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Monstrous Skull Osteomas in a Probable Gardner’s Syndrome: Case Report
Neoplasm
Monstrous Skull Osteomas in a Probable Gardner’s Syndrome: Case Report Jacques Noterman, M.D., Ph.D., Nicolas Massager, M.D., Michel Vloeberghs, M.D., and Jacques Brotchi, M.D., Ph.D. Department of Neurosurgery, Ho ˆ pital Universitaire Erasme, Brussels, Belgium
Noterman J, Massager N, Vloeberghs M, Brotchi J. Monstrous skull osteomas in a probable Gardner’s syndrome: case report. Surg Neurol 1998;49:302–5. BACKGROUND
Gardner’s syndrome includes a clinical triad of familial polyposis coli, osteomas, and soft tissue tumors. METHODS
We present a very unusual case of probable isolated Gardner’s syndrome characterized by extremely voluminous osteomas in the occipital and frontal areas associated with diffuse subcutaneous lipomas and without colic abnormality. RESULTS
The neurosurgical management included resection of the osteomas for cosmetic reasons. After a follow-up period of 5 years, the patient remains free of digestive complaints and the resected osteomas did not recur. CONCLUSIONS
The special clinical presentation of our case of possible Gardner’s syndrome is discussed. © 1998 by Elsevier Science Inc. KEY WORDS
Osteoma, leontiasis ossea, Gardner’s syndrome, polyposis coli.
Introduction ardner’s syndrome usually exhibits an autosomal dominant inheritance. A gene located on chromosome 5 has been isolated that is altered in the majority of cases [8,12]. The syndrome is characterized by three different manifestations: a familial colic polyposis (FCP), multiple osteomas, and cutaneous tumors. These characteristics are not necessarily concomitant [2,5,7,9]. The syndrome rarely requires the intervention of a neurosurgical team because of the predominance of the
G
Address reprint requests to: J. Noterman, M.D., Ph.D., Department of Neurosurgery, Ho ˆpital Universitaire Erasme, Route de Lennik 808, 1070 Brussels, Belgium. Received June 5, 1996; accepted February 19, 1997. 0090-3019/98/$19.00 PII S0090-3019(97)00220-6
FCP and the preferential location of osteomas in the maxillar and mandibular regions [6]. A few cases have been described in the neurosurgical literature; almost all of them were operated on for osteomas or metastatic brain tumors [1,3,4,10,11,14]. We present an isolated case of a probable Gardner’s syndrome with monstrous osteomas (leontiasis ossea) [13] of the cranial vault and the skull base associated with numerous subcutaneous lipomas of the limbs but without FCP. The neurosurgical procedure was requested by the patient for cosmetic reasons.
Case Report This 42-year-old caucasian woman complained for several years of growing skull deformities in the frontal and occipital areas. These deformities were painless but particularly prominent (Figure 1). In association with these hypertrophic bony tumors, the clinical examination revealed multiple subcutaneous lipomas in all four limbs. The patient never presented any abdominal complaint. Skull X ray and computed tomography (CT) demonstrated multiple osteomas of the calvaria and skull base (Figure 2A,B), but no tumor of the maxilla or mandible. X ray of the entire skeleton revealed only one other osteoma in the right femoral diaphysis. Extensive investigations of the colon and the upper digestive tract were all negative except for an asymptomatic hiatal hernia. No other member of the patient’s family presented any skull osteoma, subcutaneous tumor, or colic disease. On April 12, 1989, the voluminous osteomas of the two retromastoid regions were first operated on in a prone position and subtotally resected with an electric saw. The surgical procedure was difficult and time-consuming because of the hardness of the © 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Monstrous Osteomas in Gardner’s Syndrome
1
Surg Neurol 303 1998;49:302–5
(A,B) Lateral views of patient’s head showing the voluminous skull deformities; (C) operative view of frontal osteomas; (D) operative view of a giant retromastoid osteoma being resected.
bony tumors. During the same anesthesia, in a second procedure, the patient was placed in a supine position and the bifrontal osteomas were resected. The microscopic aspect of the tumors showed extremely compact bony tissue (ivory type) without malignant component, in accordance with the diagnosis of giant osteomas. The postoperative course was uneventful and the 5-year follow-up is characterized by no recurrence of the skull osteomas and no appearance of any colic abnormality. The cosmetic aspect of the head remains acceptable.
Discussion The case described here is unusual for several reasons. First, extensive history confirmed the fact that no other member of the patient’s family was affected by this syndrome. Some other cases of such isolated Gardner’s syndrome have been described in the literature [10,14]. Second, only two manifestations of the clinical triad of the syndrome were found in our patient, who is free of colic polyposis up to now. Patients with Gardner’s syndrome and only tardy appear-
ance of colic lesions—sometimes several years after the other manifestations— have already been reported [4,7]. Some authors talk of a “partial Gardner’s syndrome” when some characteristics of the disease are missing [2]. This case is characterized by the massive osteomas presented by the patient. In fact, every part of the calvaria was invaded, but giant osteomas were confined to the occipital region. The posterior location of bony tumors is rather unusual in this entity, as most of the published cases report mandibulofacial involvement [2– 4,13]. The surgical procedure consisted of the subtotal removal of osteomas using a powerful orthopedic saw with the aim of remoulding the vault. The procedure was particularly slow and difficult because of the extremely dense, “ivory” consistency of this category of osteomas. A review of the literature reveals a long-standing confusion between osteomas, osteitis deformans or Paget’s disease, osteitis fibrosa cystica (hyperparathyroidism), and fibrous dysplasia. Meanwhile, some well illustrated cases are referred as Fourcade’s case reported by Cruveilhier in 1829
304 Surg Neurol 1998;49:302–5
2
Noterman et al
(A,B) Preoperative skull X ray and cerebral CT scan demonstrating monstrous extracranial osteomas of the occipital and frontal areas; (C,D) postoperative controls.
[13]. The patients evolve frequently to a fatal conclusion because of the malignant transformation of the FCP [2,14,15]. To our knowledge, the other components of the syndrome are not so dangerous in their evolution.
7. 8.
9.
REFERENCES 1. Bochetto JF, Raycroft JF, De Innocentes LW. Multiple polyposis, exostosis, and soft tissue tumors. Surg Gynecol Obstet 1963;117:489 –94. 2. Camuzard JF, Vaille G, Santini J, Raspaldo H, Demard F. Le syndrome de Gardner. Revue de la litte´rature. A propos d’une forme familiale. Ann Oto-Laryngol (Paris) 1990;107:509 –13. 3. Del Vecchio A, Agrestini C, Salucci P, Manicone AM, Della Rocca C. Osteomi ed esostosi del massiccio facciale: studio morfologico e considerazioni etiopatogenetiche. Minerva Stomatol 1993;42:533– 40. 4. Douniau R, Rubay J, Stalport J, Van Den Noortgate D. Les incidences odonto-maxillaires du syndrome de Gardner. Acta Stomatol Belg 1976;73:365–79. 5. Gardner EJ, Plenk HP. Hereditary pattern for multiple osteomas in a family group. Am J Human Genet 1952; 4:31– 6. 6. Goia F, Schettino F, Tesi U, Galli C, Carezzana G.
10.
11. 12.
13. 14. 15.
Terapia degli osteomi mandibolari nella sindrome di Gardner. Minerva Stomatol 1986;35:595– 8. Halse A, Roed-Petersen B, Lund K. Gardner’s syndrome. J Oral Surgery 1975;33:673–5. Herrera L, Kakati S, Gibas L, Pietrzak E, Sandberg AA. Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet 1986;25:473– 6. Jagelman DG. Extracolonic manifestations of familial polyposis coli. Cancer Genet Cytogenet 1987;27:319–25. Jones EL, Cornell WP. Gardner’s symdrome. Review of the literature and report on a family. Arch Surg 1966;92:287–300. Katou F, Motegi K, Baba S. Mandibular lesions in patients with adenomatosis coli. J Craniomaxfac Surg 1989;17:354 – 8. Leppert M, Dobbs M, Scambler P, O’Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, Lathrop M, Wasmuth J, Lalouel JM, White R. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 1987;238:1411–3. Plenk HP, Gardner EJ. Osteomatosis (leontiasis ossea). Radiology 1954;62:830 – 40. Terao H, Sato S, Kim S. Gardner’s syndrome involving the skull, dura and brain. Case report. J Neurosurg 1976;44:638 – 41. Yaffee HS. Gastric Polyposis and soft tissue tumors. Arch Dermatol 1964;89:806 – 8.
Monstrous Osteomas in Gardner’s Syndrome
COMMENTARY
Rapid growth in the understanding of the genetic causes of various clinical conditions has provoked an important new concept: different mutations in the same gene can lead to widely different manifestations. In some cases, these conditions have been considered genetically unrelated until molecular studies indicated that they were caused by the same gene. The case described by the Belgian group is a good example of such a condition. The gene for adenomatous polyposis coli (APC) was among the first identified tumor suppressors. However, some mutations in the same gene cause primarily benign tumors at different locations. The patient with Gardner’s syndrome discussed here did not even have any intestinal abnormalities, but displayed major defects in differentiation of other tissues. We may speculate that in different tissues the APC protein interacts with different elements of regulatory pathways, and that different residues of the protein molecule participate in these interactions. Correspondingly, mutations in these residues will cause widely different symptoms: malignancies of the gastroin-
Surg Neurol 305 1998;49:302–5
testinal tract in some cases, and benign overgrowth of tissues in others. Alexander Kolchinsky, Ph.D. Departments of Neurosurgery & Genetics University of Illinois at Chicago Chicago, Illinois Gardner’s syndrome is an autosomal dominant genetic disease that usually maps to chromosome 5, but it is genetically heterogeneous and some families map outside this region. The precise molecular genetics and altered gene product are not known. Families may incompletely express the triad of cranial osteomas, subcutaneous lipomas, and FCP. Genetic counseling is important so that children of an affected parent know that they may be at risk of developing any of the three components of the triad of clinical features so that proper screening tests can be conducted at regular intervals. Roger Rosenberg, M.D. Department of Neurology UT Southwestern Medical Center Dallas, Texas
Monstrous Skull Osteomas in a Probable Gardner’s Syndrome: Case Report Jacques Noterman, M.D., Ph.D., Nicolas Massager, M.D., Michel Vloeberghs, M.D., and Jacques Brotchi, M.D., Ph.D. Department of Neurosurgery, Ho ˆ pital Universitaire Erasme, Brussels, Belgium
Noterman J, Massager N, Vloeberghs M, Brotchi J. Monstrous skull osteomas in a probable Gardner’s syndrome: case report. Surg Neurol 1998;49:302–5. BACKGROUND
Gardner’s syndrome includes a clinical triad of familial polyposis coli, osteomas, and soft tissue tumors. METHODS
We present a very unusual case of probable isolated Gardner’s syndrome characterized by extremely voluminous osteomas in the occipital and frontal areas associated with diffuse subcutaneous lipomas and without colic abnormality. RESULTS
The neurosurgical management included resection of the osteomas for cosmetic reasons. After a follow-up period of 5 years, the patient remains free of digestive complaints and the resected osteomas did not recur. CONCLUSIONS
The special clinical presentation of our case of possible Gardner’s syndrome is discussed. © 1998 by Elsevier Science Inc. KEY WORDS
Osteoma, leontiasis ossea, Gardner’s syndrome, polyposis coli.
Introduction ardner’s syndrome usually exhibits an autosomal dominant inheritance. A gene located on chromosome 5 has been isolated that is altered in the majority of cases [8,12]. The syndrome is characterized by three different manifestations: a familial colic polyposis (FCP), multiple osteomas, and cutaneous tumors. These characteristics are not necessarily concomitant [2,5,7,9]. The syndrome rarely requires the intervention of a neurosurgical team because of the predominance of the
G
Address reprint requests to: J. Noterman, M.D., Ph.D., Department of Neurosurgery, Ho ˆpital Universitaire Erasme, Route de Lennik 808, 1070 Brussels, Belgium. Received June 5, 1996; accepted February 19, 1997. 0090-3019/98/$19.00 PII S0090-3019(97)00220-6
FCP and the preferential location of osteomas in the maxillar and mandibular regions [6]. A few cases have been described in the neurosurgical literature; almost all of them were operated on for osteomas or metastatic brain tumors [1,3,4,10,11,14]. We present an isolated case of a probable Gardner’s syndrome with monstrous osteomas (leontiasis ossea) [13] of the cranial vault and the skull base associated with numerous subcutaneous lipomas of the limbs but without FCP. The neurosurgical procedure was requested by the patient for cosmetic reasons.
Case Report This 42-year-old caucasian woman complained for several years of growing skull deformities in the frontal and occipital areas. These deformities were painless but particularly prominent (Figure 1). In association with these hypertrophic bony tumors, the clinical examination revealed multiple subcutaneous lipomas in all four limbs. The patient never presented any abdominal complaint. Skull X ray and computed tomography (CT) demonstrated multiple osteomas of the calvaria and skull base (Figure 2A,B), but no tumor of the maxilla or mandible. X ray of the entire skeleton revealed only one other osteoma in the right femoral diaphysis. Extensive investigations of the colon and the upper digestive tract were all negative except for an asymptomatic hiatal hernia. No other member of the patient’s family presented any skull osteoma, subcutaneous tumor, or colic disease. On April 12, 1989, the voluminous osteomas of the two retromastoid regions were first operated on in a prone position and subtotally resected with an electric saw. The surgical procedure was difficult and time-consuming because of the hardness of the © 1998 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
Monstrous Osteomas in Gardner’s Syndrome
1
Surg Neurol 303 1998;49:302–5
(A,B) Lateral views of patient’s head showing the voluminous skull deformities; (C) operative view of frontal osteomas; (D) operative view of a giant retromastoid osteoma being resected.
bony tumors. During the same anesthesia, in a second procedure, the patient was placed in a supine position and the bifrontal osteomas were resected. The microscopic aspect of the tumors showed extremely compact bony tissue (ivory type) without malignant component, in accordance with the diagnosis of giant osteomas. The postoperative course was uneventful and the 5-year follow-up is characterized by no recurrence of the skull osteomas and no appearance of any colic abnormality. The cosmetic aspect of the head remains acceptable.
Discussion The case described here is unusual for several reasons. First, extensive history confirmed the fact that no other member of the patient’s family was affected by this syndrome. Some other cases of such isolated Gardner’s syndrome have been described in the literature [10,14]. Second, only two manifestations of the clinical triad of the syndrome were found in our patient, who is free of colic polyposis up to now. Patients with Gardner’s syndrome and only tardy appear-
ance of colic lesions—sometimes several years after the other manifestations— have already been reported [4,7]. Some authors talk of a “partial Gardner’s syndrome” when some characteristics of the disease are missing [2]. This case is characterized by the massive osteomas presented by the patient. In fact, every part of the calvaria was invaded, but giant osteomas were confined to the occipital region. The posterior location of bony tumors is rather unusual in this entity, as most of the published cases report mandibulofacial involvement [2– 4,13]. The surgical procedure consisted of the subtotal removal of osteomas using a powerful orthopedic saw with the aim of remoulding the vault. The procedure was particularly slow and difficult because of the extremely dense, “ivory” consistency of this category of osteomas. A review of the literature reveals a long-standing confusion between osteomas, osteitis deformans or Paget’s disease, osteitis fibrosa cystica (hyperparathyroidism), and fibrous dysplasia. Meanwhile, some well illustrated cases are referred as Fourcade’s case reported by Cruveilhier in 1829
304 Surg Neurol 1998;49:302–5
2
Noterman et al
(A,B) Preoperative skull X ray and cerebral CT scan demonstrating monstrous extracranial osteomas of the occipital and frontal areas; (C,D) postoperative controls.
[13]. The patients evolve frequently to a fatal conclusion because of the malignant transformation of the FCP [2,14,15]. To our knowledge, the other components of the syndrome are not so dangerous in their evolution.
7. 8.
9.
REFERENCES 1. Bochetto JF, Raycroft JF, De Innocentes LW. Multiple polyposis, exostosis, and soft tissue tumors. Surg Gynecol Obstet 1963;117:489 –94. 2. Camuzard JF, Vaille G, Santini J, Raspaldo H, Demard F. Le syndrome de Gardner. Revue de la litte´rature. A propos d’une forme familiale. Ann Oto-Laryngol (Paris) 1990;107:509 –13. 3. Del Vecchio A, Agrestini C, Salucci P, Manicone AM, Della Rocca C. Osteomi ed esostosi del massiccio facciale: studio morfologico e considerazioni etiopatogenetiche. Minerva Stomatol 1993;42:533– 40. 4. Douniau R, Rubay J, Stalport J, Van Den Noortgate D. Les incidences odonto-maxillaires du syndrome de Gardner. Acta Stomatol Belg 1976;73:365–79. 5. Gardner EJ, Plenk HP. Hereditary pattern for multiple osteomas in a family group. Am J Human Genet 1952; 4:31– 6. 6. Goia F, Schettino F, Tesi U, Galli C, Carezzana G.
10.
11. 12.
13. 14. 15.
Terapia degli osteomi mandibolari nella sindrome di Gardner. Minerva Stomatol 1986;35:595– 8. Halse A, Roed-Petersen B, Lund K. Gardner’s syndrome. J Oral Surgery 1975;33:673–5. Herrera L, Kakati S, Gibas L, Pietrzak E, Sandberg AA. Gardner syndrome in a man with an interstitial deletion of 5q. Am J Med Genet 1986;25:473– 6. Jagelman DG. Extracolonic manifestations of familial polyposis coli. Cancer Genet Cytogenet 1987;27:319–25. Jones EL, Cornell WP. Gardner’s symdrome. Review of the literature and report on a family. Arch Surg 1966;92:287–300. Katou F, Motegi K, Baba S. Mandibular lesions in patients with adenomatosis coli. J Craniomaxfac Surg 1989;17:354 – 8. Leppert M, Dobbs M, Scambler P, O’Connell P, Nakamura Y, Stauffer D, Woodward S, Burt R, Hughes J, Gardner E, Lathrop M, Wasmuth J, Lalouel JM, White R. The gene for familial polyposis coli maps to the long arm of chromosome 5. Science 1987;238:1411–3. Plenk HP, Gardner EJ. Osteomatosis (leontiasis ossea). Radiology 1954;62:830 – 40. Terao H, Sato S, Kim S. Gardner’s syndrome involving the skull, dura and brain. Case report. J Neurosurg 1976;44:638 – 41. Yaffee HS. Gastric Polyposis and soft tissue tumors. Arch Dermatol 1964;89:806 – 8.
Monstrous Osteomas in Gardner’s Syndrome
COMMENTARY
Rapid growth in the understanding of the genetic causes of various clinical conditions has provoked an important new concept: different mutations in the same gene can lead to widely different manifestations. In some cases, these conditions have been considered genetically unrelated until molecular studies indicated that they were caused by the same gene. The case described by the Belgian group is a good example of such a condition. The gene for adenomatous polyposis coli (APC) was among the first identified tumor suppressors. However, some mutations in the same gene cause primarily benign tumors at different locations. The patient with Gardner’s syndrome discussed here did not even have any intestinal abnormalities, but displayed major defects in differentiation of other tissues. We may speculate that in different tissues the APC protein interacts with different elements of regulatory pathways, and that different residues of the protein molecule participate in these interactions. Correspondingly, mutations in these residues will cause widely different symptoms: malignancies of the gastroin-
Surg Neurol 305 1998;49:302–5
testinal tract in some cases, and benign overgrowth of tissues in others. Alexander Kolchinsky, Ph.D. Departments of Neurosurgery & Genetics University of Illinois at Chicago Chicago, Illinois Gardner’s syndrome is an autosomal dominant genetic disease that usually maps to chromosome 5, but it is genetically heterogeneous and some families map outside this region. The precise molecular genetics and altered gene product are not known. Families may incompletely express the triad of cranial osteomas, subcutaneous lipomas, and FCP. Genetic counseling is important so that children of an affected parent know that they may be at risk of developing any of the three components of the triad of clinical features so that proper screening tests can be conducted at regular intervals. Roger Rosenberg, M.D. Department of Neurology UT Southwestern Medical Center Dallas, Texas