Abstract
Complete resection is usually impossible for fibrous dysplasia (FD) involving the cranial base. Incomplete resection could be followed by regrowth of FD, but there is no method for indicating disease progress. Serum alkaline phosphatase (ALP) is significantly high in patients with FD. The authors investigate the relationship between ALP, progress of FD, and age at surgery. 18 patients with craniofacial FD were separated into 3 groups: Group A, complete resection; Group B, incomplete resection followed by regrowth of FD; and Group C, incomplete resection but no regrowth of FD. Medical records and CT scans were reviewed retrospectively. ALP levels were obtained preoperatively, postoperatively and every year during follow-up. The relation between ALP and regrowth and that between age at surgery and regrowth were investigated. There was no recurrence in Group A ( n = 4). Regrowth in Group B ( n = 7) was preceded by an abrupt increase in ALP. In Group C ( n = 7), no regrowth was observed and ALP was maintained within the normal range. 6 patients (85%) in Group B and 2 (28%) in Group C were under 17 years old. The results revealed that the level of postoperative serum ALP could be a reliable marker for predicting the progress of craniofacial FD.
Although it is a benign osteopathy, fibrous dysplasia (FD) manifests with clinically malignant symptoms characterized by replacement of the normal bone with fibrous–osseous tissues. This is due to the primary developmental abnormality of the bone-forming mesenchymal tissue. The molecular etiology is somatic activating mutations in osteoprogenitor cells of the cAMP regulating protein G S α, which is coded by the GNAS gene .
In general, the pathological process of craniofacial FD begins in childhood and progresses through puberty and adolescence . The progression usually stops after adolescence . Some authors report that the progression of the lesions may continue during adulthood, resulting in facial deformity and functional problems .
There are three main types of FD: monostotic, polyostotic, and McCune Albright syndrome. The monostotic form is the most common, comprising 70% of cases. 25% of FD involves two or more bones . These lesions may be localized to one region of the body or they may be disseminated, involving almost every bone. These lesions are more likely to continue to progress even after puberty, specially craniofacial lesions .
In craniofacial FD, the base of the skull, especially the sphenoid bone and maxilla, may be the most common site of involvement . The clinical problems vary according to the anatomical location. It tends to overgrow causing facial asymmetry, disfigurement, exophthalmos, orbital dystopia, and malocclusion. It also has the potential to compress the optic nerve . Malignant transformation is rare but may occur, most likely after radiation therapy with sarcomas being the most common histological type .
The surgical treatment of craniofacial FD consists of conservative shaving (contouring), which may be repeated, or complete resection of the dysplastic bone followed by reconstruction using autologous bone . In the fronto-orbital, zygomatic and upper maxillary areas, total excision and immediate reconstruction produce good functional and esthetic results . The surgical approach and complete resection in the base of the skull are limited and difficult due to sphenoid or ethmoid bone invasion . The timing and extent of surgery is controversial, especially in children with craniofacial FD who have thriving bone metabolism . It is important to observe the progress and regrowth of remnant FD in patients who undergo incomplete resection, but there is no objective and simple method to predict clinical results and progression or regrowth. Some authors recommend serial follow-up for craniofacial FD with computed tomography (CT) to determine progression or reactivation, especially after incomplete resection .
Serum alkaline phosphatase (ALP), a marker of bone metabolism, is generally thought to correlate with the extent of disease activity in craniofacial FD and to decline in patients treated with palmidronate. The decrease is also related to aging . Campanaci et al. have reported a significant correlation between higher levels of serum ALP and malignant transformation of FD .
The authors investigated the long-term clinical outcome of craniofacial FD and changes in serum ALP levels. They also examined the relationship between disease progression and changes in serum ALP level and age at the time of surgery.
Materials and methods
The study was carried out by retrospective review of medical records and CT scans of 18 patients who were treated for craniofacial FD. The 18 patients had given their written consent and the study was performed in accordance with the guidelines of the Declaration of Helsinki. The patients who were pregnant, had liver disease or chololithiasis, or were using oral contraceptives were excluded. No patients demonstrated the typical symptoms of the McCune Albright syndrome, which was confirmed by endocrinology. 15 patients (83%) had monostotic lesion and 3 patients (17%) had polyostotic lesions. The monostotic lesions often involved adjacent craniofacial bones (the maxillary, zygomatic, sphenoid, nasal, or frontal bone) as indicated by the term ‘monofocal’, describing a condition where several adjacent skeletal segments in a single area are affected . The indications for surgery were aesthetic reason (67%), exophthalmos (28%), and optic nerve compression (6%). The age of the patients at the time of surgery ranged from 9 to 45 years (average 19.3 years). 7 patients underwent surgery after the age of 17 years, while 11 patients had surgery before 17 years of age. The follow-up period varied from 3 to 16 years (average 7.7 years). CT scans were obtained only when regrowth of FD was suspected, based on clinical findings. Clinical photographs were obtained every year during the follow-up period. Serum ALP levels were obtained before surgery, immediately after surgery, and every year during the follow-up period.
The 18 patients were divided into three groups. Group A was composed of patients who received complete resection. Group B patients received incomplete resection and had regrowth of FD. Group C comprised patients who received incomplete resection but had no regrowth of FD. Surgery was defined as incomplete resection as long as there was a remaining lesion (however small it was) after resection. Groups B and C were examined by comparing the postoperative serum ALP levels and regrowth. The association between regrowth and postoperative serum ALP levels was investigated. The influence of age at the time of surgery was also examined during the long-term follow-up.
Results
Among 18 patients, complete resection was performed in 4 possible cases (22%), and the remaining 14 patients (78%) underwent incomplete resection. Of the 14 patients who received incomplete resection, contouring surgery (shaving of the protruding part of the lesion) was carried out in 5 patients, and partial resection surgery in 7 patients because lesions were widely present in the sphenoid or ethmoid. One patient underwent partial resection after receiving contouring surgery because of regrowth of FD ( Table 1 ). There was no complication related to the surgery. Group A patients ( n = 4) achieved complete remission clinically and radiologically without recurrence during follow-up periods ranging from 4 to 16 years. In this patient group, postoperative ALP remained within the normal range ( Table 2 ).
| Extent of resection | No. of cases |
|---|---|
| Complete resection and autologous bone graft | 4 (22%) |
| Incomplete resection | |
| Partial resection and autologous bone graft | 8 (44%) |
| Contouring surgery | 5 (28%) |
| Contouring surgery followed by Partial resection and autologous bone graft | 1 (6%) |
| Total | 18 (100%) |
| Case no. | Sex | Age (year) at operation | ALP (IU/L) | Follow-up (years) | Location of lesion | Type of FD | Type of operation | Results | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Preop. | Immediate postop. | Postop. 1 year | Postop. 3 years | Postop. 5 years | Postop. 7 years | Last F/U | ||||||||
| 1 | M | 11 | 180 | 81 | 91 | 107 | 71 | – | 88 | 7 | F | Mo | CR and CB | No recurrence |
| 2 | F | 14 | 121 | 74 | 60 | 51 | – | 54 | 61 | 16 | F and T | Mo | CR and CB | No recurrence |
| 3 | F | 24 | 73 | 49 | 63 | 54 | 48 | – | 66 | 8 | F and T | Mo | CR and CB | No recurrence |
| 4 | F | 13 | 357 * | 210 | 201 | 104 | – | – | 82 | 4 | Z and Ma | Mo | CR and RB | No recurrence |
Of the 14 patients who received partial resection, the authors observed regrowth of FD through clinical findings and confirmed it with CT scans in 7 patients (Group B; Table 3 ). An abrupt drop in ALP was observed immediately after surgery. This revealed that the decreased ALP levels were attributable to the effect of surgery. Regarding the age of patient at the time of surgery, the reduction was not due to the natural history of FD. The mean time interval between the operation and regrowth was 4.4 years. Tumour invasion to the autologous grafted bone was detected in two patients (case numbers 8 and 11) ( Fig. 1 ). The 7 patients with regrowth had abnormally high postoperative ALP levels at a time point during the follow-up period ( Table 3 ). The time point of the abrupt rise in ALP was correlated with the regrowth of FD, confirmed by CT scans. Among these 7 patients, 6 underwent surgery before the age of 17 years, and 1 after the age of 17 years.
| Case no. | Sex | Age (year) at operation | ALP (IU/L) | Follow-up (years) | Location of lesion | Type of FD | Type of operation | Results | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Preop. | Immediate postop. | Postop. 1 year | Postop. 3 years | Immediate 2nd postop. | Postop. 5 year | Postop. 7 years | Last F/U | ||||||||
| 5 | F | 11 | 546 * | 508 * | 630 * | – | 297 | 237 * | 201 * | 177 * | 7 | T, S, E and Ma | Mo | 1st: C; 2nd: PR and RB | Regrowth postop. 1 year |
| 6 | F | 15 | 134 * | 126 * | 160 * | 190 * | – | – | 211 * | 297 * | 7 | F, S, E and Ma | Mo | C | Regrowth postop. 6 years |
| 7 | F | 13 | 397 * | 142 | 123 | 241 * | 123 * | 100 | 87 | 66 | 8 | F, S, Z and Mn | Po | 1st: C; 2nd: C | Regrowth postop. 3 years |
| 8 | M | 16 | 243 * | 96 | 201 * | 197 * | – | 230 * | – | 209 * | 5 | Z and Ma | Mo | PR and CB | Regrowth postop. 5 years |
| 9 | M | 16 | 79 | 68 | 127 * | 245 * | – | 218 * | 220 * | 158 * | 13 | F, S, E, and T | Mo | PR and CB | Regrowth postop. 3 years |
| 10 | F | 27 | 180 * | 170 * | 110 | 190 * | – | 270 * | 4 | F, S, E, and T | Mo | C | Regrowth postop. 4 years | ||
| 11 | M | 9 | 183 | 112 | 154 | 147 | 161 | 121 * | 216 * | 15 | F, S and E | Mo | PR and RB | Regrowth postop. 10 years | |
