Figure 1 B: H&E section shows crushing artifactual changes with round blue cells infiltrating in between the benign glands.
Discussion
Primary lymphoma in the larynx is an extremely rare disease contributing to less than 1 % of all laryngeal malignancies.(3) Although squamous cell carcinoma is the most common neoplasm seen in the larynx, it is necessary to keep the differential diagnosis broad including lymphoma of the larynx. (4)
MALToma commonly presents in the stomach accounting for 35 % of all cases but rare occurrences in the larynx have been reported. The majority of the patients with MALToma present with symptoms in Stage I and II which depend upon its localization. (1) MALT lymphoma has been associated with a history of chronic inflammatory disorders which may be the result of infection, autoimmunity, or unknown other stimuli. (1) Furthermore, there is a well-established association between H. pylori and gastric MALToma. (5) However, with MALT lymphoma of the larynx, the pathophysiological association with H. pylori is not established. Furthermore, infrequent presentation of MALT lymphoma in the larynx makes building any kind of such association with H. pylori or other stimuli challenging. (6) Likewise, there wasn’t any such chronic inflammatory condition present in our case.
The common symptoms of extranodal laryngeal lymphoma are hoarseness, dysphagia, pharyngalgia along with B symptoms. (7) Primary laryngeal lymphoma usually affects the supraglottic area with or without the involvement of the glottic or subglottic area. (8) In contrast-enhanced CT, most primary laryngeal lymphomas are usually homogenous with contrast enhancement. (9) Histologically, the characteristics of MALToma are similar regardless of the site of their origin. The microscopic features of marginal zone B cells are small to medium-sized, irregular nuclei with moderately dispersed chromatin and inconspicuous nucleoli, similar to those of centrocytes, and relatively abundant, pale cytoplasm.
However, Immunophenotype is a mandatory investigation for confirming the diagnosis. The neoplastic cells of MALT lymphoma express B cell-associated antigens CD20, and CD79, and are usually negative for CD5, CD10, CD23, and Cyclin D1.(1) As in our case, CD21 staining indicates expanded meshworks of follicular dendritic cells corresponding to colonized follicles. Like other low-grade lymphoproliferative disorders which stain positive for BCL2, here also it demonstrates low grade contrary to high-grade lymphomas. (10)
MALToma is usually indolent with recurrences that can occur after many years in other extranodal sites. (1) It has a desirable prognosis of a 5-Year relative survival rate > 80% but varies depending on the site of origin. (11) Rarity of these cases has made it difficult to establish a consensus on their prognostic factors and choice of treatments. The international guidelines recommend radiotherapy to be the preferred choice for localized non-gastric MALT lymphomas. A moderate dose (25-30 Gy) of radiation has shown a high rate of local control even in patients with local recurrences. Contrary to gastric MALT lymphomas, where antibiotic therapy to eradicate H. Pylori is the wellestablished standard of care, the role of antibiotic therapy is unclear and not recommended. Although the choice of treatment for severe or recurrent cases has not been certain, chemotherapy with chlorambucil in combination with rituximab has shown better results.(12)
Conclusion:
Although extranodal marginal zone lymphoma or MALToma of the larynx is a rare disease without any specific signs and symptoms, it should be considered in the differential diagnosis of a mass in the larynx. It has been difficult to generate a consensus regarding its management due to few cases, more case reports and research are necessary to better understand the disease and establish a treatment plan.
Acknowledgement: None
References
Swerdlow SH, Campo E, Harris NL, Jaffe ES, et al. (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017
Rizvi O, Nielsen T, Bearelly S. Mucosa-Associated Lymphoid Tissue Lymphoma of the Larynx. Case Rep Otolaryngol. 2020 Aug 18;2020:8703921. doi:
10.1155/2020/8703921. PMID: 32908756; PMCID: PMC7450344.
  1. Ansell SM, Habermann TM, Hoyer JD, Strickler JG, Chen MG, McDonald TJ. Primary laryngeal lymphoma. Laryngoscope. 1997;107(11 Pt 1):1502-1506. doi:10.1097/00005537-199711000-00014
  2. Yilmaz M, Ibrahimov M, Mamanov M, Rasidov R, Oktem F. Primary marginal zone B-cell lymphoma of the larynx. J Craniofac Surg. 2012;23(1):e1-e2. doi:10.1097/SCS.0b013e318242055a
  3. Sagaert X, Van Cutsem E, De Hertogh G, Geboes K, Tousseyn T. Gastric MALT lymphoma: a model of chronic inflammation-induced tumor development. Nat Rev GastroenterolHepatol. 2010;7(6):336-346. doi:10.1038/nrgastro.2010.58
  4. Rizvi O, Nielsen T, Bearelly S. Mucosa-Associated Lymphoid Tissue Lymphoma of the Larynx. Case Rep Otolaryngol. 2020 Aug 18;2020:8703921. doi:
10.1155/2020/8703921. PMID: 32908756; PMCID: PMC7450344.
  1. Zhao P, Zhou Y, Li J. Primary laryngeal lymphoma in China: a retrospective study of the last 25 years. J Laryngol Otol. 2019;133(9):792-795. doi:10.1017/ S0022215119001622
  2. Kato S, Sakura M, Takooda S, Sakurai M, Izumo T. Primary non-Hodgkin’s lymphoma of the larynx. J Laryngol Otol. 1997;111(6):571-574. doi:10.1017/ s0022215100137946
  3. King AD, Yuen EH, Lei KI, Ahuja AT, Van Hasselt A. Non-Hodgkin lymphoma of the larynx: CT and MR imaging findings. AJNR Am J Neuroradiol. 2004;25(1):12-15.
10.Ashton-Key M, Biddolph SC, Stein H, Gatter KC, Mason DY. Heterogeneity of bcl-2 expression in MALT lymphoma. Histopathology. 1995;26(1):75-78. doi:10.1111/j.1365-2559.1995.tb00624.x (BCL2 positive) 11.Olszewski AJ, Castillo JJ. Survival of patients with marginal zone lymphoma: analysis of the Surveillance, Epidemiology, and End Results database. Cancer. 2013;119(3):629-638. doi:10.1002/cncr.27773 12.Defrancesco I, Arcaini L. Overview on the management of non-gastric MALT lymphomas. Best Pract Res ClinHaematol. 2018;31(1):57-64. doi:10.1016/ j.beha.2017.11.001