Gardner's syndrome

Abstract

Aggressive fibromatosis is an uncommon tumor that is locally aggressive but not malignant. Therefore, its classification falls between the benign and malignant neoplasms of soft-tissue origin. In the past, these lesions were misdiagnosed as low-grade fibrosarcomas. Otolaryngologists should be familiar with these lesions because as many as 15% of them occur in the head and neck. The treatment of choice is wide surgical excision, which is often difficult. Postexcision recurrence rates are high. Nonsurgical treatment includes radiation and chemotherapy, both of which are usually reserved for recurrences. We describe two cases of aggressive fibromatosis of the parapharyngeal space, and we review the available treatment options.

Introduction

Aggressive fibromatosis, also known as desmoid, is a rare soft-tissue tumor whose classification falls between benign and malignant in most pathology texts--that is, it is locally aggressive but not metastatic or malignant. It accounts for fewer than 3% of all soft-tissue tumors. (1) Only 10 to 15% of these lesions occur in the head and neck, usually in the supraclavicular fossa. (2) Only two cases of aggressive fibromatosis of the parapharyngeal space have been reported previously. (2,3) In this article, we describe two new cases, and we review the treatment options.

Case reports

Patient 1. A 22-year-old woman came to our clinic with a 4-month history of gradually worsening hoarseness, right otalgia, and difficulty opening her mouth. Physical examination revealed right serous otitis media, a bulge in the right oropharynx that displaced the tonsil medially, right true vocal fold paralysis, and a discrete, firm, 2-cm neck mass, which was believed to be a lymph node. All of her symptoms were consistent with a possible right parapharyngeal space mass.

The workup included a biopsy of the mass, which the pathologist interpreted as a lymphoid hyperplasia. Computed tomography (CT) demonstrated that the nonenhancing mass had filled the right parapharyngeal space. Magnetic resonance imaging (MRI) reflected intensities similar to muscle (figure 1, A). In addition, the transition from fat to muscle was blurred, which suggested that the lesion was infiltrative. Arteriography showed that the mass was hypovascular.

[FIGURE 1 OMITTED]

Excision, which included a lateral mandibulotomy, was performed through the neck. Although the mass was adherent to the carotid sheath, it was successfully peeled off. The mass had infiltrated the medial pterygoid muscle.

The patient recovered uneventfully, and her vocal fold paralysis resolved. The pathology of the excised tumor was consistent with aggressive fibromatosis in that dense fibrous tissue focally infiltrated between the muscle fibers (figure 1, B).

The patient was lost to follow-up for 8 years, when she returned complaining of increasing right-sided otalgia and dysphagia. She had also had a recurrent bulge in the right oropharynx. Imaging studies were consistent with her original findings except that the recurrent mass now extended to the skull base. Given the morbidity of resection, radiation therapy was chosen to treat this recurrence.

Three years later, the patient was alive and exhibited no evidence of disease progression either clinically or radiologically.

Patient 2. A 75-year-old man was referred to our Veterans Administration clinic with a 1-month history of a rapidly enlarging left neck mass and left postauricular pain. Physical examination revealed a left oropharyngeal bulge and a large, fixed left neck mass that measured approximately 7 x 10 cm. There was no associated lymphadenopathy.

CT showed that the large nonenhancing mass had filled the left parapharyngeal space and displaced the carotid sheath anteriorly and the larynx to the right (figure 2, A). Fine-needle aspiration revealed only spindle-type cells, which suggested a mesenchymal neoplasm and helped rule out an epithelial tumor such as a squamous cell carcinoma or a lymphoma.

[FIGURE 2 OMITTED]

Excision was performed through the neck, and the mass was found to be adherent to all surrounding structures. The patient did very well postoperatively. On pathologic analysis, the tumor was consistent with aggressive fibromatosis (figure 2, B). However, the resection margins were found to contain fibromatosis that extended into normal tissue, and the tumor recurred 2 years later despite regular follow-up, which included a thorough physical examination. Surgical re-excision was offered, but the patient chose to undergo radiation therapy.

Two years later, the patient exhibited no evidence of disease progression.

Discussion

The parapharyngeal space--also known as the pharyngomaxillary, pterygomaxillary, lateral pharyngeal, and pterygopharyngeal space--is a potential space filled with connective tissue. This space is shaped like an inverted pyramid, with the apex pointing toward the hyoid bone, which is the inferior limit of the space. The parapharyngeal space is bounded superiorly by the skull base, anteriorly by the buccinator and pterygoid muscles, posteriorly by the carotid sheath, and medially by the superior constrictor, palatine, and styloglossus muscles. The ascending ramus of the mandible and the medial pterygoid muscle are the lateral limits. The parapharyngeal space is further subdivided by the styloid process into two compartments: prestyoid and poststyloid. The prestyloid compartment contains the internal maxillary artery, the lingual nerve, the inferior alveolar nerve, and the auriculotemporal nerve. The poststyloid compartment contains the internal carotid artery, the internal jugular vein, cranial nerves IX through XII, the cervical sympathetic chain, and the lymph nodes.

The differential diagnosis of parapharyngeal space tumors includes neoplasms of the deep lobe of the parotid, which account for approximately 50% of the tumors found there. (4) Tumors of neurogenic origin make up another 30%, and they include nerve sheath tumors (e.g., schwannomas and neurofibromas) as well as nerve cell tumors (e.g., neuroblastomas). (4) Paragangliomas can also occur here, and they are usually nonfunctioning. In rare cases, hemangiopericytomas and lipomas occur in the parapharyngeal space. Only two cases of aggressive fibromatosis involving the parapharyngeal space have been previously reported. (2,3)

Aggressive fibromatosis has historically been synonymous with desmoid tumors--more specifically, extra-abdominal desmoids. According to the World Health Organization's (WHO) classification of fibrous soft-tissue tumors, aggressive fibromatosis falls between benign and malignant neoplasms (table). (5) Because these tumors are locally aggressive, they are not truly benign; however, they do not metastasize or exhibit any malignant features histologically. In the past, these lesions were misdiagnosed as low-grade fibrosarcomas. The WHO subdivided the lesions of aggressive fibromatosis into two categories: superficial and deep. Enzinger and Weiss had earlier proposed the same two broad categories. (6) Aggressive fibromatosis in the head and neck is a deep tumor and is, of course, extra-abdominal.

The first report of aggressive fibromatosis was published by MacFarlane in 1832. (7) Six years later, the term desmoid was coined by Muller. (8) In 1856, Paget reported that some extra-abdominal tumors were very similar to abdominal desmoids. (9) In a landmark article published in 1966, Masson and Soule finally prompted widespread acceptance of the idea of a benign-appearing but malignant-acting head and neck tumor that was similar to an abdominal desmoid tumor. (10)

On gross examination, aggressive fibromatosis is white to gray and has infiltrative margins. Its size varies greatly (from 1 to 15 cm). The lesions feel rubbery to hard, and their edges are difficult to distinguish from surrounding structures because of the invasive nature of the tumor. Histologically, aggressive fibromatosis is made up of many fibroblasts arranged in long fascicles. There is little variation in cell or nuclear sizes, and mitoses are absent to rare. A thick collagenous background predominates, and it can trap muscle fibers and cause them to atrophy (figure 1, B).

Aggressive fibromatosis is believed to arise from within muscles or the muscular aponeurosis. (11) Trauma was once considered to be an etiologic factor, but this hypothesis has not been substantiated. (12) A relationship also exists between aggressive fibromatosis and Gardner's syndrome; patients with Gardner's syndrome can also exhibit multiple desmoid tumors. (11) Estrogen appears to play a role in aggressive fibromatosis, which might explain the occasional association of desmoid tumor with pregnancy and its higher incidence in women of child-bearing age. (1,13)

Approximately 85% of head and neck desmoids occur in the neck; the remainder occur in the face or scalp. (10) The most common subsite in the neck is the supraclavicular fossa. These uncommon tumors usually manifest as painless, enlarging neck masses with variable growth rates. Other signs and symptoms are related to the specific anatomic location and to the structures upon which they encroach. Bone erosion is common.

The treatment of choice is wide surgical excision. Of course, this can be very difficult in the head and neck because vital structures abut the mass in most cases. Therefore, resection is often inadequate. Even though removal of an entire lesion is surgically possible, the morbidity associated with wide excision and nerve involvement may be unacceptable to both the patient and surgeon. Desmoids of the head and neck have a higher propensity to recur (70%) than do desmoids at other sites (50%). (10) Although some surgeons attribute this higher recurrence rate to a belief that tumor biology is more aggressive in the head and neck, others believe that it is attributable to the fact that some neoplasm is simply left behind because the excision is so technically difficult. (14)

Nonsurgical treatments include radiation and chemotherapy. Radiation is used most often for inoperable or recurrent tumors. It is also offered to patients who retain residual disease postoperatively. Local control rates with doses of 30 to 60 Gy range from 68 to 93%. (15) Plukker et al radiated 14 patients postoperatively and followed them for 6 years; they observed only 1 recurrence, and that lesion arose outside the irradiated field. (1) It is interesting that these tumors can take as long as 2 years to regress after the completion of radiotherapy. There have been no reports of malignant degeneration of aggressive fibromatosis after radiation therapy. Prior to radiation therapy, both of our patients experienced extensive, unresectable recurrences. It is possible that administering radiation therapy up front would have decreased the risk of recurrence in these patients.

Chemotherapy has been used sparingly for aggressive fibromatosis of the head and neck. The combination of vincristine, doxorubicin, and cyclophosphamide has been successful in a few cases, but not in any large studies. (16) Antiestrogen drugs such as tamoxifen and testolactone have been used in selected cases with success. One woman was treated with testolactone daily for approximately 1 year. (13) She experienced a slowly progressive decrease in the size of her tumor and a resolution of her symptoms, and she remained disease-free 13 years later.

Even close follow-up is inadequate in patients with aggressive fibromatosis of the parapharyngeal space--as was seen in our patient 2--because this area is not easily accessible. By the time a tumor finally becomes visible as an obvious bulge in the oropharynx, its bulk is well beyond the early stage. Therefore, frequent cross-sectional imaging in addition to physical examination is recommended for follow-up of these patients.

Our two cases of aggressive fibromatosis of the parapharyngeal space are only the third and fourth that have been reported in the literature. When aggressive fibromatosis occurs in the head and neck, it poses a surgical dilemma because complete removal is not always possible when the tumor is located on or near vital structures. Excision of such a tumor is even more difficult in the parapharyngeal space.

In light of the difficulty of obtaining tumor-free surgical margins, we recommend that aggressive fibromatosis of the parapharyngeal space be treated with a combination of surgery and radiation therapy. In addition to close follow-up, we recommend yearly radiologic evaluations so that recurrence can be detected in a timely fashion. Patients who experience a recurrence have the option of undergoing radiation and/or chemotherapy, and their prognosis is promising. Further study is needed to investigate the efficacy of hormonal manipulation of this disease.

References

(1.) Plukker JT, van Oort I, Vermey A, et al. Aggressive fibromatosis (non-familial desmoid tumour): Therapeutic problems and the role of adjuvant radiotherapy. Br J Surg 1995;82:510-14.

(2.) West CB, Jr., Shagets FW, Mansfield MJ. Nonsurgical treatment of aggressive fibromatosis in the head and neck. Otolaryngol Head Neck Surg 1989;101:338-43.

(3.) Tse GM, Chan KF, Ahuja AT, et al. Fibromatosis of the head and neck region. Otolaryngol Head Neck Surg 2001;125:516-19.

(4.) Thawley SE, Panje WR, Batsakis JG, Lindberg RD. Comprehensive Management of Head and Neck Tumors. Vol. 2. Philadelphia: W.B. Saunders, 1987:1416-49.

(5.) Damjanov I, Linder J, eds. Anderson's Pathology. 10th ed. St. Louis: Mosby, 1996:2481-2.

(6.) Enzinger FM, Weiss SW. Soft Tissue Tumors. 2nd ed. St. Louis: Mosby, 1988:136-63, 185-90.

(7.) MacFarlane J. Clinical Reports of the Surgical Practice of the Glasgow Royal Infirmary. Glasgow: D. Robertson, 1832:63-6.

(8.) Muller J. Ueber den feineren Bau und die Formen der krankhaften Geschwulste. Berlin: G. Reimer, 1838:60.

(9.) Paget J. Fibro-nucleated tumour of the abdomen of fourteen years' growth: Removal. Lancet 1856;1:625.

(10.) Masson JK, Soule EH. Desmoid tumors of the head and neck. Am J Surg 1966;112:615-22.

(11.) Cotran RS, Kumar V, Robbins SL, eds. Robbins Pathologic Basis of Disease. 5th ed. Philadelphia: W.B. Saunders, 1994:1265.

(12.) Conley J, Healey WV, Stout AP. Fibromatosis of the head and neck. Am J Surg 1966;112:609-14.

(13.) Fujimoto Y, Hidai K. Aggressive fibromatosis in the neck. A case treated effectively by testolactone with a long follow-up study. Jpn J Surg 1990;20:453-7.

(14.) el-Sayed Y. Fibromatosis of the head and neck. J Laryngol Otol 1992:106:459-62.

(15.) Greenberg HM, Goebel R, Weichselbaum RR, et al. Radiation therapy in the treatment of aggressive fibromatoses. Int J Radiat Oncol Biol Phys 1981;7:305-10.

(16.) Stein R. Chemotherapeutic response in fibromatosis of the neck. J Pediatr 1977;90:482-3.

From the Department of Otolaryngology--Head and Neck Surgery (Dr. Sanders, Dr. Stucker, and Dr. Nathan), the Department of Pathology (Dr. Fowler), and the Department of Radiology (Dr. Milner), Louisiana State University Health Sciences Center, Shreveport.

Reprint requests: Cherie-Ann O. Nathan, MD, Department of Otolaryngology--Head and Neck Surgery, Louisiana State University Health Sciences Center, 1501 Kings Highway, Shreveport. LA 71130. Phone: (318) 675-6262; fax: (318) 675-6260; e-mail: cnatha@lsuhsc.edu

COPYRIGHT 2004 Medquest Communications, LLC
COPYRIGHT 2004 Gale Group