A Rare Pathology: Low-Grade Fibromyxoid Sarcoma of the Maxilla

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Sarcoma of the Maxilla

Simon Spalthoff, MD, DDS,*Martin Bredt, MD,yNils-Claudius Gellrich, MD, DDS,z and Philipp Jehn, MD, DDSx

Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a benign histologic appearance and fully malignant behavior. To date, only 5 cases of LGFMS in the maxillofacial region have been reported. This report describes the case of a 16-year-old boy who was referred to the authors’ hospital with an intraoss- eous myxofibroblastic tumor, probably of the LGFMS type, of the right maxilla. Radical resection with wide safe margins and secondary reconstruction with a free forearm flap were performed. Six-month follow-up showed no sign of recurrence or metastasis. The authors review the scientific literature and discuss different tumor locations and treatment strategies for those in the maxillofacial region. The present case is the sixth reported case of LGFMS in the maxillofacial region (intraosseous LGFMS of the maxilla), adding another facet to the literature regarding this rare soft tissue tumor.

Ó 2016 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 74:219.e1-219.e10, 2016

Low-grade fibromyxoid sarcoma (LGFMS) is an extremely rare tumor first described by Evans1 in 1987. To date, only 5 cases (Table 1) have been reported in the maxillofacial region.2-6 LGFMS presents a deceptively benign histologic appearance and very indolent, but fully malignant behavior. The tumor shows a prolonged clinical course with a late median recurrence of 3 years, but some recurrences have been noted up to 15 years later. In addition, metastases occur after a median of 5 years, with some reported as emerging as many as 45 years later.7The pri- mary tumor usually affects the extremities and trunk, whereas metastases occur mostly in the lungs.3There are currently 4 types of low-grade fibrosarcoma, namely LGFMS, hyalinizing spindle-cell tumor with giant collagen rosettes (HSCT), sclerosing epithelioid fibro- sarcoma, and fibrosarcoma not otherwise specified (adult fibrosarcoma). Some investigators also have mentioned dermatofibrosarcoma protuberans and fibrosarcomatous dermatofibrosarcoma protuberans as clinically, morphologically, and genetically distinctive subtypes.1,8-11 However, the differential diagnosis of fibrous or myxoid soft tissue neoplasms is broad and often difficult because many neoplasms have

overlapping histologic features. Cytogenetic analysis, such as fluorescence in situ hybridization (FISH) to identify a FUS gene rearrangement, can provide additional information.4,12 This report describes the case of a 16-year-old boy with LGFMS of the right maxilla. Initially, the lesion was diagnosed as a craniofa- cial osteosarcoma, but the reference pathology pro- vided a definitive diagnosis of an aggressive myxofibroblastic tumor, probably of the LGFMS type.

Report of Case

A 16-year old boy was referred to the authors’ hospi- tal in July 2014 with the histologic diagnosis of an aggressive intraosseous myxofibroblastic tumor, prob- ably the LGFMS type, of the right maxilla. A biopsy examination had been conducted previously by an oral and maxillofacial surgeon at a private practice based in Basel, Switzerland. Histologic examinations were conducted by numerous pathologists, reflecting the difficulties in providing a correct diagnosis for the present case. Then, pathology provided the definitive diagnosis described earlier. Pathology showed tumor cells growing in nests surrounded by a partly spindle

Received from the Hannover Medical School, Hannover, Germany.

*Consultant, Department of Oral and Maxillofacial Surgery.

yConsultant, Department of Pathology.

zProfessor and Department Head, Department of Oral and Maxillofacial Surgery.

xConsultant, Department of Oral and Maxillofacial Surgery.

Address correspondence and reprint requests to Dr Spalthoff:

Department of Oral and Maxillofacial Surgery, Hannover Medical

School, Carl-Neuberg-Str 1, 30625 Hannover, Germany; e-mail:

spalthoff.simon@mh-hannover.de Received July 20 2015

Accepted September 16 2015

Ó 2016 American Association of Oral and Maxillofacial Surgeons 0278-2391/15/01286-0




cell-like and partly myxoid stroma. Some cells were eosinophilic and others showed clear cell-like cyto- plasm. Many mitoses were observed, with some atyp- ical mitotic figures. Immunohistochemically, the tumor cells were positive for vimentin and weakly pos- itive for CD117, but negative for smooth muscle actin, CD31, CD34, S100, and desmin. The Ki-67 prolifera- tion index was 10 to 20%. FISH was positive for the FUS gene rearrangement, and cells showed strong and continuous expression of SOX9 and TFE3. In sum- mary, the tumor could not be classified without doubt.

Physical examination showed mild swelling of the right upper lip and some intraoral scarring in the vestib- ular region as a result of the previous biopsy examina- tion (Fig 1). The patient reported that his clinical symptoms before the biopsy examination were quite mild; he had some swelling and the sensation of pres- sure. A panoramic radiograph showed a slight rotation of the upper right second incisor and the upper right canine with some loss of bone density (Fig 2).

The patient underwent computed tomography (CT) of the head, neck, and thorax, which showed an osseo- destructive tumor of the right maxilla of approxi- mately 3 cm in diameter with no signs of metastases (Fig 3). Excision of the entire tumor, including the sur- rounding soft tissue and teeth from the upper right first molar to the upper left second incisor, was planned. After admission to the hospital in August 2014, magnetic resonance imaging of the head and neck visualized an irregular, contrast-enhanced tumor in the right maxilla that breached the bone and infil- trated the sinus, subcutis, and nasal floor. However, pathologic lymph nodes were not found (Fig 4). The patient was placed under general anesthesia and the tumor was resected en bloc without macroscopic exposure of the tumor (Fig 5). The nasal floor and lateral wall of the sinus were included in the resection.

There were no surgical complications. The defect was obliterated with a tamponade and a temporary screw- fixed prosthesis was fitted at the left maxilla (Figs 6, 7).

A final pathologic examination conducted at the end of August confirmed complete resection of the tumor (pT1bR0). It was described as a spindle cell tumor that was partly myxoid and partly fibrous, with some nuclear pleomorphism (Figs 8-10), and denoted as probably being LGFMS. Surprisingly, unlike the initial biopsy specimen, FISH of the resected specimen did not show a FUS gene rearrangement. In September 2014, the defect was successfully closed and reconstructed using a free lower arm flap from the left side (Figs 11, 12). The patient recovered quickly from the surgery and did not show any signs of an oroantral fistula or infection of the maxillary sinus after 6 months. Clinical and radiologic follow-up at 6 months showed no evidence of recurrence or metastasis.

Ethical approval was not required. All guidelines of the Declaration of Helsinki were followed in this investigation.


A long-term follow-up of 33 LGFMS cases described histologic findings of contrasting fibrous and myxoid zones, bland regular spindle cells, moderate to low cellularity, and slight nuclear polymorphism.7 Histo- logically, the present case presented with all these characteristics. In 2003, Storlazzi et al12 identified a novel gene fusion involving FUS and BBF2H7 in 2 pa- tients with LGFMS, which was the first cytogenetic characterization of this rare tumor entity. Reid et al13 found another fibrosarcoma with this mutation, the HSCT, and they suggested that LGFMS and HSCT were variations of the same entity. Furthermore, in a retrospective analysis of 19 patients with LGFMS, Rose et al14found the FUS and BBF2H7 mutation in approximately 82% of cases. They suggested that FISH of the FUS and BBF2H7 mutation was a sensitive diagnostic tool for LGFMS, but that it had no role in predicting the medium-term clinical outcome. Howev- er, the proportion of LGFMS cases positive for this



Size (cm) Treatment Follow-Up Reference

1 4 Male Mandible 4 Curettage LR at 3 mo, lung

metastasis at 160 mo


2 4 Female Mandible Unknown Resection LR at 24 mo 4

3 57 Female Parotid gland 17 Resection,


NED at 36 mo 6

4 2 Male Cheek 8 Resection NED at 6 mo 3

5 14 Male Cheek 8 Resection NED at 6 mo 2

6 16 Male Maxilla 3 Resection NED at 6 mo Present case

Abbreviations: LR, local recurrence; NED, no evidence of disease.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.



mutation varies considerably, with some suggesting a frequency of 20%,15,16whereas others have reported frequencies of 80 to 95%.14,17,18 In summary, the FUS and BBF2H7 mutation might be an important diagnostic marker, but its consequence on clinical

outcome remains unclear and warrants further study.19In the present case, the FUS and BBF2H7 mu- tation was found by the physicians in Basel; however, the pathologic analysis at the authors’ hospital did not detect the FUS and BBF2H7 mutation.

FIGURE 1. Intraoral photograph shows preoperative situs (arrow, scar from biopsy excision).

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 2. Preoperative panoramic radiograph.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.


FIGURE 3. Computed tomogram shows the osseo-destructive tumor of the right maxilla with an approximate diameter of 3 cm (arrows).

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 4. T1-weighted fat-suppressed magnetic resonance image with contrast agent shows the tumor with high contrast and extraosseous growth (arrows).



In 1996, Papadimitriou et al5reported the first case of LGFMS in the maxillofacial region in a 4-year-old boy who presented with swelling of the left side of the mandible. The tumor was curetted and histologically diagnosed as fibromyxoma. Microscopically, the tumor showed a predominantly lobular pattern of growth, and the lobes were composed of spindle-like cells

embedded within mucinous or collagenized stroma;

different degrees of cellularity and cells with pale intra- nuclear eosinophilic inclusions completed the pic- ture, and the tumor cells stained positive for vimentin. Three months later, the patient showed clin- ical and radiologic evidence of recurrence and under- went radical resection of the mandible. At 15 years

FIGURE 5. Intraoral photograph of intraoperative defect.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 6. Intraoral photograph of postoperative immediate reconstruction with prosthesis.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.


postoperatively, there was evidence of further recur- rence in the mouth floor and of a circumscribed lung nodule. These were resected, and the patient received radiation therapy. The patient remained free of disease for 2.5 years.

In 2008, Wu et al4reported the case of a 4-year-old girl who was admitted to their hospital in 2000 for a head injury. In addition, she presented with a nodule at the left angle of the mandible that was initially believed to be a lymph node. After excision, histology

FIGURE 7. Postoperative panoramic radiograph shows the intraosseous screw (arrow) holding the temporary prosthesis.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 8. Fibromyxoid sarcoma (**) growing in the maxillary bone (*) (hematoxylin and eosin stain; magnification, 100).



showed LGFMS with margin involvement. Microscop- ically, the tumor showed fibrotic and myxoid areas with variable cellularity. The tumor cells stained posi- tive for vimentin and epithelial membrane antigen;

re-excision was not performed. In 2002, the patient presented with local recurrence and a radical excision

with a clear margin was performed. The patient remained free of disease for 5 years.

In 2006 Botev et al6 reported on a 57-year-old woman with a massive tumor of the left parotid gland.

The fine-needle aspiration (FNA) biopsy finding was compatible with sarcomatous tissue. After complete

FIGURE 9. Histopathologic features of the tumor with fibroid (**) and myxoid (*) areas (hematoxylin and eosin stain; magnification, 400).

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 10. Ki-67 expression (10% positive cells) from immunohistochemical staining with MIB-1 (magnification, 200).

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.


resection of the tumor, the final histopathologic analysis confirmed LGFMS. Microscopically, the tumor consisted of fibrous and myxoid tissue with variable cellularity. The fibrous component had

spindle cells with a linear arrangement producing swirling growth patterns; the myxoid areas presented spindle- to stellate-shaped cells with an abundant intercellular matrix. Postoperative radiotherapy was

FIGURE 11. Intraoral photograph shows soft tissue reconstruction with radial forearm flap.

Spalthoff et al. Low-Grade Fibromyxoid Sarcoma of the Maxilla. J Oral Maxillofac Surg 2016.

FIGURE 12. Postoperative T1-weighted fat-suppressed magnetic resonance image shows the defect with the radial forearm flap (arrows).



conducted, and the patient remained free of disease for 36 months.

Tang et al3published the case of a 2-year-old boy who presented with a slowly growing mass of the right cheek. CT depicted a large, well-circumscribed tumor that entirely filled the right temporal, infratemporal, and buccal spaces. After complete resection, the tumor was classified as LGFMS. At 6 months postoper- atively, the boy showed no evidence of disease.

In 2013, He et al2reported on a 14-year-old boy who presented with swelling of the right cheek that had been growing for 6 months. Four months previously, an FNA biopsy specimen had been misinterpreted as a lymphatic venous malformation and the patient was treated by injection of OK-432. Afterward, the tumor enlarged rapidly; therefore, complete excision was performed under general anesthesia. The histolog- ic and immunohistochemical examination confirmed a diagnosis of LGFMS. The patient was free of disease at 6 months postoperatively.

All these cases showed the typical clinical and patho- logic signs of LGFMS as described by Evans.1LGFMS ex- hibits a wide range of histologic appearances, which somehow do not relate to tumor behavior and patient survival.1,7,20 Surprisingly, in all these case reports, cytogenetic analyses were not presented. Because the FUS gene mutation seems to provide strong evidence for LGFMS, it would be interesting to examine these cases retrospectively. Until then, some differential diagnosis-related doubt remains, especially because other fibrous or myxoid soft tissue neoplasms have overlapping histologic features.4,8-10,21,22

The treatment strategy, as shown in this study, varies considerably, and long-term follow up is widely recom- mended because local recurrence and distant metasta- ses are observed frequently, even many years after the primary diagnosis. There are no data concerning patient survival that show the benefit of radical tumor resection, although radical resection is recommended by most sur- geons as the treatment of choice. The role of adjuvant chemotherapy or radiotherapy remains unclear, but seems to have no real benefit for the patient.3,19,20,23,24

In conclusion, this report has described a case of an intraosseous LGFMS of the maxilla, adding another facet to the colorful clinical picture of this rare soft tis- sue tumor. In accordance with most studies and after extensive staging without signs of metastases, the au- thors performed a radical tumor resection with safe margins. They have scheduled close follow-up for the patient and hope that he remains free of disease.


The authors offer their gratitude to their colleagues in the Pathol- ogy Department at the University of Basel (Basel, Switzerland) for providing the initial histopathologic analysis.


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