CASO CLÍNICO

 

Desmoplastic fibroma of the jaw associated with tuberous sclerosis. Literature review and case report

Fibroma desmoplásico de mandíbula asociado a esclerosis tuberosa. Revisión de la literatura y presentación de un caso

 

 

M. Acosta Feria¹, P. Infante Cossío², D. López Vaquero¹, A. Carranza Carranza³, J.L. Gutiérrez Pérez⁴

1 Médico Residente. Servicio de Cirugía Oral y Maxilofacial.
2 Médico Adjunto. Servicio de Cirugía Oral y Maxilofacial.
3 Médico Residente. Servicio de Anatomía Patológica.
4 Jefe de Servicio. Servicio de Cirugía Oral y Maxilofacial.
Hospital Universitario Virgen del Rocío, Sevilla, España.

Correspondence

 

 

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ABSTRACT

Tuberous sclerosis is a congenital anomaly of embryonic development with an autosomal dominant inheritance. It is characterized by the presence of neurologic and dermatologic disorders and mental retardation. It can affect other organs and systems and produce orofacial manifestations. Dental enamel defects are the most frequent intraoral lesion. Bone lesions rarely occur in the upper jaw. Desmoplastic fibroma is an infrequent, slow-growing, locally aggressive intraosseous fibrous tumor that rarely is associated with tuberous sclerosis. We report the clinical case of a 33-year-old man with tuberous sclerosis and a jaw lesion diagnosed as desmoplastic fibroma. The diagnostic methods, clinical presentation, and treatment are discussed.

Key words: Tuberous sclerosis; Desmoplastic fibroma; Bourneville- Pringle disease; Oral manifestations; Jaw.

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RESUMEN

La esclerosis tuberosa es una anomalía congénita del desarrollo embrionario que se transmite de forma autosómica dominante caracterizada por la presencia por trastornos neurológicos, cutáneos o dermatológicos, y retraso mental. Se pueden afectar otros órganos y sistemas, y dar manifestaciones orofaciales. La lesión a nivel del esmalte dental constituye la lesión intraoral más frecuente. Rara vez se pueden encontrar lesiones óseas en los maxilares. El fibroma desmoplásico es un infrecuente tumor fibroso intraóseo localmente agresivo de lento crecimiento, que se asocia muy rara vez a la esclerosis tuberosa. Presentamos el caso clínico de un paciente de 33 años afecto de esclerosis tuberosa con una lesión en la mandíbula diagnosticada como fibroma desmoplásico. Se discuten los métodos diagnósticos, presentación clínica y tratamiento.

Palabras clave: Esclerosis tuberosa; Fibroma desmoplásico; Enfermedad de Bourneville; Manifestaciones orales; Mandíbula.

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Introduction

Tuberous sclerosis (TS), or Bourneville’s disease, is a congenital anomaly of embryonic development that is transmitted by autosomal dominant inheritance and has different forms of clinical expression. It is currently associated with mutations of the tumor growth suppression genes TSC1 and TSC2.¹ It is classified among the so-called phacomatoses, or developmental anomalies, which can originate tumors and/or hamartomas of the nervous system.^2,3 It is characterized by the formation of benign hamartomatous tumors, neurofibromas, and angiofibromas located in different organs.⁴ The disease occurs in 0.1-0.6% of people diagnosed as having epilepsy and mental retardation and in 1/30,000-50,000 of the general population.^5-8 The disease prevalence is 1 out of 6,000 inhabitants.⁷

The classic TS triad is epilepsy, mental retardation, and facial angiofibromas, frequently in the form of butterfly wings. However, the triad is observed in less than one-third of patients. In up to 6% of cases, none of these symptoms occurs. In incomplete or frustrated forms, the diagnosis may be overlooked, which is why it is important to suspect the disease in patients with epilepsy in addition to skin anomalies and progressive neurologic deterioration.^2,9,10 Most patients with TS die before the age of 20 years. The cause of death is generally status epilepticus, pneumonia, cachexia, or acute myocardial infarction. Paucisymptomatic or incomplete forms of the disease exist that have a greater life expectancy.⁵

The oral manifestations of TS occur in 11% of patients and include hemangiomas, maxillary cysts and pseudocysts, hyperostosis, alveolar atrophy, and tooth enamel defects. Less frequent manifestations are facial asymmetry, higharched palate, bifid uvula, cleft lip and cleft palate, diastemata and dental eruption anomalies.⁸ The purpose of this study is to report the case of a patient with TS and facial and intraoral manifestations. The patient was seen in our department for a radiopaque lesion of the jaw that was diagnosed as desmoplastic fibroma when excised. The main clinical, radiologic, evolution, and therapeutic features of the disease are discussed.

 

Clinical case

A 33-year-old man was referred for a slow-growing tumor of the right lower parasymphyseal mandibular region of several years evolution. His medical history included tuberous sclerosis and kidney transplantation after nephrectomy for renal angiomyolipoma. His disease symptoms included Pringle’s sebaceous adenoma in the nasogenial area, retinal hamartomas, and fibrotic lesions of the posterior cervical area. The clinical examination disclosed a hard lesion adhered to the jaw, approximately 2 x 2 cm in diameter, with mild tenderness (Fig. 1A). The skin of the lateral cervical region and nape exhibited multiple small, dark-colored excrescent lesions of fibrotic appearance (Fig. 1B). The intraoral examination found gingival hyperplasia that was attributed to chronic anticonvulsant treatment with hydantoin to prevent the epileptic seizures typical of the patient’s underlying syndrome.

In the panoramic radiograph, increased bone density was observed in the parasymphyseal region of the jaw. CAT showed a chondroid bone excrescence and erosion of the right mandibular cortex in the parasymphyseal area without any soft-tissue component (Fig. 2). The radiographic differential diagnosis included: ameloblastoma, odontogenic myxoma, aneurysmal cyst, chondromyxoid fibroma, central hemangioma, and eosinophilic granuloma.

Under general anesthesia and via a cutaneous approach, a hard round mass with safety margin was removed from the jaw (Fig. 3). Cervical fibromas were removed by CO₂ laser in the same surgical act. The patient was discharged on day after the intervention. During follow-up in the outpatient clinic, he has not presented any sign or symptom of recurrence of the mandibular tumor in three years (Fig. 4).

Histopathologic study of the mandibular bone mass removed disclosed scant fibroblasts in a stroma containing a large amount of hyalinized collagen. Bony spicules without an osteoid border indicative of tumoral bone infiltration were observed inside the mass. The lesion contained spindle cells with long, uniform nuclei, scant mitoses and no atypia, suggesting a benign lesion. The study concluded with a diagnosis of desmoplastic fibroma (Fig. 5).

 

Discussion

TS is a rare congenital phacomatous disease characterized by a high prevalence of multiple orofacial, neurologic, and dermatologic hamartomatous lesions. In 50% of the patients with the disease, there is a family history of the disease, which has an autosomal dominant inheritance with variable expression. Diagnosis of the disease in children can be difficult due to the existence of so-called "frustrated" disease forms that do not display the classic triad described by Vogt.^11,12 Approximately one half of patients with TS have mental disorders, the most frequent of which is epilepsy. Other neurologic manifestations are observed, such as intracranial calcifications in approximately 50% of patients, cerebral tumors like glioma, glioblastoma or ependymoma, retinal tumor, cataract, optic atrophy, phacoma, learning disorders, mental retardation, and autism.^2,6,9,10 The skin lesions include Pringle’s sebaceous adenoma of the nose and cheeks with a butterfly-wing disposition, typical skin fibromas, ungueal fibromas, or Koebnen’s tumors, café au lait spots, or shagreen plaques in the lumbar region. The presence of the pathognomonic skin lesions can lead to an early diagnosis and has prognostic interest. Skin lesions may not be present at birth.^2,6,9,10 Other TS manifestations are cardiac disease, including rhabdomyoma, ventricular tachycardia, and valvular obstruction by intracardiac masses,⁶ as well as pulmonary fibrosis, intestinal polyposis, nasal angiofibroma, astrocytoma, and retinal hamartoma. Renal disease is the major cause of morbidity and mortality in patients with tuberous sclerosis^7,8,12 and consists of renal angiomyolipomas and cysts and chronic renal failure.

The diagnosis is generally made in childhood when the first neurologic symptoms appear. EEG is essential for characterizing and monitoring epileptic seizures. Other studies made are an examination of the ocular fundus, MRI, and CAT.^2,4 The major and minor diagnostic criteria of TS are listed in table 1.⁸ Therapy is specific and symptomatic for each of the patient’s clinical manifestations. The patient’s family members must be given genetic counseling.¹² When a child with the disease is detected, family members must undergo the following examinations: dermatologic examination, ocular fundus, cerebral CT and MRI, and cardiac and renal ultrasonography.² Survival beyond 30 years is poor. The disease prognosis depends on the type of cerebral seizures that occur, their depth, and the patient’s intellectual deterioration as an adult. Above all, the appearance of renal angiomyolipomas that produce retroperitoneal hemorrhage and progressive renal failure aggravates the prognosis, as the main cause of death in these patients.^{2,4,8,9,11,12}

 

Few published studies have addressed the oral and maxillofacial manifestations of TS. The incidence of oral lesions is 11-56% of patients. They are diagnosed between 4 and 10 years of age or in puberty. They include fibrous hyperplasia, hemangioma, bifid uvula, cleft lip and cleft palate, macroglossia, high arched palate, tooth enamel abnormalities, or poor dental hygiene due to delayed dental eruption. Gingival hyperplasia may occur as a result of anticonvulsant therapy.^3-6,9,11 Tooth enamel defects affect mainly the vestibular faces of the central and lateral incisors and canines. The prevalence of tooth enamel defects is 48-100% of cases, depending on the study. Both temporary and permanent teeth are affected.^5,7 There have been few studies of the maxillofacial bone lesions in TS. Radiopaque lesions identified as fibrous osteitis are observed in the maxillary and mandibular bones. Other lesions described are epithelial calcifying odontogenic tumor, desmoplastic fibroma, central odontogenic fibroma, and odontogenic myxoma,^4,10,11 Damm et al.¹⁰ suggest that TS should be included in the differential diagnosis algorithms of radiographic mandibular lesions.

Desmoplastic fibroma is a rare, locally aggressive, intraosseous myofibroblastic tumor responsible for less than 1% of bone tumors. It is of unknown etiology, but its origin has been related to trauma, endocrine disorders, and genetic factors. It was first described by Jaffe in 1958. Griffith was the first to describe it in the jaw, in 1965. In 2006, Said-Al-Naief et al.¹² reviewed all the cases reported in the literature and found a total of 74 cases in the jaw in the last 40 years. Miyamoto et al.,³ in a review of 50 cases, described 42 mandibular versus 8 maxillary cases. In more than 80% of cases, it occurs in patients under the age of 30 years, with a slight predilection for the female sex. Although the most frequent location is the maxilla, it can appear in other bones, such as the femur, pelvis, radius, or tibia. The association of maxillary desmoplastic fibroma and TS is even more uncommon. Vargas-González et al.1 reported a case in 2004 and cited another case of Miyamoto et al.³ in 1995 and four cases of Damm et al.¹⁰ in 1999.

Desmoplastic fibroma may be asymptomatic in some cases, but it usually occurs as a firm, slow-growing mass that generally causes pain and inflammation. Other symptoms that can appear include dental loss, trismus, or restricted mouth opening, malocclusion, dysesthesia, tumoral hemorrhage or infection, infection, recurrent sinusitis, and exophthalmos. Radiologically, it usually manifests as a well defined, radiolucent or radiopaque unilocular or multilocular lesion containing connective tissue trabeculae. We can often observe thinning or interruption of the bone cortex with soft tissue involvement.^1,12

Histologically, desmoplastic fibroma is constituted by fibroblasts and abundant collagen matrix. Despite its benign nature, it may contain spicules of eroded laminar bone because its growth is more infiltrative than expansive. The histopathologic differential diagnosis must be made fundamentally with fibrous dysplasia (bone formation, osteoid rim, and fibrovascular stroma present), low-grade fibrosarcoma (nuclear pleomorphism with abundant mitoses and atypias present), and low-grade osteosarcoma (osteoformation and an osteoblastic rim).

The treatment of choice of desmoplastic fibroma is still debated. Jaffe recommends segmental resection as the treatment of choice when the lesion shows signs of aggressiveness and soft-tissue involvement. Curettage of the lesion is accepted as the first treatment, although it has a higher recurrence rate.^3,12 Sugiura 3 claims that the treatment of choice of desmoplastic fibroma is curettage followed by filling of the residual cavity with autologous bone graft, which has a recurrence rate of 24%. Eisen and Butler^1,3 recommend conservative treatment of facial lesions to avoid deformation, but tumor resection if soft-tissue infiltration by the tumor has occurred. Due to the recurrence potential of desmoplastic fibroma, the recommended postoperative follow-up period is three years.

The radiographic differential diagnosis includes lesions such as ameloblastoma, odontogenic myxoma, epithelial calcifying odontogenic tumor, aneurysmal cyst, chondromyxoid fibroma, central hemangioma, eosinophilic granuloma, and sarcoma. Epithelial calcifying odontogenic tumor is one of the odontogenic tumors considered benign. It is more common in men and in the jaw it shows predilection for the premolar and molar region. Its growth is expansive and relatively slow. Treatment consists of enucleation and aggressive curettage of the residual cavity, although recurrence has been observed.¹³ Odontogenic myxoma is a benign, but locally aggressive, tumor. It constitutes 3-8% of odontogenic tumors, occurring in 60% of cases in the second or third decade of life. It is most frequently located in the jaw, particularly in the mandibular angle or ascendant ramus. Surgery is the treatment of choice.¹⁴ Central odontogenic fibroma is a benign tumor that occurs only in the maxilla. It is generally located anterior to the first molar. Radiographically, the lesion is well defined, has sclerotic margins, and may be unilocular or multilocular. It usually does not recur after exeresis.¹⁵

 

Conclusions

Desmoplastic fibroma is a rare, locally aggressive, slowgrowing fibrous bone tumor that rarely is associated with TS. The diagnosis is based on the clinical manifestations and radiographic study, where it is observed as a relatively well defined, radiopaque, and unilocular or multilocular lesion. Diagnostic confirmation is by histopathologic study of the excised tumor. The most accepted treatment for desmoplastic fibroma of the jaw is resection of the tumor with ample safety margins to prevent recurrence. In our case, the treatment was definitive.

 

 

Correspondence:
Pedro Infante Cossío
Servicio de Cirugía Oral y Maxilofacial
Hospital Universitario Virgen del Rocío
Avda. Manuel Siurot s/n
41013-Sevilla, España
Email: pinfante@us.es

Recibido: 12.03.07
Aceptado: 04.02.08

 

 

References

1. Vargas-Gonzalez R, San Martin-Brieke W, Gil-Orduna C, Lara-Hernandez F. Desmoplastic fibroma-like tumor of maxillofacial region associated with tuberous sclerosis. Pathol Oncol Res 2004;10:237-9.        [ Links ]

2. López López J, Rodríguez de Rivera E, Márques Osares M, Finestres Zubeldia F, Chimenos Küstner E, Roselló Llabrés X. Esclerosis tuberosa y manifestaciones orales. Caso clínico. Med Oral 2004;9:216-23.        [ Links ]

3. Miyamoto Y, Satomura K, Rikimaru K, Hayashi Y. Desmoplastic fibroma of the mandible associated with tuberous sclerosis. J Oral Pathol Med 1995;24:93-6.        [ Links ]

4. López E, Escovich L, Vigna A. Esclerosis tuberosa: Presentación de un caso clínico con manifestaciones estomatológicas. Med Oral 2003;8:122-8.        [ Links ]

5. Murti PR, Bhonsle RB, Mehta F, Daftary DK. Oro-facial lesions of tuberous sclerosis. Int J Oral Surg 1980;9:292-7.        [ Links ]

6. Scully C. Oral mucosal lesions in association with epilepsy and cutaneous lesions: The Pringle- Bourneville syndrome. Int J Oral Surg 1981;10:68-72.        [ Links ]

7. Cutando A, Gil JA, López J. Oral health management implications in patients with tuberous sclerosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000; 89:430-5.        [ Links ]

8. Barron RP, Kainulainen VT, Forrest CR, Krafchik B, Mock D, Sandor GKB. Tuberous sclerosis: clinicopathologic features and review of the literature. J Craniomaxilofac Surg 2002;30:361-6.        [ Links ]

9. Scully C. Orofacial manifestations in tuberous sclerosis. Oral Surg 1977;44:706- 16.        [ Links ]

10. Damm D, Tomich C, Wite D, Drummond J. Intraosseous fibrous lesions of the jaws, a manifestations of tuberous sclerosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;87:334-40.        [ Links ]

11. Celenk P, Alkan A, Canger M, Günhan Ö. Fibrolipomatous hamartomas in a patient with tuberous sclerosis: Report of a case. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2005;99:202-6.        [ Links ]

12. Said-Al-Naief N, Fernandes R, Louis P, Bell W, Siegal G. Desmoplastic fibroma of the jaw: A case report and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2006;101:82-94.        [ Links ]

13. Rubin M, Delgado E, Cozzi G, Palladino V. Tuberous sclerosis complex and a calcifying epithelial odontogenic tumor of the mandible. Oral Surg Oral Med Oral Pathol 1987;64:207-11.        [ Links ]

14. Harrison MG, O´Neill ID, Chadwick BL. Odontogenic myxoma in an adolescent with tuberous esclerosis: A case report. J Oral Pathol Med 1997;26:339-41.        [ Links ]

15. Swarnkar A, Jungreis C, Peel RL. Central odontogenic fibroma an intracraneal aneurysm associated with tuberous sclerosis. Am J Otolaryngol 1998;19:66-9.        [ Links ]