Low-grade mucoepidermoid carcinoma of the subglottis treated with organ-preservation surgery.

Abstract

Mucoepidermoid carcinoma of the subglottis is infrequently reported in the literature. This tumor subtype is more commonly associated with the major and minor salivary glands. Mucoepidermoid carcinoma of the larynx can be difficult to diagnose, and there is no consensus as to appropriate management. We report a case of a low-grade mucoepidermoid carcinoma that was confined to the subglottis and treated with organ-preservation surgery. A conservative surgical approach was taken because of the tumor's low-grade histology and its location and in order to preserve the patient's laryngeal function. At follow-up 15 months postoperatively, the patient remained disease-free, and laryngeal function was intact.

Introduction

Mucoepidermoid carcinomas represent a distinct type of tumor. They contain three cellular elements in varying proportions: squamous cells, mucus-secreting cells, and "intermediate" cells. (1) Mucoepidermoid carcinomas were first described by Masson and Berger in 1924. (2) Since then, they have become well recognized as a common salivary gland neoplasm, accounting for approximately 10% of all salivary gland tumors and about 35% of all malignancies of the major and minor salivary glands in general. (3) Mucoepidermoid carcinomas have been reported at distant and atypical sites, including the breast, (4) finger, (5) and thyroid. (6) Reports of mucoepidermoid carcinomas of the subglottis are not common. To the best of our knowledge, only 11 cases have been previously reported in the literature. (7-17) In this article, we report a new case.

Case report

A 48-year-old woman was referred to the Department of Otorhinolaryngology--Head and Neck Surgery at the Hospital of the University of Pennsylvania with a 5-year history of intermittent stridor that had become worse during the preceding 2 months. She reported that previous symptomatic relief had been afforded by oral steroid therapy. She denied a history of smoking.

The initial examination revealed that the patient was a healthy-appearing woman who had no palpable neck disease or other notable signs (she was nonstridorous during the examination). Nasopharyngolaryngoscopy detected no evidence of glottic or supraglottic disease; the mucosa was normal and vocal fold mobility was unimpaired. However, the physical examination did detect a subglottic mass, which occluded approximately 70% of the airway. Computed tomography (CT) of the neck without contrast demonstrated a 1.3 x 1.4-cm soft-tissue mass arising from the posterior wall of the subglottis at the level of the cricoid cartilage. CT confirmed that the mass had occluded approximately 70% of the subglottic airway.

While awake, the patient underwent a tracheostomy followed by microdirect laryngoscopy with biopsy of the mass. The specimen was fixed in 10% neutral-buffered formalin and sent to the Department of Pathology and Laboratory Medicine for pathologic diagnosis. Histologic sections showed that the tumor was made up predominantly of tubules without significant numbers of epithelial nests. The epithelial cells lining these tubules were cytologically low grade. A mucicarmine stain confirmed the presence of intracellular and intracystic mucin.

All appropriate steps for preoperative assessment and planning for an organ-sparing procedure were conducted, and the patient returned for a definitive surgical resection of the tumor. The anterior aspect of the thyroid cartilage was identified, and a sagittal saw was used to make a vertical incision into the anterior spine of the cartilage; care was taken to preserve the underlying mucosa of the larynx. A vertical cricothyrotomy was performed to provide an entrance into the airway. An incision at the anterior commissure was made, and the larynx was opened. Adequate retraction of the thyroid cartilage was achieved, and the mass was appreciated in its full extent. The tumor was excised. In this case, the inner aspect of the cricoid cartilage was resected as a margin. All margins were confirmed to be tumor-free by frozen-section analysis, and all specimens were submitted for permanent sections (figure). A buccal mucosal graft was sewn into the cricoid and trachea, and a core mold stent was placed.

The patient's brief postoperative course in the hospital was unremarkable. She was able to demonstrate preservation of her swallowing function on postoperative day 1. At 1 month, the stent was removed. The patient was noted to have bilateral ankylosis of the cricoarytenoid joints, which was successfully treated with bilateral laser cordotomies. The patient was decannulated with successful closure of the stoma 10 months after the original resection. At follow-up 15 months postoperatively, the patient remained disease-free, and her laryngeal function was intact.

Discussion

Reports of mucoepidermoid carcinoma of the larynx have been infrequent. According to institutional reviews, this tumor has accounted for 0.4% (n = 771 ), (18) 0.8% (n = 2,421 ), (19) and 0.3% (n = 1,891) (20) of all cancers of the larynx. The first description was published by Arcidiacono and Lomeo in 1963. (21)

Reports of mucoepidermoid carcinoma of the subglottis are even less common. Prgomet et al reviewed 63 mucoepidermoid carcinomas of the larynx and found that the subglottis was the least common site (8%); the most common site was the supraglottis (57%). (18) Our review of the literature identified only 11 previous reports of mucoepidermoid carcinoma of the subglottis (table). (7-17) The first of these was published by Whicker et al in 1974. (7) Including our case, these patients ranged in age from 35 to 81 years (mean: 65), and the male-to-female ratio was 3:1.

It has been proposed that mucoepidermoid tumors arise from subepithelial mucus glands that line the upper respiratory and digestive tracts. (22) If so, this might explain why this tumor type is more common at the supraglottis, which is the subsite of the larynx that has the greatest concentration of subepithelial mucous glands.

Mucoepidermoid carcinoma cell types are classified histologically as low-, intermediate-, and high-grade. High-grade tumors are poorly differentiated, and they are made up primarily of squamous epithelial and intermediate cells. Low-grade tumors are well differentiated and are made up primarily of mucus-secreting and squamous epithelial cells. The histologic features of intermediate-grade tumors fall in between. Histologic tumor grade is a useful prognostic indicator for mucoepidermoid carcinomas of the major and minor salivary glands. Pires et al reviewed the literature and reported that overall 5-year survival rates ranged from 0 to 43% for patients with high-grade mucoepidermoid cancers of the salivary glands, 62 to 92% for patients with intermediate-grade tumors, and 92 to 100% for patients with low-grade tumors. (23)

The infrequency of reports of mucoepidermoid carcinoma of the subglottis, and of the larynx in general, may be attributable to the relative difficulty that physicians have in recognizing this tumor type when it occurs outside the salivary glands. In addition to the possibility of sampling errors, interpretative errors during analysis of tumor specimens obtained from atypical locations have been reported. Notably, Binder et al cited the misclassification of high-grade mucoepidermoid carcinomas as adenosquamous carcinomas. (9) Likewise, Ferlito et al reported that 10 of 11 patients who were ultimately diagnosed with mucoepidermoid carcinoma of the larynx had been initially diagnosed by histopathology with squamous cell carcinoma. (19) Finally, there is significant variability in the way mucoepidermoid carcinomas are histologically graded, even among pathologists experienced in head and neck cancer. (24)

The appropriate management of mucoepidermoid carcinomas of the larynx is unsettled, but most authors agree that different treatment approaches are indicated for different tumor subsites and histologic grades. High-grade tumors are usually treated in a more aggressive fashion, with surgery as the primary modality, (18,25) as is the case with high-grade tumors of the major and minor salivary glands. (26) There is less agreement about the appropriate management of low-grade tumors. Some have recommended a partial laryngectomy resection for low-grade supraglottic tumors and a total laryngectomy for subglottic tumors. (25) Others have recommended approaches that preserve laryngeal function provided that tumor-free margins around the resection are achieved. (18)

The issue of treatment with radiotherapy is also unsettled. As a primary treatment modality, radiotherapy has met with both success (27-29) and failure. (11) Results of its use as an adjunctive therapy have also been mixed. (18) Finally, the therapeutic role of cervical lymphadenectomy is also unresolved. (18-20,30,31)

The treatment approach in our case was determined by the tumor grade, the tumor location, and the clinical presentation. Our aim was to ensure oncologic safety by leaving tumor-free margins while preserving laryngeal function. Based on our literature review, we believe that this is the first report of a low-grade mucoepidermoid carcinoma of the subglottis being treated with larynx-preserving surgery. Our patient remained disease-tree at 15 months, and her laryngeal functions of speech and swallowing were maintained without disturbance.

The relative successes of different treatments for mucoepidermoid carcinoma will become clearer as cases continue to be reported. At this time, however, surgical management of low-grade mucoepidermoid carcinomas of the subglottis should be centered on attempts to preserve laryngeal function as long as tumor-free margins can be achieved.

Table. Summary of the 12 reported cases of
mucoepidermoid carcinoma of the subglottis

Author                         Age/sex             Extension

Whicker et al, (7) 1974        NR/M                None

Tomita et al, (8) 1977         77/M                None

Binder et al, (9) 1980         55/M                Transglottic
                                                   spread;
                                                   thyroid
                                                   cartilage

Seo et al, (10) 1980           76/F                None

Cumberworth et al, (11) 1989   81/M                Glottic
                                                   extension

Yoshimura et al, (12) 1990     56/F                None

Kimura et al, (13) 1991        74/M                Transglottic
                                                   spread

Kuriyama et al, (14) 1991      65/M                None

Gairola et al, (15) 1992       35/M                None

Kawaida et al, (16) 1993       81/M                Glottic
                                                   extension

Kawabata et al, (17) 1994      69/M                None

Monin et al, * 2006            48/F                None

Author                         Histologic grade    Management

Whicker et al, (7) 1974        NR                  NR

Tomita et al, (8) 1977         Low                 Total
                                                   laryngectomy

Binder et al, (9) 1980         Intermediate        Total
                                                   laryngectomy

Seo et al, (10) 1980           Clear cell          Total
                               variant             laryngectomy
                                                   w/partial tracheal
                                                   resection

Cumberworth et al, (11) 1989   High                Total
                                                   laryngectomy,
                                                   radiotherapy

Yoshimura et al, (12) 1990     Low                 Radiotherapy

Kimura et al, (13) 1991        NR                  Surgery
                                                   (unspecified),
                                                   chemo- and
                                                   radiotherapy

Kuriyama et al, (14) 1991      High                Surgery
                                                   (unspecified),
                                                   radiotherapy

Gairola et al, (15) 1992       NR                  Total
                                                   laryngectomy,
                                                   left radical
                                                   neck dissection

Kawaida et al, (16) 1993       Intermediate        Chemo- and
                                                   radiotherapy

Kawabata et al, (17) 1994      High                Surgery
                                                   (unspecified),
                                                   chemo- and
                                                   radiotherapy

Monin et al, * 2006            Low                 Partial
                                                   laryngectomy

Author                         Outcome

Whicker et al, (7) 1974        NR

Tomita et al, (8) 1977         Disease-free at 24 mo

Binder et al, (9) 1980         Cervical lymphadenopathy at
                               12 mo; subsequent radical neck
                               dissection and radiotherapy;
                               disease-free at 24 mo

Seo et al, (10) 1980           Death at 7 mo (unrelated cause)

Cumberworth et al, (11) 1989   Disease-free at 12 mo

Yoshimura et al, (12) 1990     NR

Kimura et al, (13) 1991        NR

Kuriyama et al, (14) 1991      Death (unspecified cause and
                               time)

Gairola et al, (15) 1992       Death after 6-mo follow-up with
                               lymph node disease after refusal
                               to undergo staged right radical
                               neck dissection

Kawaida et al, (16) 1993       NR

Kawabata et al, (17) 1994      Death (unspecified cause and
                               time)

Monin et al, * 2006            Disease-free at 15 mo

* Present case.

NR = not reported.

References

(1.) Eversole LR. Mucoepidermoid carcinoma: Review of 815 reported cases. J Oral Surg 1970;28:490-4.

(2.) Masson R Berger L. Epiteliomas a double metaphisie de la parotide. Bull Assoc Fr Atude Cancer 1924;13:366-73.

(3.) Speight PM, Barren AW. Salivary gland tumours. Oral Dis 2002;8:229-40.

(4.) Di Tommaso L, Foschini MP. Ragazzini T, el al. Mucoepidermoid carcinoma of the breast. Virchows Arch 2004;444:13-9.

(5.) Hallori H. Goblet cell predominant high-grade mucoepidermoid carcinoma of the index finger. Br J Dermatol 2003:149:1091-2.

(6.) Sharma K, Nigain S, Khurana N, Chaturvedi KU. Sclerosing mucoepidermoid carcinoma with eosinophilia of the thyroid--A case report. Indian J Pathol Microbiol 2003:46:660-1.

(7.) Whicker JH, Ned HB III, Wetland LH, Devine KD. Adenocarcinoma of the larynx. Ann Otol Rhinol Laryngol 1974:83:487-90.

(8.) Tomita T, Lotuaco L, Talbott L, Watanabe I. Mucoepidermoid carcinoma of the subglottis. An ultrastructural study. Arch Pathol Lab Med 1977;101:145-8.

(9.) Binder WJ, Som P, Kaneko M, Biller HF. Mucoepidermoid carcinoma of the larynx. A case report and review of the literature. Ann Otol Rhinol Laryngol 1980;89:103-7.

(10.) Seo IS, Tomich CE, Warfel KA, Hull MT. Clear cell carcinoma of the larynx. A variant of mucoepidermoid carcinoma. Ann Otol Rhinol Laryngol 1980;89:168-72.

(11.) Cumberworth VL, Narula A, MacLennan KA, Bradley PJ. Mucoepidermoid carcinoma of the larynx. J Laryngol Otol 1989;103: 420-3.

(12.) Yoshimura T, Suenaga T, Ozaki H. [A case of laryngeal mucoepidermoid carcinoma in subglottis]. Jibi Inkoka Rynsyo 1990;40(suppl):60.

(13.) Kimura T, Hashiba M, Baba S, et al. [Mucoepidermoid carcinoma of the larynx: A case report]. Jibi Inkoka Rynsyo 1991;52(suppl): 161-8.

(14.) Kuriyama Y, Sakai N, Kashiwamura M, et al. [A case of mucoepidermoid carcinoma of the larynx]. Nippon Kikan Syokudo Kagaku Gakkai Kaiho 1991;42:493-6.

(15.) Gairola A, Bahadur S, Tandon DA. Primary subglottic carcinoma. Indian J Cancer 1992:29:143-7.

(16.) Kawaida M, Fukuda H, Kohno N, et al. [Mucoepidermoid tumor of the larynx: A case which responded completely to radiotherapy]. Jibi to Rynsyo 1993;39:429-34.

(17.) Kawabata I, Koba R, Okamura K, Masuda S. [Mucoepidermoid carcinoma of the larynx: A case report]. Nippon Kikan Syokudo Kagaku Gakkai Kaiho 1994:45:30-5.

(18.) Prgomet D, Bilic M, Bumber Z, et al. Mucoepidermoid carcinoma of the larynx: Report of three cases. J Laryngol Otol 2003;117: 998-1000.

(19.) Ferlito A, Recher G, Bottin R. Mucoepidermoid carcinoma of the larynx. A clinicopathological study of 11 cases with review of the literature. ORL J Otorhinolaryngol Relat Spec 1981;43:280-99.

(20.) Alavi S, Namazie A, Calcaterra TC, Blackwell KE. Glandular carcinoma of the larynx: The UCLA experience. Ann Otol Rhinol Laryngol 1999; 108:485-9.

(21.) Arcidiacono G, Lomeo G. [Salivary muco-epidermoid tumors (apropos of a case with laryngeal localization)]. Clin Otorinolaringoiatr 1963;15:95-108.

(22.) Spiro RH, Hajdu SI, Lewis JS, Strong EW. Mucus gland tumors of the larynx and laryngopharynx. Ann Otol Rhinol Laryngol 1976;85:498-503.

(23.) Pires FR, de Almeida OR de Araujo VC, Kowalski LR Prognostic factors in head and neck mucoepidermoid carcinoma. Arch Otolaryngol Head Neck Surg 2004:130:174-80.

(24.) Brandwein MS, Ivanov K, Wallace DI, et al. Mucoepidermoid carcinoma: A clinicopathologic study of 80 patients with special reference to histological grading. Am J Surg Pathol 2001;25: 835-45.

(25.) Snow RT, Fox AR. Mucoepidermoid carcinoma of the larynx. J Am Osteopath Assoc 1991:91 : 182-4, 187-9.

(26.) Jones AS, Beasley NJ, Houghton DJ, et al. Turnouts of the minor salivary glands. Clin Otolaryngol Allied Sci 1998;23:27-33.

(27.) Shonai T, Hareyama M, Sakata K, et al. Mucoepidermoid carcinoma of the larynx: A case which responded completely to radiotherapy and a review of the literature. Jpn J Clin Oncol 1998;28:339-42.

(28.) Thomas K. Mucoepidermoid carcinoma of the larynx. J Laryngol Otol 1971;85:261-7.

(29.) Tandon DA, Deka RC, Chowdhury C. Mucoepidermoid carcinoma of the larynx. Ear Nose Throat J 1985;64:555-7.

(30.) Okinaka Y, Sekitani T. Mucoepidermoid carcinoma of the vocal cord. Report of a case. ORL J Otorhinolaryngol Relat Spec 1984;46:139-46.

(31.) Mahlstedt K, Ussmuller J, Donath K. Malignant sialogenic tumours of the larynx. J Laryngol Otol 2002; 116:119-22.

Daniel L. Monin, MD; Anthony Sparano, MD; Leslie A. Litzky, MD; Gregory S. Weinstein, MD

From the Department of Otorhinolaryngology-Head and Neck Surgery (Dr. Monin, Dr. Sparano, and Dr. Weinstein) and the Department of Pathology and Laboratory Medicine (Dr. Litzky), Hospital of the University of Pennsylvania, Philadelphia.

Reprint requests: Gregory S. Weinstein, MD, Department of Otorhinolaryngology--Head and Neck Surgery, Hospital of the University of Pennsylvania, Ravdin Bldg., 5th Floor, 3400 Spruce St., Philadelphia, PA 19104. Phone: [phone]; fax: [phone]; e-mail: [e-mail]

/// References

(1.) Olney DR, Greinwald JH Jr., Smith RJ, Bauman NM. Laryngomalacia and its treatment. Laryngoscope 1999; 109:1770-5.

(2.) Zeitouni A, Manoukian J. Epiglottoplasty in the treatment of laryngomalacia. J Otolaryngol 1993;22:29-33.

(3.) McSwiney PF, Cavanagh NR Languth P. Outcome in congenital stridor (laryngomalacia). Arch Dis Child 1977;52:215-18.

(4.) Prescott CA. The current status of corrective surgery for laryngomalacia. Am J Otolaryngol 1991; 12:230-5.

(5.) Nussbaum E, Maggi JC. Laryngomalacia in children. Chest 1990;98:942-4.

(6.) Roger G, Denoyelle F, Triglia JM, Garabedian EN. Severe laryngomalacia: Surgical indications and results in 115 patients. Laryngoscope 1995; 105:1111-17.

(7.) Shah UK, Wetmore RF. Laryngomalcia: A proposed classification form. Int J Pediatr Otorhinolaryngol 1998;46:21-6.

(8.) Liu HC, Lee KS, Hsu CH, Hung HY. Neonatal vallecular cyst: Report of eleven cases. Changgeng Yi Xue Za Zhi 1999;22:615-20.

(9.) Lee KS, Chen HL, Yang CC, et al. Surgical management of severe laryngomalacia. J Taiwan Otolaryngol Soc 1997;32:235-40.

(10.) Nielson DW, Ku PL, Egger M. Topical lidocaine exaggerates laryngomalacia during flexible bronchoscopy. Am J Respir Crit Care Med 2000;161 : 147-51.

(11.) Seid AB, Park SM, Kearns MJ, Gugenheim S. Laser division of the aryepiglottic folds for severe laryngomalacia. Int J Pediatr Otorhinolaryngol 1985;10:153-8.

(12.) Garabedian EN, Roger G, Denoyelle F, Triglia JM. Severe laryngomalacia: Surgical indications and results. Pediatr Pulmonol Suppl 1997;16:292.

(13.) Polonovski JM, Contencin R Francois M, et al. Aryepiglottic fold excision for the treatment of severe laryngomalacia. Ann Otol Rhinol Laryngol 1990;99:625-7.

(14.) Zalzal GH, Anon JB, Cotton RT. Epiglottoplasty for the treatment of laryngomalacia. Ann Otol Rhinol Laryngol 1987;96:72-6.

(15.) Marcus CL, Crockett DM, Ward SL. Evaluation of epiglottoplasty as treatment for severe laryngomalacia. J Pediatr 1990; 117:706-10.

(16.) Jani P, Koltai P, Ochi JW, Bailey CM. Surgical treatment of laryngomalacia. J Laryngol Otol 1991; 105:1040-5.

(17.) Kelly SM, Gray SD. Unilateral endoscopic supraglottoplasty for severe laryngomalacia. Arch Otolaryngol Head Neck Surg 1995:121:1351-4.

(18.) Remacle M, Bodart E, Lawson G, et al. Use of the CO2-laser micropoint micromanipulator for the treatment of laryngomalacia. Eur Arch Otorhinolaryngol 1996;253:401-4.