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Granular cell ameloblastoma (GCA) is a rare histologic variant of ameloblastoma characterized by the presence of granular cells, which have abundant cytoplasm filled with eosinophilic granules that resemble lysosomes. A 37-year-old male patient was referred to a maxillofacial surgery clinic with swelling in the mandible noticed 10 years earlier. Two previous biopsy results were suggestive of ameloblastoma. Intraorally, there was a nodular swelling in the right alveolar ridge involving the region of premolars and molars, and computed tomography showed an expansible and multilocular lytic lesion. Histologic examination revealed a lesion composed of fibrous stroma with cell sheets presenting extensive granular cell transformation, surrounded by peripheral ameloblast-like cells. Immunohistochemistry showed negativity for Ki-67. The diagnosis was GCA. A marginal resection of the mandible was performed, and the microscopic examination confirmed the diagnosis. The patient remains in monitoring, and the reconstruction surgery of the mandible will be held soon.

We report a case of a granular cell ameloblastoma appeared 41 years after extirpation of a follicular type ameloblastoma. A 42-year-old woman underwent segmental resection of the right side of her mandible without mandibular reconstruction in 1964. The postoperative course has been uneventful until an otorhinolaryngologist found her right cheek swollen and referred her to us on February in 2005. A fine needle aspiration biopsy revealed the presence of granular cells in the sample. As the radiographic feature implied the recurrence of the previous ameloblastoma, we removed the lesion. The enucleated tumor (4.5 cm × 3.2 cm × 3.3 cm) was a cystic lesion that was encapsulated by a brown fibrous tissue and contained serous fluid. Microscopically, the lesion contained tumor nests consisted of numerous granular cells and some stellate cells, and each nest was surrounded by tall columnar cells. Immunohistochemistry for Ki-67, CD68, α1-antichymotrypsin, cytokeratin, S-100 protein, and p53 was performed on the specimens from both the primary and the recurrent lesions: the incidence of Ki-67-positive nuclei in the recurrent lesion was 5.1%, while that in the primary lesion was 0.5%. Besides, positive signals of both CD68 and α1-antichymotrypsin, indicative of phagocytosis, were broadly localized within tumor cells in the recurrent lesion. Taken these observations together, we assume that the extremely low proliferative potential of the primary tumor cells together with change to granular cells related to apoptosis might cause the tardy growth of the recurrent tumor after the initial tumorectomy.

Granular cell odontogenic tumours (GCOT) are rare neoplasms that usually manifest a benign clinical behaviour. We document the first case of GCOT exhibiting clinico-pathological features of malignancy that occurred in the maxilla of a 40-year-old male. The lesion appeared as an intra-oral polypoid mass and, at CT scan, as a poorly demarcated radiolucency eroding the cortical plate. Histologically, the tumour consisted of clusters of granular cells, exhibiting nuclear pleomorphism, prominent nucleoli and mitotic figures, and spindle cells in a collagenous stroma containing cementicles and strands of odontogenic epithelium. Morphologic transition from fibroblast-like to granular cells was frequently detected. The tumour cells extensively invaded the oral and respiratory mucosae and the adjacent soft tissues and exhibited vimentin and CD 68 immunoreactivity and high (21%) Ki 67 immunolabeling but not cytokeratins, E.M.A. actin, desmin, myosin or S-100 protein positivity. The patient experienced tumour recurrence 16 months after radical surgery. While the histogenesis of GCOT remains to be clarified, we document the existence of a malignant counterpart of this tumour and propose the name of malignant GCOT or granular cell odontogenic sarcoma for such entity.

SUMMARY Granular cell ameloblastoma is characterized by nests of large, eosinophilic granular cells. These latter have long been the subject of debate. Two cases of granular cell ameloblastomas have been immunocytochemically stained with a panel of antibodies against human mitochondria, S-100 protein, CD 68, low molecular weight cytokeratins, chromogranin, laminin, vimentin, PCNA, bcl-2 and p-53. Granular cells exhibited a membranous positivity with cytokeratins while the non granular cells ofthe same tumors showed a diffuse cytoplasmic reactivity. Moreover, granular cells showed marked cytoplasmic positivity with CD68 antiserum only while human mitochondria, as well as S-100 protein antisera, were consistently negative. PCNA, bcl-2 and p-53 did not stain the granular cells. These results allow easy distinction of granular cell ameloblastomas from similar tumors exhibiting granular cell changes and indicate that the granularity in ameloblastoma cells is consequent to lysosomal overload.

Plexiform granular cell odontogenic tumor of the mandible has recently been described. The cardinal histopathologic feature, as its name suggests, is a monophasic plexiform pattern of granular cells; the principal tumor in the differential diagnosis is granular cell ameloblastoma. Unlike the two previously reported cases of plexiform granular cell odontogenic tumor, which occurred as solid tumors in elderly men, the lesion reported here is a unicystic variant occurring in a middle-aged woman.

A case of granular cell ameloblastoma (GCA) was studied by light microscopy and histochemistry. Microscopically, the lesion showed small groups or large clusters of granular neoplastic cells, with pyknotic and hyperchromatic nuclei, oriented away from the basement membrane, in a back-to-back arrangement. The “granular change” is thought to be due to a dysfunctional status of neoplastic cells, and the pathogenesis of this tumour seems to be age-related. The prognosis of GCA is good, generally corresponding to that of the classical ameloblastoma; as yet, only one case has been described with a more aggressive biological behaviour (high recurrence rate).

This report is a follow-up of the original case of granular cell odontogenic cyst described by Gold and Christ in 1970. The lesion, originally treated by enucleation in 1965, recurred 18 years later as a follicular ameloblastoma with prominent plexiform and acanthomatous histologic patterns. No histologic evidence of granular cells was noted in the recurrent lesion. The recurrent ameloblastoma was treated by marginal resection of the body of the mandible and immediate reconstruction with an iliac bone graft. The anatomic restoration was excellent, and there is no recurrence 5 years postoperatively. This case supports the view that the granular cell odontogenic cyst is a unicystic (monocystic) granular cell ameloblastoma, and that the presence of granular cells in ameloblastoma is not a permanent feature and may be of little value as a prognostic indicator of aggressiveness.

To investigate the histogenesis of the granular cell, a large series of granular cell tumors was studied for clinical and histopathologic features with emphasis on immunocytochemical markers. The nongingival granular cell tumors (NGGCT) were found to be more prevalent among females than males by a ratio of 2:1 and arose on the tongue (67%), the buccal mucosa (13%), the lips (8%), the soft palate (6%), and other sites (6%). With the use of the avidin-biotin-peroxidase method, polyclonal rabbit antisera were employed. The antisera were directed to the following antigens: S-100 protein, myoglobin, myosin, actin, desmin, alpha-1-antitrypsin, and muramidase. Results indicated that granular cell tumors are not homogenous for immunocytochemical markers. Nongingival granular cell tumors were universally positive for S-100 protein and failed to exhibit immunoreactivity for myogenous or histiocytic markers. Alternatively, the gingival granular cell tumor of infancy was negative for all markers, whereas rhabdomyoma was reactive with myogenous markers and a subpopulation of tumor cells displayed S-100 protein immunoreactivity. The granular cell ameloblastoma was reactive only with antiserum to alpha-1-antitrypsin. Ultrastructurally, granular cells from one of two NGGCT showed a direct evolution from skeletal muscle fibers. It is concluded that the oral NGGCT is a tumor positive for S-100 protein that may arise from muscle or nerve sheath.

A rare type of ameloblastoma has been discussed. This tumor is of special interest because of our lack of knowledge of cellular changes consistent with granular cells and “ghost” cells. These specific cellular changes warrant a special place for this tumor in the general classification of ameloblastomas.

Two cases of an unusual odontogenic tumor have been presented. Both lesions were considered to be ameloblastic fibromas with extensive granular-cell change in the mesodermal component. The patients were considerably older than the typical patient with ameloblastic fibroma. We suggest that the granular-cell alteration in the mesodermal component represents an aging or degenerative response in the lesion. These lesions possibly are related to the granular-cell congenital epulis. The granular-cell ameloblastic fibroma appears to be a quite benign lesion, and curettage is probably sufficient for cure.