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 Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 7  |  Issue : 2  |  Page : 72-78

Surgical excision with the negative margins offers best cure rates for ameloblastoma: A case series and review of literature


Department of Head and Neck Surgery, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Submission10-Jan-2020
Date of Acceptance26-Jan-2020
Date of Web Publication21-Feb-2020

Correspondence Address:
Ameya A Pai
Department of Head and Neck Surgery, Tata Memorial Hospital, E. Borges Road, Parel, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jhnps.jhnps_1_20

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  Abstract 


Objectives: The purpose of the study was to report a case series of ameloblastoma treated by radical approach with a negative margin. Study Design: The clinical, demographic, and the histopathological data of 24 biopsy-proven ameloblastoma were obtained and analyzed retrospectively from the electronic medical records. Statistical analysis was done using the software SPSS 20.0. Disease-free survival was calculated using Kaplan–Meier analysis. Results: The mean age of the patients in the study group was 46.6 (range, 17–69) years with male to female ratio of 1.18:1. The most common site of origin was mandible (75%). There was a significant positive linear correlation between size and age of the patients with a correlation coefficient of 0.85 (P = 0.042). Patients having multicystic ameloblastoma had a significantly higher age of presentation and larger size than unicystic ameloblastoma (P < 0.05). The mean distance of the closest mucosal/bony cut margin from the lesion was 6 mm (range 1–45 mm). All patients were alive, and 95.8% of the patients were disease free at a mean follow-up of 48 months. Conclusion: We recommend appropriate radical treatment for most of the patients of ameloblastoma with a negative margin except for small unicystic ameloblastoma. Thus, it is time to revisit the concept of conservative procedures in the management of ameloblastoma.

Keywords: Ameloblastoma, neck dissection, negative margins, radical resection, reconstruction


How to cite this article:
Singhavi HR, Pai AA, Mair M, Nair S, Nair D, Chaturvedi P. Surgical excision with the negative margins offers best cure rates for ameloblastoma: A case series and review of literature. J Head Neck Physicians Surg 2019;7:72-8

How to cite this URL:
Singhavi HR, Pai AA, Mair M, Nair S, Nair D, Chaturvedi P. Surgical excision with the negative margins offers best cure rates for ameloblastoma: A case series and review of literature. J Head Neck Physicians Surg [serial online] 2019 [cited 2020 Jul 14];7:72-8. Available from: http://www.jhnps.org/text.asp?2019/7/2/72/278884




  Introduction Top


Ameloblastoma has been defined as “usually unicentric, nonfunctional, intermittent in growth, anatomically benign, and clinically persistent.”[1] It constitutes 1% of all the tumors affecting the maxillomandibular complex and 11% of all the odontogenic tumors.[2] A recent publication has even suggested that it is the most common odontogenic tumor.[3] The mandible is the most common site of origin for ameloblastoma, followed by maxilla. It usually presents as a painless, slow-growing lesion, and thus, there is a significant delay by the patient in reporting it to the concerned doctor. Although it is slow-growing and benign, it has a tendency of local invasion and has the high rate of recurrence. It is reported in literature that the rate of recurrence after radical treatment is up to 20% and up to 90% after conservative treatment.[4],[5],[6],[7],[8],[9],[10],[11],[12] Despite such a high recurrence rate, there are no definite guidelines for the management of ameloblastoma. Thus, we report a study of 24 cases of ameloblastoma with regards to its demography and histopathology details treated with the radical approach.


  Materials and Methods Top


We performed a retrospective chart review of 24 biopsy-proven ameloblastomas of maxilla or mandible operated at a tertiary cancer center. All these patients underwent surgery as a primary modality of treatment from January 2010 to December 2016. Appropriate imaging (contrast-enhanced computed tomography face and neck) was done for all patients before surgery. The neck was explored mainly to provide vessels for microanastomosis of free flaps in the majority of the cases. As the neck was explored, Level Ib dissection was performed in most of the cases. As per the decision of tumor board, postoperative adjuvant radiotherapy (RT) was advised in one case as the patient had multiple recurrences. The clinical and demographic details, as well as the histopathological data of these patients, were obtained from the electronic medical records. All patients were under regular clinical follow-up at 3 monthly interval and in case of clinical suspicion of recurrence, imaging was performed. The statistical analysis was done using the software SPSS 20.0 (IBM, Armonk, NY, USA). Disease-free survival (DFS) was calculated using the Kaplan–Meier analysis. We defined DFS as the period from the date of diagnosis until date of the first recurrence: locoregional or systemic. Dates of disease recurrences were collected from the medical records when they were diagnosed radiologically or histologically. Since it is a retrospective studies with no patient contact thus it was exempted by our institutional board. Since this study was granted an exception by the local IRB and did not require consent from patients thus it was within the framework of Helsinki declaration.


  Results Top


The mean age of the patients in the study group was 46.6 (range, 17–69) years. There were 13 males and 11 females with male to female ratio of 1.18:1 [Table 1]. There was no significant difference between mean age of presentation among males (age – 44.62 years) and females (age - 49 years; P= 0.936). Comorbidities such as diabetes mellitus and hypertension were seen in 8.33% of the cases. History of addiction to alcohol or tobacco was seen in only 33.6% of patients. Before presenting to us, conservative surgery was performed in 21% of the cases. Most of the patients presented mainly as a painless swelling (75%). Among 13 male and 11 female patients, 5 (38.47%) males and 1 (9.1%) female presented with a painful swelling. As most of the patients had painless swelling, there was a delay of 27 months from the presenting symptoms to the patients reporting it to the concerned doctor. The most common site of origin was mandible (75%) while the remaining 25% of the patients had origin in maxilla. Ameloblastoma arising in this maxilla-mandibular complex was situated mainly in the premolar and molar region (79%). There was significant positive linear correlation between presenting size of the lesion and age of the patients with the correlation coefficient of 0.85 (P = 0.042). On the final histopathology report, multicystic and unicystic ameloblastoma was seen in 18 (75%) and 6 (25%) patients, respectively. Patients having multicystic ameloblastoma had a higher mean age of presentation (48 years) as compared to unicystic ameloblastoma (42 years; P= 0.442). It was also seen that the size of the multicystic ameloblastoma (mean – 63.2 mm) was significantly larger as compared to unicystic variant of ameloblastoma (mean – 53.67 mm; P= 0.048). Majority of the patients in the study group had intraosseous (79.2%) ameloblastoma while peripheral variant was seen in 20.8% cases. Mandible was the site of origin for most of the intraosseous ameloblastomas (94.4%) while peripheral ameloblastoma mostly originated from the maxilla (80%; P= 0.001). Our center being a tertiary referral center and as all the cases presented to us at an advanced stage, radical surgery in the form of segmental mandibulectomy and various forms of maxillary resection were performed in all patients. Reconstruction was done using free flaps in 79.1% whereas primary closure was done in 16.7% and local flap was used for 4.2% of the patients [Table 2]. The neck was primarily explored to provide vessels for microanastomosis. Level 1b dissection was done in these patients and as expected, none of the neck nodes dissected was found to be positive for metastasis. None of the patients had a positive margin in the study group. The mean distance of the closest mucosal/bony cut margin from the lesion was 6 mm (range 1–45 mm). The mean and the median follow-up period was 48.5 and 39.13 months, respectively. Follow-up details were available for all patients. All patients were alive and 95.8% of the patients were disease free. Two patients developed recurrences and both of them had multicystic peripheral ameloblastoma excised with negative margin of more than 6 mm. Among these two patients with recurrences, one had recurrence at the same site after disease-free interval of 22 months while other developed recurrence at a different subsite, i.e., maxilla which was diagnosed after 42 months of the previous surgery and thus this could be considered as a second primary. The initial site of primary in the later patient was mandible and he is the only patient in the study group who has received adjuvant radiation. Mortality was not seen in any of the patients.
Table 1: Clinical, demographic, and histopathological details

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Table 2: Demographic data of the patients including type of ameloblastomas, surgery offered, and reconstruction done

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  Discussion Top


The World Health Organization (WHO) (1992) defined ameloblastoma as a benign but locally aggressive tumor with a high tendency to recur and lying in fibrous stroma.[13] Reichart et al.[14] found that the average age of presentation for ameloblastoma was 36 years which is a decade lower than what we found in our study (46 years). In the same study, they found that women presented at an earlier age as compared to males. However, we found that mean age of presentation was 5 years higher in females as compared to males. As far as, gender distribution is concerned, it has slightly higher male predilection [3] which is similar to our study. The most common site of ameloblastoma is mandible followed by maxilla with a ratio of 80:20 with a higher propensity to involve the posterior region of the jaw.[3] This is consistent with our study where mandible was the most commonly affected facial bone and 79% of the patients had the disease in the posterior region. Higher predilection of the posterior mandible can be attributed to the later eruption of molars as it is proposed to be arising from the remnants of the enamel organ of the dental tissues.

The most common complaint of our patients was jaw swelling seen in all the patients, followed by pain seen in 25% of the cases. Similar findings were seen by Medeiros et al.[15] and Neville et al. which affirmed that these tumors are painful only when they become secondarily infected and that signs or symptoms of nerve impairment are not commonly seen, even in large tumors. As most of these patients had painless swelling, the lag time in our study between the onset of symptom and proper specialty assistance was 27 months. Other causes of delay may be fear of the operative procedure, financial constraints, or due to lack of proper medical guidance to the patients. It is also important to note that most of the patients present with painless swelling, which may be easily confused with other pathological entities like odontogenic disease, etc., further delaying the treatment. Kahairi et al.,[16] have also shown that it takes about 2 years before patients with this tumor to develop any symptoms such as significant facial asymmetry, malocclusion, and difficulty in chewing. In spite of being painless, a recent meta-analysis showed a mean annually specific growth rate for ameloblastomas was 87.84%.[17] Thus, the delay might lead to higher patients undergoing radical surgery.

Various studies led to a new classification by the WHO in 2005 that defines various macroscopic types of ameloblastomas as solid/multicystic, extraosseous/peripheral, desmoplastic, and unicystic. Most of the cases in this study were multicystic (75%) while unicystic ameloblastoma was seen in 25%. This is in sync with the published literature where the proportion of multicystic ameloblastoma ranges from 70% to 85%, and unicystic as 10%–26% [Table 3]. Unicystic ameloblastomas were further divided into three types by Ackermann et al.,[18] namely luminal, intraluminal, and mural. The mural type is known to be aggressive and requires radical treatment. However, to obtain histopathological subtype of ameloblastomas on biopsy may not be feasible at every center. Thus, a rational approach for the treatment of ameloblastoma can be decided only after a thorough consideration of different histologic patterns, clinical features, and behavior of the lesion. Thus, the selection of a particular modality depends, to a large extent, on its clinical subtype, its location in the jaws, its size, age of the patient, and the patient's availability for follow-up examinations. Conservative modalities have been advocated for smaller lesions whereas large lesions were mandated to be treated radically.[7],[19] Similarly, conservative treatment has been proposed for unicystic ameloblastomas while multicystic ameloblastomas renders radical treatment this is due to the fact that multicystic variant behaves as a locally invasive lesion, following the path of least resistance and it may infiltrate cancellous bone up to 2–8 mm from the plain radiographic margin of the lesion.[2],[3],[5]
Table 3: Review of literature comparing conservative versus radical management of ameloblastomas

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The management of ameloblastoma is controversial, and treatment protocol is not defined clearly. Recent studies show that the recurrence rates in conservative treatment modalities such as curettage, marsupialization, enucleation, cryosurgery, and cauterization (thermal and chemical) are as high as 91% while that following radical treatment is 9% [Table 3]. The rationale for the conservative approach in treating ameloblastoma is its benign nature and the cosmetic and functional defect inherited due to radical surgery which is very morbid. Being a tertiary care center, size of the lesion with which the patients presented to us were larger, mean size being 61 mm × 41 mm × 32 mm and most of them had aggressive variants (multicystic or intraosseous), thus mandating radical surgery in all the patients. Pogrel and Montes [19] reviewed 101 published articles to determine the appropriate treatment for ameloblastoma. They concluded that the enucleation procedure is not adequate for solid/multicystic ameloblastoma as they have recurrence rates as high as 80%. Enucleation may not be an adequate procedure for unicystic ameloblastomas either, as various subtypes of unicystic variant cannot be diagnosed preoperatively and more aggressive variant requires radical treatment.[5] A meta-analysis by Antonoglou and Sándor on nonrandomized studies comparing conservative and radical approach also favored the later for both for unicystic and multicystic ameloblastomas.[20] A recent meta-analysis by Almeida Rde et al. showed that the risk of recurrence was 3.15-fold greater with conservative treatment in comparison to radical treatment, which was a statistically significant result (P < 0.00001).[21] Hammarfjord et al.[22] conducted a study to evaluate the outcome of treatment given to the patient with intraosseous ameloblastoma. They observed no recurrence in cases undergoing radical resection, while conservative treatment approach leads to recurrence in 60% of the cases who eventually required secondary resection. In another study by Pogrel and Samson,[23] conservative option leads to high recurrence especially in cases with extraosseous spread. They also suggested that the first surgery provides the best chance of cure and second surgery for recurrence would lead to larger resection. Considering the increased incidence and the controversy in the management of ameloblastoma, it is important to formulate treatment guidelines. However, one of the factors preventing us from drawing concrete results is inherent difficulty of achieving histological classification on biopsy specimen.[19] Therefore, upfront radical surgery with safety margin may be the best treatment for most of the patients except for small unicystic ameloblastoma in young patients. Huang et al.[24] also suggested that patients under 18 years of age should be treated conservatively as such a group of patients have higher growth potential and in the event of recurrence, a second surgery can be successful. However patient compliance, in such cases, is of prime importance.[24],[25] Two of our patients aged 17 years had large-sized multicystic mandibular ameloblastoma. There was only a rim of mandible left after destruction by the disease, thus segmental resection with appropriate free flap reconstruction was done in both the patients and they are disease free with the mean follow-up of 4 years.

Maxillary ameloblastoma is rare, accounting for 15% of all the ameloblastoma and is often associated with the aggressive course. Anatomically, cortical bone is rare in the maxilla, and it is mainly formed by membranous bone with more medullary content which makes its growth pattern of different from that of the mandible. Thus, it extends earlier than mandible beyond bony boundaries and infiltrates into the pterygomaxillary space, infratemporal fossa as well as the central nervous system.[26] Surgical control of lesions significantly decreases once the tumors extend beyond these bony boundaries, thus making them surgically challenging limited by anatomical restraints which eventually results in higher recurrence rate mandating radical treatment for all patients.[5],[10] Compared to the incidence in published literature, we had a higher incidence of ameloblastoma in maxilla, i.e., six (25%); four underwent total maxillectomy (Class III and Class IV) while partial maxillectomy (Class II) was done for two patients. Of these, one patient who underwent partial maxillectomy for a small (15 mm × 15 mm × 10 mm) intraosseous maxillary ameloblastoma presented with recurrence after 22 months. We have conglomerated the literature on the management of ameloblastomas comparing conservative versus radical management [Table 3].

Considering the benign nature of ameloblastoma the significance of closed or positive margin is not defined. Based on a review of the literature, Carlson and Marx [27] and Hammarfjord et al.[22] recommended wide resection margins to reduce the rate of recurrences. Hammerfjord mentioned that ameloblastoma cells can be seen up to 8 mm from the clinical margin of the lesion thus proposed the principle of 1 cm of safe bony margin to be included around the radiographic limits of the lesion. Our mean margin of resection was 6 mm (1–45 mm), and we had only one recurrent disease. RT was given in one patient in our study group as he had multiple recurrences. Carlson and Marx [27] reported that ameloblastoma is radioresistant and chemoresistant. However, the indication of RT has some role in the recurrent setting as studied in a case series by Gardner.[28]


  Conclusion Top


We found ameloblastoma was more common in males. The mean age of presentation was higher in females compared to males. The intraosseous lesions are more common in posterior parts of the mandible. Delay in seeking medical treatment remains a global challenge due to its resemblance to other odontogenic lesions and lack of proper medical guidance. Conservative surgical excisions are reported to have significantly high recurrence rate. We report high cure rate with radical surgery and appropriate reconstruction in such patients. Therefore, we recommend appropriate radical treatment for most of the patients of ameloblastoma with the negative margin except for small unicystic lesion in young patients. Thus, it is time to revisit the concept of conservative procedures such as enucleation, curettage, and marsupialization in the management of ameloblastoma.

Summary

  • The most common site of ameloblastoma is mandible followed by maxilla with a ratio of 80:20 with higher propensity to involve the posterior region of the jaw
  • The most common complaint of patients is jaw swelling. Pain is present only when the lesion is secondarily infected. Signs or symptoms of nerve impairment are not commonly seen, even in large tumors
  • Maxillary ameloblastomas are more aggressive in nature and should be treated more radically as compared to mandibular counterparts
  • Recurrence rates in conservative treatment modalities are as high as 91% while that following radical treatment is 9%
  • Immediate reconstruction, preferably with a free graft offers the best cosmetic outcomes thus preserving the quality of life postsurgery
  • Long-term follow-up is mandatory as the lesion is known to recur.


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclosure

This material has never been published and is not currently under evaluation in any other peer reviewed publication.

Ethical approval

The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

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



 
  References Top

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Ghandhi D, Ayoub AF, Pogrel MA, MacDonald G, Brocklebank LM, Moos KF. Ameloblastoma: A surgeon's dilemma. J Oral Maxillofac Surg 2006;64:1010-4.  Back to cited text no. 4
    
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Hong J, Yun PY, Chung IH, Myoung H, Suh JD, Seo BM, et al. Long-term follow up on recurrence of 305 ameloblastoma cases. Int J Oral Maxillofac Surg 2007;36:283-8.  Back to cited text no. 5
    
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Fregnani ER, da Cruz Perez DE, de Almeida OP, Kowalski LP, Soares FA, de Abreu Alves F. Clinicopathological study and treatment outcomes of 121 cases of ameloblastomas. Int J Oral Maxillofac Surg 2010;39:145-9.  Back to cited text no. 6
    
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França LJ, Curioni OA, Paiva DL, Vianna DM, Dedivitis RA, Rapoport A. Ameloblastoma demographic, clinical and treatment study: Analysis of 40 cases. Braz J Otorhinolaryngol 2012;78:38-41.  Back to cited text no. 12
    
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Reichart PA, Philipsen HP, Sonner S. Ameloblastoma: Biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995;31B: 86-99.  Back to cited text no. 14
    
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Medeiros M, Porto GG, Laureano JF, Portela L, Vasconcellos RH. Ameloblastoma in the mandible. Braz J Otorhinolaryngol 2008;74:478.  Back to cited text no. 15
    
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Kahairi A, Ahmad RL, Wan Islah L, Norra H. Management of large mandibular ameloblastoma - a case report and literature reviews. Archives of Orofacial Sciences 2008;3:52-5.  Back to cited text no. 16
    
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Chae MP, Smoll NR, Hunter-Smith DJ, Rozen WM. Establishing the natural history and growth rate of ameloblastoma with implications for management: Systematic review and meta-analysis. PLoS One 2015;10:e0117241.  Back to cited text no. 17
    
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Ackermann GL, Altini M, Shear M. The unicystic ameloblastoma: A clinicopathological study of 57 cases. J Oral Pathol 1988;17:541-6.  Back to cited text no. 18
    
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Antonoglou GN, Sándor GK. Recurrence rates of intraosseous ameloblastomas of the jaws: A systematic review of conservative versus aggressive treatment approaches and meta-analysis of non-randomized studies. J Craniomaxillofac Surg 2015;43:149-57.  Back to cited text no. 20
    
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Almeida Rde A, Andrade ES, Barbalho JC, Vajgel A, Vasconcelos BC. Recurrence rate following treatment for primary multicystic ameloblastoma: Systematic review and meta-analysis. Int J Oral Maxillofac Surg 2016;45:359-67.  Back to cited text no. 21
    
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Hammarfjord O, Roslund J, Abrahamsson P, Nilsson P, Thor A, Magnusson M, et al. Surgical treatment of recurring ameloblastoma, are there options? Br J Oral Maxillofac Surg 2013;51:762-6.  Back to cited text no. 22
    
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Sampson DE, Pogrel MA. Management of mandibular ameloblastoma: The clinical basis for a treatment algorithm. J Oral Maxillofac Surg 1999;57:1074-7.  Back to cited text no. 23
    
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  [Table 1], [Table 2], [Table 3]



 

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