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Recent methods for the diagnosis and

differentiation of ameloblastoma: a narrative
review

Ke Hu, Xudong Zhang, Ruixue Chen & Xiangjun Li

To cite this article: Ke Hu, Xudong Zhang, Ruixue Chen & Xiangjun Li (2024) Recent methods
for the diagnosis and differentiation of ameloblastoma: a narrative review, All Life, 17:1,
2354675, DOI: 10.1080/26895293.2024.2354675

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ALL LIFE
2024, VOL. 17, NO. 1, 2354675
https://doi.org/10.1080/26895293.2024.2354675

REVIEW ARTICLE

Recent methods for the diagnosis and differentiation of ameloblastoma: a

narrative review
Ke Hu, Xudong Zhang, Ruixue Chen and Xiangjun Li
Department of Oral & Maxillofacial Surgery, College and Hospital of Stomatology, Hebei Medical University, The Key Laboratory of Stomatology,
Shijiazhuang, People’s Republic of China

ABSTRACT ARTICLE HISTORY

Ameloblastoma is a benign but locally invasive tumour. Early diagnosis of ameloblastoma and formu- Received 29 August 2023
lating an appropriate treatment plan play a crucial role in reducing the postoperative recurrence rate. Accepted 24 April 2024
The imaging features of ameloblastoma are similar to those of other odontogenic diseases; thus, the KEYWORDS
diagnosis of ameloblastoma remains challenging. This review summarises the diagnostic techniques Ameloblastoma; technology,
used for the detection of ameloblastoma and the methods for differentiating it from other benign radiologic; biopsy,
odontogenic tumours to aid in the clinical diagnosis. A comprehensive review was conducted by fine-needle; biopsy, incision;
searching the database of PubMed for studies published up to May 2023. Panoramic radiography, positron emission
computed tomography, and magnetic resonance imaging have been used to detect ameloblas- tomography; computed
toma, whereas fine-needle aspiration cytology and biopsies have been used to enhance diagnostic tomography
precision and clinical diagnosis. 18 F-fluorodeoxyglucose (FDG) and FDG positron emission tomogra-
phy(PET) have been used to detect metastasis of ameloblastoma to determine the prognosis of the
disease. Laboratory tests are more suitable for detecting genetic alterations and identifying certain
markers. Different diagnostic techniques aid in differentiating ameloblastoma from other odonto-
genic diseases. Combining these techniques may increase the diagnostic accuracy in patients with
suspected ameloblastoma.

Key policy highlights

• This review summarises the methods for diagnosing ameloblastoma. This is the first comprehen-
sive review of the procedures used for diagnosing ameloblastoma.
• The benefits and limitations of several diagnostic techniques were examined in this review.
• Cone-beam computed tomography is the most appropriate radiological technique for the
detection of ameloblastoma. 18 F-FDG PET/CT showed high diagnostic accuracy in identifying
metastatic/recurrent lesions postoperatively.
• The detection of cytokines and gelatinase in the cyst fluid further aids in the diagnosis.
• The techniques discussed in this article aid in the diagnosis of various types of ameloblastoma,
which will increase diagnostic precision.

Introduction
Ameloblastoma is defined as a slow-growing benign
but locally aggressive odontogenic lesion that fre-
quently develops in the mandible. Ameloblastoma typ-
ically manifests as a painless swelling on the outer
margins of the cheeks and lips. Oppressive growth of
the lesion can result in dysfunction and facial dysmor-
phisms. Expansion of ameloblastoma developing in
the mandible results in the compression and thinning
of the bone as well as mobility or loss of teeth in the
vicinity of the tumour.
Ameloblastoma is the most prevalent odontogenic
tumour in developing countries, and it is observed
more frequently in individuals between the ages of 30
and 60 years. The discovery of mutations in the BRAF
V600E and SMO genes in patients with ameloblas-
toma in the last decade has provided insights into the
pathophysiology of this disease (Ghai 2022). Although

CONTACT Xudong Zhang zxdcrx@hebmu.edu.cn Department of Oral & Maxillofacial Surgery College and Hospital of Stomatology, Hebei Medical
University, 383 East Zhongshan Road, Shijiazhuang, Hebei Province 050017, People’s Republic of China
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits
unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow
the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
2 K. HU ET AL.

ameloblastoma is a benign tumour, it has a malignant Study selection

transformation rate of 70%. The rate of metastasis
All retrieved articles were reviewed to ensure that the
is higher in the mandible than that in the maxilla,
inclusion and exclusion criteria were met.
and the lungs and lymph nodes are the most frequent
The inclusion criteria used in this review were as fol-
secondary sites (Effiom et al. 2018; Ghai 2022).
lows: (1) studies published after 2017 and their studies
Surgery, including both conservative and aggres-
on conventional ameloblastoma, unicystic ameloblas-
sive measures, remains the treatment of choice
toma, extraosseous/peripheral ameloblastoma, and
for ameloblastoma. Although conservative treatment
metastatic (malignant) ameloblastoma were included
results in fewer facial abnormalities, the recur-
in accordance with the ameloblastoma classification
rence rate is higher than that of aggressive ther-
criteria put forward in 2017; (2) articles published
apy. Consequently, the treatment and prognosis of
before 2017 were re-evaluated by combining the four
ameloblastoma are determined based on the clinical
versions of the classification criteria and were included
and histological results.
if they still belonged to the classification put forward
The diagnosis of ameloblastoma is the first step
in 2017; (3) studies that also discussed diagnostic
in the treatment of ameloblastoma (Effiom et al.
predictors of ameloblastoma and differences between
2018). Arriving at the correct diagnosis and formu-
ameloblastoma and other odontogenic disorders; (4)
lating an appropriate treatment plan are the key to
studies that used various diagnostic techniques for
reducing the postoperative recurrence rate. Benign
diagnosing ameloblastoma; and (5) studies that eval-
odontogenic lesions, such as ameloblastoma, odon-
uated the benefits of various diagnostic techniques.
togenic keratocysts, and dentigerous cysts, are the
The exclusion criteria were as follows: (1) reports
most prevalent odontogenic lesions encountered in
of simple clinical cases without a diagnosis; (2) arti-
clinical practice. Although these lesions are odon-
cles published before 2017 that were still not part of
togenic, significant biological and treatment differ-
the classification criteria put forward in 2017 after
ences have been observed among them. Different
re-evaluation were excluded.
treatment approaches have been developed owing to
Seventy articles were included in this review. All
the differences in the recurrence rates. Thus, the
articles that met the inclusion criteria were processed
accurate diagnosis and identification of ameloblas-
for information extraction. Data regarding the year of
toma is crucial (Liu et al. 2021; Wamasing et al.
publication, authors, contents, and the main results
2022).
were extracted. Tables 1 and 2 present the details
This review aims to summarise and analyse the
regarding the articles and primary findings of the
methods for diagnosing ameloblastoma and the meth-
studies.
ods for differentiating ameloblastoma from other
benign odontogenic lesions to aid in the clinical diag-
nosis of ameloblastoma, reduce the recurrence and
Results
metastasis of ameloblastoma, and improve the diag-
nostic accuracy. Odontogenic keratocysts and dentigerous cysts were
frequently distinguished from ameloblastoma in the
70 studies included in this review. Techniques such as
Materials and methods fine-needle aspiration cytology, biopsy, the detection
of genetic alterations, and the identification of cer-
Search strategy
tain markers aided in the diagnosis of ameloblastoma.
The PubMed database was searched to retrieve arti- Imaging techniques, such as panoramic radiography
cles published between 1965 and May 2023 on the (PR), computed tomography (CT), and magnetic res-
diagnosis of ameloblastoma and the identification of onance imaging (MRI), have been used for the detec-
ameloblastoma and other odontogenic diseases. The tion of ameloblastoma. The diagnostic precision of
following terms were used to search the database: these imaging techniques would benefit from the
‘ameloblastoma’ and ‘diagnosis’ or ‘diagnostic imag- application of convolutional neural networks and tex-
ing.’ Only studies published in English or Chinese ture analysis. The metastasis of ameloblastoma has
language were included in this review. been detected using 18 F-fluorodeoxyglucose (FDG)
 ALL LIFE 3

Table 1. Suitable diagnostic technique for clinical diagnosis.

Study Year Study contents Study results
Cardoso LB et al. 2020 Panoramic Radiography (PR) and Cone CBCT images revealed that the size and degree of expansion of ameloblas-
Beam Computed Tomography (CBCT) toma are larger than those of odontogenic keratocysts and dentigerous
cyst.
Wamasing N et al. 2022 Conventional Magnetic Resonance The apparent diffusion coefficient (ADC) helped distinguish unicystic
Imaging (MRI) and diffusion-weighted ameloblastoma from dentigerous cyst and odontogenic keratocysts; how-
imaging (DWI) ever, it cannot be used to distinguish dentigerous cyst from odontogenic
keratocyst.
Alves DBM et al. 2018 PR and Computed Tomography (CT) Although PR is very useful and widely used, CT provides more accurate
information on buccolingual expansion, calcification, bone septa, perfora-
tion of cortical bones, and tooth resorption.
Apajalahti S et al. 2015 CT and MRI Enhanced CT and MRI can help distinguish between ameloblastoma and
other cyst-like lesions as they enable the visualisation of the mixed cystic
and solid content characteristic of non-unicystic ameloblastoma. CT and
MRI aid in determining the differential diagnosis of unicystic ameloblas-
toma.
Wakoh M et al. 2011 PR The degree of observer reliance on diagnostic elements is more consis-
tent for ameloblastoma than for odontogenic keratocysts in PR. In par-
ticular, ‘radicular state adjacent to a lesion’ may be a decisive factor for
distinguishing ameloblastoma from odontogenic keratocyst.
Cihangiroglu M et al. 2002 CT and MRI Both CT and MRI show the extent of the tumours.
Crusoe-Rebello I et al. 2009 CT CT parameters facilitate the evaluation of ameloblastoma and odontogenic
keratocysts as well as other lesions.
Shokri A et al. 2017 CBCT CBCT can clearly visualise the borders and internal structures, cortical
expansion, and effect of lesion on adjacent tissues; thus, its use is recom-
mended.
Li D et al. 2018 CBCT The rotated three-dimensional CBCT images clearly display the exact size,
location, and borders of the tumour, as well as the internal changes in
the tumour in the jaw cyst and the adjacent tissues. Therefore, CBCT aids
clinicians in evaluating lesions and developing better treatment plans.
Surenthar M et al. 2021 CBCT CBCT plays a crucial role in addressing the diagnostic challenges faced and
separating it from other cystic lesions.
Luo J et al. 2014 CBCT CBCT can provide more information for preoperative radiologic assessment
of desmoplastic ameloblastoma compared with PR.
Meng Y et al. 2018 Spiral CT and CBCT Ameloblastoma, odontogenic keratocyst, and dentigerous cyst are com-
mon benign lesions of the maxilla, and the three-dimensional imaging
information provided by spiral CT and CBCT facilitates their diagnosis and
differential diagnosis.
Saati S et al. 2017 CBCT CBCT may be beneficial for dentomaxillofacial imaging considering the low
radiation dose and high resolution.
Kawai T et al. 1998 CT and MRI MRI is the optimal method for displaying tumours. MRI is crucial for deter-
mining the exact degree of advanced maxillary ameloblastoma.
Heffez L et al. 1988 MRI MRI is superior to CT in evaluating recurrent diseases as it can distinguish
tissues based on their proton composition
Cassetta M et al. 2014 MRI The acquisition sequence enables us to emphasise the diagnostic efficacy of
MRI in characterising the morphology and structure of maxillofacial lesions,
and demonstrates the importance of this imaging method as an additional
technique to CT in maxillofacial surgery planning, thereby reducing the risk
of injury to the inferior alveolar nerve during surgery.
Gupta A et al. 2018 Fine – needle Aspiration Cytology FNAC is a simple, rapid, accurate, inexpensive, and minimally invasive pro-
(FNAC) cedure for the diagnosis of ameloblastoma.
Günhan O et al. 1989 FNAC A case of ameloblastoma diagnosed preoperatively as ‘benign tumoural
lesion, suggestive of ameloblastoma’ using FNAC has been presented.
Uçok O et al. 2005 FNAC FNAC is used more commonly for the diagnosis of intraosseous and soft tis-
sue lesions in the oral and maxillofacial regions to obtain sufficient material.
It is convenient, inexpensive, and non-invasive.
Perić M et al. 2012 FNAC Adequate sampling patterns and correct cytological and histopathological
diagnosis are important factors for FNAC.
Thambi R et al. 2012 Cytological Ameloblastoma provides a good cell yield on aspiration and has distinct
cytological features. It is almost as effective as histopathology in appropri-
ate clinical and radiological setting.
Desai KM et al. 2023 FNAC Careful evaluation of FNAC helps diagnose ameloblastoma and must be
considered a vital diagnostic tool.
Reid-Nicholson M et al. 2009 FNAC Although cytological examination is helpful in diagnosing ameloblastoma,
it is not helpful in distinguishing conventional ameloblastoma from malig-
nant ameloblastoma. sufficient sampling is necessary to distinguish con-
ventional ameloblastoma from malignant ameloblastoma.
Hallikeri K et al. 2021 FNAC Compared with FNAC, cell block technology better preserves the structural
patterns and morphology of cells.
4 K. HU ET AL.

Table 1. Continued.
Study Year Study contents Study results
Zaidi A et al. 2021 FNAC The cell blocks created from the aspirate can serve as small biopsies that
facilitate accurate diagnosis of mandibular ameloblastoma. Moreover, they
contribute to the appropriate treatment of the tumour.
Renapurkar SK et al. 2022 Incisional Biopsies The findings of incision biopsy is not always consistent with the final
diagnosis. The possibility of sampling errors should be considered during
biopsy.
Chen S et al. 2016 Incisional Biopsy The diagnosis of incisional oral biopsy was consistent with the final patho-
logical results in 88.9% of cases. Multiple-site biopsy and larger volume
samples facilitate more accurate diagnosis.
Perry KS et al. 2015 Incisional Biopsy Incisional biopsy is an important first step.
Gliddon MJ et al. 2005 Incisional Biopsy and Endoscopy Endoscopy may prove to be an important tool. This would especially be the
case for large cysts that extend into areas that are difficult to inspect and
sample through a standard ‘bony window’ technique.
Hai HK et al. 1988 Incisional Biopsy Regression of large ameloblastoma has been observed after performing a
biopsy.
Lin Y et al. 2014 Incisional Biopsy and CT CT-guided percutaneous transthoracic lung biopsy and lymph node biopsy
are important methods for confirming metastatic ameloblastoma.
Fahradyan A et al. 2019 Incisional Biopsy If the biopsy site of ameloblastic carcinoma is not removed from the malig-
nant site, there will be a lack of evidence supporting the presence of a
malignant tumour, leading to a lack of diagnosis.
Otsuru M et al. 2008 18 F-Fluorodeoxyglucose Positron Emis- GLUT-1 expression and FDG uptake may serve as indicators of the prolifer-
sion Tomography(18 F-FDG PET/CT) ation and recurrence of ameloblastoma
Nguyen BD et al. 2005 18 F-FDG PET/CT 18 F-FDG PET/CT aided in the early detection of asymptomatic thoracic spine
dissemination, which was not conspicuous on CT examination
Niu N et al. 2013 18 F-FDG PET/CT 18 F-FDG PET/CT is an excellent tool for assessing different malignant pro-
cesses. Multiple organ metastases from ameloblastoma can be detected
using 18 F-FDG PET/CT

and FDG positron emission tomography (PET) to
determine the prognosis of the disease. In addi-
tion, tomoelastography, medical infrared thermog-
raphy, and ultrasonic imaging have also been used
to diagnose and treat ameloblastoma. These diag-
nostic techniques, which aid in the identification of
ameloblastoma in clinical settings, have been dis-
cussed in further detail below. Table 3 lists the benefits
and limitations of these strategies.
Discussion
Clinical diagnostic methods
Panoramic radiography
A radiological examination provides important infor-
mation to the clinician and aids in the clinical
assessment; thus, radiological examinations play an
important part in determining the differential diagno-
sis of ameloblastoma (Cardoso et al. 2020). PR is the
most frequently performed radiological evaluation. PR
has been used to determine the site of the lesion and
sclerosis, in addition to visualising teeth that have not
erupted completely. Furthermore, it has enabled the
magnification of the lower edge of the cortical bone
of the mandible (Alves et al. 2018). PR has numerous
variables that may affect diagnostic accuracy, including
the image quality of the radiograph and the clinicians’
understanding of the radiological characteristics of the
tumour. A higher image quality results in better diag-
nostic accuracy. Similarly, the clinicians’ understand-
ing of the radiological characteristics of the tumour
also affects the accuracy of the diagnosis (Alves et al.
2018; Cardoso et al. 2020).
PR can only yield two-dimensional images; thus,
the identification of ameloblastoma and other cys-
tic lesions remains challenging. Cortical dilation and
perforation are two significant differential diagnostic
points that cannot be observed on panoramic radio-
graphs of ameloblastoma (Apajalahti et al. 2015). PR
cannot facilitate a detailed examination, especially in
patients with maxillary lesions, as the anatomy of
the jaw and the overlapping teeth limit the diag-
nostic accuracy of two-dimensional PR (Vanagundi
et al. 2020). In contrast, CT, which facilitates three-
dimensional imaging, provides clinicians with more
precise information about the lesions (Alves et al.
2018).
Cone-beam computed tomography (CBCT) has
several other advantages over PR. Nevertheless, clin-
icians continue to use PR for the identification of
ameloblastoma in the initial examination of patients
despite the increasing use of CBCT and MRI (Wakoh
et al. 2011; Cardoso et al. 2020).
PR is acquired during the initial clinical diagnos-
tic process if the clinical symptoms are typical or
 ALL LIFE 5

Table 2. Advanced imaging techniques and molecular techniques suitable for experimental use.
Study Year Study contents Study results
Poedjiastoeti W et al. 2018 Convolutional Neural Network CNN can be used to distinguish ameloblastoma from odontogenic ker-
(CNN) atocyst. Its accuracy is comparable with that of manual diagnosis of
oral and maxillofacial surgeons. CNN can screen for ameloblastoma and
odontogenic keratocysts in a shorter period of time.
Yang H et al. 2020 CNN Automatic detection convolution network aids in pathological detec-
tion and incidence rate prevention in the field of oral and maxillofacial
surgery.
Kwon O et al. 2020 CNN CNN can automatically diagnose odontogenic cysts and tumours of
both jaws on PR using data augmentation with high sensitivity
Ariji Y et al. 2019 CNN Radiolucent lesions of the mandible can be detected with high sensi-
tivity using deep learning.
Lee A et al. 2021 Deep learning neural networks The present algorithm is expected to be a useful tool for clinicians,
as it can be used to diagnose Stafne bone cavity in PR to prevent
unnecessary examinations for patients.
Liu Z et al. 2021 CNN This algorithm improves the diagnostic accuracy of ameloblastoma and
odontogenic keratocyst, thereby providing reliable recommendations
before surgery.
Vanagundi R et al. 2020 Diffusion-weighted MRI Addition of diffusion-weighted sequences to MRI jaw protocols can
assist in the characterisation of odontogenic keratocyst, unicystic
ameloblastoma, and dentigerous cyst.
Oda M et al. 2019 Texture Analysis CT texture analysis can be used as a non-invasive method to obtain
additional quantitative information to differentiate cystic and cystic-
appearing odontogenic lesions of the jaw.
Chai ZK et al. 2021 CNN CNN may provide assistance for clinical diagnosis, especially for inexpe-
rienced surgeons.
Yuan XP et al. 2008 Spiral CT Multi-layer spiral CT can clarify the scope of jaw tumour and changes in
the bone. It aids in the qualitative diagnosis and differential diagnosis
of diseases. Moreover, it aids in the selection of appropriate treatment
options.
Hayashi K et al. 2002 Dynamic Multi-slice Helical CT Dynamic multi-slice Helical CT distinguishes ameloblastoma and odon-
togenic keratocyst based on the contrast enhancement values of intra-
tumoural vascularities during the arterial phase.
Hisatomi M et al. 2011 Dynamic contrast-enhanced MRI CE-T1WI and DCE-MRI were helpful in the differential diagnosis of
(DCE-MRI) unilocular cystic-type ameloblastoma with homogeneously bright high
signal intensity on T2WI or STIR
Hisatomi M et al. 2006 MRI and DCE-MRI They retrospectively evaluated MRI and DCE-MRI of ameloblastoma.
Sumi M et al. 2008 Diffusion-Weighted MRI ADC values can be used as an adjunct tool for differentiating ameloblas-
toma from odontogenic keratocysts.
Han Y et al. 2018 Diffusion-Weighted MRI Diffusion weighted imaging (DWI) and ADC determination can be used
as a tool to differentiate unicystic ameloblastoma from odontogenic
keratocyst.
Asaumi J et al. 2005 Contrast-Enhanced MRI(CE-MRI) CE-MRI is considered useful for diagnosing unicystic ameloblastoma, as
only CE-MRI can detect thick enhancement of the tumour wall and small
intraluminal nodules.
Gomes JPP et al. 2022 Texture Analysis MRI texture analysis has the potential to differentiate ameloblastoma
from odontogenic keratocyst. MRI texture analysis can be an additional
tool to differentiate ameloblastoma from odontogenic keratocyst.
Sant’Ana MSP et al. 2021 BRAF p.V600E BRAF V600E may aid in establishing the correct diagnosis in cases that
microscopically resembling other odontogenic lesions
Pereira NB et al. 2016 BRAFV600E BRAFV600E may aid in the differential diagnosis of unicystic ameloblas-
toma with dentigerous and radicular cyst, in conjunction with clinical,
radiologic, and histopathological features.
Mendez LD et al. 2022 BRAF VE1 BRAF VE1 is an excellent tool for the diagnosis of mandibular ameloblas-
toma but of limited utility in the maxilla, where BRAF VE1 and
BRAFV600E mutation occur less commonly
Duarte-Andrade FF 2019 BRAF V600E BRAF-V600E may contribute to metabolic alterations in ameloblastoma.
Metabolic alterations might play a role in tumour pathogenesis.
Joshi J et al. 2015 Immunohistochemical markers Immunohistochemical markers play a very vital role in diagnosingcases
Coleman H et al. 2001 Calretinin Calretinin appears to be a specific immuno-histochemical marker for
neoplastic ameloblastic epithelium and it may be an important diag-
nostic aid in the differential diagnosis of cystic odontogenic lesions and
ameloblastoma.
Kubota Y et al. 2001 Cytokine levels and gelatinase Ameloblastoma can be aid in distinguishing it from odontogenic kera-
species of the intracystic fluids tocysts by measuring the IL-1a and IL-6 levels, as well as the gelatinase
species, in the fluids.
Lu L et al. 2009 Ultrasonography Ultrasonography can be an effective auxiliary diagnostic method for
mandibular ameloblastoma.
Shinohara EH et al. 2013 Ultrasonography Ultrasonography is the preferred diagnostic tool for evaluating soft
tissue lesions in the head and neck region
6 K. HU ET AL.
Table 2. Continued.
Study Year Study contents
Beier M et al. 2020 Tomoelastography
Delarue M et al. 2021 Medical infrared thermography
(MIT)
only routine examinations are performed owing to the
advantages of PR, such as the cost and ease of use.
Conventional computed tomography
PR is frequently utilised and labelled as recommended;
however, as it yields two-dimensional images, it can-
not be used for in-depth analysis. More precise and
detailed information can be obtained from CT images.
Thus, CT provides more resources than other radio-
logical modalities and enables a clearer depiction of
all anatomical components, especially the molars, the
three roots of which frequently overlap in PR. CT
also enables the modification and recreation of high-
resolution pictures. CT enables a detailed analysis of
the size, location, and internal structure of the lesion,
as well as an assessment of whether the septa are sep-
arated. Lesions without loci may not be separated by
septa. CT can be used to identify multilocular features
(Alves et al. 2018).
CT shows the extent of the tumour more clearly
than PR, (Cihangiroglu et al. 2002; Alves et al. 2018)
which simplifies the process of selecting the optimal
biopsy site. Buccolingual expansion, calcification, the
presence of inner bone septa, perforation of the cor-
tical bone, and root resorption can also be visualised
on CT images. Furthermore, the diagnostic accuracy
of CT images is higher than that of PR. As some of
these features can only be visualised on CT images,
CT is the only imaging modality that can be used to
confirm their presence (Alves et al. 2018). The abil-
ity to determine the attenuation coefficient of the tis-
sue being examined is another advantage of CT. The
attenuation coefficient, which is correlated with tis-
sue density, is a measure of the radiation absorbed by
the structures being examined. The CT density pat-
terns of ameloblastoma and odontogenic keratocysts
have been determined using the density and hetero-
geneity on axial CT images. However, the density of
odontogenic keratocysts was found to be lower than
that of ameloblastoma. The presence of keratin in
odontogenic keratocysts also increases the density on
Study results
Stiffness and fluidity measured by tomoelastography can sensitively
detect the presence and extent of bone tumours and metastatic spread
to cervical lymph nodes.
MIT can monitor whether there is any diseased tissue passing through
the resection edge at the end of the surgery to minimize the risk of
recurrence.
axial CT images, and odontogenic lesions, such as
ameloblastoma and odontogenic keratocysts, can be
evaluated based on these CT characteristics. Although
the resulting CT density and heterogeneity can be used
to explain the CT characteristics of various disorders
more effectively, there is no definitive standard for
differentiation (Crusoé-Rebello et al. 2009).
Cone-Beam computed tomography
CBCT has been the preferred imaging modality owing
to several advantages, such as better spatial resolu-
tion, widespread availability, reduced cost, and lower
radiation dose.
Soft tissue imaging with CBCT is subpar, mak-
ing it impossible to determine the soft tissues sur-
rounding the lesion. However, it facilitates the three-
dimensional imaging of the cortical bone and bone
structures (Apajalahti et al. 2015; Alves et al. 2018).
In contrast to conventional PR, CBCT yields three-
dimensional images of the bone structure of the lesions
and cortical bone and displays the internal bone struc-
ture of ameloblastoma, which is characterised by a
honeycomb or soap bubble appearance (Apajalahti
et al. 2015). Thus, the use of CBCT is beneficial as it
enables the visualisation of the internal structure of the
tumour and the distinct boundaries of the tumour, as
well as the impact of the tumour on nearby structures.
CBCT can identify the traits of various odontogenic
lesions more accurately than PR, thereby providing
accurate and trustworthy information for preopera-
tive diagnosis, the formulation of treatment plans, and
postoperative follow-up (Shokri et al. 2017; Li et al.
2018).
CBCT offers several advantages over three-dimen-
sional imaging. For instance, oral contours can be visu-
alised without overlapping structures or distorted or
exaggerated images via CBCT. In addition, cysts can
be identified more accurately on three-dimensional
images owing to the accurate imaging of hard tis-
sue enabled by CBCT. Moreover, CBCT is more
cost-effective and convenient to use than other CT
 ALL LIFE 7

Table 3. Advantages and disadvantages of various methods.

Advantage Disadvantage
Panoramic Radiography Simple technique Two-dimensional imaging
Lower radiation dosage Overlap of structures
Wide inspection scope
Low cost
Conventional computed tomog- Three-dimensional imaging High cost
raphy (CT)
Clearer anatomical structure High radiation dose
Provide more information Technique is more difficult than panoramic
radiography
Poor resolution of soft tissue
Cone Beam Computed Tomogra- Three-dimensional imaging Cost and radiation dose are higher than those
phy (CBCT) of panoramic radiography
Higher spatial resolution. Poor resolution of soft tissue
Cost and radiation are lower than those of traditional computed
tomography.
Presents the boundaries, internal structure, and relationship with
surrounding structures of the tumour
Spiral CT Three-dimensional imaging Low resolution in dental lesions
Display lesions from multiple directions, such as cross-section High cost and radiation dose
High accuracy The quality of multi-slice spiral CT for fine struc-
tures is lower than that of cone beam computed
tomography
Conventional magnetic High soft-tissue resolution High radiation and high cost
resonance imaging (MRI)
Displays the internal and wall components of the solid cavity
More suitable for recurrent tumours.
Effectively images the soft tissue around the lesion, especially dis-
tinguishing the surrounding nerves
Diffusion-weighted MRI ADC values provide valuable information for the differentiation of
ameloblastoma
Dynamic contrast-enhanced MRI Provide diagnostic features for single cyst ameloblastoma (Thick
enhancement, intramural nodules)
Fine needle Aspiration Cytology Simple, fast, safe, minimally invasive, and cost-effective The sample size is small and sufficient material
(FNAC) must be aspirated
Patient comfort level is good Requires the assistance of cytologists
No special equipment required The sensitivity and specificity of its diagnosis
depend on the type of facility and the experi-
ence of the cytologists
Safe for pregnant women, children, and other at-risk patients
Gene mutation BRAF V600E mutation has certain specificity and frequency, and can BRAF V600E mutations are not detected in all
be used as a supplementary diagnosis patients with ameloblastoma, and this method
requires laboratory personnel and special
equipment
Biopsy Appropriate organizational size and depth provide valuable infor- Reliant on the professionalism of pathologists
mation, which could aid in improving diagnostic consistency
Sampling errors, insufficient tissue removal,
and the presence of inflammation can affect
diagnosis
Ultrasonography Economical, non-invasive, easy to use, and provides real-time If the tumour is small or the cortical bone is
images not damaged, ultrasound cannot penetrate the
bone tissue and can only detect the appearance
of the bone tissue
Can be used without contrast agents and is not subject to ionizing
radiation
Can also provide blood flow information to distinguish between Large tumours cannot be evaluated
cystic and solid lesions
18 F-Fluorodeoxyglucose
Positron Can identify recurrence and metastasis of ameloblastoma
Emission Tomography (18 F-FDG
PET/CT)
Tomoelastography Can detect the presence, range, and neck lymph node metasta-
sis of bone tumours, owing to its excellent mechanical parameters
(stiffness and fluidity)
Medical Infrared Thermography Non-invasive, non-ionising, real-time imaging, thermal imaging
Effectively demonstrates the extension of lesions in soft tissue
Convolutional Neural Network As a feature extractor, especially for two-dimensional images, it
greatly improves diagnostic accuracy
Texture Analysis Can be applied to computer tomography and magnetic resonance
imaging
As it is based on different texture features, it can differentiate lesions
non-invasively and accelerate biopsy and treatment.
Markers Can identify the levels of cytokines and gelatinase types in the cyst-
fluid or the calretinin
8 K. HU ET AL.
modalities and is associated with a lower radiation
dose. Furthermore, CBCT is superior to PR in terms
of diagnostic sensitivity and specificity (Cardoso et al.
2020; Surenthar et al. 2021).
Desmoplastic ameloblastoma can be differentiated
using PR despite its resemblance with fibro-osseous
tumours. CBCT can be used to obtain precise details
regarding the internal structure. Distinct imaging
characteristics of desmoplastic ameloblastoma, such as
the honeycomb appearance owing to the presence of
the coarse trabecular septum, can also be visualised
using CBCT. CBCT can also be used to detect buc-
cal/labial cortex expansion with perforation; thus, it
can be used to differentiate desmoplastic ameloblas-
toma from fibro-osseous tumours (Luo et al. 2014).
Furthermore, as CBCT is superior to PR in terms
of evaluating lesions, convolutional neural network is
superior to CBCT evaluations performed by physi-
cians in the detection of ameloblastoma and kerato-
genic cysts; moreover, it is more accurate (Chai et al.
2021).
CT has enabled the visualisation of the radiologi-
cal features of tumours and determining an optimal
site for performing a biopsy. Nevertheless, clinicians
should utilise texture analysis to assess CT images, as
it may aid in avoiding unnecessary biopsies and has-
ten the development of alternate treatment strategies.
CBCT is frequently used for clinical diagnosis, as it
can circumvent issues such as overlap. Furthermore,
the characteristics of the tumour are displayed more
efficiently. The radiation dose and cost of CBCT are
lower than those of other CT modalities. Thus, CBCT
is recommended as an additional imaging examina-
tion when the clinical or two-dimensional features of
a lesion make differentiation challenging. CBCT has
been used to extract highly impacted third molars,
in addition to diagnosing tumours, in clinical prac-
tice. CBCT imaging is often performed repeatedly to
prevent harm to the nerves and other tissues.
Conventional magnetic resonance imaging
MRI has a higher soft-tissue contrast resolution com-
pared with CT. MRI has been used to enable better
visualisation of the internal and wall components of
solid cavities (Konouchi et al. 2006; Hisatomi et al.
2011; Apajalahti et al. 2015; Vanagundi et al. 2020).
Although CT provides details regarding the bone
structure, not all recurrent tumours result in evident
bone structure damage. Tumours may recur in the
soft tissue at the site of the last surgery; MRI is a
more effective imaging modality than CT in such cases
(Kawai et al. 1998). Preliminary research suggests that
MRI may be more suitable than CT for recognising
recurrent disorders as it enables physicians to iden-
tify tissues by examining the proton composition. CT
images reflect the electron density of the tissue (Heffez
et al. 1988).
MRI has also been used to detect soft tissue around
a lesion. Determining the anatomical relationship
between the tumour and the peripheral nerve, partic-
ularly when it comes to avoiding the inferior alveolar
nerve in patients with mandibular tumours, remains a
challenge. MRI is particularly helpful in the detection
of the inferior alveolar nerve. Michele et al. modified
various MRI sequences to provide a more precise esti-
mate of the distance from the inferior alveolar nerve
and a more accurate representation of the anatomical
structure to facilitate surgical therapy (Cassetta et al.
2014).
MRI may be more beneficial for identifying tumours
that recur during the postoperative follow-up period.
Recurrent tumours in the soft tissue can be recognised
more easily owing to their superior soft tissue resolu-
tion. MRI also facilitates superior visualisation of the
connection between the tumour and the surrounding
soft tissue. Thus, MRI can be used to obtain more accu-
rate data in cases with the mandibular tumour adjacent
to the inferior alveolar nerve, thereby lowering the risk
of nerve injury.
18 F-fluorodeoxyglucose and 18 F-fluorodeoxyglucose
positron emission tomography
Ameloblastoma has a strong propensity to recur and
may even spread to other areas if the resection is
incomplete. Therefore, is crucial to identify recur-
rence at the earliest during the postoperative follow-
up period. However, recurrence cannot be recognised
solely via PR, CT, or MRI. 18 F-FDG PET/CT plays an
important role in the early recognition of recurrent
or metastatic ameloblastoma. Consequently, 18 F-FDG
PET/CT imaging has been used for the detection of the
metastasis of ameloblastoma in other organs (Nguyen
2005; Otsuru et al. 2008; Niu et al. 2013). Analysis of
glucose metabolism in patients with ameloblastoma
has revealed active glucose metabolism and absorp-
tion of a large amount of FDG by the tumour tissue.
Moreover, the expression of the glucose transporter
GLUT-1 was also observed in tumour cells. The active

expression of GLUT-1 and the high FDG uptake reflect
the proliferation and recurrence of ameloblastoma,
respectively; however, the FDG uptake and expres-
sion of GLUT-1 were low in patients with unicystic
ameloblastoma, reflecting low proliferation. Notably,
the recurrence rate of unicystic ameloblastoma is the
lowest in clinical practice (Otsuru et al. 2008).
18 F-FDG PET/CT has demonstrated superior per-
formance in the detection of the metastasis of
ameloblastoma, suggesting that it can effectively
detect metastatic tumours. Thus, performing 18 F-FDG
PET/CT during the postoperative follow-up period
has been recommended to detect metastasis. However,
18 F-FDG PET/CT is associated with high costs.
Fine-needle aspiration cytology
Fine-needle aspiration cytology (FNAC), a cytological
technique used for identifying lesions, involves pen-
etrating the lesion with fine needles and aspirating
the contents of the lesion for cytological examination.
FNAC has been widely used for identifying lymph
node, salivary gland, thyroid, and parathyroid lesions
since its introduction. Compared with other diagnos-
tic techniques, FNAC is a simple, rapid, safe, cost-
effective, and minimally invasive procedure, that is
virtually painless. Moreover, it is associated with good
patient comfort and does not require special equip-
ment. Thus, FNAC can be performed safely in children
and pregnant women.
FNAC requires sufficient material to be present
within the lesion to be aspirated, and the assistance
of a cytologist may be required in cases wherein the
lesion size is small. Consequently, the type of facility
and the skills and experience of the cytologist impact
the sensitivity and specificity of the diagnosis (Gün-
han et al. 1989; Uçok et al. 2005; Gupta et al. 2018).
Radiological diagnostic tools have been used to for-
mulate surgical strategies for the majority of patients
with cystic lesions. However, FNAC offers potential
utility in preoperative diagnosis, in addition to eluci-
dating the clinical and radiographic symptoms of the
tumour. Preoperative cytological examination enables
complete excision of the lesion without involving the
margin and lowers the postoperative recurrence rate
(Uçok et al. 2005; Perić et al. 2012; Thambi et al.
2012). The presence of clusters of basaloid cells in a
myxoid background is the most important and char-
acteristic cytological feature of ameloblastoma that
ALL LIFE 9
can be used for determining the differential diagno-
sis (Perić et al. 2012; Desai et al. 2023). The FNAC
aspirate comprises degeneration, myxoid changes, and
hyalinisation, which represent the cells and stromal
components of the tumour. Ameloblastoma can be
diagnosed in early stages based on important cellu-
lar and stromal characteristics (Desai et al. 2023).
Specific cells must be present in the cytological aspi-
rate. Clusters of basaloid cells, followed by clusters
of the other two cell types, are the most noticeable
features. Notably, the contents of the FNAC aspi-
rates obtained at two different time points varied in
the study by Perić et al. Predominance of phago-
cytes lacking characteristic epithelial elements was
observed in the FNAC aspirate acquired first, whereas
predominance of basaloid cells was observed in the
FNAC aspirate acquired subesquently (Perić et al.
2012).
Cytology has been used to diagnose granular
ameloblastoma, the most aggressive type of ameloblas-
toma that requires maximal excision (Gupta et al.
2018). Although the histological subtype of ameloblas-
toma has no impact on the treatment strategy,
cytological traits can aid clinicians in determining an
appropriate course of action during the resection of
lesions and while performing biopsies. Furthermore,
benign tumours can be differentiated from malig-
nant tumours via cytological analysis, thereby enabling
patients to seek more effective treatment (Uçok et al.
2005; Desai et al. 2023).
FNAC presupposes adequate sampling modality
and correct cytological and histopathological diag-
noses. The acquisition of insufficient samples or the
presence of atypical material in the aspirate may result
in the absence of epithelial elements (Uçok et al. 2005;
Perić et al. 2012). This may lead to false-negative
results being obtained and the clinicians being misled.
Malignant tumour cells cannot be detected if the
sampling is insufficient, and malignant lesions may
be misclassified as conventional ameloblastoma con-
sequently. This is particularly true for malignant or
metastatic ameloblastoma and ameloblastic carcino-
mas, which are excessively large and do not enable fur-
ther development into a widespread cyst. Thus, ade-
quate and suitable sampling plays a crucial role in the
differentiation of ameloblastic carcinoma from other
lesions. Furthermore, cytologists must also maintain
a high level of scepticism when making a diagnosis
(Reid-Nicholson et al. 2009).
10 K. HU ET AL.
FNAC, a non-invasive diagnostic technique, can
assist in the diagnosis of ameloblastoma. It aids
in the preoperative and postoperative evaluation of
ameloblastoma if an adequate amount of sample can
be acquired to facilitate careful examination by expe-
rienced cytologists.
Cell blocks are created from the aspirated material
after centrifugation, embedding in paraffin, section-
ing, and staining. The diagnostic accuracy of FNAC
is low. Comparison of the cytological smear with cell
block technology and comparison of the smear and
cell block technology with the histopathological diag-
nosis have revealed that cell block technology and
histopathology results are more consistent. Aspiration
of more liquid during the sampling process results in
better cell production and higher diagnostic accuracy.
Similarly, moving the needle back and forth in differ-
ent directions may also increase production (Hallikeri
et al. 2021). Cell block technology has assisted in the
retention of cell structure and morphology. Moreover,
it has benefits similar to those of FNAC. Thus, cell
blocks offer additional data for the diagnosis. How-
ever, cell block technology is time-consuming and
prone to material loss (Hallikeri et al. 2021; Zaidi et al.
2021).
Although it has some limitations, the use of FNAC
is favoured in clinical practice. Cell block technology
has been used as an adjunct to FNAC for diagnosing
lesions in the jawbone. This can increase the precision
of the diagnosis and assist in appropriate postoperative
monitoring. FNAC is more cost-effective and simpler
than imaging modalities. Furthermore, it is a more
convenient and less invasive diagnostic method com-
pared with biopsy. Although the sampling procedure
has some restrictions, the operator must acquire a suf-
ficient number of samples. Imaging examination can
be paired with FNAC to determine the diagnosis if
the physical condition of the patient is amenable. Care
should be taken to ensure that adequate samples are
acquired. A direct clinical diagnosis cannot be made
using cell block technology.
Biopsy
An incisional biopsy is performed to determine the
histological diagnosis following the detection of a
mass in the jaws. Formulating an appropriate treat-
ment plan for jaw cysts relies on the correct histolog-
ical diagnosis. Biopsy of cystic lesions is performed
to obtain lining tissue specimens representing the
lesion. Thus, incisional biopsy, which aids in deter-
mining the next step of treatment, is performed as
the first step in most cases of ameloblastoma. This
step aids in avoiding the overtreatment of ameloblas-
toma and improves the aesthetic effect. Furthermore, it
also enables the wide resection of the ameloblastoma,
thereby eradicating the lesion (Gliddon et al. 2005;
Perry et al. 2015). Regression of a large ameloblas-
toma has been observed following a biopsy in some
cases (Hai 1988). Endoscopy is another important
tool in the biopsy process that enables the acquisi-
tion of samples from the condylar neck and coronoid
process, especially during the biopsy of large cysts.
Endoscopy can also be performed in cases wherein the
lesions are present in areas that are difficult to detect
and sample (Gliddon et al. 2005). CT-guided percu-
taneous transthoracic lung biopsy, wherein a biopsy
of the metastatic ameloblastoma can be performed
percutaneously through the chest and lungs under
CT guidance, and lymph node biopsy are important
methods for confirming the diagnosis of metastatic
ameloblastoma (Lin et al. 2014). Isolated epithelial
islands with loosely arranged polygonal or polygonal
cells in the central area that occasionally form cysts
are characteristic histological features of ameloblas-
toma. The central region is surrounded by a layer of
columnar cells with opposite nuclear polarity. How-
ever, the diagnosis of ameloblastic carcinoma may be
missed if the biopsy site is not removed from the malig-
nant site, resulting in a lack of evidence supporting
the presence of a malignant tumour (Fahradyan et al.
2019).
Incisional biopsy is a good diagnostic technique for
oral lesions. However, similar to other diagnostic tech-
niques, the accuracy of incisional biopsy also varies.
The diagnosis made on the basis of the findings of
preoperative biopsy and the final diagnosis may dif-
fer in some cases. Sampling errors may occur during
biopsy and result in undertreatment or overtreatment,
as there are several different types of ameloblastoma
(Renapurkar et al. 2022).
The discrepancy between the final diagnosis and
results of incision biopsy may be attributed to the
differences in histopathological expertise, insufficient
tissue collection, and the presence of inflammation.
Disparities in the diagnosis made by histopatholo-
gists may be attributed to the differences in specialty
and subjectivity during the diagnostic procedure. The
lack of an organisational structure may result in

the acquisition of inadequate diagnostic specimens,
whereas inflammation may impair histological inter-
pretation (Chen et al. 2016).
It is advisable to integrate clinical and radiological
signs to arrive at a diagnosis if an incisional biopsy
is performed. Different biopsy procedures must be
used as needed to acquire more typical samples. A
second incision biopsy may have to be performed
if the findings of the incision biopsy are discordant
with the symptoms. Similarly, several specimens can
be acquired from various locations to diagnose large
lesions as the information obtained may be more thor-
ough than that obtained from a single specimen. Addi-
tional information can be obtained based on the size
and depth of the lesion tissue (Chen et al. 2016; Rena-
purkar et al. 2022).
Biopsy, which is an invasive diagnostic procedure
that can be used for diagnosing ameloblastoma, has
some limitations and must be performed after consid-
ering the health status and willingness of the patient.
Therefore, biopsy is not performed if the diagnosis can
be made using FNAC. However, FNAC is also per-
formed in conjunction with radiological techniques to
identify the type of tumour in some cases. The size of
the tissue and biopsy site must be considered during
the procedure.
Experimental/innovative diagnostic methods
Imaging systems
Spiral computed tomography. Spira CT has also
been used in addition to CBCT to acquire three-
dimensional images for the assessment of the oral cav-
ity. The resolution of spiral CT is not adequate for
evaluating dental lesions, and this affects the visual-
isation of the tissue present within the lesion (Meng
et al. 2018). Spiral CT is expensive and radiation-
intensive; nevertheless, it has been used in clinical
practice owing to its ability to depict lesion locations
from cross sections and multiple directions with good
accuracy (Li et al. 2018). Multilayer spiral CT has been
used to determine the range of jaw tumours and the
changes in the bone (Yuan et al. 2008). However, mul-
tilayer spiral CT is inferior to CBCT in terms of the
image quality of the fine structures in the maxillofa-
cial region (Saati et al. 2017). The percentage of density
increase (Enh%) obtained from dynamic multilayer
spiral CT during the arterial stage has shown a sig-
nificant correlation with microvessel density (MVD)
ALL LIFE 11
in patients with ameloblastoma and odontogenic ker-
atocyst. The Enh% and MVD were significantly higher
in patients with ameloblastoma than those in patients
with odontogenic keratocysts. These findings indicate
that dynamic multilayer spiral CT can be an effective
tool for discriminating ameloblastoma from odonto-
genic keratocysts (Hayashi et al. 2002).
However, spiral CT is not performed in patients
who can undergo CBCT as it is more expensive, emits
more radiation, and has lesser precision for depicting
fine structures compared with CBCT.
Diffusion-weighted MRI. Ameloblastoma presents as
a multilocular lesion with enhanced and non-enhan-
ced solid cystic components, as well as increased
surrounding cystic components. However, unicystic
ameloblastoma may resemble dentigerous cysts and
odontogenic keratocysts morphologically. Diffusion-
weighted imaging (DWI) can be used to differentiate
ameloblastoma from these lesions (Vanagundi et al.
2020).
DWI is a functional MRI technique that identi-
fies different tissue components based on the Brow-
nian motion of water molecules within the tissues.
DWI has been used for the imaging of various head
and neck diseases. The apparent diffusion coefficient
(ADC) is a measure of the movement of water (Vana-
gundi et al. 2020). Physical and physiological charac-
teristics, particularly physiological parameters, affect
diffusion and changes in the physiological parame-
ters may induce changes in the pixel intensities of the
diffusion-weighted sequences (Sumi et al. 2008).
ADCs have been used to differentiate unicystic
ameloblastoma without solid components from odon-
togenic keratocysts. The ADC of unicystic ameloblas-
toma was found to be significantly higher than that of
odontogenic keratocysts in some studies, (Sumi et al.
2008; Han et al. 2018) and the accuracy of distinguish-
ing ameloblastoma from dentigerous cysts and odon-
togenic keratocysts was 82% and 96%, respectively
(Wamasing et al. 2022).
DWI can be used to diagnose odontogenic disor-
ders; however, it lengthens the time to diagnosis. The
considerable difference in the ADC values aids in the
differentiation of ameloblastoma from other illnesses.
Dynamic contrast-enhanced MRI. Ameloblastoma
has several histological characteristics. Unicystic amel-
oblastoma exhibits uniform and bright high signal
12 K. HU ET AL.
strength on T2-weighted imaging and short tau inver-
sion recovery, thereby indicating the water content
within the internal components. Thus, differentiating
these lesions from other cystic lesions is challenging.
The use of contrast-enhanced MRI (CE-MRI) and
dynamic contrast-enhanced MRI (DCE-MRI) for the
diagnosis of ameloblastoma has proven to be beneficial
(Asaumi et al. 2005; Hisatomi et al. 2011).
Solid components present as small areas of enhan-
cement on contrast-enhanced T1-weighted imaging
(CE-T1WI). Thicker edge enhancement is observed
on CE-T1WI. Slight enhancement of some areas on
DCE-MRI indicates the presence of solid compo-
nents and/or intramural nodules with focal ameloblas-
toma tissue invasion. Pronounced enhancement of the
tumour wall and intramural nodules, which are char-
acteristic features of unicystic ameloblastoma, can be
observed on CE-MRI and DCE-MRI. Therefore, the
use of CE-MRI and DCE-MRI may aid in the differen-
tial diagnosis of unicystic ameloblastoma (Konouchi
et al. 2006; Hisatomi et al. 2011).
The ADC value of ameloblastoma may be higher
than that of odontogenic keratocysts on diffusion-
weighted MRI in some cases. However, this method is
time-consuming and unsuitable for clinical diagnosis.
Similarly, DCE-MRI is used less frequently in clinical
practices as it provides limited information.
Analytical methods applied in imaging systems
Convolutional neural network for panoramic
radiography. Information can be acquired from only
two-dimensional images in PR. Convolutional neural
networks (CNNs), one of the most efficient deep learn-
ing structures, play a significant role in the field of
medicine owing to the widespread use of AI in sev-
eral fields. A CNN based on transfer learning has been
used to retrieve features from PR to increase the diag-
nostic accuracy of ameloblastoma. CNN is capable of
learning various types of data, particularly from two-
dimensional images. Various levels of features can be
extracted from several datasets. However, the capacity
to extract features decreases as the size of the dataset
decreases. Transfer learning has enabled the identifi-
cation of high-level features in smaller datasets as it
can perform the extraction process without requiring a
large amount of data. The diagnostic accuracy of CNN
is similar to that of physicians. Thus, the use of CNN
for the screening of ameloblastoma would aid physi-
cians (Poedjiastoeti and Suebnukarn 2018; Yang et al.
2020; Liu et al. 2021). Data enhancement technology
can also be applied to increase the number of images in
the dataset, thereby improving the diagnostic perfor-
mance of CNN (Kwon et al. 2020). This technique can
also add a parallel structure to conventional transfer
learning to facilitate the simultaneous extraction of the
characteristics of the two tumours. The diagnostic pre-
cision of CNNs has led to unprecedented advancement
(Liu et al. 2021). Deep learning has shown promise
in the detection of mandibular radiolesions, with a
sensitivity of up to 90% (Ariji et al. 2019). Thus, its
implementation as a diagnostic tool would aid physi-
cians and also help distinguish odontogenic cysts or
tumours from the Stafne bone cavity (Lee et al. 2021).
Clinicians can use artificial intelligence/CNN to
extract features from panoramic radiographs and dif-
ferentiate ameloblastoma based on the presence of
these features. The advancement of artificial intelli-
gence has enabled physicians to utilise CNN to extract
imaging features from PR to boost diagnostic accu-
racy and develop treatment regimens; however, this
method is unrealistic and rarely employed in clinical
practice.
Texture analysis for MRI and CT. Texture analysis,
defined as a quantitative analysis of images, extracts
texture features from medical images. Pixels are the
fundamental building blocks of an image. Texture
analysis has also been used to identify the distribution
of pixel signal intensity and the relationships between
adjacent pixel values. High-dimensional data and sub-
tle differences in the internal components of lesions
can be retrieved via texture analysis. Most of these
data cannot be observed by humans; however, they
can be used to differentiate between different lesions,
which in turn enables physicians to diagnose and treat
patients with greater accuracy.
Texture analysis has been used in conjunction with
CT to obtain additional information for the differen-
tial diagnosis of jaw cystic lesions. Different texture
features can be used to assist in the non-invasive diag-
nosis of cystic lesions in the jaw, as the different cystic
components present within the lesion show variations
in texture properties. Texture analysis may even help
avoid biopsy and accelerate the treatment process (Oda
et al. 2019).
Texture analysis can also be performed in conjunc-
tion with MRI, in addition to the aforementioned
MRI applications, which can be used to discriminate

odontogenic keratocyst from ameloblastoma. Texture
analysis has been used previously to differentiate
benign tumours from malignant tumours in human
patients. Texture analysis also facilitates the removal
of the subjectivity of human vision from the quantita-
tive evaluation of images. Entropy and the sum average
are two texture parameters with statistically significant
values. Entropy is defined as a measure of the degree
of disorder between the pixels in an image, whereas
the sum average is defined as a measure of the aver-
age value of the sum of two pixel values. Odontogenic
keratocyst has lower entropy and total average values
than those of ameloblastoma (Gomes et al. 2022).
Molecular systems
Gene mutation and marker diagnosis. Incision biopsy
is associated with a considerable error rate owing to the
variations in the histological forms of ameloblastoma,
particularly in cases of unicystic ameloblastoma or sig-
nificant inflammatory infiltration. As the mechanism
of gene mutation is better understood, BRAF V600E
has been detected in 80% of patients with ameloblas-
toma but not in patients with other odontogenic cysts.
Although the BRAF V600E mutation has not been
detected in all patients with ameloblastoma, it can be
used as an additional tool for differential diagnosis
in some cases that are challenging to diagnose using
conventional methods.
Sanger sequencing and quantitative real-time PCR
are considered the most precise techniques for detect-
ing mutations (Pereira et al. 2016; Sant’Ana et al. 2021).
Immunohistochemistry (IHC) can also be performed
using BRAF VE1 mutation-specific antibodies. The
results of BRAF VE1 IHC are highly consistent with
the mutation status of BRAF V600E, indicating that
BRAF VE1 antibodies can be used to accurately predict
the presence of BRAF V600E mutation. BRAF V600E
can also be used to identify mandibular ameloblas-
toma and serves as a key marker for the disease. How-
ever, the application of this method in the maxilla is
limited owing to the rarity of the incidence of BRAF
V600E mutation (Mendez et al. 2022).
Several markers play important roles in the differen-
tial diagnosis, in addition to detecting mutated genes.
These markers reflect the cell lineage and tissue origin
of various lesions; therefore, they can be used for the
differential diagnosis. For example, one such marker,
cytokeratin, varies with the epithelial type (Joshi et al.
2015). Calretinin, a 29-kDa calcium-binding protein,
ALL LIFE 13
is present in human tissues and tumours. However,
calretinin is only detected in ameloblastoma among
cystic odontogenic lesions. Thus, calretinin may be a
specific marker and an auxiliary tool for differentiating
ameloblastoma (Coleman et al. 2001).
Ameloblastoma can also be differentiated based on
the cytokine content and the type of gelatinase in the
cyst fluid. The levels of interleukin (IL)−1α and IL-1β
were significantly lower in the cyst fluid of ameloblas-
toma; however, the IL-6 levels in the cyst fluid of
ameloblastoma were higher than those in the cyst
fluid of odontogenic keratocyst. No significant differ-
ences were observed in terms of tumour necrosis factor
(TNF)-α levels in the cyst fluid.
Matrix metalloproteinases (MMP)−9, a type of
MMP, is a gelatinase. Active MMP-9 is secreted by
the inactive pro-MMP-9, and MMP-9 can degrade and
remodel the extracellular matrix. Only a small amount
of pro-MMP-9 has been detected in ameloblastoma.
In contrast, pro-MMP-9 and its active form have been
detected in most odontogenic keratocysts. This detec-
tion method can also be used for small cystic lesions
as cytokines and gelatinase can be detected using 200
and 0.2 microlitres of cyst fluid, respectively (Kubota
et al. 2001).
Gene mutation and marker content detection are
time-consuming and expensive techniques that neces-
sitate the use of specialised equipment and laboratory
personnel. Furthermore, BRAF V600E mutations are
uncommon in the maxilla. Therefore, it is not advis-
able to use cytokines or altered genes to detect lesions.
Gene mutation and biomarker changes have been
used in laboratory research. Changes occurring in the
macromolecular substances of upstream genomics are
reflected in metabolomics. Thus, the impact of the
mutation affects the downstream metabolites when
BRAF V600E is mutated in ameloblastoma (Duarte-
Andrade et al. 2019). Gene mutations are closely
related to these metabolites. Therefore, future stud-
ies must aim to further improve the diagnostic rate
of ameloblastoma and identify therapeutic targets for
ameloblastoma.
Other methods
Ultrasonography
Soft tissue lesions in the head and neck can be diag-
nosed using ultrasonography. Ultrasonographic exam-
ination is a cost-effective, non-invasive, and simple
14 K. HU ET AL.
examination technique that produces real-time images
without exposing patients to ionising radiation or
contrast agents. Ultrasonographic examination has
been used to elucidate the differences between cystic
and solid tumours and provide real-time data regard-
ing blood flow within tumours. However, the examina-
tion of bone tissue is associated with some limitations.
The internal structure of the bone is typically not vis-
ible in ultrasonographic imaging, which only depicts
the external bone tissue. The mandible is compressed,
and the cortical bone becomes thin as ameloblastoma
continues to grow. Ultrasound can penetrate through
the bone tissue, thereby enabling the imaging of these
structures. However, ultrasonography is challenging to
use in cases wherein the tumour size is small or the cor-
tical bone is not thin. High-frequency ultrasonography
cannot be performed in cases with large tumours, as
the tumour size on the image will be smaller than
the actual measurement. Ultrasonography has also
been used to detect the presence of ameloblastoma in
the mandible. Blood flow signals detected by colour
Doppler flow imaging can determine the active pro-
liferation of tumours. Abundant blood flow signals
indicate active tumour proliferation (Lu et al. 2009;
Shinohara et al. 2013).
Tomoelastography
Tomoelastography, a type of magnetic resonance elas-
tography, produces high-resolution quantitative maps
based on the mechanical properties of soft biolog-
ical tissues, such as tumours. The measured stiff-
ness and fluidity can be used to determine the pres-
ence, range, and neck lymph node metastasis of
bone tumours. Tomoelastography provides important
mechanical characteristics for the evaluation of bone
malignancies (Beier et al. 2020).
Medical infrared thermography
The edge of the lesion must be removed to lower the
recurrence rate. Routinely used radiological modal-
ities may not define the surgical resection edge for
smaller lesions or lesions without bone damage effec-
tively. Clinical signs and palpation frequently fail to
accurately locate the border of the tumour. There-
fore, real-time imaging must be performed in such
cases using medical infrared thermography (MIT), a
non-invasive and non-ionised method. The thermal
imaging technology used in MIT enables surgeons to
clearly observe the progression of lesions in soft tis-
sues. Surgeons can optimise the resection edge to pre-
vent recurrence (when the temperature of the lesion
area is typically higher than that of healthy tissue).
Since it cannot be used for diagnosis, MIT is better
suited for determining the edges of small lesions or
other difficult-to-determine lesions. This has aided in
lowering the recurrence rate (Delarue et al. 2021).
Ultrasonography is useful only in cases wherein
the cortical bone within the lesion shows thinning.
However, tomoelastography cannot be used to directly
identify ameloblastoma owing to the mechanical prop-
erties of tomoelastography. Although MIT aids in sur-
gical resection, it cannot be used as a diagnostic tool.
The edges of small lesions are easier to visualise and
tumours can be removed more precisely. Therefore,
professionals must use medical infrared imaging dur-
ing surgical resection.
Main differential diagnosis
Odontogenic keratocyst
Odontogenic keratocyst is the third most frequently
occurring cyst in the oral cavity. The differences
between the imaging findings of odontogenic kerato-
cysts and those of ameloblastoma are negligible. Thus,
it is difficult to distinguish ameloblastoma from odon-
togenic keratocysts. However, it is crucial to differ-
entiate ameloblastoma from odontogenic keratocysts
as the treatment approaches for ameloblastoma and
odontogenic keratocysts vary.
Odontogenic keratocysts present as unilocular
lesions with smooth margins, and more than half
of these lesions occur in the maxilla. In contrast,
ameloblastoma presents as a unilocular or multilocu-
lar lesion with a fan-shaped edge and often occurs in
the mandible, which is more likely to cause resorption
of the tooth roots and mobility or displacement of the
tooth (Kitisubkanchana et al. 2020). The area with high
density and bone expansion is the key to differentiating
between these entities. The average bone expansion
of ameloblastoma is greater than that of odontogenic
keratocysts; however, high-density areas are observed
only in odontogenic keratocysts. Lesions associated
with impacted teeth can also be used to differentiate
between the two lesions. Odontogenic keratocysts are
more likely to be associated with impacted teeth (Ariji
et al. 2011). The diagnostic accuracy of CT for the
detection of ameloblastoma is usually higher than that

of PR. Thus, the lesion is likely to be ameloblastoma if
it presents as a multilocular lesion in the mandible with
a scalloped border associated with root absorption
and loosening or displacement of the tooth. Incisional
biopsy and FNAC can be performed to exclude other
diagnoses if the lesion is indistinguishable.
It is recommended to perform an incisional biopsy
in the case of lesions associated with visible dilation.
FNAC can be performed to determine whether the
lesion is an odontogenic keratocyst if expansion is not
observed (Chapelle et al. 2004).
Some of these markers can be used to differentiate
these two entities. Unlike ameloblastoma, calretinin is
not detected in odontogenic keratocysts. The detection
of cytokines, such as IL-1 α, IL-1, and IL-6, as well as
gelatinase, in the cyst fluid will also aid clinicians in
determining the diagnosis.
Dentigerous cyst
Dentigerous cyst is another cyst that must be distin-
guished from ameloblastoma. In addition to amelobl-
astoma and odontogenic keratocysts, dentigerous cysts
are also common odontogenic lesions. Almost all
dentigerous cysts present as unilocular lesions during
imaging. Ameloblastoma occasionally contains teeth
and generally results in the resorption of the root; in
contrast, the presence of the crown with an unerupted
tooth is a typical imaging feature of dentigerous cysts
(Meng et al. 2018). The diagnosis of dentigerous cyst
must be considered in cases where the lesion contains
only an unerupted crown and the site is related to
the age of the patient. Histopathological examinations
must be performed via an incisional biopsy to confirm
the diagnosis.
Ameloblastic carcinoma is another disease that
should be considered. Metastatic ameloblastoma usu-
ally exhibits the same characteristics as primary
tumours and must be differentiated from other
tumours that may occur at the metastatic site. How-
ever, ameloblastic carcinoma, a malignant tumour, dif-
fers from conventional ameloblastoma and exhibits
typical malignant features, such as nuclear pleomor-
phism, mitotic abnormalities, and necrosis. These
cytological features are the key to identifying amelobl-
astic carcinoma (Khalbuss et al. 2006; Reid-Nicholson
et al. 2009; Nai and Grosso 2011). FNAC has achieved
safety, simplicity, and high efficiency; however, great
attention should be paid to the adequacy of sampling
as it is a malignant tumour. Incorrect diagnosis may be
ALL LIFE 15
obtained if typical and malignant cytological features
are not obtained during aspiration.
Conclusion
Although ameloblastoma is a benign tumour, it is a
locally invasive lesion. Similar imaging characteris-
tics have been observed in other odontogenic lesions
despite the variations in biological traits and therapeu-
tic approaches in clinical practice. Careful differenti-
ation of odontogenic lesions plays a key role in the
development of surgical treatment plans.
PR is the most commonly used imaging technique
for the detection of ameloblastoma; however, this tech-
nique typically only allows two-dimensional imag-
ing and cannot provide detailed information. The use
of CT and MRI for the diagnosis of oral tumours
has increased significantly owing to the continued
advancements in technology. CBCT yields three-
dimensional images of bone structure, whereas MRI
enables the visualisation of the characteristics of the
soft tissue surrounding the lesion. FNAC and biopsy
have been used to confirm the diagnosis of ameloblas-
toma. The diagnosis of ameloblastoma can be con-
firmed via gene mutation detection owing to the preva-
lence and specificity of BRAF v600E mutations, which
are being developed continuously to provide insights
into the molecular basis of ameloblastoma. Ameloblas-
toma can be diagnosed more accurately using dif-
ferent specialised techniques, such as cytokine levels,
gelatinase species in the cyst fluid, ultrasonography,
18 F-FDG PET/CT, tomoelastography, and MIT. Other
diagnostic techniques may be selected, in addition to
radiological examinations, to obtain more useful infor-
mation about the lesion and establish a diagnosis of
ameloblastoma if the diagnosis of ameloblastoma is
uncertain.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Ke Hu and Xudong Zhang contributed to the concep-
tion and design of the study. Ke Hu carried out the
literature search, produced the tables, and drafted the
paper. Ruixue Chen and Xiangjun Li carried out
the literature search, assessed the included literature.
Xudong Zhang, Ruixue Chen and Xiangjun Li revised
16 K. HU ET AL.
the manuscript for important intellectual content.
Xudong Zhang approved the final manuscript. All
authors agree to be accountable for all aspects of this
study.
Funding
This study was supported by the Natural Science Foundation
of Hebei Province, China [grant number H2021206165]. Hebei
Provincial Department of Finance Project, PR China [grant
number ZF2023016 and 361029].
Data availability statement
Data sharing is not applicable to this article as no new data were
created or analysed in this study.
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