Recurrent Ameloblastoma: Long Term Outcomes with Free Fibular Bone Graft

Abstract

Ameloblastoma is a locally aggressive benign neoplasm of jaw that has high propensity to recur. Pathological subtype and intent of surgical excision during primary surgery are two factors that are known to affect the prognosis in these cases. Nevertheless, there are hardly any studies which have studied recurrent ameloblastoma cases. Apart from sharing a tertiary care cancer center’s experience in managing a series of recurrent ameloblastoma cases, we discuss some of the recent literature related to pathophysiology and principles related to their surgical management. Retrospective chart review of all those recurrent ameloblastoma cases which were operated between October 2013 and January 2016 and were subsequently followed up for minimum of 3 years. Total of 9 recurrent ameloblastoma cases were operated in the study period. All our patients had less—radical or non-curative intent surgical treatment in the past, and current treatment consisted wide excision of the involved segment of mandible with free fibular reconstruction. Among the 6 patients who were followed up for more than 3 years, none developed recurrence at 56.5 months of mean follow up duration. Almost all these patients had optimal results with good quality of life in terms of oral speech intellectuality and cosmetic perception of self. Complete excision of the involved segment of bone with reconstruction using the composite free fibular graft can provide optimal functional outcomes and can significantly lessen the chances of further recurrences.

Introduction

Ameloblastoma is a benign but locally aggressive jaw tumor with a high propensity to recur [1]. It commonly presents as slow-growing painless neoplasm involving posterior mandible but very rarely can arise from maxilla as well [1]. Many clinico-pathological characteristics of the ameloblastoma predict its natural course and its prognosis post-treatment. The bone of origin, the proximity to surrounding critical structures, the molecular changes, and the how early the treatment is given are some of the factors that could affect the prognosis in ameloblastoma [2, 3]. The pathological sub-type, and to some extent even the microscopic pattern of tumor cells’ distribution are also known to predict the behaviour of this neoplasm [1, 4, 5]. The reported recurrence rate of some of the aggressive pathological subtypes of ameloblastoma is as high as 60–90%, especially, when they have been managed by sub-optimal or non-curative intent therapy [1, 2, 4, 6–8]. In other words, the high recurrence rates of ameloblastoma can at least partly be attributed to the surgical approach during the primary treatment [4, 6–8]. Though the consensus with respect to surgical treatment of ameloblastoma has been shifting towards radical resection of the involved bone with primary reconstruction using vascularized bone graft [1, 2], there is still an ongoing debate in this regard, with some authors backing the so-called conservative intent procedures for various reasons [4, 6, 9–13]. One of the persuasive argument favouring conservative approach is the morbidity associated with surgical excision of the diseased bone and the complexities in reconstructing the bony defect [6]. The other disceptation point is lack of explicit evidence of high quality literature supporting the better outcomes with radical surgery [8, 13–15]. The evolving literature in this regard is changing horizons, and as per the latest literature review, both the conservative procedures and the radical surgery have their role in ameloblastoma and should be chosen on an individual basis depending on the size, the site, the pathology and the patient-surgeon characteristics [16].

With this background of diverse thought processes in the surgical management of ameloblastoma, we share our experience in the management of recurrent ameloblastoma cases. As such, there are a limited number of studies in the literature that have looked upon the recurrent ameloblastoma cases and have reported the surgical outcomes in such cases [4, 6, 17, 18]. Apart from describing the clinic-pathological characteristics of our cohort, we have tried to analyze the reasons for recurrence in these patients. We briefly discuss the surgical method of tumor excision and reconstruction, and the morbidity associated with them. Besides, we have analyzed the long term functional as well as oncological outcomes in these recurrent cases. The discussion here also includes the peculiar advantages offered by the complete excision of the involved bone with margin, and by the vascularized composite fibular graft repair.

Materials and Methods

It is a retrospective study conducted at the Department of Otorhinolaryngology and Head and Neck surgery of a tertiary care center in the northern part of India. The patients of recurrent ameloblastoma who were operated in the institute between October 2013 and January 2016 were included in the study. Patients with the incomplete medical records were excluded from the analysis. The follow-up data till August 2019 were taken into consideration for analyzing the surgical outcomes in terms of oncological results. The functional results was assessed in all those patients who were available for follow up for more than 3 years. The functional status was assessed during the last follow up period in four different domains, namely the swallowing, the speech intellectuality, the mouth opening and the cosmetic appearance. For each domain, the patient was asked to rate his/her perception of the particular function as satisfactory, average and unsatisfactory.

Results

A total of nine patients with recurrent ameloblastoma were operated between the October of 2013 and January of 2016. Mean age of these patients at the time of present surgery was 35 years, and the average number of previous surgeries for ameloblastoma excision was two. All of our patients had undergone some surgical procedure like enucleation, curettage, or marsupialisation before presenting with the recurrent disease to us, and none had undergone any reconstruction of bone in the past. Table 1 shows the clinic-pathological details and surgical outcomes of all the included patients. The recurrent tumors in most of our patients had involved more than one sub-site of the mandible and all the patients except one had involvement of the body. Figure 1 shows the site distribution of the disease in our cohort. One of our patient’s orthopantomogram and the surgical specimen of segmental mandibulectomy have been shown in Fig. 2 highlighting the disease extent. All the patients in our study underwent the radical excision of the tumor in the form of segmental mandibulectomy of involved bone with a margin of around 1 cm and the primary reconstruction of the defect by composite osseocutaneous free fibular flap. In each patient, the fibular graft was refabricated as per the defect to be reconstructed and plated at the donor site itself before the division of donor site vessels. Figure 3 shows the computed tomography of another case of large recurrent ameloblastoma involving left side hemimandible, central arch, and anterior half of the right side body. The segmental resection of the involved bone and the disease in this patient resulted in a loss of more than two-thirds of the mandible. The fibula was refabricated to reconstruct the central arch, the mandibular body as well as the ipsilateral ramus at the donor site keeping the donor vessels intact, as shown in Fig. 3c. Once the appropriately shaped graft was pre-platted matching the dimensions of the defect, the donor site vessels were ligated, the graft was transferred to the recipient site and was fixed to the residual part of the mandible after microvascular anastomosis of the vessels. In all the patients, the cutaneous portion of the graft was used to reconstruct the mucosal defect. No procedure-related complications were encountered intraoperatively except for an inadvertent injury to the posterior tibial artery in one patient, which was repaired with a saphenous vein graft. No graft failure was noted in our study, and none of our patients had any donor site morbidity. All the patients had uneventful postoperative recovery except for one who had progressive neck hematoma, which was managed by re-exploration. Pathologically, all but one of our cases were solid/multicystic ameloblastoma in our series, and one was unicystic in nature. The resected margins were negative in all the cases. Except for three patients who lost to follow up before three years of the surgery, the follow-up duration in the remaining six patients is ranged from 44.5 to 69.5 months with the mean duration of 56.5 months. Till date, none of these patients have had any recurrent disease after the radical surgery. In those patients who were available for long term follow up, almost all of them had optimal results with good quality of life in terms of oral speech intellectuality and cosmetic perception of self. However, one patient was not satisfied with over all cosmetic appearance, and the oral phase of swallowing per se had been rated average in two of our patients mainly due to difficulty in chewing of the food. Only one of our patient opted for the dental rehabilitation, who underwent the titanium dental implantation done after one and half years of the index surgery.

Table 1.

Demographic details, the clinic-pathological characteristics, the surgical results and the functional outcomes

Case no	Age	Sex	Previous surgeries	Segment involved	Pathology	Disease clearance	Follow up duration (months)	Status	Appearance	Mouth opening	Feeding	Speech
1	40	M	2	B, R	Conventional	R0 N0	69	DF	S	S	S	S
2	47	M	1	C	Conventional	R0 N0	64.5	DF	US	S	A	S
3	37	M	3	B, R	Conventional	R0 N0	61	DF	S	S	S	S
4	38	M	3	C, B	Conventional	R0 N0	6a	DF	–	–	–	–
5	24	M	1	B, R	Conventional	R0 N0	51.5	DF	S	S	S	S
6	45	F	2	B, C, B, R, J	Conventional	R0 N0	6a	DF	–	–	–	–
7	23	F	1	B, C, B,	Conventional	R0 N0	48.5	DF	S	S	S	S
8	26	F	1	B, R	Conventional	R0 N0	45	DF	S	S	A	S
9	38	M	1	B, R	Unicystic	R0 N0	18a	DF	–	–	–	–

A average, B body, C central arch, DF disease free, F female, J Temporomandibular joint, M male, N0 no pathological nodes, R ramus, R0 resection with microscopic negative margin, S satisfactory, US unsatisfactory

^aLost to follow up after the duration mentioned hence the long term functional outcomes couldn’t be assessed

Fig. 1.

Pictorial representation of extent of the recurrent ameloblastoma cases in our cohort. The number on the left corner of the line represent the patient number

Fig. 2.

a Orthopantomogram of a patient showing the extent of disease; b segmental mandibulectomy specimen of the same patient

Fig. 3.

a Coronal images of the plain computed tomography of a patient showing extensive disease; b surgical specimen after excision of the tumor; c re-fabricated fibular flap to match the shape of the defect in the same patient. Kindly note the plating been done keeping the donor vessels intact

Discussion

For many years, the therapeutic options for ameloblastoma are broadly being categorized into either as a conservative approach incorporating enucleation, curettage, cryotherapy, marsupialization, etc. or as radical surgery that involves the complete removal of diseased portion of the bone with or without a margin of the healthy surrounding bone. As per the review of existing literature the results with conservative approaches are non-predictable and often sub-optimal with unacceptably high rates of residual or recurrent disease [7]. Many of the latest systematic reviews and meta-analyses have concluded in favor of ‘radical approach’ in terms of significantly better cure rates irrespective of pathological sub-type of ameloblastoma [8, 14–16, 19]. Interestingly, in the approaches for surgical treatment of aggressive neoplasm like ameloblastoma, the usage of terms' conservative' and ‘radical’ has been discouraged or rather criticized many years ago [20]. Instead, the suggested appropriate terms for such approaches are non-curative intent and curative intent, respectively. In other words, the only predictable curative therapy for this otherwise benign but aggressive neoplasm is the complete resection, and preferably, that should be the consideration during the primary surgery itself [20]. All of our patients had undergone at least one of those non-curative intent surgical procedure during the primary presentation, which we think is the most probable reason for recurrences in them. Many studies attribute recurrences in ameloblastoma to incomplete removal of the disease during primary surgery, especially in high risk or aggressive pathological sub-type of ameloblastoma [4, 8, 16, 18].

The pathological characteristic of the ameloblastoma is another factor which has been shown to predict its clinical behavior and its response to therapy. Pathologically, ameloblastomas were classified into four types, solid/multicystic type constituting 90% of cases followed by less common unicystic, peripheral/extraosseous, and desmoplastic variants. Unicystic is further sub-divided into intraluminal and intramural subtypes [1]. As per the existing literature, the solid/multicystic, desmoplastic and intramural subtype of unicystic ameloblastoma are known to be aggressive with higher recurrence rates, especially when treated by non-curative procedures, whereas the intraluminal unicystic subtype and peripheral ameloblastoma recur less frequently [1, 4, 8, 14, 16, 19, 21]. These facts were reflective even in our series since the solid/multicystic ameloblastoma was the pathological type in more than 90% of our recurrent cases. Interestingly, based on the recent genetic updates of the ameloblastoma, the WHO's ‘classification of Head and Neck Tumors’ modified the terminology and the classification of ameloblastoma in its 4^th edition published in January 2017 [22, 23]. In this simplified version, the adjective “solid/multicystic” for the conventional ameloblastoma has been dropped, and the “desmoblastic” has also been reclassified from a clinicopathological specific type to a histological subtype of conventional ameloblastoma. Accordingly, the three pathological types of ameloblastoma are conventional, unicystic, and extraosseous/peripheral types [22]. Additional changes in this latest edition of the classification include the complete deletion of odontoameloblastoma and the shift of metastasizing ameloblastoma from malignant to benign, to represent the conventional ameloblastoma with distant metastasis [23]. Nevertheless, the treatment principles of ameloblastoma remains unchanged, wherein the complete excision of the involved bone with primary reconstruction must be first choice in all cases of the conventional ameloblastoma, and should be preferred over the conservative procedures whenever feasible even in other less aggressive sub-types [8, 13, 14, 16, 19]. On the other hand, this approach of complete disease removal taking adequate margin is the procedure of choice in recurrent ameloblastoma, irrespective of the pathological type [4, 11, 18].

After excising the segment of the diseased mandible reconstruction using the vascularised bone graft is the current standard of care in ameloblastoma, owing to some of the distinct technical, functional and cosmetic advantages offered by the vascularised osseous grafts [24–27]. Technically, the vascularized bone gives a peculiarly strong bone to withstand the masticatory force empowered onto the reconstructed mandible, compared to the non-vascularised bone grafts. The advantage of using fibula for reconstructing the mandible is that it provides a significant length of the bone as well as vascular pedicle as compared to other vascularized osseous grafts like the iliac crest. Such long length of harvested fibula could either be used for reconstructing the long segment of mandible if indicated or can be modified as a double-barrel fibular graft for better aesthetics and functionality [27]. Since almost all our recurrent tumors had involved more than one part of the mandible and also had aggressive pathological sub-types, the segmental excisions of bone were quite extensive, and yet, satisfactory reconstruction could be achieved in all the cases by using the vascularized osseocutaneous free fibular grafts, with appropriate reshaping to match the peculiar defects of each case. The ability to re-structure the fibular bone by micro-osteotomy and pre-plating to match the dimension and the shape of the mandibular defect is probably the most critical advantage of the free fibular graft both technically and practically. An additional technical advantage of using such a composite graft, especially in the previously operated cases like in our series, is the availability of skin that would help in revitalizing the scarred mucosa or the fibrosed soft tissue of previous surgery.

In terms of functionality, vascularized fibular graft for reconstruction after segmental resection of mandibular ameloblastoma provides the optimal outcomes by re-establishing regular oral diet in almost 90% of the patients without any donor site functional disturbance [26, 28]. Additional to oral feeding, we have also evaluated some of the other functional modalities, including mouth opening. All our patients had adequate mouth opening and uncompromised oral swallowing. Though, 90% of our patients did not undergo any dental rehabilitation, and most of them cited the satisfactory functional results in terms of chewing and swallowing. Two of our patients rated their chewing as average, however, both of whom had refused dental rehabilitation due to financial constraints. As in literature, our study results also imply that the low rates of dental rehabilitation don't seem to affect patients’ satisfaction in terms of functionality [26]. Nevertheless, the uptake of osseointegrated titanium implant for the dental rehabilitation is excellent with fibular or any other vascularised bone graft and should be considered in affordable patients [24, 25, 27–29]. As for the cosmetic appearance is concerned, the fibular flap is one of the ideal options for reconstructing segmental defects of mandible. Most of our patients did rate the appearnce as satisfactory except one, who reported suboptimal outcome after the reconstruction of resected central arch. Nevertheless, unlike any other vascularised or non-vascularised bone grafts, the fibular graft can provide a pleasing appearance of the face in more than 95% of the patients [26, 28]. Even with respect to operative results and postoperative morbidity, free fibular flap for reconstructing mandible is very reliable and safe, with 100% success rate of flap uptake and negligible postoperative complications, respectively [29]. Our results in all these aspects are at par with the literature rates supporting the utility of composite fibular flap reconstruction for the segmental reconstruction of the mandible after complete ameloblastoma excision with margin.

The long term outcome in our cohort with no subsequent recurrences is reassuring, and this also could probably be attributable to the surgical approach and the reconstruction method we followed. The availability of a reliable and effective vascularised bone graft clears the uncertainty in the surgeons thought, concerning morbidity of the defect and constrains related to the reconstruction. This allows the surgeon to perform the excision of diseased bone with adequate margin all around, without having to worry about the amount of bone loss, which in turn increases the probability of complete disease clearance and thus, lessens the recurrence rates. Most of the literature reports almost similar results of zero or negligible recurrence rates after complete excision and primary reconstruction of recurrent ameloblastoma [6, 17, 18, 24, 29]. The mean follow-up duration of close to five years in our series is also very much in par with the other studies in the literature [6, 17, 18, 26, 29]. The main drawbacks of our study include the small sample size and the lost to follow up rates of 33%. Nevertheless, considering that this study is about the recurrent cases of rare tumor-like ameloblastoma treated over two and a half years, the numbers are not too small. Since the study was done at a tertiary care referral hospital that caters the patients referred from all around the country and outside, we could get this cluster of recurrent cases in that short duration of time, and for the very same reason, some of our patients lost to follow up after being disease-free for few months after surgery. The other shortcoming of this study is lack of quantification of qualitative functional outcomes. Since there are no validated scales to measure the functional outcomes after free flap in the clinical relevant domains we have defined, we use the simple three scale system representing the respective ordinal outcome measures.

Conclusions

Recurrent ameloblastoma is commonly associated with prior non-curative surgical treatment like marsupialization or curettage and are likely to have aggressive pathological characteristics. Complete excision of the involved segment of bone with margin and reconstruction using vascularized bone graft like composite free fibula can provide optimal functional outcomes and can significantly lessen the chances of further recurrences to practically nil.

Funding

This study was not funded by any agency.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

Since it was a retrospective study done on already available data, institute ethical committee approval was not obtained, however, departmental scientific and ethical committee has approved the study.

Informed Consent

Informed consent was obtained from all individual participants included in the study.