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Malignant ossifying fibromyxoid tumor of the tongue: case report and review of the literature
© Ohta et al.; licensee BioMed Central Ltd. 2013
Received: 28 December 2012
Accepted: 30 May 2013
Published: 24 June 2013
Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm that arises in subcutaneous tissue, with that in the oral cavity extremely rare. We present a case of malignant OFMT in the tongue. A 26-year-old male noticed a painless mass in the tongue, which was extracted at a general hospital. Four years later, the tumor recurred and was resected at our department. Histologically, the recurrent tumor was composed of the closely packed cells positive for vimentin and S-100 proliferating in a nodular fashion. It showed high cellularity and mitotic activity. In the primary tumor, some tumor cells were arranged in a diffuse or cord-like manner within an abundant fibromyxoid matrix, along with a small amount of metaplastic ossification, corresponding with the histopathological characteristic of OFMT. Accordingly, a diagnosis of malignant OFMT arising in typical OFMT was established. This is the first reported case of malignant OFMT in the tongue. Long-term follow-up is needed for confirmation of prognosis and biological behavior.
Ossifying fibromyxoid tumor (OFMT) is an uncommon soft tissue neoplasm of uncertain origin, that is composed of relatively uniform round to ovoid cells often arranged in a corded or trabecular pattern and embedded in a fibromyxoid matrix [1–3]. In addition, a band of dense collagen with spicules of metaplastic bone is commonly encountered at the tumor periphery [1, 2].
OFMT mostly arises in subcutaneous tissue or skeletal muscle of the extremities, while it has been reported at other sites, such as the trunk, head and neck, mediastinum and retroperitoneum at low frequency [1, 2, 4–6]. However, this tumor located in the oral cavity is extremely rare [2–4, 7–9], with no cases of OFMT arising in the tongue previously reported.
OFMTs are presented as a slow growing painless, well-defined mass, and generally regarded as benign. Although most reported cases were cured by local excision, local recurrence rates ranging from 20% to 27% have been reported. In recent years, it was emphasized that a subset of OFMTs with conventional morphology displays atypical cytoarchitectural features, such as high cellularity or elevated mitotic activity and shows correspondingly more aggressive clinical behavior, which is called as atypical or malignant OFMTs [10, 11]. We present a case of malignant OFMT arising in primary typical OFMT of the tongue.
A 26-year-old male was referred to an otolaryngology at a general hospital in August 2003, because he became aware of a painless mass in the dorsal tongue before two weeks ago. The mass was a hard, smooth and 7 mm diameter, and was resected with narrow safety margin as diagnosis of a benign mesenchymal tumor. The histological diagnosis was chondromyxoid tumor, which is unusual, but that was not finally confirmed. After 4 years, he noticed a painless, mass gradually increasing in the same part, and consulted our oral and maxillofacial surgery clinic in January 2007.
Primary antibodies used in the analysis of OFMT
Source of antibody
Dako Cytomation, Carpinteria, CA
Invitrogen, Carlsbad, CA
Becton Dickinson, Frankin Lakes, NJ
Nichirei Biosciences Inc, Tokyo, Japan
Reported cases of ossifying fibromyxoid tumor in the oral cavity
N / D
N / D
N / D
N / D
N / D
N / D
N / D
N / D
Between buccal and gingival mucosa
Less than 2/10 HPFs
N / D
N / D
N / D
N / D
N / D
N / D
N / D
N / D
N / D
N / D
0-1 / 10 HPFs
N / D
N / D
N / D
0-11 / 10 HPFs
N / D
N / D
Reddish, lobulated surface
Painless, firm, reddish, lobulated surface
More than 2/10 HPFs
Clinically, OFMT is usually presented as a slow growing painless mass. It is most common in the fifth to seventh decades of life, with male predominance [1, 2]. The masses are usually less than 10 cm in diameter [1, 2]. However, Harris et al. reported 9 cases of giant OFMTs, which had diameters greater than 10 cm . Most of OFMT occurring in oral cavity range in the size from 60 mm to 10 mm (Table 2), which was also seen in the present case .
Microscopically, OFMTs are composed of uniform round, ovoid or spindle-shaped cells arranged in nests and cords with fibromyxoid stroma partially surrounded by shell of mature bone. Immunohistochemical findings have revealed that 74% of these tumor are positive for vimentin and 94% positive for S-100 protein [1, 2], features consistent with neural crest lineage or cartilaginous differentiation. The primary tumor in the present case showed the characteristics of OFMT. The mitotic activity and nuclear grade were low, although the areas exhibiting hypercellularity were mixed. The recurrent tumor maintained the morphological features of OFMT, but was composed of closely packed cells with higher cellularity and mitotic activity in spite of inconspicuous cell atypia and lacked bone or osteoid formation. Clinicopathologic study of 70 cases of OFMT by Folpe indicated that the tumors having 1) high nuclear grade or 2) high cellularity and mitotic activity >2 mitotic figures/50HPF have a substantial risk of metastasis . The histological features of the recurrent tumor are consistent with those of malignant OFMT. After revealing the features of the primary tumor, the recurrent tumor was finally diagnosed as malignant OFMT arising in typical OFMT. In 15 cases of malignant OFMTs reported by Graham et al., malignant foci could be identified in subsequent local recurrences of initially typical OFMTs . The percentage of the cases with bone formation in malignant OFMT is low (47%) than that in typical one (60%).
Awareness of OFMT occurring in the oral cavity is important to avoid confusion with other tumors with a fibromyxoid matrix. Differential diagnosis of OFMT in the oral cavity includes myoepithelioma and ectomesenchymal chondromyxoid tumor (ECT) of the anterior tongue. The absence of epithelial and myoepithelial markers excludes myoepithelioma as a diagnostic consideration. ECT is an extremely rare benign tumor that usually arises in the submucosa of the anterior dorsum of the tongue. Its histogenesis is unclear, though it is possibly derived from undifferentiated ectomesenchymal progenitor cells that have migrated form the neural crest. ECT is composed of round, fusiform or polygonal cells with a chondromyxoid matrix, resembling the features of OFMT. However, the tumor cells of ECT strongly express GFAP, which is different from the immuno-profile of OFMT. Furthermore, ECT lacks bone and osteoid formation. The line of differentiation of OFMT remains controversial. Graham et al. described that expression of neuron-related markers, in addition to Schwann cell and cartilage-associated markers, suggests a “scrambled” phenotype in this tumor.
Genetic studies on OFMT are limited. Graham et al. suggested that OFMT develops primarily through inactivation of the SMARCB1 (also known as INI-1 or SNF5) gene in chromosome band 22q11 . Furthermore, gene expression profiling showed typical and malignant OFMTs to cluster together. Whereas, Gebre-Medhin et al. reported that the pathogenetic basis of OFMT frequently involves rearrangement of the PHF1 gene, suggesting that epigenetic deregulation of PRC2 target genes is crucial for tumor development regardless of types such typical, atypical and malignant . Therefore, cytogenetic assay and FISH tests for reaarangment of these genes may be useful diagonstic tools in ambiguaous cases of OFMT.
In the series of Graham et al., all patients with typical and atypical OFMT were alive without local recurrence and metastasis, but adverse events were seen in 33% of patients with malignant OFMT, including 2 patients with local recurrences, 3 patients with distant metastases, and 3 deaths from disease . Therefore, careful follow-up examinations will be mandatory for the present patients.
We present the first reported case of malignant OFMT with recurrence arising in typical OFMT of the tongue. In the primary tumor, some tumor cells were arranged in a diffuse or cord-like manner within an abundant fibromyxoid matrix, along with a small amount of metaplastic ossification, corresponding with the histopathological characteristic of OFMT, whereas the recurrent tumor was regarded as a malignant OFMT because of increased cellularity and mitotic activity. Therefore, long-term follow-up is needed for confirmation of the biological behavior.
The authors declare that the patient had given consent for the case report to be published.
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