Leiomyosarcoma of the larynx: Diagnosis aided by advances in immunohistochemical staining.
We present only the 12th reported case of a laryngeal leiomyosarcoma. This tumor was diagnosed with the aid of the newer immunohistochemical stains on archival paraffin-embedded tissue. The diagnosis and management of these tumors is based largely on the patterns seen in the small number of earlier reported cases of head and neck leiomyosarcomas and laryngeal sarcomas.
Primary leiomyosarcoma of the head and neck is rare, and laryngeal neoplasms are even moreso. To date, only 11 cases have been reported in the literature. The diagnosis and management of laryngeal leiomyosarcoma are based on the patterns seen with other high-grade head and neck sarcomas. The local recurrence rate is high, and the prognosis is generally poor. The standard treatment is a wide local excision.
In this paper, we present only the 12th reported case of laryngeal leiomyosarcoma. This patient had a 1-cm subglottic soft-tissue mass on the right true vocal fold. A preliminary pathologic diagnosis of pleomorphic sarcoma was based on a biopsy specimen. The patient underwent a total laryngectomy and has remained disease-free for 11 years.
A retrospective analysis of the archival paraffin-embedded tissue, along with additional immunohistochemical stains (including alpha smooth muscle actin), led us to subcategorize this lesion as a pleomorphic leiomyosarcoma. Our finding suggests that other pleomorphic sarcomas can now be correctly subtyped. It is our hope that improved identification and further study will benefit the future management of head and neck sarcomas.
A white 62-year-old man came to our institution with a complaint of hoarseness of 3 years' duration. He smoked approximately 50 packs of cigarettes per year and drank 1 glass of wine per day. His significant medical history included a hiatal hernia, for which he was taking cimetidine. Over the course of the previous 3 years, he had been evaluated on multiple occasions. During these evaluations, his hoarseness had been ascribed to various etiologies, including postnasal drainage, chronic hypertrophic laryngitis, and vocal fold polyps. Biopsies on three occasions had revealed a benign pathology. Accordingly, the man had been treated with combinations of speech and language modification, antireflux medication, polypectomies, and vocal fold strippings.
At the initial presentation, the patient complained of a recurrence of hoarseness. X-rays revealed a soft-tissue density in the region of the true vocal folds, which bulged into the upper trachea. Computed tomography with contrast confirmed the presence of the soft-tissue mass in the right true vocal fold and showed that the mass extended across the midline and involved the anterior commissure (figure 1). No adenopathy was noted, but there was a slight enlargement of the right lobe of the thyroid and an area of calcification. The patient subsequently underwent a direct laryngoscopy, esophagoscopy, and a proximal tracheostomy and biopsy. The laryngeal lesion was observed to be a whitish-yellow polypoid mass with granulation-like surface tissue that extended 1 cm below the glottis. The mass was debulked and sent for frozen section, which revealed a sarcomatous spindle-cell lesion.
The patient subsequently underwent a workup for metastasis, which was negative. A total laryngectomy and right hemithyroidectomy were performed. The patient has done well and has not experienced any tumor recurrence during the past 11 years.
The laryngeal tissue was sent for ultrastructural analysis, which revealed the presence of elongated pleomorphic cells with irregularly shaped nuclei. The cytoplasm was well developed, with a prominent rough endoplasmic reticulum and bundles of microfilaments and frequent condensations. Additionally, the cells contained attachment plaques and adjacent collagen bundles. The presumptive diagnosis was a pleomorphic sarcoma suggestive of a malignant fibrous histiocytoma. Immunohistochemical staining at the time of the diagnosis was unable to identify the subtype of the sarcoma. However, in later years, a retrospective analysis of the archival paraffin-embedded tissue allowed us to correctly categorize this lesion as a pleomorphic leiomyosarcoma (figures 2 and 3). The pathologic examination of the thyroid tissue revealed a small, unrelated papillary thyroid carcinoma.
The incidence of laryngeal cancer is roughly 5 per 100,000 population, and laryngeal cancer accounts for between 1 and 5% of malignancies diagnosed annually.  Most of these tumors are squamous cell carcinomas; roughly 1% are sarcomas. The subclassification of these sarcomas often requires immunohistochemical and/or ultrastructural analysis. The sarcoma's subtype--in addition to its size, site, and location--has been shown to be a significant predictor of survival. 
Leiomyosarcomas originate in smooth muscle tissue. Thus, they are most common in the uterus, gastrointestinal tract, and the retroperitoneum, where smooth muscle is abundant. Head and neck lesions account for only 3% of all leiomyosarcomas.  This low incidence is attributed to the scarcity of smooth muscle in the head and neck, which is limited to erector pili muscles, vessel walls, and the esophagus. When leiomyosarcomas do occur in the head and neck, the most common sites are the paranasal sinuses, scalp, and cervical esophagus.
Unlike the etiology of carcinomas of the larynx, which are known to be strongly linked to tobacco and alcohol use, the inciting factors for sarcomas of the head and neck remain elusive. The scarcity of smooth muscle in the head and neck compels one to consider that an aberrant differentiation of mesenchyma might be a causative factor.  A postsurgical aberrant differentiation in the healing process has also been suggested as an etiologic factor. 
The presentation of laryngeal leiomyosarcoma is similar to that of laryngeal carcinoma. Symptoms of hoarseness are common. As it did in the case reported here, a leiomyosarcoma can arise in a patient with a history of hoarseness attributed to benign entities. Obstruction of the airway is also a risk factor for leiomyosarcoma. Tewary and Pahor reported a case of leiomyosarcoma that required an emergency laryngectomy for airway preservation.  Head and neck leiomyosarcomas rarely present with lymph node metastasis. 
On histology, low-grade leiomyosarcomas appear as spindle cells with cytoplasmic extensions arranged in bundles and containing cigar-shaped nuclei.  Histologic subtyping can be especially difficult in pleomorphic tumors. The differential diagnosis includes rhabdomyosarcoma, melanoma, schwannoma, malignant fibrous histiocytoma, and sarcomatoid carcinoma. Ultrastructural analysis can play a role in subclassification. Moreover, diagnosis has been greatly improved with the advent of new immunohistochemical staining techniques. Eleven years ago, when our patient first presented, the available stains were too limited to adequately distinguish among several of the spindle-cell sarcomas. The increased scope of today's monoclonal antibody tests has made the identification of these distinctions feasible (table). For example, the alpha smooth muscle actin stain, an isoform of alpha actin, is now quite specific for identifying smooth muscle.
The treatment of leiomyosarcoma of the head and neck area has generally been a wide local excision. Results have generally been satisfactory, except that the local recurrence rate is 35 to 50%. Radical neck dissection is usually withheld unless there is a regional node metastasis.  Our patient was treated with a total laryngectomy and has remained disease-free for 11 years. The role of postoperative radiation therapy remains to be defined. Given the small number of reported cases, survival statistics for laryngeal leiomyosarcoma are inconclusive. From the data we do have, patients with head and neck leiomyosarcoma generally have a 5-year survival of 35 to 50%. 
From the Jefferson Medical College, Philadelphia (Dr. Wadhwa), and the Department of Otolaryngology-Head and Neck Surgery (Dr. Gallivan and Dr. Lowry), the Department of Pathology (Dr. O'Hara), and the Department of Radiology (Dr. Rao), Thomas Jefferson University Hospital, Philadelphia.
Reprint requests: Louis D. Lowry, MD, Department of Otolaryngology-Head and Neck Surgery, 6th Floor, Thomas Jefferson University Hospital, 925 Chestnut St., Philadelphia, PA 19107. Phone: (215) 955-6760; fax: (215) 923-9532; e-mail: Louis.Lowry@mail.TJU.edu
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Staining identification patterns  Tumor ASMA [*] S-100 [+] Desmin [ss] Keratin [n] Leiomyosarcoma + + Rhabdomyosarcoma + Melanoma + Schwannoma + Malignant fibrous histiocytoma Sarcomatoid cancer + Tumor Kp-1 [#] Lys [**] Leiomyosarcoma Rhabdomyosarcoma Melanoma Schwannoma Malignant fibrous histiocytoma + + Sarcomatoid cancer
(*.)Alpha smooth muscle actin: smooth muscle and myofibroblasts
(+.)Neural crest-derived tissue (schwannoma and melanoma)
(ss.)Muscle-derived tumors (cardiac, smooth, and skeletal)
(n.)Cytokeratin: epithelial tumors
(**.)Salivary and histiocytic tumors
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|Comment:||Leiomyosarcoma of the larynx: Diagnosis aided by advances in immunohistochemical staining.|
|Author:||Lowry, Louis D.|
|Publication:||Ear, Nose and Throat Journal|
|Article Type:||Brief Article|
|Date:||Jan 1, 2000|
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