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Familial polyostotic fibrous dysplasia
Familial polyostotic fibrous dysplasia M. Reitzik, B.D.S.(Rand), P.D.S.R.C.S.(Eng.), M.B. Ch.B., and J. F. Lownie, B.D.S., H.Dip.Dent.(Rand), Johannesburg, Xouth, Africa DEPARTMENT UNIVERSITY
OF MAXILLO-FACIAL OF THE
AND
ORAL
SURGERY,
WITWATERSRAND
A case of polyostotic fibrous dysplasia of the craniofacial type is presented, together with substantial evidence that this condition had a genetic basis in this patient. A review of the literature indicates that there is absolutely no previous evidence of a genetic basis to this condition. The possibility that the propositus suffered from polyostotic fibrous dysplasia of the Jaffe or the Albright type was excluded.
T
he term fibrous dysplasia was first used by Lichtensteiq3 in 1938, to describe a benign, self-limiting, nonencapsulated lesion that occurs mainly in young subjects. Fibrous dysplasia may be either monostotic or polyostotic. Monostotic fibrous dysplasia is twenty to thirty times as common as the polyostotic form.2 When the polyostotic type is found, the bones generally affected are the femur, the tibia, the fibula, the humerus, the radius, the ulna, and the pelvic bone. In half the patients with polyostotic fibrous dysplasia there are associated skull lesions. Zimmerman and associates9 and Sherman and G1auser6 report that 15 per cent of all patients with the polyostotic form of the disease have lesions in the maxilla and mandible. Usually the lesions are first noticed in childhood or early adolescence, girls being affected twice as often as boys. Although polyostobic fibrous dysplasia involving the jaws has been well documented, a survey of the literature reveals no evidence of a familial basis to the disease. CASE REPORT A lo-year-old Caucasian boy presented for treatment of a bony hard swelling of the right side of the mandible in the premolar region (Fig. 1). The boy’s parents had first noticed the swelling 6 months previously. On int,raoral examination, it was observed that the patient was in the mixed-dentition stage, and there was an obvious deformity of the mandible in the region of the right mental foramen. The expansion of the bone extended from the mandibular right canine to the first permanent molar on the same side. The swelling was
769
Fig.
8.
hard, smooth, and nontender to palpation. The overlying mucosa appeared normal, and there was no paresthesia or anesthesia of the lower lip. On further examination of this patient, several similar bone-hard swellings, varying from 1 to 3 em in diameter, were found to be present in various regions of the skull (Fig. 2). No other such lesions were detected clsowhere in the body; nor was there any evidence of caf6-aulait pigmentation or premature puberty. The patient’s father, his paternal grandmother, and several other mrmbers of his family had similar lesions all over the skull. Radiographic
findings
Radiologic examination revealed a well-defined unilocular radiolucency, about 4 cm. in diameter, in the right body of the mandible, with a peripheral radiopaque band. This lesion demonstrated a slight expansion of the lower border of the mandible and also extended
Volume 40 Number 6
ETamilial
polyostotic
fibrous
dys@sia
771
Fig. 3. to the developing apices of the right first and second mandibular premolars (Fig. 3). The maxilla and the remainder of the mandible appeared normal. The lateral-skull and posteroanterior radiographs showed several lesions scattered at random throughout the skull (Fig 4). Some of these lesions were well-demarcated radiolucent areas with a peripheral radiopaque band similar to the mandibular lesion, while others showed mottled radiopacities throughout the lesions. A full skeletal survey revealed no further abnormalities in any other bones. Biochemical
investigations
The serum alkaline phosphatase was 28.9 King-Armstrong units (normal, 3 to 12 KingArmstrong units). The serum calcium, phosphorus, and acid phosphatase levels were within normal limits. This significant increase in the serum alkaline phosphatase level is indicative of increased osteoblastic activity in the absence of other causes, such as liver disease. Histologic
findings
A biopsy yielded granular gelatinous material with no obvious lining. Histologic examination of the lesion revealed a mass of cellular fibrous tissue containing osteoid and woven bone and showing marked osteoblastic activity (Fig. 5). In view of the associated lesions in the skull, a diagnosis of polyostotic fibrous dysplasia of the craniofacial type was made. Family
History
As the patient’s father and several other members of his family had similar multiple skull lesions, the family was questioned in an effort to establish a family tree and to determine whether the condition as described in the patient might have a genetic basis. The family tree is shown in Fig. 6. Finally, a radiologic examination of the patient’s father revealed several identical lesions
772
Oral Rurg. December, 1975
Reitzik ami Lowmie
E‘ig. 4. Note numerous radiopaque
Fig.
stroma.
5 . Characteristic
(‘Chinese letter”
lesions with occasional radiolueent
appearance
of bony trabeculae
lesions.
in fibrl 3US ti! 3sue
scattered :tt random throughout the skull (Fig. 7). The fact that it has appeared in exrery generation in this family but occurs only in the children of an affected parent su cw :sts an autosomal dominant trait.
DISCUSSI ON
Fibm IUS dysplasia is usually found in the maxilla, where the 110x-nnal blone is replacl ed by a cellular fibrous tissue containing islands of trabeculae of mc:ta-
B’amilial
Volume 40 Number 6
polyostotic
fibrous dysphia
773
Fig. 6. Paternal grandmother, aged 65 years, had similar cranial lesions and her sister, aged 59 years, had both cranial lesions and a mandibular lesion. The latter’s daughter, aged 26 years, was confirmed by biopsy to have fibrous dysplasia of the mandible. All other affected members were known to have had multiple skull lesions. Black square denotes affected male; black circle, affected female; white square, unaffected male; white circle, unaffected female; X, confirmed by biopsy.
Fig. 7. Lytic the propositus.
lesions with
sclerotic
borders
present
in the cranial
vault
of the father
of
Oral Surg. December, 1975
plast,ic l~one.5 The cause of tht condition is unknown, although Standish ant1 (+orlin’ state: ” It tloes not appear to be neoplastic, i!lltd t,hcrc is 110cvidcncc for a gcnctic basis.” Lic~htensteiii~’ is of the opinion that some perverted activity of the specific bone-forming mcsenchyme may he responsible for the condition. Ilowcver, a high alkaline phosphatase activity in the osteoblasts in the lesions seems to suggest that there may be an exaggerated response of these ostcoblasts to some kind of stimulus whose origin is unknown.’ Three distinct radiologic types of fibrous dysplasia are recognized. The first shows a diffuse homogeneous sclerosis followin, 0 the contour of the bone. The second is a multilocular lytic lesion, oval in shape, with septa, vertical thinning, and expansion of the involved bone. The third is of a unilocular radiolucent pattern.“, 6 The cases described here thus showed a radiologic pattern consistent with the diagnosis of fibrous dysplasia. In view of the fact that the patient had no associated skin pigmentation or endocrinal disturbances, it is evident that the condition is not of the ,Jaffe or Albright types. This particular entity is craniofacial polyostotic fibrous dysplasia with a strong familial history. The authors would like to express their thanks to Professor M. Shear for the histologic for typing study, Mrs. M. Jansen for the photographic assistance, Mrs. J. Pearson-Buffoni the manuscript, and Mrs. A.-K. van den Hoek for the illustration. REFERENCES
Hyperplasia of Bone; a Histochemical Appraisal of Fibrous Dysplasia of bone, Cancer 10: 1157-1161, 1965. Jaffe, H. L.: Fibrous Dysplasia of Bone, a Disease Entity and Specifically Not an Expression of Neurofibromatosis, J. Mt. Sinai Hosp. 12: 364-381, 1945. Lichtenstein, L. : Polyostotic Fibrous Dysplasia, Arch. Surg. 36: 874-898, 1938. Pindborg, J. J.: The Manifestations of Fibrous Dysplasia in Mandible and Maxilla, Br. Dent. J. 92: 6-9, 1952. Pindborg, J. J., and Kramer, T. R. FT.: Histological Typing of Odontogenic Tumours, Jaw Cysts and Allied Lesions, Geneva, 1971, World Health Organization, p. 37. Sherman, R. S., and Glauser, 0. J.: Radiological Identification of Fibrous Dysplasia of the Jaws, Pathology 71: 553.558, 1958. Standish, 8. M., and Gorlin, R. J.: In Gorlin, R. J., and Goldman, H. M. (editors) : Thoma’s Oral Pathology, ed. 6, St. Louis, 1970, The C. V. Mosby Company, vol. 1, p. 541. Windholz, F. : Cranial Manifestations of Fibrous Dysplasia of Bone: Their Relation to Leontiasis Ossea and to Simple Bone Cysts of the Vault, Am. J. Roentgenol. 58: 51-63, 1947. Zimmerman, D. C., and others: Fibrous Dysplasia of the Maxilla and Mandible, ORAL SURG. 11: 55-68, 1958.
1. Changus, G. W. : Osteoblastic
2. 3. 4. 5. 6. 7. 8. 9.
Reprint requests to: Dr. M. Reitzik Department of Maxillo-Facial and Oral Surgery University of the Witwatersrand Johannesburg, South Africa
OF MAXILLO-FACIAL OF THE
AND
ORAL
SURGERY,
WITWATERSRAND
A case of polyostotic fibrous dysplasia of the craniofacial type is presented, together with substantial evidence that this condition had a genetic basis in this patient. A review of the literature indicates that there is absolutely no previous evidence of a genetic basis to this condition. The possibility that the propositus suffered from polyostotic fibrous dysplasia of the Jaffe or the Albright type was excluded.
T
he term fibrous dysplasia was first used by Lichtensteiq3 in 1938, to describe a benign, self-limiting, nonencapsulated lesion that occurs mainly in young subjects. Fibrous dysplasia may be either monostotic or polyostotic. Monostotic fibrous dysplasia is twenty to thirty times as common as the polyostotic form.2 When the polyostotic type is found, the bones generally affected are the femur, the tibia, the fibula, the humerus, the radius, the ulna, and the pelvic bone. In half the patients with polyostotic fibrous dysplasia there are associated skull lesions. Zimmerman and associates9 and Sherman and G1auser6 report that 15 per cent of all patients with the polyostotic form of the disease have lesions in the maxilla and mandible. Usually the lesions are first noticed in childhood or early adolescence, girls being affected twice as often as boys. Although polyostobic fibrous dysplasia involving the jaws has been well documented, a survey of the literature reveals no evidence of a familial basis to the disease. CASE REPORT A lo-year-old Caucasian boy presented for treatment of a bony hard swelling of the right side of the mandible in the premolar region (Fig. 1). The boy’s parents had first noticed the swelling 6 months previously. On int,raoral examination, it was observed that the patient was in the mixed-dentition stage, and there was an obvious deformity of the mandible in the region of the right mental foramen. The expansion of the bone extended from the mandibular right canine to the first permanent molar on the same side. The swelling was
769
Fig.
8.
hard, smooth, and nontender to palpation. The overlying mucosa appeared normal, and there was no paresthesia or anesthesia of the lower lip. On further examination of this patient, several similar bone-hard swellings, varying from 1 to 3 em in diameter, were found to be present in various regions of the skull (Fig. 2). No other such lesions were detected clsowhere in the body; nor was there any evidence of caf6-aulait pigmentation or premature puberty. The patient’s father, his paternal grandmother, and several other mrmbers of his family had similar lesions all over the skull. Radiographic
findings
Radiologic examination revealed a well-defined unilocular radiolucency, about 4 cm. in diameter, in the right body of the mandible, with a peripheral radiopaque band. This lesion demonstrated a slight expansion of the lower border of the mandible and also extended
Volume 40 Number 6
ETamilial
polyostotic
fibrous
dys@sia
771
Fig. 3. to the developing apices of the right first and second mandibular premolars (Fig. 3). The maxilla and the remainder of the mandible appeared normal. The lateral-skull and posteroanterior radiographs showed several lesions scattered at random throughout the skull (Fig 4). Some of these lesions were well-demarcated radiolucent areas with a peripheral radiopaque band similar to the mandibular lesion, while others showed mottled radiopacities throughout the lesions. A full skeletal survey revealed no further abnormalities in any other bones. Biochemical
investigations
The serum alkaline phosphatase was 28.9 King-Armstrong units (normal, 3 to 12 KingArmstrong units). The serum calcium, phosphorus, and acid phosphatase levels were within normal limits. This significant increase in the serum alkaline phosphatase level is indicative of increased osteoblastic activity in the absence of other causes, such as liver disease. Histologic
findings
A biopsy yielded granular gelatinous material with no obvious lining. Histologic examination of the lesion revealed a mass of cellular fibrous tissue containing osteoid and woven bone and showing marked osteoblastic activity (Fig. 5). In view of the associated lesions in the skull, a diagnosis of polyostotic fibrous dysplasia of the craniofacial type was made. Family
History
As the patient’s father and several other members of his family had similar multiple skull lesions, the family was questioned in an effort to establish a family tree and to determine whether the condition as described in the patient might have a genetic basis. The family tree is shown in Fig. 6. Finally, a radiologic examination of the patient’s father revealed several identical lesions
772
Oral Rurg. December, 1975
Reitzik ami Lowmie
E‘ig. 4. Note numerous radiopaque
Fig.
stroma.
5 . Characteristic
(‘Chinese letter”
lesions with occasional radiolueent
appearance
of bony trabeculae
lesions.
in fibrl 3US ti! 3sue
scattered :tt random throughout the skull (Fig. 7). The fact that it has appeared in exrery generation in this family but occurs only in the children of an affected parent su cw :sts an autosomal dominant trait.
DISCUSSI ON
Fibm IUS dysplasia is usually found in the maxilla, where the 110x-nnal blone is replacl ed by a cellular fibrous tissue containing islands of trabeculae of mc:ta-
B’amilial
Volume 40 Number 6
polyostotic
fibrous dysphia
773
Fig. 6. Paternal grandmother, aged 65 years, had similar cranial lesions and her sister, aged 59 years, had both cranial lesions and a mandibular lesion. The latter’s daughter, aged 26 years, was confirmed by biopsy to have fibrous dysplasia of the mandible. All other affected members were known to have had multiple skull lesions. Black square denotes affected male; black circle, affected female; white square, unaffected male; white circle, unaffected female; X, confirmed by biopsy.
Fig. 7. Lytic the propositus.
lesions with
sclerotic
borders
present
in the cranial
vault
of the father
of
Oral Surg. December, 1975
plast,ic l~one.5 The cause of tht condition is unknown, although Standish ant1 (+orlin’ state: ” It tloes not appear to be neoplastic, i!lltd t,hcrc is 110cvidcncc for a gcnctic basis.” Lic~htensteiii~’ is of the opinion that some perverted activity of the specific bone-forming mcsenchyme may he responsible for the condition. Ilowcver, a high alkaline phosphatase activity in the osteoblasts in the lesions seems to suggest that there may be an exaggerated response of these ostcoblasts to some kind of stimulus whose origin is unknown.’ Three distinct radiologic types of fibrous dysplasia are recognized. The first shows a diffuse homogeneous sclerosis followin, 0 the contour of the bone. The second is a multilocular lytic lesion, oval in shape, with septa, vertical thinning, and expansion of the involved bone. The third is of a unilocular radiolucent pattern.“, 6 The cases described here thus showed a radiologic pattern consistent with the diagnosis of fibrous dysplasia. In view of the fact that the patient had no associated skin pigmentation or endocrinal disturbances, it is evident that the condition is not of the ,Jaffe or Albright types. This particular entity is craniofacial polyostotic fibrous dysplasia with a strong familial history. The authors would like to express their thanks to Professor M. Shear for the histologic for typing study, Mrs. M. Jansen for the photographic assistance, Mrs. J. Pearson-Buffoni the manuscript, and Mrs. A.-K. van den Hoek for the illustration. REFERENCES
Hyperplasia of Bone; a Histochemical Appraisal of Fibrous Dysplasia of bone, Cancer 10: 1157-1161, 1965. Jaffe, H. L.: Fibrous Dysplasia of Bone, a Disease Entity and Specifically Not an Expression of Neurofibromatosis, J. Mt. Sinai Hosp. 12: 364-381, 1945. Lichtenstein, L. : Polyostotic Fibrous Dysplasia, Arch. Surg. 36: 874-898, 1938. Pindborg, J. J.: The Manifestations of Fibrous Dysplasia in Mandible and Maxilla, Br. Dent. J. 92: 6-9, 1952. Pindborg, J. J., and Kramer, T. R. FT.: Histological Typing of Odontogenic Tumours, Jaw Cysts and Allied Lesions, Geneva, 1971, World Health Organization, p. 37. Sherman, R. S., and Glauser, 0. J.: Radiological Identification of Fibrous Dysplasia of the Jaws, Pathology 71: 553.558, 1958. Standish, 8. M., and Gorlin, R. J.: In Gorlin, R. J., and Goldman, H. M. (editors) : Thoma’s Oral Pathology, ed. 6, St. Louis, 1970, The C. V. Mosby Company, vol. 1, p. 541. Windholz, F. : Cranial Manifestations of Fibrous Dysplasia of Bone: Their Relation to Leontiasis Ossea and to Simple Bone Cysts of the Vault, Am. J. Roentgenol. 58: 51-63, 1947. Zimmerman, D. C., and others: Fibrous Dysplasia of the Maxilla and Mandible, ORAL SURG. 11: 55-68, 1958.
1. Changus, G. W. : Osteoblastic
2. 3. 4. 5. 6. 7. 8. 9.
Reprint requests to: Dr. M. Reitzik Department of Maxillo-Facial and Oral Surgery University of the Witwatersrand Johannesburg, South Africa