Granular cell ameloblastoma is a rare histological subtype of ameloblastoma accounting for less than 5% of the total. The characteristic microscopic features of granular cells are attributed to the increased presence of lysosomes in the cytoplasm of the tumour cells.
A case of bone expansion in the mandible of 65 year old patient was examined on the basis of the clinical examination, radiographic imaging and microscopic features. A complete surgical removal was performed.
The radiographic imaging characteristics were consistent with a locally aggressive jaw lesion. Histological examination of the tumour revealed typical features of granular cell ameloblastoma. The specimen margins were free of tumour and the postoperative course was uneventful. No evidence of recurrence was noticed during a 1.5 years follow-up period.
The rarity of the granular cell ameloblastoma subtype and the possibility of confusion with other odontogenic and non-odontogenic lesions with a granular cell component require an understanding of the salient features of this locally aggressive neoplasm. A literature review is provided focusing on emerging molecular parameters in the pathogenesis of these tumours and the differential diagnosis of oral lesions featuring granular cells.
The ameloblastoma is a benign odontogenic tumour located almost exclusively in the
jaws. It has a distinctive microscopic appearance characterized by the presence of
peripheral columnar cells with hyperchromatic, reversely polarized nuclei, arranged
in a palisaded pattern [
Based on clinicopathologic criteria, ameloblastomas are divided into three fairly
distinct types: solid or multicystic (about 86% of all cases), unicystic (about 13%
of all cases) and peripheral (about 1% of all cases) [
Ameloblastomas usually manifest as a hard-tissue swellings that may assume very large
dimensions if left untreated. Pain and paresthesia are unusual clinical features
[
Several microscopic subtypes of the ameloblastoma, especially of its
solid/multicystic variant, are recognized, although these microscopic patterns
generally have little bearing on the behavior of tumour. Large tumours often show a
combination of microscopic patterns. The follicular and plexiform patterns are the
most frequent. Less common histopathologic subtypes include the acanthomathous,
granular cell, desmoplastic, and basal cell [
The granular cell subtype of ameloblastoma is characterized by the groups of granular
cells, which have abundant cytoplasm filled with eosinophilic granules that resemble
lysosomes, both ultrastructurally and histochemically [
The purpose of this paper is to present an unusual case of granular cell ameloblastoma and to review the pertinent literature highlighting its unique microscopic features that allow its distinction from other jaw tumours with a granular cell constituency and discussing the molecular aspects of its pathogenesis.
A 65 years old male presented with a chief complaint of a painless swelling in his
mandible. Clinical examination revealed a well-circumscribed bone expansion on the
body of left mandible. Panoramic radiograph revealed a large, multilocular
radiolucency with ill-defined borders, located in the body of partial edentulous
left mandible and extending from the first premolar to the second molar area (
Panoramic radiograph showing large, multilocular radiolucency, located in the left mandible.
Computed tomography showing a hypodense lesion with aggressive imaging features: it thinned bone margins both on the buccal and lingual sides of the mandible.
Photograph demonstrating intraoperative findings of destruction of the buccal cortical plate of the mandible.
Photograph of surgical specimen appearing as a lobulated soft tissue mass.
Photomicrographs showing tumour islands with a peripheral layer of ameloblassts and extensive central areas of granular cells with large, eosinophilic cytoplasmic granules.
A = hematoxylin and eosin stain, original magnification x100.
B = hematoxylin and eosin stain, original magnification x200.
Granular cell ameloblastoma is a rare variant of ameloblastoma. In the
clinicopathologic study of Kameyama et al. [
The biological behavior of granular cell ameloblastoma does not seem to differ from
the other histologic subtypes of ameloblastoma; it can be locally aggressive and has
a relatively high chance of recurrence [
Granular cell ameloblastoma is diagnosed by the presence of granular cells, which
typically occur within the central area of tumour and progressively replace the
stellate reticulum. Originally they were considered to represent an aging or
degenerative process [
The differential diagnosis of granular cell ameloblastomas includes other oral
lesions with a similar morphology of granular cell accumulation, including granular
cell odontogenic tumour, granular cell tumour and congenital epulis. These lesions
have different biologic behavior and should be discriminated from granular cell
ameloblastomas [
The granular cell odontogenic tumour is a type of odontogenic tumour featuring a
proliferation of large cells with eosinophilic granular cytoplasm, which appear
similar to the cells of granular cell ameloblastoma. They are very rare lesions
which have been reported in patients of a wide age range with a female predilection
[
The granular cell tumour is an uncommon benign soft tissue neoplasm that shows
predilection for the oral cavity. The most common site is the tongue, followed by
the buccal mucosa [
Congenital epulis is an uncommon soft tissue tumour which occurs almost exclusively
on the alveolar ridges of newborns or rarely on the tongue. Although this lesion is
also composed of granular cells, the necessity of distinction from a granular cell
ameloblastoma appears unlikely, considering occurrence of the latter in patients of
older age. Interestingly, immunohistochemical investigation is negative for S-100
protein. The lesion is treated with conservative excision and there have been no
reports of the recurrence. Additionally, it appears to stop growing after birth and
may even diminish in size [
In recent years, research efforts have attempted to elucidate the molecular factors
that govern the pathogenesis and progression of ameloblastoma and its subtypes by
regulating critical cell processes, such as cell proliferation, apoptosis and
differentiation. Numerous signaling pathways and molecules have been investigated
including integrins [
An investigation of the role of the mitochondria-mediated apoptosis signaling pathway
showed decrease or loss of immunoreactivity for the APAF-1 (apoptotic
protease-activating factor-1), caspase-9 and AIF (apoptosis-inducing factor) in the
granular cells of granular cell ameloblastomas [
As far as the role of angiogenic factors in the development and progression of
odontogenic tumours is concerned, Kumamoto et al. [
It has been proposed that BMPs and their associated molecules may regulate the
cytodifferentiation of normal and neoplastic odontogenic epithelium via
epithelial-mesenchymal interactions [
The possible contribution of novel signaling pathways such as Notch, sonic hedgehog
(SHH) and PI3K/Akt/mTOR in the pathogenesis of ameloblastomas has recently been in
the center of attention. Kumamoto et al. [
The granular cell ameloblastoma is a rare condition with unique histopathologic and immunohistochemical findings; its treatment and prognosis do not significantly differ from those of the other subtypes of the solid/multicystic ameloblastoma. However, it should be differentiated from the other granular cell lesions primarily because of its higher recurrence rate. A better understanding of the molecular pathogenesis of ameloblastoma and its subtypes is under way and may provide diagnostic and therapeutic benefits.
The authors report no conflicts of interest related to this study. There was no external source of funding for the study.