A 62 year-old woman from Sierra Leone presented with a left-sided
mass of her face that has been progressively enlarging over the last 2 years. The patient complained of
occasional pain, but no dysphagia or mastication problems and no systemic symptoms. On physical
examination, a firm 10 cm mass extended from the left temporal area over the temporo-mandibular joint and
covered the parotid and jaw area. Her medical history was significant for a left mandibular mass
excision with mandibular reconstruction 25 years prior to presentation. The FNA of the mass is
illustrated (Figures 1-3).
Case 2 - Figure 1 - Low to moderately cellular smears revealed an abundant mucoid/ proteinaceous material in the background and histiocytes compatible with the grossly cystic nature of the mass. A population of large polygonal or round squamous epithelial cells forming small sheets was present. Some of the squamous groups displayed variably sized large vacuoles with a double cytoplasmic membrane rim, containing bright eosinophilic /metachromatic granular material reminiscent of mucin. (Diff-Quik stain, medium power)
Case 2 - Figure 2 - Groups of tightly packed basaloid cells were scattered. These groups consisted of cells with elongated, oval nuclei with scant or minimal amount of indistinct cytoplasm. The chromatin was dense and uniform and small nucleoli were discernable in some cells. In some of the three-dimensional groups, a well-defined border peripheral and peripheral palisading of the cells is noted. Focally in the background surrounding these clusters were single ovoid bland cells with a thin rim of cytoplasm (Diff-Quik stain, medium power)
Case 2 - Figure 3 - Hyalinized metachromatic stromal fragments were identified within some of the basaloid cell groups. The stroma was dense and non-fibrillar, however it displayed no spherical or cylindrical shape and was closely apposed to the basaloid cells. Isolated squamous cells with rounded shapes or small groups of squamous epithelium are present in the vicinity of the basaloid group. A histiocyte is a reminder of the cystic nature of the lesion. (Diff-Quik stain, medium power)
Diagnosis: Recurrent Ameloblastoma
The fine needle aspirate yielded 15 cc of clear tea-colored
fluid. Smears revealed an abundant mucoid/ proteinaceous material and numerous histiocytes compatible
with the grossly cystic nature of the mass. Groups of tightly packed basaloid cells were scattered.
These groups consisted of cells with elongated , oval nuclei with scant or minimal amount of indistinct
cytoplasm. The chromatin was dense and uniform and small nucleoli were discernable in some cells. In
some of the three-dimensional groups, a well-defined border peripheral and peripheral palisading of the
cells is noted. Hyalinized metachromatic stromal fragments were identified within in some of the
basaloid cell groups. The stroma was dense and non-fibrillar however it displayed no spherical or
cylindrical shape and was closely apposed to the basaloid cells. In some areas, the stroma appeared as a
core within pseudo-acinar structures. Focally in the background surrounding these clusters were single
ovoid cells with a thin rim of cytoplasm. Also present was a second cell population of larger polygonal
or round squamous epithelial cells. These were either isolated but in the vicinity of the basaloid
groups or forming small epithelial sheets. Some of the squamous groups also displayed variably sized
large vacuoles with a double cytoplasmic membrane rim, containing bright eosinophilic /metachromatic
granular material reminiscent of mucin.
The identification of basaloid , squamous, and single cells together with the presence of a cystic
component containing mucus-appearing material in a mass arising in the area of the parotid were
suggestive of a salivary gland neoplasm. Exact classification of the tumor based on the cytologic
findings could not be made however a differential diagnosis was suggested to include a cystic adenoma
with metaplasia, a low grade mucoepidermoid carcinoma, and an adenoid cystic carcinoma. Excision was
Histologic and Clinical Follow up:
A preoperative CT scan was performed
and revealed a large mass extending from the nasopharynx area into the lateral pharyngeal space laterally
to the parotid. The mass caused erosion of bone in the middle cranial fossa leaving the dura intact.
Bony erosion of the lateral orbital wall was also present. The patient was taken to surgery for
resection of a left lateral skull-based tumor with superficial parotidectomy and dissection of the facial
nerve, followed by reconstruction. At the completion of the resection, it was evident that the mandible
was missing and that the dura overlying the temporal lobe was exposed but intact. A 320 gm, 12.0x9.0x6.0
cm mass was excised. The cut surface was multiloculated. Cystic spaces filled with brown, sometimes
pasty material were interspersed between soft cream-colored areas and firm yellow areas. Focal
hemorrhage and presumed areas of calcifications were also present. Intraoperative consultation smears
were highly cellular reproducing the patterns identified in the FNA. Again a diagnosis of salivary gland
neoplasm not further classified was rendered. Permanent sections revealed an ameloblastoma with
follicular, acanthomatous and basaloid patterns extending into parotid gland. Areas of necrosis and
hemorrhage were also present. Given the patient's past history, the tumor was thought to likely
represent a recurrence of a prior ameloblastoma.
Ameloblastoma is the most common epithelial odontogenic tumor. It arises from the epithelial lining
of a dentigerous cyst, the remnant of dental lamina and enamel organ or from the basal layer of the oral
mucosa. It represents approximately 1% of cysts and tumors of the jaws, and 11% of tumors of odontogenic
epithelium. Eighty percent (80%)of ameloblastomas occur in the mandible with 70% arising in the molar
ramus and the remaining 20% occurring in the posterior maxilla. Most commonly the tumor is encountered
in the 3-5th decade, however it can be seen in any age group including children. It has no
sex or racial predilection.
The clinical and radiologic appearance may simulate those of several odontogenic cysts. Patients
present with a slow growing mass or swelling in the parotid region that progresses over weeks to years
(50). Radiologically, the tumor is most commonly an intraosseous multiloculated, radiolucent, lytic and
expansile lesion. Ameloblastoma is locally invasive with tendency to recur and metastasize. In younger
individuals, it is occasionally unicystic and radiologically well-defined. The bony wall around the
lesion is thin enough to be penetrated by a needle, rendering FNA an appropriate diagnostic procedure.
However oral tumor are easily accessible to biopsy, obviating the need for cytologic evaluation. The
radiologic differential diagnosis include non-odontogenic tumors and tumor-like conditions, giant cell
granuloma, eosinophilic granuloma, aneurysmal bone cyst, brown tumor and metastatic tumor. Extraosseous
ameloblastoma ,can also occur as a pedunculated mass in the gingival.
Histologically, ameloblastomas may display a mixture of patterns. Several patterns have been
described and include follicular and plexiform, the two most common patterns, as well as acanthomatous,
basal cell, papilliferous-keratotic, granular cell, and desmoplastic-vascular. The follicular pattern
mimics dental organ epithelium. It consists of follicles of neoplastic odontogenic epithelium with
mature fibrous connective tissue stroma containing blood vessels. The periphery of the follicles shows a
single row of columnar epithelium with palisaded nuclei polarized away from the basement membrane.
Basally located subnuclear vacuoles may be conspicuous. Some stellate-shaped cells in a loose network
are centrally placed in follicles. Squamous metaplasia in the stellate reticulum yields the
acanthomatous type. Pleomorphism or mitoses are not identified. In ameloblastoma, an ill-defined
fibrous capsule surrounding the nests may be present. Focal degeneration, with cyst formation is a
common finding. Occasional osteoclast-like giant cells may be found. By immunohistochemistry, tumor
cells exhibit keratin CK5 and 14 positivity and a continuous layer of laminin. CK 8,18, 19 are
coexpressed in the stellate reticulum and calretinin positivity in stellate reticulum is characteristic.
Granular cell ameloblastoma is S100-protein, cytokeratin and CD68 positive.
Cytologic smears of ameloblastoma characteristically contain two types of epithelial cells: basaloid
or ameloblast-like cells and squamous epithelial cells. The basaloid cells are monomorphic and arranged
in tight three-dimensional clusters with well-defined edges and peripheral palisading. The cells have
round to oval nuclei with finely dispersed chromatin and indistinct nucleoli, and minimal to moderate
amount of basophilic cytoplasm with indistinct outlines. Isolated polygonal or round bland squamous
cells with abundant refractile cytoplasm and well-defined cell borders, or small loosely cohesive
clusters of squamous epithelial cells with anastomozing cytoplasmic projections constitute the second
cell population. Eosinophilic to dense basophilic, spherical, keratinized bodies are present. These
characteristic structures show well-defined, double-contoured cell membranes and bright eosinophilic
granular cytoplasm. Mitotic figures are absent. A third cell population composed of spindle or fusiform
mesenchymal-type cells can sometimes be distinguished. In cases with significant cystic changes foamy
histiocytes and mucus debris are present in the background. The hyalinized stroma identified in the case
illustrated corresponds to the ill-defined fibrous capsule surrounding the nests of cells on histology.
The cytologic differential diagnosis includes entities that may have a basaloid cell population as
well as those with a squamous cell component. In a similar mandibular location, odontogenic keratocyst
may occur and has abundant anucleated squamous cells similar to superficial and intermediate cells of
normal stratified squamous epithelium, but lacks the basaloid cell component of ameloblastoma. Other
odontogenic tumors exhibit enamel, cementum, and/or dentin production, none of which are produced by
ameloblastoma. Ameloblastic fibroma occurs in a younger age group as a solid tumor and shows
cytologically a predominance of cuboidal epithelial cells in cohesive sheets, loose clusters and
tubules. Some fragments will have peripheral palisading and deep pink hyaline globules in the center of
some tubules. Stellate or polygonal squamous cells are not seen. Other bone lesion such as giant cell
granuloma and eosinophilic granuloma may enter the differential diagnosis radiographically, but do not
show the characteristic basaloid and polygonal cell populations of ameloblatoma and therefore have no
significant overlap in cytologic features. Giant cell tumor shows an admixture of osteoclast-like giant
cells and mononuclear stellate/spindle stromal cells and eosinophilic granuloma consists predominantly of
histiocytoid Langerhans' cells with a variable admixture of eosinophils, giant cells and histiocytes.
Because of the vicinity of this tumor primary site to the parotid as well as some of the cellular
component, salivary gland neoplasms enter the differential diagnosis. The presence of clusters of
basaloid cells brings into the differential diagnosis pleomorphic adenoma and adenoid cystic carcinoma.
Pleomorphic adenoma can be cystic and may have squamous metaplasia, two component encountered in
ameloblastoma. However, characteristically, pleomorphic adenoma comprises epithelial cells with a scant
to moderate amount of cytoplasm, in clusters with glandular features or honeycomb sheets rather than the
tightly packed basaloid cells of ameloblastoma. The stromal component of pleomorphic adenoma may become
focally hyalinized and similar to the stroma encountered in the illustrated case. Adenoid cystic
carcinoma is characterized by its metachromatic hyaline basement membrane forming spheres and cylinders
amidst discohesive basaloid cells. The stroma identified in the illustrated case is hyalinized but lacks
the distinctive large spheres and branching cylinder that are sharply contoured and demarcated from the
surrounding basaloid cells. The basaloid component of ameloblastoma more closely overlaps with the solid
variant of adenoid cystic carcinoma that usually harbors a scant stromal component. Squamous
differentiation seen in ameloblastoma is not a feature of adenoid cystic carcinoma and should help
exclude that possibility. Other basaloid tumors of the salivary gland may be considered such as
myoepithelial carcinoma or basal cell adenocarcinoma. The presence of a two cell population in
ameloblastoma, including the squamous component with the eosinophilic, spherical, keratinized bodies that
mimics mucus-containing vacuoles, and the cystic mucoid background may lead to consideration of
mucoepidermoid carcinoma in the differential diagnosis. Mucoepidermoid carcinoma consists of an
admixture of various cells including mucus secreting columnar cells, goblet cells squamous cells and
intermediate cells and typically does not include tight clusters of basaloid cells. Metastatic basaloid
squamous cell carcinoma, and high-grade neuroendocrine carcinoma have a cellular component that may mimic
the basaloid cells of ameloblastoma, however those can be excluded based on their overt malignant
appearance and features such as necrosis and nuclear molding.
Ameloblastoma is a lesion of low-grade malignant potential. It has locally invasive properties and
tendency for local recurrence. Rare distant metastases to lungs, pleura, lymph nodes and CNS have been
described. Ameloblastic carcinoma is a malignant neoplasm with architectural features of ameloblastoma
but clearly malignant cytologic features such as nuclear atypia, pleomorphism, hyperchromasia, numerous
mitotic figures and apoptosis. A firm preoperative diagnosis helps prevent suboptimal surgery.
Ameloblastoma requires complete excision with adequate margins to minimize recurrence
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