INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Vol. 27, no. 3, 461-465 (2014)
LETTER TO THE EDITOR
SUBGLOTIC MALT-LYMPHOMA OF THE LARYNX: AN UNUSUAL PRESENTATION OF CHRONIC COUGH M. ZAPPAROLP, AR. TROLESE2, A REM03, S. SINA3, A BONETTPand C. MICHELETTOI I
Pneumology Unit, Mater Salutis Hospital, Legnago (VR), Italy; 'Oncology Unit, Mater Salutis Hospital, Legnago (VR), Italy; 'Pathology Unit, Mater Salutis Hospital, Legnago (VR), Italy Received June 11, 2014 - Accepted August 4,2014
Extranodal non-Hodgkin lymphomas limited to the larynx are rare, accounting for less than 1 % of all laryngeal neoplasms. The most common site of development of primary laryngeal lymphomas is the supraglottic region. In most cases, the presenting symptoms are hoarseness, dysphagia, dyspnea, and cervical lymphadenopathy. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report a case of a primary extranodal marginal zone of mucosa-associated lymphoid tissue (Malt Lymphoma) of the larynx in a 73-year-old non-smoker woman, presented as chronic cough, unresponsive to oral corticosteroid. We present a detailed report of her clinical and paraclinical data as well as treatment options. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes. If a cough persists after consideration of the most common causes, CT scan and a bronchoscopic evaluation are fundamental for the diagnosis of tumors of the upper and lower respiratory tract. Malignant lymphoma (ML) of the larynx are rare tumors accounting for less than I % of primary malignant laryngeal tumors (I). However, nonHodgkin B-cell lymphoma (NHL-B) together with plasmacytoma are the most common primary hematologic tumors of the larynx (2). Fewer than 100 cases have been reported in the Literature, mainly predominantly located in the supraglottic larynx because of the follicular lymphoid tissue present in this area (3). Among the subtypes of NHL-B, diffuse large B-cell lymphoma (ICD-O 9680/3) and the extranodal marginal zone of mucosa associated lymphoid tissue (ICD-O 9699/3, MALT lymphoma, ML) are the most common primary laryngeal lymphomas (I). The ML of the larynx is a rare but well-documented entity which may arise from chronic inflammatory process (4). We report a
case of primary ML of the larynx in a 73-year-old female, with a review of the main features of this subset of extranodal lymphoma. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Casepresentation We report the case of a 73-year-old woman, non-smoker, non-atopic, who was not taking any drugs. The patient had been hospitalized two months previously in another hospital for "chronic laryngitis", she had reported chronic cough (particularly during the night), hoarseness, dysphonia, dry sore, burning throat, exercise induce and nocturnal dyspnea. The patient was treated with systemic corticosteroids (prednisolone 25 mg day for 3 weeks), with partial improvement of the symptoms. The patient was
Key words: lymphoma ofthe larynx, chronic cough, bronchoscopy Mailing address: Dr. Claudio Micheletto, UOC di Pneumologia, Ospedale Mater Salutis, Via Gianella 1, 37045, Legnago (VR), Italy e-mail: [email protected]
0394-6320 (2014)
461
Copyright © by BlOLIFE. s.a.s. This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties DISCLOSURE: ALL AUTHORS REPORT NO CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.
462
M. ZAPPAROLI ET AL.
admitted to our hospital for increasing exertional dyspnea and persistent cough . A physical examination found no laterocervical lymphnodes; no abnormal pulmonary sounds. The patient's history and physical examination were silent. Blood workup was uneventful. Spirometry was normal but with a typical morphology of extra thoracic airway compression. Chest radiograph findings were also normal. A bronchoscopy was then performed, according to the ACCP guidelines on Diagnosis and Management of Cough (5); in patients with a suspicion of airway involvement by a malignancy, even when chest radiograph is normal, bronchoscopy is indicated. The endoscopic examination of the airways (Fig. I) revealed a subglottic, submucosal lump with no tracheal or lung involvement. The endoscopic biopsy showed a laryngeal mucosa infiltrated by small B-cell lymphocytes resembling centrocytes (irregular nuclei with dispersed chromatin and inconspicuous nucleoli) with a pale monocitoid-like cytoplasm (Fig. 2A). The immunoistochemistry profile showed expression for C020 (Fig. 3B), BCL-2, IgO (Fig. 20) and negative staining for C05 , COlO, C056 and TCL-IA (Fig. 3C). The proliferating index was 5-10%. These morphologic and immunoistochemical
features supported the diagnosis ofML. Importantly, computed tomography (CT) scans of the neck and of the thorax failed to demonstrate pathological subglottic findings, only showing a discrete enhancement between the superior trachea and the esophagus with a lack of cervical or mediastinal lymphadenopathy. Magnetic Resonance (MR) of the neck confirmed the concentric thickening of the larynx, at the level of the vocal folds, a little more developed in the right areas and with an average thickness of 6-7 mm. No significant lymphnodes in the lateral cervical were found. A bone-marrow biopsy did not show any anomalies. The diagnostic staging revealed no other organ or systemic involvement. The esophagogastroscopy showed antral gastritis associated with the presence of Helicobacter pylori, no signs of reflux disease; gastric biopsies were negative for gastric ML. A repeat laringoscopy was performed about a week later with another biopsy, that confirmed the findings of the first examination. The patient was treated with radiotherapy for a total of2800 Gy. Post treatment endoscopy of the upper airway showed a reduction of the concentric wall thickening of the larynx previously described . This finding was
Fig. 1. The endoscopic examination of the airways revealed a subglottic, submucosal lump and no tracheal or lung involvement.
Int. J. Immunopathol. Pharmacol.
463
A
B
c
D
Fig. 2. A) Laryngeal mucosa biopsy consisting oflymphocytic B infiltration around and in glandular annex(magnification JOOX). B) CD20 expression in lymphocytes (magnification JOOX). C) Negative expression ofTCL- JAin B-celllymphocytes as reported in MALT-lymphoma (magnification JOOX). D) The IgD expression in neoplastic cell supports the marginal zone origin ofthe lymphoma (IgD; 200X).
confirmed by MR. Clinically the patient showed improvement in the absence of hoarseness and cough and dyspnea, even after cessation of steroid therapy that was continued during radiotherapy. To date, the patient has no signs or symptoms of disease progression. DISCUSSION We present the case of 73-year-old patient with chronic dry cough who showed a subglottic lesion at bronchoscopy. Cough is a nonspecific reaction to irritation anywhere from the pharynx to the lungs. Based on its clinical presentation, cough can be divided into acute self-limiting cough, lasting less than 3 weeks, or chronic persistent cough, which usually lasts for more than 8 weeks. In patients with chronic cough, treatment ofthe most common causes of cough is the most frequent approach (i.e., upper
airway cough syndrome, asthma, non asthmatic eosinophilic bronchitis, and gastro-esophageal reflux disease). These three causes are responsible for up to 90% of all cases of chronic cough. Less common causes include infections, medications, and lung diseases. In patients with chronic cough, therapy should be given in sequential and additive steps because more than one cause of cough may be present. A careful clinical history may provide important diagnostic clues that allow for targeted therapeutic trials without the need for further investigation. If cough persists after consideration of the most common causes, uncommon causes should be considered. A chest CT and, if necessary, bronchoscopy should then be performed (5). Extranodal NHL accounts for 20-30% of all lymphomas, while ML represents only 6% of all NHL subtypes, both nodal and extranodal (3, 4). Laryngeal NHL is extremely rare, with very few
464
M. ZAPPAROLI ET AL.
published reports. Most lymphomas of the larynx also involve other sites, including the salivary glands, thyroid, nasopharynx and tonsils (I). The most common site of primary laryngeal lymphomas is the supraglottic region, as it contains lymphoid collections in the lamina propria and in the entricles (2). In the case of our patient, the tumor was located in the subglottic region of the larynx and involved no other sites as assessed by a thorough ear, nose and throat examination and CT scans. The age of onset for laryngeal lymphomas varies between 4 and 81 years, with the mean age of occurrence being in the seventh decade (our patient was 73 years old); the distribution between males and females is similar. The symptoms at presentation are common to other laryngeal neoplasms, i.e. hoarseness, dysphonia, dysphagia, stridor, cough and other systemic symptoms, such as weight loss and fever (5). In some cases, the disease is revealed by a threatening dyspnea requiring an urgent tracheotomy. The mechanical airway obstruction explains the obvious similarity with laryngeal squamous cell carcmorna. Primary laryngeal lymphomas constitute a diagnostic challenge because they are characterized by the absence of clinical and gross differential criteria, as compared to squamous cell carcinoma. A survey of primary lymphomas of the larynx published from 1996 to 2008 shows that 47% were located in the supraglottic region, 25% in the glottic area, and the remainder were either subglottic or transglottic (6). Regarding the macroscopic characteristics of the reported cases, 20 of 36 cases (55%) were described either as smooth or submucosal masses, whereas only two cases (5.5%) were ulcerated lesions (6). While imaging techniques such as CT and magnetic resonance imaging may be helpful in the assessment of any laryngeal neoplasm (7), a definitive diagnosis requires histological examination of a biopsy specimen. A wide spectrum of histological subtypes of laryngeal lymphomas has been reported. The great majority of laryngeal NHL are of B-cell lineage, frequently presenting as diffuse large cell lymphoma; very few are of T-cell lineage (8, 9). Among the NHLB, several laryngeal cases of ML have been reported from that first described in the 1990 by
Diebold and coIl. (10) even if the gastrointestinal tract is the most common site ofML, comprising 50% of all cases. Other common sites include salivary gland, (lung 14%), head and neck (14%) ocular adnexa (12%), skin (11%) thyroid (4%) and breast (4%) (II). In many cases of ML there is a history of a chronic inflammatory disorder that results in accumulation of extranodal lymphoid tissue. The chronic inflammation may be the result of infection, autoimmunity or other unknown stimulus (II). Four cases of laryngeal ML are reported in patients with autoimmune disease (12-15) and Helicobacter pylori (the main ML etiology in gastrointestinal tract) has been reported in laryngeal disease (1617). The neoplastic cell of classic ML is composed predominantly of small B-cells including marginal zone (centrocyte-like) cells, cells resembling monocytoid cells, small lymphocytes and scattered immunoblasts and centroblast-like cells. A plasma cell differentiation could be present. In epithelial tissue, glandular cells or epithelium are often invaded and destroyed by discrete aggregates of lymphoma cells, resulting in the so-called Iymphoepithelial lesions (II). The neoplastic cells of ML express the antigens CD20, CD79, and immunoglobulin D. They usually are negative for CD5, CDIO,CD23 CyclinDI. There is no specific marker for MALT lymphoma at present, although the lack ofTCL-IA is considered a feature useful in diagnosing ML (18). While there is no consensus regarding the treatment of MCL, localized stage I and II patients are usually treated with chemotherapy and/or radiotherapy, while those with disseminated forms (stages III and IV) are treated with chemotherapy only. Conclusion. Laryngeal ML is exceedingly rare, and currently there is no consensus for a standardized treatment for this type oflymphoma. New therapeutic protocols, however, are under evaluation and may improve outcome. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes and when the diagnostic evaluation suggests that an uncommon cause, pulmonary as well as extrapulmonary, may be contributing. Until uncommon causes that potentially may be contributing to the patient's cough have been ruled out, the diagnosis of unexplained cough should not be made by CT scan and bronchoscopy
Int. J. Immunopalhol. Pharmacol.
evaluation. REFERENCES I.
2.
3.
4.
5.
6.
7.
8.
9.
Franzen A, Kurrer MO. Malignant lymphoma of the larynx: a case report and review of the literature. Laryngorhinootologie 2000; 79( I0):579-83. Horny HP, FerlitoA, CarboneA. Laryngeal lymphoma derived from mucosa-associated lymphoid tissue. Ann Otol Rhinol Laryngol 1996; 10(7):577-83. Velders GA, Kluin-Nelemans JC, De Boer CJ, et al. Mantle-cell lymphoma: a population-based clinical study. J Clin Onco11996; 14(4):1269-74. Steffen A, Jafari C, Merz H, Galle J, Berger G. Sublottic MALT lymphoma of the larynx. In Vivo 2007; 21:695-98. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough. Executive summary. Chest 2006; 129: IS-23S. Markou K, Goudakos J, Constantinidis J, Kostopoulos I, Vital V, Nikolaou A. Primary laryngeal lymphoma: report of 3 cases and review of the literature. Head Neck 2010; 32(4):541-49. Siddiqui NA, Branstetter BF 4th, Hamilton BE, Ginsberg LE, Glastonbury CM, Harnsberger HR, Barnes EL, Myers EN. Imaging characteristics of primary laryngeal lymphoma. Am J Neuroradiol 2010; 31(7):1261-65. Cheng CJ, Chen PR, Liu MC, Kuo MS, Hsu YH. Primary malignant lymphoma of mucosa-associated lymphoid tissue of larynx. Otolaryngol Head Neck Surg 1999; 121(5):661-62. Fung EK, Neuhauser TS, Thompson LD. Hodgkinlike transformation of a marginal zone B-cell lymphoma of the larynx. Ann Diagn Pathol 2002; 6(\ ):61-66.
465
10. Diebold J, Audouin J, Viry B, Ghandour C, Betti P, D'Omano G. Primary Iymphoplasmacytic lymphoma of the larynx: a rare localization of MALT-type lymphoma. Ann Otol Rhinol Laryngol 1990; 99:57780. II. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, Thiele J, Vardiman Jw. WHO classification of tumors of haematopoietic and Lymphoid tissues. IARC press Lyon 2008. 12. Gonzalez N, Xicoy B, Olive A, Jove J, Ribera JM, Feliu E. Systemic lupus erythematosus in a patient with primary MALT lymphoma of the larynx. Ear Nose Throat J 2009; 88(8):E4-5. 13. Fischer M, Hom IS, Bertolini J, Dietzsch S, Fuchs M, Dietz A. Laryngeal MALT lymphoma with known Sjogren syndrome. HNO 20 II; 59( I): 111-14. 14. Gonzalez-Murillo EA, Castro-Rodriguez A, Sanchez-Venegas JC, Pefia-Ruelas CI. Subglottic MALT lymphoma of the larynx in a patient with rheumatoid arthritis. Acta Otorrinolaringol Esp 2013. 15. Patiar S, Ramsden JD, FreelandAP. B-celllymphoma of the larynx in a patient with rheumatoid arthritis. J Laryngol Otol 2005; 119(8):646-48. 16. Kania RE, Hartl DM, Badoual C, Le Maignan C, Brasnu DF. Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx. Head Neck 2005; 27(3):258-62. 17. Titiz A, Ozcakir 0, Ceyhan S, Yilmaz YF, Unal A, Akyon Y. The presence of Helicobacter pylori in the larynx pathologies. Auris Nasus Larynx. 2008; 35(4):534-38. 18. Munari E, Rinaldi M, Ambrosetti A, Bonifacio M, Bonalumi A, Chilosi M, Zamo A. Absence of TCL IA expression is a useful diagnostic feature in splenic marginal zone lymphoma. Virchows Arch 2012; 461(6):677-85.
Vol. 27, no. 3, 461-465 (2014)
LETTER TO THE EDITOR
SUBGLOTIC MALT-LYMPHOMA OF THE LARYNX: AN UNUSUAL PRESENTATION OF CHRONIC COUGH M. ZAPPAROLP, AR. TROLESE2, A REM03, S. SINA3, A BONETTPand C. MICHELETTOI I
Pneumology Unit, Mater Salutis Hospital, Legnago (VR), Italy; 'Oncology Unit, Mater Salutis Hospital, Legnago (VR), Italy; 'Pathology Unit, Mater Salutis Hospital, Legnago (VR), Italy Received June 11, 2014 - Accepted August 4,2014
Extranodal non-Hodgkin lymphomas limited to the larynx are rare, accounting for less than 1 % of all laryngeal neoplasms. The most common site of development of primary laryngeal lymphomas is the supraglottic region. In most cases, the presenting symptoms are hoarseness, dysphagia, dyspnea, and cervical lymphadenopathy. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report a case of a primary extranodal marginal zone of mucosa-associated lymphoid tissue (Malt Lymphoma) of the larynx in a 73-year-old non-smoker woman, presented as chronic cough, unresponsive to oral corticosteroid. We present a detailed report of her clinical and paraclinical data as well as treatment options. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes. If a cough persists after consideration of the most common causes, CT scan and a bronchoscopic evaluation are fundamental for the diagnosis of tumors of the upper and lower respiratory tract. Malignant lymphoma (ML) of the larynx are rare tumors accounting for less than I % of primary malignant laryngeal tumors (I). However, nonHodgkin B-cell lymphoma (NHL-B) together with plasmacytoma are the most common primary hematologic tumors of the larynx (2). Fewer than 100 cases have been reported in the Literature, mainly predominantly located in the supraglottic larynx because of the follicular lymphoid tissue present in this area (3). Among the subtypes of NHL-B, diffuse large B-cell lymphoma (ICD-O 9680/3) and the extranodal marginal zone of mucosa associated lymphoid tissue (ICD-O 9699/3, MALT lymphoma, ML) are the most common primary laryngeal lymphomas (I). The ML of the larynx is a rare but well-documented entity which may arise from chronic inflammatory process (4). We report a
case of primary ML of the larynx in a 73-year-old female, with a review of the main features of this subset of extranodal lymphoma. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Casepresentation We report the case of a 73-year-old woman, non-smoker, non-atopic, who was not taking any drugs. The patient had been hospitalized two months previously in another hospital for "chronic laryngitis", she had reported chronic cough (particularly during the night), hoarseness, dysphonia, dry sore, burning throat, exercise induce and nocturnal dyspnea. The patient was treated with systemic corticosteroids (prednisolone 25 mg day for 3 weeks), with partial improvement of the symptoms. The patient was
Key words: lymphoma ofthe larynx, chronic cough, bronchoscopy Mailing address: Dr. Claudio Micheletto, UOC di Pneumologia, Ospedale Mater Salutis, Via Gianella 1, 37045, Legnago (VR), Italy e-mail: [email protected]
0394-6320 (2014)
461
Copyright © by BlOLIFE. s.a.s. This publication and/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties DISCLOSURE: ALL AUTHORS REPORT NO CONFLICTS OF INTEREST RELEVANT TO THIS ARTICLE.
462
M. ZAPPAROLI ET AL.
admitted to our hospital for increasing exertional dyspnea and persistent cough . A physical examination found no laterocervical lymphnodes; no abnormal pulmonary sounds. The patient's history and physical examination were silent. Blood workup was uneventful. Spirometry was normal but with a typical morphology of extra thoracic airway compression. Chest radiograph findings were also normal. A bronchoscopy was then performed, according to the ACCP guidelines on Diagnosis and Management of Cough (5); in patients with a suspicion of airway involvement by a malignancy, even when chest radiograph is normal, bronchoscopy is indicated. The endoscopic examination of the airways (Fig. I) revealed a subglottic, submucosal lump with no tracheal or lung involvement. The endoscopic biopsy showed a laryngeal mucosa infiltrated by small B-cell lymphocytes resembling centrocytes (irregular nuclei with dispersed chromatin and inconspicuous nucleoli) with a pale monocitoid-like cytoplasm (Fig. 2A). The immunoistochemistry profile showed expression for C020 (Fig. 3B), BCL-2, IgO (Fig. 20) and negative staining for C05 , COlO, C056 and TCL-IA (Fig. 3C). The proliferating index was 5-10%. These morphologic and immunoistochemical
features supported the diagnosis ofML. Importantly, computed tomography (CT) scans of the neck and of the thorax failed to demonstrate pathological subglottic findings, only showing a discrete enhancement between the superior trachea and the esophagus with a lack of cervical or mediastinal lymphadenopathy. Magnetic Resonance (MR) of the neck confirmed the concentric thickening of the larynx, at the level of the vocal folds, a little more developed in the right areas and with an average thickness of 6-7 mm. No significant lymphnodes in the lateral cervical were found. A bone-marrow biopsy did not show any anomalies. The diagnostic staging revealed no other organ or systemic involvement. The esophagogastroscopy showed antral gastritis associated with the presence of Helicobacter pylori, no signs of reflux disease; gastric biopsies were negative for gastric ML. A repeat laringoscopy was performed about a week later with another biopsy, that confirmed the findings of the first examination. The patient was treated with radiotherapy for a total of2800 Gy. Post treatment endoscopy of the upper airway showed a reduction of the concentric wall thickening of the larynx previously described . This finding was
Fig. 1. The endoscopic examination of the airways revealed a subglottic, submucosal lump and no tracheal or lung involvement.
Int. J. Immunopathol. Pharmacol.
463
A
B
c
D
Fig. 2. A) Laryngeal mucosa biopsy consisting oflymphocytic B infiltration around and in glandular annex(magnification JOOX). B) CD20 expression in lymphocytes (magnification JOOX). C) Negative expression ofTCL- JAin B-celllymphocytes as reported in MALT-lymphoma (magnification JOOX). D) The IgD expression in neoplastic cell supports the marginal zone origin ofthe lymphoma (IgD; 200X).
confirmed by MR. Clinically the patient showed improvement in the absence of hoarseness and cough and dyspnea, even after cessation of steroid therapy that was continued during radiotherapy. To date, the patient has no signs or symptoms of disease progression. DISCUSSION We present the case of 73-year-old patient with chronic dry cough who showed a subglottic lesion at bronchoscopy. Cough is a nonspecific reaction to irritation anywhere from the pharynx to the lungs. Based on its clinical presentation, cough can be divided into acute self-limiting cough, lasting less than 3 weeks, or chronic persistent cough, which usually lasts for more than 8 weeks. In patients with chronic cough, treatment ofthe most common causes of cough is the most frequent approach (i.e., upper
airway cough syndrome, asthma, non asthmatic eosinophilic bronchitis, and gastro-esophageal reflux disease). These three causes are responsible for up to 90% of all cases of chronic cough. Less common causes include infections, medications, and lung diseases. In patients with chronic cough, therapy should be given in sequential and additive steps because more than one cause of cough may be present. A careful clinical history may provide important diagnostic clues that allow for targeted therapeutic trials without the need for further investigation. If cough persists after consideration of the most common causes, uncommon causes should be considered. A chest CT and, if necessary, bronchoscopy should then be performed (5). Extranodal NHL accounts for 20-30% of all lymphomas, while ML represents only 6% of all NHL subtypes, both nodal and extranodal (3, 4). Laryngeal NHL is extremely rare, with very few
464
M. ZAPPAROLI ET AL.
published reports. Most lymphomas of the larynx also involve other sites, including the salivary glands, thyroid, nasopharynx and tonsils (I). The most common site of primary laryngeal lymphomas is the supraglottic region, as it contains lymphoid collections in the lamina propria and in the entricles (2). In the case of our patient, the tumor was located in the subglottic region of the larynx and involved no other sites as assessed by a thorough ear, nose and throat examination and CT scans. The age of onset for laryngeal lymphomas varies between 4 and 81 years, with the mean age of occurrence being in the seventh decade (our patient was 73 years old); the distribution between males and females is similar. The symptoms at presentation are common to other laryngeal neoplasms, i.e. hoarseness, dysphonia, dysphagia, stridor, cough and other systemic symptoms, such as weight loss and fever (5). In some cases, the disease is revealed by a threatening dyspnea requiring an urgent tracheotomy. The mechanical airway obstruction explains the obvious similarity with laryngeal squamous cell carcmorna. Primary laryngeal lymphomas constitute a diagnostic challenge because they are characterized by the absence of clinical and gross differential criteria, as compared to squamous cell carcinoma. A survey of primary lymphomas of the larynx published from 1996 to 2008 shows that 47% were located in the supraglottic region, 25% in the glottic area, and the remainder were either subglottic or transglottic (6). Regarding the macroscopic characteristics of the reported cases, 20 of 36 cases (55%) were described either as smooth or submucosal masses, whereas only two cases (5.5%) were ulcerated lesions (6). While imaging techniques such as CT and magnetic resonance imaging may be helpful in the assessment of any laryngeal neoplasm (7), a definitive diagnosis requires histological examination of a biopsy specimen. A wide spectrum of histological subtypes of laryngeal lymphomas has been reported. The great majority of laryngeal NHL are of B-cell lineage, frequently presenting as diffuse large cell lymphoma; very few are of T-cell lineage (8, 9). Among the NHLB, several laryngeal cases of ML have been reported from that first described in the 1990 by
Diebold and coIl. (10) even if the gastrointestinal tract is the most common site ofML, comprising 50% of all cases. Other common sites include salivary gland, (lung 14%), head and neck (14%) ocular adnexa (12%), skin (11%) thyroid (4%) and breast (4%) (II). In many cases of ML there is a history of a chronic inflammatory disorder that results in accumulation of extranodal lymphoid tissue. The chronic inflammation may be the result of infection, autoimmunity or other unknown stimulus (II). Four cases of laryngeal ML are reported in patients with autoimmune disease (12-15) and Helicobacter pylori (the main ML etiology in gastrointestinal tract) has been reported in laryngeal disease (1617). The neoplastic cell of classic ML is composed predominantly of small B-cells including marginal zone (centrocyte-like) cells, cells resembling monocytoid cells, small lymphocytes and scattered immunoblasts and centroblast-like cells. A plasma cell differentiation could be present. In epithelial tissue, glandular cells or epithelium are often invaded and destroyed by discrete aggregates of lymphoma cells, resulting in the so-called Iymphoepithelial lesions (II). The neoplastic cells of ML express the antigens CD20, CD79, and immunoglobulin D. They usually are negative for CD5, CDIO,CD23 CyclinDI. There is no specific marker for MALT lymphoma at present, although the lack ofTCL-IA is considered a feature useful in diagnosing ML (18). While there is no consensus regarding the treatment of MCL, localized stage I and II patients are usually treated with chemotherapy and/or radiotherapy, while those with disseminated forms (stages III and IV) are treated with chemotherapy only. Conclusion. Laryngeal ML is exceedingly rare, and currently there is no consensus for a standardized treatment for this type oflymphoma. New therapeutic protocols, however, are under evaluation and may improve outcome. In patients with chronic cough, uncommon causes should be considered when the cough persists after evaluation for common causes and when the diagnostic evaluation suggests that an uncommon cause, pulmonary as well as extrapulmonary, may be contributing. Until uncommon causes that potentially may be contributing to the patient's cough have been ruled out, the diagnosis of unexplained cough should not be made by CT scan and bronchoscopy
Int. J. Immunopalhol. Pharmacol.
evaluation. REFERENCES I.
2.
3.
4.
5.
6.
7.
8.
9.
Franzen A, Kurrer MO. Malignant lymphoma of the larynx: a case report and review of the literature. Laryngorhinootologie 2000; 79( I0):579-83. Horny HP, FerlitoA, CarboneA. Laryngeal lymphoma derived from mucosa-associated lymphoid tissue. Ann Otol Rhinol Laryngol 1996; 10(7):577-83. Velders GA, Kluin-Nelemans JC, De Boer CJ, et al. Mantle-cell lymphoma: a population-based clinical study. J Clin Onco11996; 14(4):1269-74. Steffen A, Jafari C, Merz H, Galle J, Berger G. Sublottic MALT lymphoma of the larynx. In Vivo 2007; 21:695-98. Irwin RS, Baumann MH, Bolser DC, et al. Diagnosis and management of cough. Executive summary. Chest 2006; 129: IS-23S. Markou K, Goudakos J, Constantinidis J, Kostopoulos I, Vital V, Nikolaou A. Primary laryngeal lymphoma: report of 3 cases and review of the literature. Head Neck 2010; 32(4):541-49. Siddiqui NA, Branstetter BF 4th, Hamilton BE, Ginsberg LE, Glastonbury CM, Harnsberger HR, Barnes EL, Myers EN. Imaging characteristics of primary laryngeal lymphoma. Am J Neuroradiol 2010; 31(7):1261-65. Cheng CJ, Chen PR, Liu MC, Kuo MS, Hsu YH. Primary malignant lymphoma of mucosa-associated lymphoid tissue of larynx. Otolaryngol Head Neck Surg 1999; 121(5):661-62. Fung EK, Neuhauser TS, Thompson LD. Hodgkinlike transformation of a marginal zone B-cell lymphoma of the larynx. Ann Diagn Pathol 2002; 6(\ ):61-66.
465
10. Diebold J, Audouin J, Viry B, Ghandour C, Betti P, D'Omano G. Primary Iymphoplasmacytic lymphoma of the larynx: a rare localization of MALT-type lymphoma. Ann Otol Rhinol Laryngol 1990; 99:57780. II. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, Thiele J, Vardiman Jw. WHO classification of tumors of haematopoietic and Lymphoid tissues. IARC press Lyon 2008. 12. Gonzalez N, Xicoy B, Olive A, Jove J, Ribera JM, Feliu E. Systemic lupus erythematosus in a patient with primary MALT lymphoma of the larynx. Ear Nose Throat J 2009; 88(8):E4-5. 13. Fischer M, Hom IS, Bertolini J, Dietzsch S, Fuchs M, Dietz A. Laryngeal MALT lymphoma with known Sjogren syndrome. HNO 20 II; 59( I): 111-14. 14. Gonzalez-Murillo EA, Castro-Rodriguez A, Sanchez-Venegas JC, Pefia-Ruelas CI. Subglottic MALT lymphoma of the larynx in a patient with rheumatoid arthritis. Acta Otorrinolaringol Esp 2013. 15. Patiar S, Ramsden JD, FreelandAP. B-celllymphoma of the larynx in a patient with rheumatoid arthritis. J Laryngol Otol 2005; 119(8):646-48. 16. Kania RE, Hartl DM, Badoual C, Le Maignan C, Brasnu DF. Primary mucosa-associated lymphoid tissue (MALT) lymphoma of the larynx. Head Neck 2005; 27(3):258-62. 17. Titiz A, Ozcakir 0, Ceyhan S, Yilmaz YF, Unal A, Akyon Y. The presence of Helicobacter pylori in the larynx pathologies. Auris Nasus Larynx. 2008; 35(4):534-38. 18. Munari E, Rinaldi M, Ambrosetti A, Bonifacio M, Bonalumi A, Chilosi M, Zamo A. Absence of TCL IA expression is a useful diagnostic feature in splenic marginal zone lymphoma. Virchows Arch 2012; 461(6):677-85.
