ABSTRACTBACKGROUND: Paragangliomas of the larynx are exceedingly rare tumors, with less than 80 reported cases in the literature. These submucosal vascular lesions arise from neural crest cells and are effectively treated with surgical resection. A role for external beam radiation in this disease has not yet been explored. We present the successful management of four cases of laryngeal paragangliomastreated at a large tertiary-care cancer center over a 35 year period and review the diagnostic and therapeutic management of this disease. DESIGN: 124 cases of head and neck paragangliomas treated at a single institution from 1970 to 2005 were retrospectively studied. Patients with laryngeal paragangliomas were identified, and a comprehensive clinico-pathological review was undertaken. RESULTS: We identified 4 patients with tumors arising in the larynx at the following subsites: supraglottis (2), glottis (1), and subglottis (1). Three patients were treated successfully with surgery alone; two with total laryngectomy and one with a supraglottic laryngectomy. One patient with a glottic paragangliomawas treated with definitive radiation alone and had no tumor progression after five years of follow-up. At last follow-up, no patients developed local recurrence. CONCLUSIONS: Surgical resection has been advocated in the past for these lesions and still remains the gold standard for treatment. Furthermore, most patients will require a total laryngectomy for oncological control. CLINICAL SIGNIFICANCE: 4 cases of laryngeal paragangliomas are added to the literature base. Though predominately surgical management has been used in the past, radiation is now a treatment consideration for these tumors. Pathological findings and clinical management of epiglottic and subglotticparagangliomas are compared to the more common ventricular paragangliomas. Finally, with only one other case of metastatic paraganglioma in the literature, a treatment plan for this rare presentation is explored.

Laryngeal Paragangliomas: A 35 year review

Joseph Ryan Smolarz, M.D., Ehab Y. Hanna, M.D., F.A.C.S., Michael E. Kupferman, M.D.

Department of Head and Neck Surgery, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, U.S.A.

STUDY DESIGN AND SETTING• A retrospective review of the last 35 years was IRB approved•124 patients with paragangliomas were identified by ICD-9 codes• 5 cases of pharyngolaryngeal paragangliomas were identified•1 patient with a hypopharyngeal paraganglioma was excluded

CONCLUSION • Immunohistochemistry is the standard of care for

diagnosis • Surgical resection is the standard of care for

treatment• Due to unique circumstances, radiotherapy was

shown to be a valid option for treatment• The second case of distant metastatic disease

from a laryngeal paraganglioma is presented• The first regionally metastatic laryngeal

paraganglioma is added to the literature

Case #3• A 67 y/o woman presented with a submucosal

subglottic tumor• The mass extended to the vocal folds at

the anterior commisure• A total laryngectomy was performed• Cartilage destruction evident on histology• The patient died later from other causes

Case #4• A 50 year old man presented with a recurrent

mass of the left supraglottis• Previously treated with a supraglottic

laryngectomy• A surgical salvage total laryngectomy was done• 8 months after surgery, the patient developed

lung and brain metastasis • He was treated with systemic chemotherapy• The patient died 16 months after diagnosis

Case #1 (Fig. 1, 2)• An 85 year old woman presented with a right supraglottic lesion• The mass extended to the epiglottis• The tumor was diagnosed as spindle cell CA• One year evaluation showed progression• Biopsy revealed paraganglioma• Patient preferred external beam radiation• On 5 year follow-up, tumor was stable

Case #2 (Fig. 3, 4, 5, 6, 7)• A 39-year-old black female presented with a glottic lesion• Tracheostomy was done for airway protection due to tumor bulk• The lesion extended from the posterior aspect of the left arytenoid to the

epiglottis superiorly and to the subglottis inferiorly• Treated with embolization and an extended supraglottic laryngectomy• On last follow-up she had no evidence of disease

Sx vs Rad Type of Sx Functioning Multicentric Misdiagnosis Familial Recurrence Death Metastasis Location

1 Sx SGL/TL No No Yes No Yes Yes Yes SG RM/DM

2 Sx TL No No No No No Yes No Subglottis

3 Rad None No No Yes No No No No Right SG4 Sx ESGL No No No No No No No Left SG/G

Subglottis

Fig.3 - The paraganglioma is bulky in the left aryaretenoid area with extension into the subglottic area

Fig. 4 - There is involvement of the entire epiglottis – both the glottic and lingual surface

SGL – Supraglottic Laryngectomy, ESGL - Extended Supraglottic Laryngectomy, TL – Total Laryngectomy, SG – Supraglottis, G – Glottis, RM – Regional Metastasis, DM – Distant Metastasis

Fig. 1 Pretreatment stroboscopy revealed tumor involvement in the right AE fold, extending down into the right piriform sinus

Fig. 2 Post-radiation – Only a small remnant of tumor remained after radiation and continued to be stable throughout follow-up

Fig. 7A. Shows the tumor pushing the airway to the rightB. Complete obstruction at the origin of the tumorC. Subglottic extension D. Right benign thyroid cyst found incidentally on CT

Fig. 5 Overlying squamous epithelium with the tumor in the submucosa. The circular focus is a post embolized vessel with inflammatory reaction

Fig. 6 Higher power 400X - Zellballen nests of tumor cells with thin supporting sustenacular cells around each nest