1

Introduction

Embryonal rhabdomyosarcoma is a rare tumor, which is usually described in children . While it is extremely rare to find this tumor in adults, involvement of the larynx has been described in an even more limited fashion, which leads to difficulty in management decisions. Multi-modality therapy including wide local excision is generally advocated given the recurrent nature of these lesions . Some authors note that micrometastasis is presumed given the high rate of failure with surgery alone , while other authors note an overall less aggressive course and excellent response by these lesions to surgery alone .

Genetically, tumorigenesis has been suggested to involve pathways of cell cycle, cell adhesion, and signaling . Specific pathways involved in the degeneration of these mesodermal sarcomas have not been fully elucidated, and the rarity of these lesions has limited the available information regarding these tumors . Other authors have therefore called for increased reporting of laryngeal embryonal rhabdomyosarcomas . This case highlights the difficulty of managing adult patients with an organ sparing strategy when a specific subsite, the interarytenoid muscle, is involved.

2

Case

A 45 year old male presented with an eleven month history of hoarseness and mild laryngitis symptoms. An outside hospital otolaryngologist had noted a cyst on the right posterior glottis and had completed a direct laryngoscopy with biopsy of the firm lesion, with final pathology at that time consistent with fibromuscular tissue with inflammation. A CT was obtained pre-operatively, and noted a 2.5 × 1.5 centimeter laryngeal mass extending to the level of the cricoid without involvement of the cartilage.

Flexible laryngoscopic examination at presentation noted a bulky, posterior sub-mucosal glottic mass, larger on the right side, which seemed to originate from the interarytenoid muscle ( Fig. 1 ). This was obstructing the majority of the glottic inlet, and the subglottis was only poorly visualized. Direct laryngoscopy was advised, and deeper biopsies were obtained. Intraoperative frozen section histopathologic review confirmed representative sampling of the abnormal mass but was of limited value in its exact diagnosis. The final pathology, however, demonstrated spindle cells invading the local musculature and entrapping nerve structures ( Fig. 2 ). The morphology and immunohistochemical profile were most consistent with embryonal rhabdomyosarcoma, stage I grade III.

Flexible laryngoscopy demonstrating bulky, submucosal, mass of the posterior glottis.

H&E stain at 400× magnification demonstrating spindle cells with abundant eosinophilic cytoplasm and large nuclei with prominent nucleoli.

His case, including images and pathology, was reviewed at a multi-disciplinary tumor board. Due to the presumed aggressive nature of the disease and the rarity of the lesion, total laryngectomy was recommended at that time, in part due to the limited evidence of the efficacy of organ preservation strategies in adults and its anatomic location precluding partial laryngeal surgery. The patient refused this option, and sought enrollment in an oncology study utilizing vincristine, actinomycin, and cyclophosphamide (VAC) combined with radiation therapy (ARST 0331). As this protocol had been effective in a pediatric population, the study did attempt to reduce the burden of chemotherapy, followed by a predefined radiation dose of 50.4 Gy. He met age criteria for enrollment in this pediatric study.

As his post-chemotherapy flexible laryngoscopic examinations demonstrated minimal structural response of the tumor, the decision was made to “boost” the total dose of radiation to 69.6 Gy. Subsequent examinations noted only minimal interval decrease in the size of the lesion, concerning for persistent disease. Biopsies obtained on repeat direct laryngoscopy were again positive for embryonal rhabdomyosarcoma. He was recommended total laryngectomy for salvage, which he refused. He has since undergone further experimental chemotherapy at another institution using sodium phenylbutyrate, pazopanib, and everolimus, and was alive at last follow up 34 months after completion of his initial chemoradiation.