholar
A. Fujita, H. Sugimoto, O. Sakai, H. Tanaka, T. Matsuyama, and A. Tanaka, “Mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx: a case report with MR imaging findings,” European Journal of Radiology Extra, vol. 62, no. 3, pp. 69–72, 2007.View at: Publisher Site | Google Scholar
R. E. Kania, D. M. Hartl, C. Badoual, C. Le Maignan, and D. F. Brasnu, “Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx,” Head and Neck, vol. 27, no. 3, pp. 258–262, 2005.View at: Publisher Site | Google Scholar
C.-J. Cheng, P.-R. Chen, M.-C. Liu, M.-S. Kuo, and Y.-H. Hsu, “Primary malignant lymphoma of mucosa-associated lymphoid tissue of larynx,” Otolaryngology—Head and Neck Surgery, vol. 121, no. 5, pp. 661–662, 1999.View at: Publisher Site | Google Scholar
R. de Bree, H. F. Mahieu, G. J. Ossenkoppele, and P. van der Valk, “Malignant lymphoma of mucosa-associated lymphoid tissue in the larynx,” European Archives of Oto-Rhino-Laryngology, vol. 255, no. 7, pp. 368–370, 1998.View at: Publisher Site | Google Scholar
S. Kato, M. Sakura, S. Takooda, M. Sakurai, and T. Izumo, “Primary non-Hodgkin's lymphoma of the larynx,” The Journal of Laryngology & Otology, vol. 111, no. 6, pp. 571–574, 1997.View at: Publisher Site | Google Scholar
J. O. Armitage and D. D. Weisenburger, “New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes,” Journal of Clinical Oncology, vol. 16, no. 8, pp. 2780–2795, 1998.View at: Google Scholar
K. E. Smedby, E. Baecklund, and J. Askling, “Malignant lymphomas in autoimmunity and inflammation: a review of risks, risk factors, and lymphoma characteristics,” Cancer Epidemiology, Biomarkers & Prevention, vol. 15, no. 11, pp. 2069–2077, 2006.View at: Publisher Site | Google Scholar
R. J. Bende, F. van Maldegem, and C. J. M. van Noesel, “Chronic inflammatory disease, lymphoid tissue neogenesis and extranodal marginal zone B-cell lymphomas,” Haematologica, vol. 94, no. 8, pp. 1109–1123, 2009.View at: Publisher Site | Google Scholar
J. H. Yi, S. J. Kim, J. Y. Choi, Y. H. Ko, B. T. Kim, and W. S. Kim, “18F-FDG uptake and its clinical relevance in primary gastric lymphoma,” Hematological Oncology, vol. 28, no. 2, pp. 57–61, 2010.View at: Publisher Site | Google Scholar
E. J. Beswick, G. Suarez, and V. E. Reyes, “H. pylori and host interactions that influence pathogenesis,” World Journal of Gastroenterology, vol. 12, no. 35, pp. 5599–5605, 2006.View at: Google Scholar
N. R. Schechter, C. S. Portlock, and J. Yahalom, “Treatment of mucosa-associated lymphoid tissue lymphoma of the stomach with radiation alone,” Journal of Clinical Oncology, vol. 16, no. 5, pp. 1916–1921, 1998.View at: Google Scholar
E. Zucca, C. Copie-Bergman, U. Ricardi, C. Thieblemont, M. Raderer, and M. Ladetto, “Gastric marginal zone lymphoma of MALT type: ESMO clinical practice guidelines for diagnosis, treatment and follow-up,” Annals of Oncology, vol. 24, no. 6, pp. vi144–vi148, 2013.View at: Publisher Site | Google Scholar
T. Illidge, L. Specht, J. Yahalom et al., “Modern radiation therapy for nodal non-hodgkin lymphoma—target definition and dose guidelines from the international lymphoma radiation oncology group,” International Journal of Radiation Oncology Biology Physics, vol. 89, no. 1, pp. 49–58, 2014.View at: Publisher Site | Google Scholar
N. A. Siddiqui, B. F. Branstetter IV, B. E. Hamilton et al., “Imaging characteristics of primary laryngeal lymphoma,” The American Journal of Neuroradiology, vol. 31, no. 7, pp. 1261–1265, 2010.View at: Publisher Site | Google Scholar