Oral and Maxillofacial Surgery Cases 9 (2023) 100299

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Oral and Maxillofacial Surgery Cases

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Granular cell ameloblastoma in maxilla: A report of rare case

Siwakorn Rattanakuntee a, Wacharaporn Thosaporn b, Natnicha Ketchaikosol b,
Napatsorn Imerb c, *
a Dental Department, Phrae Hospital, Phrae, Thailand
b Department of Oral Biology and Diagnostic Sciences, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand
c Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, Thailand

ARTICLE INFO ABSTRACT

Handling Editor: Stephanie Drew Ameloblastoma is the most common odontogenic tumor found at the posterior region of
mandible. Granular cell ameloblastoma is one of the histological subtypes of ameloblastoma,
Keywords:
mainly characterized by nests of large eosinophilic granular cell. Here, we reported a rare case of
Ameloblastoma
75-year-old female patient presented with granular cell ameloblastoma in maxilla region. The
Granular cell
Maxillectomy
conventional surgery was performed by upper lip-splitting technique and partial maxillectomy.
The prosthetic obturators were delivered to rehabilitate a maxillofacial integrity, improving fa-
cial appearance and functional abilities. Long-term follow up revealed a favorable outcome with-
out an evidence of tumor recurrence.

1. Introduction
Ameloblastoma is a most common benign odontogenic tumor derived from the epithelial mesenchymal origin i.e., dental lamina,
developing enamel organ, epithelial lining of an odontogenic cyst, or from the basal cells of the oral mucosa. Clinicopathological fea-
tures of ameloblastoma are slow-growing and locally invasive tumor which rarely associated with painful or altered sensation. Al-
though ameloblastoma has been recognized as a most common benign tumor of the jaw but epidemiological studies showed that
ameloblastoma represented only 1% of all jaw tumors [1].
Epidemiologic studies demonstrated that regardless of gender dimorphism and no significant racial disparities, this tumor is gen-
erally presented between the third to seventh decades of life. Particularly, ameloblastoma is commonly found at the angle region of
mandible [2]. Microscopically, ameloblastoma characterized by the presence of epithelial-like hyperchromatic peripheral columnar
cells with reversely polarized nuclei arranged in a palisaded pattern [3]. Based on clinicopathologic criteria, there were three distinct
types of ameloblastoma: solid or conventional (86%), unicystic (13%) and peripheral (1%) which are determining to differential ther-
apeutic considerations and prognosis [2]. Asymmetrical facial swelling with cortical bone expansion, bone perforation, and root di-
vergence or root resorption of adjacent tooth are commonly revealed as the clinical manifestation of ameloblastoma [4]. The treat-
ment and prognosis are related to the histological subtype. Specifically, as compared to unicystic ameloblastoma, the solid or multi-
cystic ameloblastoma are locally more aggressive and highly related with high recurrence rate after local excision as well as robustly
require more aggressive treatment approach i.e., peripheral ostectomy [4].
Granular cell ameloblastoma is one of the rare histological variants of ameloblastoma, significantly presents a transformation of
the cytoplasm of stellate reticulum like cells into a coarse associated with granular eosinophilic appearance [2]. This subtype of
ameloblastoma is characterized by the groups of granular cells, which have abundant cytoplasm filled with eosinophilic granules that

* Corresponding author. Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Chiang Mai University, Chiang Mai, 50200, Thailand.
E-mail address: Napatsorn.i@cmu.ac.th (N. Imerb).

https://doi.org/10.1016/j.omsc.2023.100299
Received 21 February 2023; Accepted 10 March 2023
Available online 15 March 2023
2214-5419/© 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
S. Rattanakuntee et al. Oral and Maxillofacial Surgery Cases 9 (2023) 100299

resemble lysosomes, both ultrastructurally and histochemically [2]. Patients with granular cell ameloblastoma frequently experience
atypical symptoms of pain and swelling due to an expansion of jawbone. Collectively, previous studies revealed that granular cell
ameloblastoma commonly presented in the posterior aspect of mandible [5]. The radiographic features of granular cell ameloblas-
toma usually exhibited in multilocular radiolucency as similarly found in other type of conventional ameloblastoma [6]. Interest-
ingly, the recurrence rate was approximately 33.3% which greater than other common types of ameloblastoma as well as its metasta-
tic behavior were shown by spreading to distinct organ and tissue i.e., lung and thoracic vertebra [7–9]. An unpleasant rate of recur-
rence and its metastatic potential suggested that granular cell ameloblastoma is an aggressive neoplasm [10].
The treatment of conventional ameloblastoma by curettage alone is highly related to increased recurrence rate when compared
with resection. Hong et al. recently showed that the histopathological variant of an ameloblastoma is significantly associated with a
recurrence [11]. It was shown that the follicular, acanthomatous and granular cell types have a relatively high likelihood of recur-
rence [2]. In contrast, the unicystic desmoplastic and plexiform types show a relatively low potential for recurrence [12]. Noticeably,
follicular Ameloblastoma is characterized by higher recurrence rate (29.5%) compared to plexiform ameloblastoma (16.7%) and
acanthomatous ameloblastoma (4.5%) [12].
The purposes of this case report were to present a rare case of granular cell ameloblastoma in the maxillary region and to review a
literature regarding to tumor behavior, the uniqueness of microscopic features, therapeutic surgical approach, treatment, prosthetic
reconstruction, and long-term outcome belonging to this case.

2. Case presentation
A 75-year-old female patient was referred to the dental department with a chief complaint of a painless unilateral progressive
swelling of maxilla on left side. The swelling was chronically growing and noticed for two months before the presentation of patient.
Moreover, there was no history of severe medical problem or head and neck injury in the past. On inspection, extra-oral examination
showed swelling of the left cheek with a shallow right nasolabial fold and normal appearance of skin color and texture (Fig. 1a). Intra-
oral examination revealed a bone expansion toward buccal and palatal region on left side of maxilla with disappearance of bone per-
foration clinically. The positive finding of lesion was horizontally extended across the midline, from upper right central incisor to up-
per left first molar (Fig. 1b). Panoramic radiograph revealed a large well-defined multilocular radiolucency lesion involving from the
upper left central incisor to the upper left first molar without any signs of root resorption. Vertically, the lesion enlarged from the
alveolar crest to the floor of left maxillary sinus (Fig. 1c). Computed tomography clearly showed buccal and palatal bone perforation
of left maxilla in either coronal view (Fig. 2a) or axial view (Fig. 2b).

Fig. 1. (a) An extraoral photograph showing a swelling in the left middle third of face, shallowing of left nasolabial fold with normal appearance of skin. (b) Intra oral
photograph showing buccal and palatal expansion of cortical bone. An incisional biopsy was performed intraorally through the upper left premolar socket. (c)
Panoramic radiograph showing a well-defined multilocular radiolucency lesion extended from the upper right central incisor to the upper left first molar without the
presence of root resorption. The floor of left maxillary sinus was markedly involved (white arrows).

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Fig. 2. (a) Coronal view of a computed tomography showing a cortical bone perforation on the left side of maxilla. (b) Axial view of a computed tomography showing
tumor margin involved the floor of left maxillary sinus.

The clinical appearance and radiographic findings provided us a differential diagnosis impression for benign odontogenic neo-
plasm. We firstly performed an incisional biopsy; the specimen was obtained through a tooth socket after extraction on an upper left
premolar under local anesthesia. An excised gross specimen was a firm, well-circumscribed nonencapsulated intraosseous dark brown
mass size 1 × 1 cm, obtained for the specific histological investigation. Microscopic findings revealed a typical histological appear-
ance of odontogenic epithelium. The connective tissue was intermingled by numerous islands of ameloblastic epithelium which are
bounded by columnar ameloblast-like cells surrounding by presence of granular cells, which typically occur within the central area of
tumor and progressively replace the stellate reticulum. (Fig. 3a,b). Taken together, the definitive diagnosis of granular cell pattern
ameloblastoma was given.
The definitive diagnosis indicated an appropriate surgical management following a standard treatment protocol from Gardner and
Pecak in 1980 [13]. Specifically, upper lip-splitting incision was conventionally performed, the tumor was then total resected with
1–2 cm margins of clinically normal bone remaining (Fig. 3c). Intraorally, the palatal incision and vestibular incision were made over
the hard palate from just posterior to the right upper canine till the junction with that of soft palate is reached. Mucoperiosteal flap at
left maxilla was laterally off the alveolar bone to the gingivobuccal sulcus. Teeth 13 and 27 were extracted, then osteotomies of the
palatal and alveolus were made with 1 cm safety resection margins from all directions by using reciprocating surgical saw and os-
teotomes. Subsequently, the maxillary tuberosity was also partially resected, and the mucosal edges were sutured to the remaining
bone. In gross, the obtained tumor was firmed in consistency appeared brownish and whitish as a combination of cystic and solid ar-

Fig. 3. (a,b) Photomicrograph of the tumor showing an odontogenic epithelium and the connective tissue was intermingled by numerous islands of ameloblastic ep-
ithelium which are bounded by columnar ameloblast-like cells surrounding by many granular cells. (Hematoxylin and eosin staining, original magnification 40x, 400x
respectively). (a) Hematoxylin and eosin stain, original magnification 40x. (b) Hematoxylin and eosin stain, original magnification 400x. (c) Intra-operative photo-
graph showing a surgical procedure by upper lip-splitting incision and intraoral incision for surgical removal on the tumor by using reciprocating surgical saw and os-
teotomes.

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eas at the cut surface, measured 9 × 7 × 6 cm. Postoperative surgical obturator was inserted immediately for a critical initial pur-
pose including local hemostasis, closing the palatal defect and to maintain facial appearance. The specimen was sent to histopathol-
ogy department for further investigation to confirm a final diagnosis. The patient recovered from the general anesthesia without any
immediate postoperative complications. After a period of 4 weeks post-resection, the presence of satisfactory healing was noticed
then a definitive obturator with prosthetic teeth was delivered to rehabilitate the patient by improvement of esthetic and functional
outcome (Fig. 4a and b). Recently, two-year follow-up examination presented an excellent facial profile and integration of healed tis-
sue (Fig. 4c and d). The routine follow-up was carried out by evaluation of panoramic radiograph (Fig. 4e). Postoperative panoramic
radiography showed that there was neither clinical nor radiographic evidence of tumor recurrence. The patient was satisfied with a
favorable functional and esthetic outcome of restoration. Notwithstanding, a further continuous follow-up in long-term is required for
early management of recurrent ameloblastoma.

3. Discussion
Odontogenic tumor is derived from epithelial or mesenchymal elements which have been part of the tooth-forming apparatus.
Ameloblastoma is an epithelial odontogenic tumor usually found in the posterior aspect of mandible i.e., angle of mandible and de-
scending ramus [2]. Although ameloblastoma is a rare tumor that occurs for 1% of all the cysts and tumors in the jaw, it is the most
important and common of epithelial odontogenic tumor of the jaw [14,15]. This tumor arises with great frequency during the third to
fifth decades of life with no significant difference in gender or racial predilection. Solid or multicystic ameloblastoma are considered
as a highly local aggressive subtype with a higher recurrence rate after local excision, in comparison to unicystic ameloblastoma [16].
There are six histopathological subtypes of ameloblastoma consist of follicular, plexiform, acanthomatous, desmoplastic, granular
cell, and basal cell pattern, that may occur singly or as a combination of two or more types [17]. Follicular and plexiform are common
than other variants presenting for 32.5% and 28.2% respectively, followed by the acanthomatous subtype 12.1% while desmoplastic
is extremely rare with incidence rates about 4–13% [7]. Granular cell ameloblastoma is a rare histological subtype of ameloblastoma
which first introduced in 1981 for only 5% of all ameloblastoma [5,18]. Granular cell ameloblastoma developed by transformation of
groups of lesional epithelial cells to granular cells. These cells displayed abundant cytoplasm filled with eosinophilic granules that re-
semble lysosomes ultrastructurally and histochemically [15]. Accumulated evidences revealed a sparse prevalence of cases that was
classified as the granular cell subtype [19]. In fact, from 1960 to 1993, there were only 56 cases of the granular cell histological sub-
type (3.5%) found from all 1593 ameloblastoma case [7]. Moreover, the age distribution of patient with granular cell ameloblastoma
is not significantly difference, comparison to other types. Nevertheless, a painful and jaw expansion were mostly presented symptoms

Fig. 4. (a,b) Functional obturator with prosthetic teeth was inserted after a period of 4 weeks post-resection. Two-year postoperative follow-up of patient (c) pre-
senting an improved facial appearance. (d) Intra oral photograph showing a normal oral mucosa without sign of infection and recurrence. (e) Panoramic radiograph
showing no radiographic evidence of recurrence at the present follow-up period.

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Table 1
Summarizing data of the previous cases of granular cell ameloblastoma.

Case Age Sex Site of lesion Detailed radiographic appearance Treatment Reference

1 65 Male Left Posterior mandible Well defined multilocular radiolucency Enucleation [20]
2 35 Female Right posterior mandible Well defined multilocular radiolucency Segmental mandibulectomy [21]
3 42 Female Left posterior mandible Well defined multilocular radiolucency Segmental mandibulectomy [22]
4 29 Male Anterior mandible Well defined multilocular radiolucency Intra oral surgical removal [23]
5 47 Male Right posterior mandible Large multilobular radiolucency with ill-defined borders Surgical removal [24]

when compared to the other ameloblastoma subtypes. In this regard, the lower incidence of granular cell ameloblastoma was re-
ported in the maxillary region, as compared to mandibular region (Table 1).
Here, we reported a rare case of maxillary granular cell ameloblastoma found in a female elderly patient which occurring in the
eighth decade of her life. Clinical examination revealed a large, painless expansive solid mass covered by normal mucosa in the left
side of maxilla, which is uncommon area of this tumor. Radiography showed a well-defined multilocular radiolucency lesion from the
upper left central incisor to the upper left first molar without any root resorption and the lesion extended from the alveolar crest to the
floor of left maxillary sinus. As with the maxillary region, the relevant surrounding anatomical structures i.e., maxillary sinus and
floor of nose are extremely complex. The specific surgical approach and maxillofacial prosthetic treatment should be critically con-
cerned to maintain the quality of life in patient. Additionally, the clinicopathologic condition in elderly is a major health care chal-
lenge due to the complexity of age-related disease and its influence on tissue regeneration and treatment outcome. According to previ-
ous evidence reported that conventional ameloblastoma treated by conservative treatment i.e., enucleation or curettage, exhibited a
high recurrence rate in follow-up period [7,25]. Moreover, posterior maxillary tumor is not well confined by the thin maxillary corti-
cal bone, indicated that the tumor can easily spread outside maxillary boundaries and higher risk of recurrence [26]. Therefore, mar-
ginal resection methods and accurate preoperative diagnosis and regular follow-up are recommended [7]. Our treatment was accom-
plished by partial maxillectomy combined with upper lip-splitting technique, and reconstruction with prosthesis obturator, providing
pleasant patient satisfaction in term of esthetic and oral function. The patient was routine yearly monitored using clinical and radi-
ographic examination. Pleasant soft tissue and hard tissue healing accompanied with a satisfactory oral function and facial appear-
ance were presented after two-year follow-up. In fact, a long-term monitoring is necessary and required for early management of re-
current ameloblastoma, especially this rare invasive subtype. Accordingly, a further annual follow-up and routine checking of the
maxillofacial prosthesis in this patient will be continuously performed.

4. Conclusion
The granular cell ameloblastoma is a rare histological subtype of ameloblastoma with the uniqueness histopathologic that pre-
sented a large number of granular cells and usually found at the posterior region of mandible. Our case is the rare case of the granular
cell ameloblastoma in maxilla, treated with a specific surgical approach combined with the upper lip-splitting technique as well as
postsurgical rehabilitation was achieved with the maxillofacial prosthesis. The treatment and prognosis do not significantly different
from the other subtypes of ameloblastoma. However, a higher recurrence rate as well as its metastatic behavior were shown by
spreading to distinct organ and tissue suggested a highly effective surgical procedure, productive reconstruction and close follow-up
are required. An understanding of clinicopathological features of this tumor type may provide an increased diagnosis accuracy, lower
recurrence rate and higher treatment success.

Credit author statement

SR: Conceptualization, Methodology, Writing- Original draft preparation. WT and NK: Investigation and Validation. NI: Methodol-
ogy, Writing- Reviewing and Editing.

Declaration of competing interest

The authors declare no conflict of interests.

Acknowledgement
Financial support for publication from Chiang Mai University.

References
[1] Masthan K.M.K, Anitha N, Krupaa J, Manikkam S. Ameloblastoma. J Pharm Bioallied Sci 2015;7:S167–70.
[2] Neville B.W, Damm D.D, Allen C.M, Chi A.C. Oral and maxillofacial pathology. Elsevier Health Sciences; 2015.
[3] Nikitakis N.G, Tzerbos F, Triantafyllou K, Papadimas C, Sklavounou A. Granular cell ameloblastoma: an unusual histological subtype report and review of
literature. J Oral Maxillofac Res 2011;1. e3-e.
[4] Regezi J.A, Sciubba J, Jordan R.C. Oral pathology: clinical pathologic correlations. Elsevier Health Sciences; 2016.
[5] Hartman K.S. Granular-cell ameloblastoma. Oral Surg Oral Med Oral Pathol 1974;38:241–53.
[6] Martin Y, Sathyakumar M, Premkumar J, Magesh K.T. Granular cell ameloblastoma. J Oral Maxillofac Pathol 2017;21:183.
[7] Reichart P, Philipsen H, Sonner S. Ameloblastoma: biological profile of 3677 cases. Eur J Cancer B Oral Oncol 1995;31:86–99.
[8] Yogesh T.L, Sowmya S.V. Granules in granular cell lesions of the head and neck: a review. ISRN Pathology 2011;2011:215251.

5
S. Rattanakuntee et al. Oral and Maxillofacial Surgery Cases 9 (2023) 100299

[9] Bansal A, Bhatnagar A, Saxena S. Metastasizing granular cell ameloblastoma. J Oral Maxillofac Pathol 2012;16:122–4.
[10] Shafer W.G.H.M, Levy B.M. Shafer’s textbook of oral pathology. fifth ed. Amsterdam: Elsevier Health Sciences; 2006.
[11] Hong J, Yun P.Y, Chung I.H, Myoung H, Suh J.D, Seo B.M, et al. Long-term follow up on recurrence of 305 ameloblastoma cases. Int J Oral Maxillofac Surg
2007;36:283–8.
[12] Hong J, Yun P.-Y, Chung I.-H, Myoung H, Suh J.-D, Seo B.-M, et al. Long-term follow up on recurrence of 305 ameloblastoma cases. Int J Oral Maxillofac Surg
2007;36:283–8.
[13] Gardner D.G, Pelcak A.M. The treatment of ameloblastoma based on pathologic and anatomic principles. Cancer 1980;46:2514–9.
[14] Reichart P, Philipsen H, Reichart P, PhilipsenHP, editors. Early normal Odontogenesis with special reference to the development and fate of the dental laminae.
Odontogenic tumors and allied lesions. London: Quintessence Publishing Corporation Limited; 2004.
[15] Chi A.C, Neville B.W, Damm D.D, Allen C.M, Bouquot J. Oral and maxillofacial pathology-E-Book. Elsevier Health Sciences; 2008.
[16] Ord R.A, Blanchaert Jr R.H, Nikitakis N.G, Sauk J.J. Ameloblastoma in children. J Oral Maxillofac Surg : official journal of the American Association of Oral
and Maxillofacial Surgeons 2002;60:762–70. ; discussion, 70-1.
[17] Al-Khateeb T, Ababneh K.T. Ameloblastoma in young Jordanians: a review of the clinicopathologic features and treatment of 10 cases. J Oral Maxillofac Surg :
official journal of the American Association of Oral and Maxillofacial Surgeons 2003;61:13–8.
[18] Yamunadevi A, Madhushankari G.S, Selvamani M, Basandi P.S, Yoithapprabhunath T.R, Ganapathy N. Granularity in granular cell ameloblastoma. J Pharm
BioAllied Sci 2014;6:S16–20.
[19] Kameyama Y, Takehana S, Mizohata M, Nonobe K, Hara M, Kawai T, et al. A clinicopathological study of ameloblastomas. Int J Oral Maxillofac Surg 1987;16:
706–12.
[20] Nikitakis N.G, Tzerbos F, Triantafyllou K, Papadimas C, Sklavounou A. Granular cell ameloblastoma: an unusual histological subtype report and review of
literature. J Oral Maxillofac Res 2011;1:e3.
[21] Mathew A. A case report on granular cell ameloblastoma – a rare histological entity. Indian J Radiol Imag 2020;30:225–8.
[22] Martin Y, Sathyakumar M, Premkumar J, Magesh K. Granular cell ameloblastoma. J Oral Maxillofac Pathol 2017;21:183.
[23] Arora S, Mujhib A, Diwakar G, Amberker V. Granular cell ameloblastoma : a case report with a brief note on review of literature. Egyptian Journal of Ear, Nose,
Throat and Allied Sciences 2014;15:267–9.
[24] Jahanshahi G, Arzhang E, Derisavy S, Davoodi L, Shakeri S. Granular cell type of ameloblastoma. Dent Res J 2018;15:224–7.
[25] Dandriyal R, Gupta A, Pant S, Baweja H.H. Surgical management of ameloblastoma: conservative or radical approach. Natl J Maxillofac Surg 2011;2:22–7.
[26] Feinberg S.E, Steinberg B, Peterson L.J. Surgical management of ameloblastoma: currents status of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod 1996;81:383–8.