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Primary NK/T-cell lymphoma of the larynx.


Laryngeal extranodal non-Hodgkin lymphoma is uncommon, accounting for less than 1% of all laryngeal neoplasms; the B-cell phenotype is predominant. Lymphomas outside the nasal cavity are rare and highly aggressive. We present a case of primary natural killer T-cell (NK/T-cell) lymphoma of the larynx that arose in a 45-year-old man. Because only a limited amount of data is available on laryngeal NK/T-cell lymphoma, the mainstay of treatment remains unclear, although some data suggest that radiotherapy alone is the best option. Our patient was treated with chemotherapy and radiotherapy, and he remained in remission 2 years later.


Primary lymphoma of the larynx is rare, accounting for less than 1% of all primary laryngeal neoplasms. (1) Extranodal natural killer T-cell (NK/T-cell) lymphoma, which is extremely rare and highly aggressive, mainly affects the nasopharyngeal area and the nasal cavity; when it occurs in other remote sites, the prognosis is usually unfavorable. Treatment modalities include radiation, chemotherapy, immunotherapy, and a combination thereof.

To the best of our knowledge, only a few reports of primary NK/T-cell lymphomas of the larynx have been published in the English-language literature. (2-5) We report a highly unusual case of a primary NK/T-cell lymphoma that arose in the vocal folds and mimicked the clinical presentation of a squamous cell carcinoma of the larynx.

Case report

A 45-year-old man, a heavy smoker, was referred to our outpatient clinic with a 2-month history of a sore throat, pain on the right side of the neck, hoarseness, and otalgia. Dyspnea had occurred seldom and had resolved spontaneously. The patient had no difficulty swallowing, and he reported no related weight loss, fever, or night sweats. According to his history, 5 years earlier he had undergone laryngoscopy and biopsy of a benign polyp on his right vocal fold.

During our evaluation, flexible nasolaryngoscopy detected a keratotic mass on the posterior one-third of the right true vocal fold; the mass extended to the right arytenoid cartilage. The vocal folds were symmetrically mobile. A biopsy analysis of the mass revealed fragments of squamous mucosa that exhibited a dense, expansile, pleomorphic lymphoid infiltrate with an angiocentric growth pattern and prominent coagulative necrosis. The infiltrate was diffuse and composed of small, medium-sized, and large atypical lymphocytes with granular chromatin and clear cytoplasm (figure, A).

Numerous mitotic figures were identified. Immunohistochemically, the cells were positive for CD3 (cytoplasmic stain), CD56 (figure, B), CD43, CD30, TIA-1, and granzyme B. The neoplastic cells were negative for CD4, CD8, CDT, CDS, CD57, CD20, ALK-1, and Epstein-Barr virus (EBV). Based on the histopathologic and immunophenotyping results, a final diagnosis of extranodal NK/T-cell lymphoma, nasal type, was made.

Computed tomography (CT) of the neck, thorax, abdomen, and pelvis found no enlarged lymph nodes and normal intra-abdominal solid organs. Serology and histology for EBV were negative. Immunophenotyping of bone marrow aspiration showed 8% of CD[2.sup.+], CD[.sup.+], CD[7.sup.+], CD[56.sup.+], and CD[57.sup.+] lymphocytes. Bone marrow was not involved.

The patient was referred to the hematology clinic, where his disease was staged as IE. He was treated with two courses of CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) and then referred for radiotherapy (60 Gy). Two years after the completion of treatment, he remained disease-free.



Non-Hodgkin lymphoma usually occurs in the lymph nodes; extranodal origin accounts for approximately 25% of cases. (6) The most common site of lymphoma in the head and neck region is the Waldeyer ring. In the larynx, most cases arise in the supraglottic area (epiglottis and aryepiglottic folds) and spread to involve the glottis and, less commonly, the subglottis.

In a large international study of lymphoma cases, NK/T-cell lymphoma accounted for only 2 to 12% of all cases of non-Hodgkin lymphoma. (7) This type of tumor was found to be strongly associated with EBV infection, (6) and it has a predisposition to the Asian population. Since the nasopharynx and the nasal cavity are the most common sites of the NK/T-cell type of lymphoma, it is also called the nasal type. Most reported cases of primary lymphoma of the larynx have been non-Hodgkin lymphomas of B-cell/T-cell phenotypes; there have been only a few reports of primary extranodal NK/T-cell lymphoma of the larynx. (2-5)

Lymphoma of the larynx may present as hoarseness/ dysphonia, dysphagia, and a globus sensation. (8) Most patients present with stage I or II disease.

The most common consistently expressed NK-cell-associated markers are CD56 and CD2. Other common immunophenotypes are surface CD3- and cytoplasmic CD3+, as well as TIA-1 and perforin. The extent of the tumor can be determined by CT or magnetic resonance imaging.

Treatment includes radiotherapy, chemotherapy, immunotherapy, or a combination thereof. According to Li et al, the administration of radiotherapy as the primary treatment for stage IE and IIE NK/T-cell lymphoma improved 5-year overall survival and progression-free survival. (9) In their series of 105 patients, rates of 5-year overall survival and progression-free survival were 78 and 63%, respectively, for patients with stage IE disease and 46 and 40%, respectively, for those with stage IIE disease. The addition of chemotherapy to radiotherapy conferred no advantage in terms of overall survival or progression-free survival. Therefore, it seems that radiotherapy should be considered the treatment of choice for patients with this rare disease. However, relapses are common.

Our patient was treated with two courses of CHOP and then referred for radiotherapy. He tolerated the treatment regimen without any complications, and he remained in remission 2 years later.


(1.) Anderson HA, Maisel RH, Cantrell RW. Isolated laryngeal lymphoma. Laryngoscope 1976;86(8):1251-7.

(2.) Mok JS, Pak MW, Chan KF, et al. Unusual T- and T/NK-cell non-Hodgkin's lymphoma of the larynx: A diagnostic challenge for clinicians and pathologists. Head Neck 2001;23(8):625-8.

(3.) Chan JK, Sin VC, Wong KF, et al. Nonnasal lymphoma expressing the natural killer cell marker CD56: A clinicopathologic study of 49 cases of an uncommon aggressive neoplasm. Blood 1997;89(12):4501-13.

(4.) Friedmann D, Troob SH, Suurna MV, et al. Primary natural killer T cell lymphoma of the supraglottis. Otolaryngol Head Neck Surg 2011;145(2 Suppl):S196.

(5.) Monobe H, Nakashima M, Tominaga K. Primary laryngeal natural killer/T-cell lymphoma--report of a rare case. Head Neck 2008;30 (11):1527-30.

(6.) Jaffe ES, Chan JK, Su IJ, et al. Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology. Am J Surg Pathol 1996;20(1):103-11.

(7.) Cho KJ, Cho SG, Lee DH. Natural killer T-cell lymphoma of the tongue. Ann Otol Rhinol Laryngol 2005;114(1 Pt 1):55-7.

(8.) Agada FO' Mistry D' Grace AR' Coatesworth AP. Large B-cell non-Hodgkin's lymphoma presenting as a laryngeal cyst. J Laryngol Otol 2005;119(8):658-60.

(9.) Li YX, Yao B, Jin J, et al. Radiotherapy as primary treatment for stage IE and IIE nasal natural killer/T-cell lymphoma. J Clin Oncol 2006;24(1):181-9.

Nechama Uri, MD; Yaakov Schindler, MD; Miriam Quitt, MD; Olga Valkovsky, MD; Geva Barzilai, MD

From the Department of Otolaryngology, Head and Neck Surgery (Dr. Uri and Dr. Barzilai), the Department of Pathology (Dr. Schindler), and the Department of Haematology (Dr. Quitt and Dr. Valkovsky), Carmel Medical Center, Technion-Israel Institute of Technology, Haifa, Israel.

Corresponding author: Dr. Nechama Uri, Department of Otolaryngology, Head and Neck Surgery, Carmel Medical Center, 7 Michal St., Haifa, 34362 Israel. Email:
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Title Annotation:natural killer; ORIGINAL ARTICLE
Author:Uri, Nechama; Schindler, Yaakov; Quitt, Miriam; Valkovsky, Olga; Barzilai, Geva
Publication:Ear, Nose and Throat Journal
Article Type:Case study
Date:May 1, 2012
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