Fibromatosis

Abstract

Infantile fibromatosis is an uncommon, usually cutaneous, nonmetastasizing but locally aggressive fibroblastic proliferation. Involvement of the sinonasal area is extremely uncommon, and only 5 cases have been previously reported We report a new case, which occurred in a 2-year-old boy. The mass involved the nasal cavity and the paranasal sinuses and extended into the cranial cavity. We also discuss the clinicopathologic features of this lesion, including its ultrastructural characteristics, and we review the literature.

Introduction

Infantile fibromatosis represents the pediatric counterpart of musculoaponeurotic fibromatosis (desmoid fibromatosis). It was first described as a distinct clinicopathologic entity by Stout in 1954. (1) Also called aggressive juvenile fibromatosis, it is characterized by a destructive, locally invasive process and a high rate of local recurrence, especially in cases of inadequate excision. The nose and paranasal sinuses are extremely unusual sites of this disease process, and to the best of our knowledge, only 5 cases have been previously reported in the literature. (2-6)

In this article, we describe a new case, which involved the right nasal cavity, ethmoid sinus, and pterygomaxillary fossa and extended into the cranial cavity. We discuss the clinicopathologic features of this lesion, including its ultrastructural characteristics, and we review the pertinent literature on this topic.

Case report

A 2-year-old boy presented with a history of nasal obstruction and a slowly growing soft-tissue mass in the right nasal cavity that had been present since he was 6 months old. He had no history of epistaxis. Local examination identified a pinkish soft-tissue mass in his right middle meatus. The lesion had caused the hard palate to protrude into the oral cavity. His right eye had been displaced laterally, and there was evidence of proptosis. The condition of the overlying facial skin was unremarkable.

Computed tomography (CT) demonstrated a mildly enhancing, heterogenous soft-tissue mass involving the right nasal cavity, right maxillary sinus, frontal sinus, and ethmoid air cells (figure 1). Lateral displacement of the lamina papyracea was also evident, and the nasal septum was deviated toward the left. The mass also extended into the right masticator space through the pterygomaxillary fissure. It had eroded the base of the pterygoid plates and infiltrated the lateral pterygoid muscle. Intraorbital extension of the mass had eroded the floor of the right orbit. Finally, there was evidence of intracranial but extra-axial extension into the anterior cranial fossa, which had damaged the frontal sinus.

[FIGURE 1 OMITTED]

With the patient under general anesthesia, the lesion was explored via a lateral rhinotomy approach. The mass was adherent to the dura, and therefore the intracranial portion was left to be excised during a second-stage intracranial procedure. The remainder of the mass was removed in a piecemeal fashion from the nasal and paranasal areas. The patient tolerated the procedure well, and his postoperative period was uneventful. No adjuvant therapy was administered. The patient was lost to follow-up, and his subsequent disease status could not be assessed.

On examination of the gross specimen, the excised lesion was made up of several firm soft-tissue bits that measured 5 x 3 x 1 cm in the aggregate. Microscopic examination revealed that a spindle-cell lesion had infiltrated the bony trabeculae in places. The individual cells were monomorphic and arranged in short fascicles, lying in a densely collagenous stroma (figure 2). Neither atypical mitotic activity nor necrosis was detected. The individual cells exhibited positive immunoreactivity for smooth-muscle actin (dilution: 1:100) (figure 3) and vimentin (1:50), but they were negative for desmin (1:50) and S-100 protein (1:300). These features were consistent with those of infantile fibromatosis.

[FIGURE 2-3 OMITTED]

The excised tissue was processed for electron microscopic evaluation following standard protocol. The individual ceils were oval to elongated and contained a smooth plasma membrane that limited the cytoplasm of each cell. Pinocytic vesicles were not prominent. No specialized cell junction was apparent when two or more cells were in close proximity.

One common feature exhibited by all these cells was an abundance of rough endoplasmic reticulum (RER) with dilated cisternae (figure 4). The Golgi complex and mitochondria were normal. A few cells showed the presence of microfibrils beneath the plasma membrane. The nuclei showed that the chromatin was evenly dispersed, and there was a mild indentation of the nuclear membrane in places. The intercellular stroma contained an abundance of collagen fibers. Intracellular collagen was present in a few cells.

[FIGURE 4 OMITTED]

Discussion

Fibromatoses are a group of curious connective tissue lesions. Stout characterized fibromatoses as a "term used without qualifying words for all fibrous growths that cannot be assigned to any other category." (1) In the spectrum of fibroblastic proliferations, fibromatosis occupies a position between a reparative process (such as keloid development) and frank neoplasia.

It is difficult to ascertain the incidence of fibromatosis of the head and neck because the classification schemata used by different authors are so varied. Of 284 desmoid tumors reviewed by Masson and Soule at the Mayo Clinic, 34 (12%) were located in the head and neck. (7) Das Gupta et al reported head and neck involvement in 11% of their cases. (8) When infantile fibromatosis is considered separately, the propensity for head and neck involvement appears to be higher, in the range of 25 to 33%. (9) The most common sites in the head and neck are the tongue, mandible, maxilla, and mastoid process. (10)

Involvement of the sinonasal region in children is uncommon, as only 5 cases have been previously reported. In Conley's series of 40 patients with head and neck fibromatosis, 1 case (2.5%) involved the paranasal sinuses in a child. (2) Likewise, in an evaluation of 23 fibrous tissue tumors involving the sinonasal and nasopharyngeal area by Fu and Perzin, 1 case (4.3%) involved a child--a 2-year-old boy who had a lesion in the right maxillary antrum that had destroyed the orbital floor. (3) Naidu et al described a case of aggressive juvenile fibromatosis that involved the nasal cavity and anterior maxilla in a 15-month-old boy. (4) Another case of infantile fibromatosis of the sinonasal area was reported by Thompson et al. (5) Finally, Maillard and Kountakis reported the case of a 2 1/2-year-old boy with desmoid fibromatosis that involved the left antrum and ethmoid air cells and eroded the orbital floor. (6)

Histologic features. Microscopically, infantile fibromatosis must be differentiated from infantile myofibromatosis and infantile fibrosarcoma because their histologic resemblance is close. (10) Infantile myofibromatosis is distinguished by its well-circumscribed margins, central hemangiopericytomatous pattern, and necrosis. (11) Infantile fibrosarcoma is more cellular; it is characterized by a herringbone pattern, it is mitotically more active, and hemorrhage and necrosis are common. (12) However, there have been reports of a morphologic transition from infantile fibromatosis to infantile fibrosarcoma (12) and vice versa. (10)

Ideally, the pathologic diagnosis of the whole group of fibromatoses should be restricted to tumors that are derived from fibroblasts. However, several lesions in the fibromatosis category have been found to contain myofibroblasts, which have features common to both fibroblasts and smooth-muscle cells. (13,14) Immunohistochemistry alone is not sufficient to allow for an exact categorization of a particular cell as a myofibroblast because these cells display an immunophenotypic heterogeneity that is, a variable positivity for vimentin, alpha smooth-muscle actin, desmin, and heavy-chain smooth-muscle myosin. (14) The ultimate defining criteria for a myofibroblast are its ultrastructural features. (14,15) They include:

* bundles of intracytoplasmic microfilaments with dense bodies that run parallel to the long axis of the cell (stress fibers)

* a well-developed RER

* a prominent Golgi complex

* nuclear indentations or folds

* pinocytic vesicles

* surface differentiation in the form of a desmo-some-like intercellular connection

* the presence of a basal lamina-like material surrounding the cells

In our patient, the neoplastic ceils exhibited an abundance of dilated PER, a prominent Golgi complex, a focal presence of microfilament, and mild nuclear indentation. These findings met some but not all of ultrastructural criteria that define a fully developed myofibroblast. In addition, the presence of intracytoplasmic collagen, which we observed in our patient, has also been described in cases of fibromatosis. (16)

Many authors have tried to distinguish between the fibrous growths that occur in adults and the more aggressive juvenile variety. Aggressive juvenile fibromatosis is a potentially dangerous lesion because it has a propensity to grow in a locally invasive manner and erode bone and soft tissue, thereby placing at risk the vital structures of the head and neck. Although these lesions do not metastasize, the rate of local recurrence is quite high, especially after an inadequate excision. For example, Faulkner et al reported that 65% of patients in their series developed a local recurrence; of these recurrences, 51% arose within 1 year of the initial excision and 90% within 3 years. (17) Masson and Soule found that the recurrence rate in patients with head and neck fibromatosis was 70%, compared with only 50% for lesions in all locations. (7) Uncontrolled local growth, especially in the head and neck, can lead to death secondary to the lesion's encroachment on vital structures. (7,8)

Treatment. Complete excision with ample margins is the treatment of choice for infantile fibromatosis. Of course, excising a lesion in the paranasal sinuses without causing significant cosmetic deformity or sacrificing critical structures can be difficult, as was the case with our patient. (4)

The role of radiotherapy or adjuvant chemotherapy is controversial, and for now these modalities should be reserved for advanced unresectable or recurrent lesions. (18,19) However, some reports of the efficacy of tamoxifen in the treatment and prevention of recurrent disease have been encouraging. (6,20) Apart from its antiestrogenic effect (fibromatoses are known to contain estrogen and/or progesterone receptors), tamoxifen stimulates the production of transforming growth factor beta, an inhibitory growth factor that also inhibits angiogenesis. (21) Therefore, it is possible that tamoxifen might also be useful for patients whose fibromatoses do not contain estrogen and/or progesterone receptors.

References

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

(3.) Fu YS, Perzin KH. Nonepithelial tumors of the nasal cavity, paranasal sinuses, and nasopharynx. A clinicopathologic study. VI. Fibrous tissue tumors (fibroma, fibromatosis, fibrosarcoma). Cancer 1976;37:2912-28.

(4.) Naidu RK, Aviv JE, Lawson W, Biller HE Aggressive juvenile fibromatosis involving the paranasal sinuses. Otolaryngol Head Neck Surg 1991; 104:549-52.

(5.) Thompson DH, Khan A, Gonzalez C, Auclair R Juvenile aggressive fibromatosis: Report of three cases and review of the literature. Ear Nose Throat J 1991;70:462-8.

(6.) Maillard AA, Kountakis SE. Pediatric sino-orbital desmoid fibromatosis. Ann Otol Rhinol Laryngol 1996; 105:463-6.

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

(8.) Das Gupta TK, Brasfield RD, O'Hara J. Extra-abdominal desmoids: A clinicopathological study. Ann Surg 1969;170:109-21.

(9.) Barnes L, ed. Surgical pathology of the head and neck. New York: Dekker, 1985:769-77.

(10.) Weiss SW, Goldblum JR. Fibrous tumors of infancy and childhood. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St. Louis: Mosby, 2001:347-408.

(11.) Chung EB, Enzinger FM. Infantile myofibromatosis. Cancer 1981;48:1807-18.

(12.) Chung EB, Enzinger FM. Infantile fibrosarcoma. Cancer 1976;38: 729-39.

(13.) Rodu B, Weathers DR, Campbell WG, Jr. Aggressive fibromatosis involving the paramandibular soft tissues. A study with the aid of electron microscopy. Oral Surg Oral Med Oral Pathol 1981;52: 395-403.

(14.) Schurch W, Seemayer TA, Gabbiani G. The myofibroblast: A quarter century after its discovery. Am J Surg Pathol 1998;22:141-7.

(15.) Gabbiani G, Ryan GB, Maine G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia 1971;27:549-50.

(16.) Welsh RA, Meyer AT. Intracellular collagen fibers in human mesenchymal tumors and inflammatory states. Arch Pathol 1967;84: 354-62.

(17.) Faulkner LB, Hajdu SI, Kher U, et al. Pediatric dermoid tumor: Retrospective analysis of 63 cases. J Clin Oncol 1995; 13:2813-18.

(18.) Wara WM, Phillips TL, Hill DR, et al. Desmoid tumors--treatment and prognosis. Radiology 1977; 124:225-6.

(19.) Goepfert H, Cangir A, Ayala AG, Eftekhan F. Chemotherapy of locally aggressive head and neck tumors in the pediatric age group. Desmoid fibromatosis and nasopharyngeal angiofibroma. Am J Surg 1982; 144:437-44.

(20.) Maddalozzo J, Tenta LT, Hutchinson LR, et al. Juvenile fibromatosis: Hormonal receptors, Int J Pediatr Otorhinolaryngol 1993;25: 191-9.

(21.) Weidner N, Semple JP, Welch WR, Folkman J. Tumor angiogenesis and metastasis--correlation in invasive breast carcinoma. N Engl J Med 1991;324:1-8.

From the Department of Pathology (Dr. Mannan and Dr. Ray), the Department of Otorhinolaryngology--Head and Neck Surgery (Dr. Sharma), and the Department of Radiodiagnosis (Dr. Hatimota), All India Institute of Medical Sciences, New Delhi.

Reprint requests: Ruma Ray, MD, Associate Professor, Department of Pathology, All India Institute of Medical Sciences, New Delhi-110029, India. Phone: 91-11-2686-4851, ext. 4376; fax: 91-11-2658-8641; e-mail: rumasrc2@hotmail.com

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