1

Keratoameloblastoma of the mandible; a case report on a

rare entity
R P N K Rajapaksha, P A G Nawaratne, R M A S Rathnayaka, N S Wadusinghearachchi

Abstract
Keratoameloblastoma is an extremely rare histopathological subtype of ameloblastoma
characterized by keratin formation within the odontogenic islands and connective tissue
stroma. This was first discovered in 1958, since then only 19 case reports have been
published in the literature. We present a case of keratoameloblastoma in a 55-year-old
Buddhist monk with a cystic lesion of anterior mandible in the view of clinical, radiological
and histopathological features and management along with the literature review.

Key words- Ameloblastoma, Keratoameloblastoma, odontogenic, keratin

Introduction
Ameloblastoma is a benign intra or extra osseous progressively growing epithelial
odontogenic neoplasm characterized by expansion and local recurrence if not adequately
excised. It is the most common odontogenic tumour, excluding odontomas. The World
Health Organization (WHO) Classification of Head and Neck Tumors 2017 classified this
entity into three categories; Conventional Ameloblastoma, Unicystic Ameloblastoma and
Extraosseous/Peripheral Ameloblastoma [1]. It is considered to be a group of highly
polymorphic tumors since it can go through diverse forms of metaplasia, giving rise to
various histological variants [2]. Of them, follicular and plexiform types are the main subtypes
and both of which consist of an odontogenic epithelium lined by columnar ameloblast-like
cells oriented in follicles or interconnecting nests, cords or strands in a fibrous stroma. Laying
in the middle of these epithelial structures is the loosely arranged spindle or stellate shaped
cells reminiscent of stellate reticulum of the enamel organ [1,2,3]. Other less common
histopathological subtypes include granular cell, desmoplastic, basal cell, clear cell,
acanthomatous, papilliferous keratoameloblastoma, and keratoameloblastoma [1,3]. This
diversity elicits the fact that the odontogenic epithelium bears a high degree of
multipotentiality [3]. However, the cause or the stimulus for this metaplasia is not certain and
is still poorly understood.

Genetic profile of ameloblastoma reveals that the mutations in genes belonging to the
MAPK pathway are present in almost 90% of all ameloblastomas , with BRAF V600E
being the most common mutation. Other MAPK pathway mutations include KRAS, NAAS,
HAAS, and FGFR2 mutations. The high frequency and the pattern of mutual exclusivity of
these mutations emphasize the importance of the MAPK pathway in the pathogenesis of
ameloblastoma [1].

Keratoameloblastoma is an extremely rare variant of ameloblastoma with a limited number of

cases reported in the literature [2,3]. It is one of the variants of ameloblastoma that exhibit
keratinization in their parenchyma apart from acanthomatous ameloblastoma, papilliferous
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keratoameloblastoma [3]. It was first discovered by Pindborg and Weinmann in 1958. In

1970, Pindborg again described an atypical ameloblastoma consisting keratin filled
microcysts lined by parakeratinized stratified squamous epithelium and partly by non-
keratinized epithelium [2]. Siar and Ng reported four examples of a tumor characterized by
hallmark features of ameloblastoma along with abundant keratinization and cystic changes
which are usually found in odontogenic keratocyst [4]. In 1992, the WHO vaguely defined
keratoameloblastoma as an ameloblastoma with extensive keratinization, although the
latest WHO classification for head and neck tumors released in 2017 has not even
mentioned this term due to the fact of its extreme rarity [5].

Case Presentation
A 55-year-old Buddhist monk presented to Oral and Maxillofacial Surgery unit of National
Dental Teaching Hospital-Colombo with a complaint of pain and swelling of the anterior
region of the lower jaw. The initial swelling had started to appear about 1 year ago and had
been gradually enlarging over the period slowly. He had been experiencing tenderness of
lower anterior teeth and gingivae for 4 months duration. It was an intermittent non radiating
aching type pain and had been worsening over past 2 weeks with 5-6 pain episodes per day
persisting for 5-10 minutes at a time. It had well responded to Paracetamol alone. No history
of trauma or infection could be related to the onset of signs and symptoms. He was devoid of
any past medical or surgical history. He had undergone multiple dental extractions due to
caries and tooth mobility. The last dental procedure he had undergone was the extraction of
45. It had been done due to tooth mobility about 2 years back. The patient denied the habit of
betel chewing.

He was averagely built and looked fit and healthy. Extraoral examination revealed a subtle
swelling of left side chin. The swelling was bony hard and non tender. The skin overlying it
was intact and there was no parasthesia. Mouth opening was found satisfactory. There was no
cervical lymphadenopathy. Intraoral examination revealed a non tender bony hard swelling of
lower anterior buccal vestibular sulcus in relation to 41,42,31,32 and missing 43. Palpation
disclosed an eroded buccal cortex of the swelling but lingual cortex remained intact. There
was a mild erythema of overlying mucosa and no discharging sinus tract noted. The teeth
involved had grade 1 mobility but no tenderness on percussion. There was an obvious
fanning of 41 and 42.Vitality test was done and showed that the teeth were vital.

The orthopantomograph (OPG) showed multilocular radiolucent lesion with well defined
margins in relation to teeth 41, 42, 31, 32, 33 and impacted 43. Considering the tentative
diagnoses of dentigerous cyst, residual cyst, solid multicystic ameloblastoma, odontogenic
keratocyst, aneurysmal bone cyst and Langerhan cell histocytosis, surgical removal of
impacted canine along with enucleation and curettage of cystic lesion was planned.

Surgery was performed as planned under general anesthesia. Two sided mucoperiostal flap
was raised after infiltration of local anesthetics to the surgical site. The lesion associated with
buccal cortex resorption was negotiated. Straw colored fluid was aspirated and cyst lining
was enucleated. Surgical removal of impacted canine was done with further bone removal
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and bone curettage was done. After through irrigation with normal saline heamostasis was
achieved with oxidized cellulose. The flap was repositioned and sutured with absorbable
synthetic sutures. The specimen was sent for histopathological assessment. The recovery was
uneventful and wound healing was satisfactory.

The biopsy revealed cystic odontogenic tumor lined by ameloblastomatous epithelium in

most areas and reverse polarity of basal cells. Stellate reticulum - like cells were present
towards the lumen. Prominent epithelial proliferation with associated squamous metaplasia
and keratin pearl formation were present in the cyst wall. Separate lamella keratin formation
was evident in the cystic lumen. Areas of dentinoid material and multiple foci of calcification
were noted elsewhere. Some areas of cystic wall were lined by parakeratinized stratified
squamous epithelium with basal cell palisading, representing features of odontogenic
keratocyst. These histopathological features were consistent with those of
keratoameloblastoma.

The patient was informed about the diagnosis and further discussed on the importance of
radical surgical intervention with safe margins, reconstruction methods, possible
complications of the surgery, the risk of recurrence and possible deleterious consequences if
resection is not adequately done. He refused an aggressive surgical intervention at that
moment. Therefore, surgery was postponed to time when he develops recurrences or
complications such as pathological fractures. He is currently on close follow ups. The
postoperative OPG on 6th month showed a healing lesion with no evidence of recurrences.

Discussion
Ameloblastoma is a benign locally aggressive neoplasm of the jaws that develops from
odontogenic epithelium [1,2]. It demonstrates multiple histopathological subtypes due to
metaplastic changes of odontogenic epithelium. Keratoameloblastoma is one of the rarest
subtypes described in the literature [2]. This lesion was first described by Pindborg and
Weinmann in 1958 [3]. Since then, only 19 cases reports have been published. Interestingly,
this disease entity has not been even mentioned in WHO Classification of Head and Neck
Tumors 2017 [5]. However, in 1992 WHO classification has recognized it as an
ameloblastoma with extensive keratinization. It demonstrates more male predilection than
female in the ratio of 3:1 [5]. The present case was diagnosed in a male Buddhist monk.
The peak incidence of diagnosis is in the third to seventh decade of life, with a patient age
range of 26 to 76 years. The mean age occurrence is 43.8 years. Approximately 75% of all
KA are found in mandible. They occur most often in the posterior region of the mandible
, followed by the anterior mandible, posterior maxilla, and anterior maxilla [5]. In this
case the lesion was present at the age of 58 in the anterior region of the mandible crossing the
midline associated with an impacted canine. According to the previous case reports, the
common clinical signs and symptoms are swelling, tenderness, loosening of teeth, spacing of
teeth, parasthesia, facial deformity, limited mouth opening, difficulty in mastication and air
way obstruction in severe cases [1,2,6]. This patient also presented with the same clinical
picture compatible for KA.
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Radiographically, solid types of ameloblastoma may present as corticated multilocular so-

called soap-bubble or honeycomb radiolucenccy on plain images in general [7]. A unilocular
appearance is less common. It may also show displacement and root resorption of
neighboring teeth. KA may show a mixed radiolucent and radiopaque appearance mimicking
that of a fibro-osseous lesion. This appearance is due to scattered hard tissue attenuation
within the mass. Presence of calcified masses within the lesion is characteristic for KA.
Scientists have put forward two possible explanations for existence of dense materials with in
KA. One possibility is development of hard substances from extensive keratin production and
concentrating them with in a closed chamber. Other possibility is the pathological
calcification which occurs due to destruction of tissues in the process of cyst formation and
expansion and dystrophic classification of necrotic cells. The lesion commonly shows
expansion and perforation of the cortical plates in computer tomogarphic or magnetic
resonant images [7]. In the present case, the lesion was investigated with only plain images.
An OPG was taken and it showed a mixed radiolucent-radiopaque lesion with soap bubble
appearance associated with an impacted canine tooth and displacement of roots of adjacent
teeth. Similarly, this patient’s radiographical features of the lesion were also going in the line
with those described in previous case reports.

The histopathologic appearance of odontogenic tumors or cysts varies extensively as a result

of multipotentiality of odontogenic epithelium. KA differs from other forms of
ameloblastomas because of the presence of keratinization. Other lesions that exhibit keratin
formation can be tabulated as odontogenic keratocyst, acanthomatous ameloblastoma,
calcifying odontogenic cyst, squamous odontogenic tumor, and squamous odontogenic
carcinoma [3]. Therefore, these lesions should also be considered as valuable differential
diagnoses. A comprehensive dialogue of the histologic classification of KA was reviewed by
Whit et al by appreciating previously published articles [8,9]. Based upon the location,
radiographic features, histopathology and treatments, they have categorized KA into 4
histologic subtypes as- (1) Papilliferous type- in which the odontogenic epithelium is
arranged in finger like projections into the cystic spaces; (2) Simple type- in which
histology represents epithelial follicles rimmed by ameloblast like- cells with reversed
polarity and filled with parakeratin or orthokeratin ; (3) Simple with Odontogenic
keratocyst like features- in which histology represents an admix of both simple type KA
and odontogenic keratocyst features; (4) Complex- in which histology represents hard
tissue formation resembling cementum and woven bone in addition to odontogenic epithelial
components [9]. The present case biopsy reveals a simple KA with odontogenic keratocyst
like features.

The treatment for odontogenic tumors is decided by bearing in the mind the factors such as
behavior of the tumour, the growth rate and pattern, the anatomical site of lesion, size and
extension of the tumor, the histopathological assessment and patient’s factors. Since the KA
is a variant of ameloblastoma, it can be managed with the same protocol as for
ameloblastoma [3]. There are two main therapeutic strategies for ameloblastoma mentioned in
the literature;(1) radical procedures- in which tumor and adjacent tissues are excised with a
safe margin of 1-2 cm and (2) non radical conservative procedures like enucleation and
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curettage, liquid nitrogen spray cryosurgery, marsupialisation, and dredging are mentioned to
be useful in unicystic ameloblastoma, especially in children and young individuals [10].
There have been extensive discussions on treatment options available for common types of
ameloblastoma. Gardner et al suggest radical resection for solid multicystic ameloblastoma
and non radical therapy for unicystic ameloblastoma. Sehdev et al (1974) reported more than
90% recurrence rate after the curettage of 92 ameloblastomas. Shatkin and Hoffmeister in
1965 reported a 86% recurrence rate after comprehensive treatments as opposed to a 14%
recurrence rate after radical treatments [11]. Ackermann et al 1988 reported a series of 57
ameloblastomas in which they found a 52% rate of recurrence in patients treated
conservatively and a 25% rate of recurrence in patients with primary tumor treated by the
radical approach [10, 11]. However, limited data on KA management and follow up in previous
case reports does not warrant any treatment modality is superior to the other. In previous
cases, en block resection, enucleation and curettage have been practiced. But as a whole, it
has shown that conservative management carries high recurrence rate compared to radical
resection. Out of 19 cases reported in the literature, four cases had recurred. Therefore,
the incidence of recurrence of KA can be given as 21% according to available evidences.
This patient underwent only the enucleation and curettage of cystic lesion. He denied radical
resection at that moment and we decided to follow up him and postponed the surgery to a
time when recurrence occurs. He is currently on follow up with no evidence of recurrences.

Conclusion
The adverse effects caused by KA cannot be underestimated even if it is a rare tumor.
Pathogenesis, prognosis and effective treatment modalities are still poorly understood due to
the matter of scarcity of the cases reported. Therefore further research and long term follow
up of the cases is warranted to evaluate its biologic behaviors and effectiveness of treatments
offered.

R P N K Rajapaksha Registrar in Oral and Maxillofacial Surgery, National Dental

(Correspondence) (Teaching) Hospital, Colombo 07.
E-mail- rpnkrajapaksha@gmail.com

P A G Nawaratne Consultant in Oral and Maxillofacial Surgery, National Dental

(Teaching) Hospital, Colombo 07.

R M A S Rathnayaka Consultant in Oral and Maxillofacial Surgery, National Dental

(Teaching) Hospital, Colombo 07.

N S Wadusinghearachchi Consultant in Oral Pathology, National Dental (Teaching)

Hospital, Colombo 07.
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References

1. EI-Naggar AK., Chan J.K.C., Grandis J.R., Takata T., Slootweg P. J. (Eds):WHO
Classification of Head and Neck Tumours (4th edition). IARC: Lyon 2017; 215-219.

2. Raj V, Chandra S, Bedi RS, Dwivedi R. Keratoameloblastoma: Report of a rare

variant with review of literature. Dent Res J. 2014;11:610-14.

3. Ketabi MA, et al.,. Keratoameloblastoma, a very rare variant of ameloblastoma.

JCraniofac Surg. 2013;24(6):2182-86.

4. Takeda Y, Satoh M, Nakamura S, et al.,. Keratoameloblastoma with unique

histological architecture: An undescribed variation of ameloblastoma. Virchows Arch.
2001;439:593.

5. Palaskar SJ, Pawar RB, Nagpal DD, Patil SS, Kathuriya PT. Keratoameloblastoma a
rare entity: a case report. J Clin Diagn Res 2015;9:ZD05-7.

6. Adeyemi B, Adisa A, Fasola A, et al. Keratoameloblastoma of the mandible. J Oral

Maxillofac Pathol 2010;2:77-79.

7. Barnes L, Eveson JW, Reichart P, Sidransky D. Pathology and Genetics of Head and
Neck Tumours. Lyon: IARCPress: 2005: 290-300.

8. JM Sisto, GG Olsen. Keratoameloblastoma: complex histologic variant of

Ameloblastoma. J Oral Maxillofac Surg. 2012;70:860-64.

9. Whitt JC, Dunlap CL, Sheets JL, Thompson ML. Keratoameloblastoma: a

tumour sugeneris or a chimera? Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2007;104:368-76.

10. Mahmood JU, Hydar IA, Amin N. Rational approach to the surgical management
of ameloblastoma. International Journal of Oral and Maxillofacial Surgery. 2015 1;
44:e107-8.

11. Sehdev MK, Huvos AG, Strong EW, Gerold FP, Willis GW. Ameloblastoma of
maxilla and mandible. Cancer. 1974;33:324–33.
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Figure Legends

Figure 1- Initial clinical presentation. Note the swelling of labial vestibular sulcus in
relation to 41, 42, 31 and 32 and fanning of involved teeth.
Figure 2- Pre operative dental panoramic tomography. Note the mixed radiolucent-
radiopaque lesion with scalloped margins of symphyseal region of mandible
associated with an impacted canine.
Figure 3- Intra operative view of the lesion. Note the straw colored fluid leaking out
from it.
Figure 4- After enucleation of the lesion. Note the impacted canine.
Figure 5- Intra operative view after surgical removal of impacted canine and bone
curettage. Note the buccal bone cortical resorption.
Figure 6- Post operative DPT after 6 months. Note the healing of lesion with no
evidence of recurrences.
Figure 7- Microphotograph of KA (Stained with Hematoxylin and Eosin). A-
Ameloblastomatous epithelium, B- Epithelial proliferations with keratin
pearls, C- Odontogenic Keratocyst features, D- Dentinoid material
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Figure 1- Initial clinical presentation.

Note the swelling of labial vestibular
sulcus in relation to 41, 42, 31 and 32 and
fanning of involved teeth.

Figure 2- Pre operative dental panoramic tomography. Note the mixed radiolucent-radiopaque lesion
with scalloped margins of symphyseal region of mandible associated with an impacted canine

Figure 3- Intra operative view of the lesion.

Note the straw colored fluid leaking out from
it.
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Figure 4- After enucleation of the lesion. Note

the impacted canine.

Figure 5- Intra operative view after surgical

removal of impacted canine and bone
curettage. Note the buccal bone cortical
resorption.

Figure 6- Post operative DPT after 6 months. Note the healing of lesion with no evidence of
recurrences.
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A B

C D
Figure 7- Microphotograph of KA (Stained with Hematoxylin and Eosin). A-
Ameloblastomatous epithelium, B- Epithelial proliferations with keratin pearls, C-
Odontogenic Keratocyst features, D- Dentinoid material