The larynx is an extremely rare site of involvement by lymphomatous disease.We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management.peer-reviewe

Azzopardi, Charles Paul

Betts, Alexandra

Camilleri, David J.

Degaetano, James

Farrugia, Eric

Gatt, Alexander

Magri, Claude

Refalo, Nicholas

Case Reports in Medicine

English

PubMed

The larynx is an extremely rare site of involvement by lymphomatous disease. We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management

Charles Paul Azzopardi

James Degaetano

Alexandra Betts

Eric Farrugia

Claude Magri

Nicholas Refalo

Alexander Gatt

David J. Camilleri

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Laryngeal Lymphoma: The High and Low Grades of Rare Lymphoma Involvement Sites

The larynx is an extremely rare site of involvement by lymphomatous disease. We present two cases of isolated laryngeal high-grade and another low-grade lymphoma, together with a literature review of laryngeal lymphoma management.</jats:p

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Case ReportLaryngeal Lymphoma: The High and Low Grades ofRare Lymphoma Involvement SitesCharles Paul Azzopardi,1 James Degaetano,2 Alexandra Betts,2 Eric Farrugia,3Claude Magri,1 Nicholas Refalo,1 Alexander Gatt,1 and David J. Camilleri11 Department of Haemato-Oncology, Mater Dei Hospital, Tal-Qroqq, Msida MSD 2090, Malta2 Pathology Department, Mater Dei Hospital, Tal-Qroqq, Msida MSD 2090, Malta3 Department of Surgery, Mater Dei Hospital, Tal-Qroqq, Msida MSD 2090, MaltaCorrespondence should be addressed to Charles Paul Azzopardi; charles.a.azzopardi@gov.mtReceived 5 January 2014; Accepted 5 May 2014; Published 22 July 2014Academic Editor: David W. EiseleCopyright © 2014 Charles Paul Azzopardi et al.This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.The larynx is an extremely rare site of involvement by lymphomatous disease.We present two cases of isolated laryngeal high-gradeand another low-grade lymphoma, together with a literature review of laryngeal lymphoma management.1. Case 1An 82-year-old Caucasian lady known to suffer from ischa-emic heart disease, hypertension, and mild renal impairmentwas admitted to hospital in November 2010 complainingof a 3-month history of increasing facial pain and dif-ficulty breathing. She had previously undergone surgeryfor a complicated diverticular abscess two years prior tothis presentation and this had resulted in a defunctioningcolostomy. Physical examination showed no lymphadenopa-thy or organomegaly. Indirect laryngoscopy showed a massat the base of the tongue, involving the epiglottis and causingairway obstruction. The patient underwent an emergencytracheostomy to secure the airway. Investigations showed awhite blood count of 11.3 × 109/L, haemoglobin of 104 g/L,platelets of 296 × 109/L, and a normal serum lactate dehy-drogenase level of 209U/L. Staging with computed tomog-raphy only confirmed disease in the laryngeal area (Figure 1)and did not show any thoracic, abdominal, or pelvic lym-phadenopathy. Bone marrow aspiration and biopsy showedno evidence of bone marrow involvement.Biopsy of the laryngeal mass showed that the mucosaand submucosa were infiltrated by large atypical lymphoidcells with irregular nuclear outlines and multiple prominentnucleoli.The cells were positive for CD45 and CD20 and neg-ative for CD3 and bcl2 on immunohistochemistry (Figure 2).These findings were consistent with a diagnosis of diffuselarge B-cell (high-grade) non-Hodgkin lymphoma of thelarynx, stage IE, with an R-IPI score of 1 (age > 60, ECOG0–2, normal LDH of 209U/L, 0-1 extranodal sites, and stageI/II disease).The patient was administered three cycles of R-CEOP(rituximab, cyclophosphamide, etoposide, vincristine, andprednisone) followed by involved field radiotherapy. Anthra-cyclines were avoided in view of a decreased left ventricularejection fraction of 40% on echocardiography performed atdiagnosis.The first cycle of chemotherapy was complicated by anacute coronary syndrome, from which the patient recoveredwith supportive care.The tracheostomy was removed follow-ing the second cycle of cytotoxics and the patient remainsalive and well 5 years later.2. Case 2A 65-year-old Caucasian gentleman, with a history ofischaemic heart disease, presented to ENT with a two-month history of hoarseness. Physical examination wasunremarkable, with no lymphadenopathy or organomegaly.Investigations showed a white blood count of 5.7 × 109/L,haemoglobin of 148 g/L, platelets of 213 × 109/L, and a normalserum lactate dehydrogenase level of 192U/L.Hindawi Publishing CorporationCase Reports in MedicineVolume 2014, Article ID 284643, 4 pageshttp://dx.doi.org/10.1155/2014/2846432 Case Reports in MedicineFigure 1: Computed tomography at presentation.Indirect laryngoscopy showed vocal polyps, which wereexcised. Histology showed a monotonous population of lym-phoid cells within the lamina propria of mucosal polyps, withslightly irregular nuclear contours and inconspicuous to clearcytoplasm. Immunohistochemistry was positive for CD45,CD20, and bcl2 and negative for CD5, CD23, bcl6, CD138,CD43, CD10, and cyclin D1 (Figure 3), consistent with adiagnosis of extranodal marginal zone (low-grade) non-Hodgkin lymphoma.Staging with computed tomography and bone marrowaspiration and biopsy showed no evidence of disease involve-ment outside of the larynx.Thepatient wasmanagedwith involved field radiotherapyto the larynx with clinical resolution of symptoms and noradiological evidence of residual disease. He remains aliveand well 5 years later.3. DiscussionExtranodal lymphomas confined to the larynx are rare,accounting for <1% of all laryngeal neoplasms, with onlyabout 100 cases having been described in the literature to date[1]. A ten-year review involving 2631 laryngeal biopsies in alarge Spanish hospital revealed only one case of diffuse large Bcell lymphoma [2].This rare occurrence is due to the relativelylow lymphoid content in the larynx when compared to otherareas in the respiratory tract. The mean age at diagnosis is 70years, with a range from 4 to 81 years. The male : female ratiohas been reported to be variable in different series [3–5].Laryngeal lymphoma presents clinically in a similarfashion to squamous cell carcinoma, with symptoms such ashoarseness, dyspnoea, a foreign body sensation in the throat,or stridor. Uncommonly, it may present catastrophicallywith acute airway obstruction requiring immediate surgicalintervention, as in Case 1 presented above. Systemic symp-tomatology is unusual, since laryngeal lymphomas tend toremain localized for prolonged periods, thoughmore aggres-sive forms tend to spread earlier [6]. Interestingly, thesetumors usually spread to other mucosal sites such as bowel,lung, and orbit rather than nodal sites [7, 8].The commonest anatomical site involved is the supraglot-tic region (47%), with glottic involvement accounting for 25%of cases.The transglottic and subglottic regions are much lesscommonly affected [6].Macroscopically, these tumors present as smooth or poly-poid masses as depicted in our two cases, respectively, ratherthan ulcerated masses [6]. In fact, both the macroscopic andradiological appearances of a large laryngeal tumour with asupraglottic submucosal component should alert the report-ing investigators to the possibility of laryngeal lymphoma [3–5], though the definite diagnosis always rests on histology.Histologically, primary laryngeal lymphoma is more com-monly of B-cell origin, though some T-cell and NK-cell lym-phomas may occur. The latter are more difficult to diagnoseand usually require deep and sometimes repeated biopsy.This latter subgroup of laryngeal lymphoma is commoner inHIV patients.The B-cell to T/NK-cell Lymphoma ratio is 6 : 1[1, 5, 7].There is some emerging evidence in the literature of theassociation ofH. pylori and other urease-splitting organisms,which may colonize the larynx, and the development ofPrimary Marginal Zone Laryngeal Lymphoma. When inves-tigating Primary Marginal Zone Laryngeal Lymphoma oneshould also exclude autoimmune conditions such as Sjo¨gren’ssyndrome [7, 8].It is imperative to stage the lymphomatous process cor-rectly, since treatment varies depending on both the gradeand the stage of the disease. PET-CT, in particular, is findingan important place for radiological staging in laryngeal lym-phoma, both low-grade and high-grade [9, 10]. In our caseswe did not perform PET-CT since these cases predated theadvent of this radiological modality in our country.A review of the literature on isolated laryngeal lym-phomas published over the last 2 years (from 1994–2014)mainly revealed case reports and reviews. No specific studieshave been carried out specifically looking at the managementof this rare type of lymphoma.Most reports described cases ofMALT lymphomas as in our Case 2 and others related toT/NK lymphomas [11]. Therapy was nonhomogenous due tothe different types of lymphomas as well as small numbers.However, the main modalities of treatment were IFRT (30–50G) alone or in combination with chemotherapy. We optedfor 3 cycles of chemoimmunotherapy for Case 1 with DLBCLand IFRT in Case 2 with MALT according to internationalguidelines on limited stage disease [12]. Surgical interventionis only usually required in cases presenting with acute airwayobstruction [6]. This disparity in treatment modalities, inde-pendent of lymphoma histology, is depicted in a table of caseseries reports found in the literature, spanning the periodof 1986 to 2013, presented by Bayoumi et al. [11]. A combinedchemotherapy-radiotherapy, seems to be, however, theemerging preferred modality of treatment, especially forhigh-grade lymphomas [6, 11].From this review, the most important points to emergeare as follows.(1) One should have a high index of suspicion for lym-phoma of the larynx, since the management is veryCase Reports in Medicine 3(a) (b)(c) (d)Figure 2: Infiltrate of vocal cord by large lymphoid cells on H&E ((a) and (b)), positive for CD20 ((c) and (d)) on immunohistochemistry.(a) (b)(c) (d)Figure 3: Infiltrate of vocal cord by small sized lymphoid cells on H&E ((a) and (b)), positive for CD20 (c) and bcl-2 (d) onimmunohistochemistry.different from that of other more commonly occur-ring tumors at this site.(2) Due to the small number of cases reported, there isno definite consensus regarding best management oflaryngeal lymphoma; it would be advisable that for thetime being one follows international lymphomaguidelines on limited stage disease for the manage-ment of laryngeal lymphoma [12].(3) The discussions ensuing from case reports regardinglymphoma affecting unusual sites highlight the lack ofevidence regarding the actual biology of these tumorsand best treatment options for patients.Thismay spur4 Case Reports in Medicinethe formation of regional/international databases forthe description of lymphomas affecting specific un-usual sites. With this approach these cases may bestudied in greater depth and may prompt the devel-opment of comparative treatment trials, provid-ing patients with more evidence-based therapeuticmodalities.Conflict of InterestsThe authors declare that there is no conflict of interestsregarding the publication of this paper.References[1] H.-P. Horny and E. Kaiserling, “Involvement of the larynx byhemopoietic neoplasms—an investigation of autopsy cases andreview of the literature,” Pathology Research and Practice, vol.191, no. 2, pp. 130–138, 1995.[2] M. J. Ferna´ndez-Acen˜ero, F. Larach, and C. Ortega-Ferna´ndez,“Non-epithelial lesions of the larynx: review of the 10-year expe-rience in a tertiary Spanish hospital,” Acta Oto-Laryngologica,vol. 129, no. 1, pp. 108–112, 2009.[3] S. M. Ansell, T. M. Habermann, J. D. Hoyer, J. G. Strickler, M.G. Chen, and T. J. McDonald, “Primary laryngeal lymphoma,”Laryngoscope, vol. 107, no. 11, part 1, pp. 1502–1506, 1997.[4] S. Kato, M. Sakura, S. Takooda, M. Sakuria, and T. Izumo,“Primary non-Hodgkin’s lymphoma of the larynx,”The Journalof Laryngology & Otology, vol. 111, pp. 571–574, 1997.[5] A. D. King, E. H. Y. Yuen, K. I. K. Lei, A. T. Ahuja, and A. vanHasselt, “Non-Hodgkin lymphoma of the larynx: CT and MRimaging findings,” American Journal of Neuroradiology, vol. 25,no. 1, pp. 12–15, 2004.[6] K. Markou, J. Goudakos, J. Constantinidis, I. Kostopoulos, V.Vital, and A. Nikolaou, “Primary laryngeal lymphoma: reportof 3 cases and review of the literature,” Head and Neck, vol. 32,no. 4, pp. 541–549, 2010.[7] K.Morgan, K. A.MacLennan, A. Narula, P. J. Bradley, and D. A.Morgan, “Non-Hodgkin's lymphoma of the larynx (stage IE),”Cancer, vol. 64, no. 5, pp. 1123–1127, 1989.[8] J.-R. Kuo, Y.-Y. Hou, S.-T. Chu, and C.-C. Chien, “Subglotticstenosis induced by extranodal mucosa-associated lymphoidtissue lymphoma,” Journal of the Chinese Medical Association,vol. 74, no. 3, pp. 144–147, 2011.[9] N. A. Siddiquia, B. F. Branstetter, B. E. Hamiltond et al., “Imag-ing characteristics of primary laryngeal lymphoma,”The Amer-ican Journal of Neuroradiology, vol. 31, no. 7, pp. 1261–1265, 2010.[10] K. Zhao, Y.-Z. Luo, S.-H. Zhou et al., “18F-fluorodeoxyglucosepositron emission tomography/computed tomography findingsin mucosa-associated lymphoid tissue lymphoma of the larynx:a case report and literature review,” Journal of InternationalMedical Research, vol. 40, no. 3, pp. 1192–1206, 2012.[11] Y. Bayoumi, A. Marzouk Maklad, M. Ali Tunio et al., “Clin-icopathological features and treatment outcomes of primarylaryngeal lymphomas in Saudi population,” Haematology &Leukaemia, 2013.[12] “NCCNGuidelines for Treatment of Cancer,” 2014, http://www.nccn.org/professionals/physician gls/f guidelines.asp.Submit your manuscripts athttp://www.hindawi.comStem CellsInternationalHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014MEDIATORSINFLAMMATIONofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Behavioural NeurologyEndocrinologyInternational Journal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Disease MarkersHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014BioMed Research InternationalOncologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Oxidative Medicine and Cellular LongevityHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014PPAR ResearchThe Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Journal ofObesityJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014 Computational and  Mathematical Methods in MedicineOphthalmologyJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Diabetes ResearchJournal ofHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Research and TreatmentAIDSHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Gastroenterology Research and PracticeHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014Parkinson’s DiseaseEvidence-Based Complementary and Alternative MedicineVolume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

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Laryngeal lymphoma : the high and low grades of rare lymphoma involvement sites

Laryngeal lymphoma : the high and low grades of rare lymphoma involvement sites

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