Ⅰ. INTRODUCTION

Fibrous histiocytoma is characterized as a mixed proliferation of fibroblast-like and histiocyte-like cells, rarely showing characteristics of malignant tumors, in which case it is referred to as a malignant fibrous histiocytoma (MFH) [1]. The term MFH has recently been changed to undifferentiated pleomorphic sarcoma (UPS) as it exhibits similar morphologic patterns to those of other types of sarcoma [2]. UPS has been reported to occur in the limbs and in the retroperitoneum, and the incidence of UPS in the mandible has been reported to comprise 3% of all UPS cases [3]. UPS in the mandible is common among men aged between 50 and 79, and clinical symptoms include pain that has spread over a period of several weeks or months. UPS that invades hard tissue in the head and neck region exhibit considerably more aggressive characteristics than UPS localized to the soft tissues [4]. In general, UPS has a poor prognosis, since it exhibits chemoresistance as a high-grade sarcoma occurring in soft and hard tissues, and also exhibits a high metastatic potential [5]. However, previous studies have shown that UPS in the mandible has a more favorable prognosis due to smaller size and lower grade compared with UPS in the trunk and extremities [6]. Here, we report on the case of a patient diagnosed with a DBFH following a pre-operative incisional biopsy performed on a tumor that had developed in the right mandible area. The diagnosis was then changed to a UPS, based on post-operative biopsy results, and the patient underwent follow-up radiation therapy, and a second operation due to recurrence. This study analyzes the treatment process, progress, and characteristics from the time of diagnosis to recurrence.

Ⅱ. CASE REPORT

This case report was reviewed by the Institutional Review Board (IRB) of Samsung Medical Center and was approved from deliberation (SMC 2018-06-047). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A 23-year-old Korean woman with no history of systemic disease visited a hospital due to masticatory pain present for three months in the right jaw and was admitted to the present institution in January 2015. On examination, no malocclusion was observed, and evaluation of the face revealed that the right facial area was noted to be slightly larger than the left side (Fig. 1A). Preoperative computed tomography (CT) scans showed medial cortical bone resorption in the right mandibular ramus, and expansion of the lateral cortical bone. A 5.3-cm sized malignant tumor with signs of invasion in most condyles was also found. Magnetic resonance imaging (MRI) (T2) showed a soft tissue tumor invading the nearby masticator and parotid space (Fig. 1B). An incisional biopsy was performed on lymph nodes within the soft and hard tissues of the lesion, submaxillary gland, and parotid gland, using a transparotid approach prior to surgery. Biopsy results showed no signs of malignancy, and the patient was diagnosed with a deep benign fibrous histiocytoma (DBFH) (Fig. 1C).

Mass excision was performed on the benign tumor at the present institution in March, 2015, in addition to reconstruction of the ramus condyle unit using a costochondral graft. No significant changes to the face, functional loss, or complications occurred postoperatively (Figs. 2A, 2B).

However, the patient was diagnosed with UPS (French Federation of Comprehensive Cancer Centers [FNCLCC] grade 2/3) based on the final biopsy results of the main mass postoperatively (Fig. 2C). A tumor was found around the specimen margin. Accordingly, 27 radiotherapy sessions were performed using a radiation dose of 64 Gy for the tumor margin, and a dose of 54 Gy for the tumor bed postoperatively. Positron emission tomography-computed tomography (PET-CT) scans obtained after the completion of radiotherapy showed reduced uptake in the condylar area (Fig. 3).

From May 2015 to December 2017, no signs of recurrence were observed during this follow-up period. However, panoramic radiographs obtained in December 2017 showed patterns of bone resorption in the right condyle head. CT and PET examinations were performed accordingly, and signs of recurrence were observed (Fig. 4).

The costal cartilage implanted on the existing reconstruction plate and the tumor were removed in January, 2018, and mandibular reconstruction using a scapular free flap was performed (Fig. 5A). The resected tumor was diagnosed as UPS (FNCLCC grade 2/3) based on biopsy results. Although there was premature contact in the left posterior molar region in the early postoperative period, the patient currently has stable occlusion. No recurrence or unusual signs in the lymph nodes and satisfactory bone healing at the graft site have been observed on CT scans obtained in May 2018, and the maximum mouth opening has been maintained at 30 mm (Figs. 5B,C).

Ⅲ. DISCUSSION

UPS, as its name suggests, is a soft mass sarcoma whose origin or differentiation cannot be defined, and which cannot be classified according to its site of occurrence [2]. UPS does not show clinical characteristics of other types of sarcoma, and exhibits widespread pleomorphism, and spindle cells in terms of histological characteristics, as well as poor tissue differentiation [7]. The characteristics of UPS are similar to those of metastatic carcinoma or melanoma [8], and it is morphologically similar to histiocytes or fibroblasts due to its elongated shape. DBFH is a benign fibrous histiocytoma that is usually observed in the subcutaneous tissues or deep soft tissues, and it almost never metastasizes to other tissues [9]. According to the World Health Organization classification, DBFH is a benign tumor belonging to a group of fibrohistiocytic tumors, and usually occurs in the upper and lower limbs, and rarely in the oral and maxillofacial area [10,11]. Its indolent nature and tendency to grow are characteristics similar to those of cysts, and its histological structure resembles that of a storiform pattern [12]. Similar characteristics were observed in the first biopsy performed in this study. The first biopsy, performed using the transparotid approach, showed no signs of malignancy or invasion into bone tissues from the lymph nodes within the soft tissue, submandibular duct tissues, and parotid gland. The characteristic DBFH storiform pattern was observed in the soft tissues and there were no unusual findings observed following immunohistochemical staining (Fig. 1C). Based on these results, the patient was diagnosed with DBFH, and surgery was performed. The resection site was limited to the benign tumor, which was the main reason for including the tumor in the resection margin. The tissue resected during the first surgery exhibited heterogeneity, showing various histological characteristics. In one region of the tumor, hyperchromatic multinucleated cells clustering in a storiform pattern were observed. In another part, cells with increased pleomorphism could be observed. These cells did not form a particular structure, and it was difficult to identify their origin histologically, suggesting the tumor had poor differentiation. In addition, tumor giant cells that are characteristically observed in malignant tumors could be observed. Immunohistological chemical staining gave negative results in most tests, indicating that the tumor had poor differentiation, and locating its origin would be difficult (Figs. 2C,D,E,F). According to the FNCLCC grading system, the tumor’s differentiation was graded as score 3, mitotic count as score 2, and tumor necrosis as score 0. The total score was 5, and the tumor was classified as Grade 2. In a UPS case reported by Kim et al. [13], tumor resection was performed in a 44-year old male patient with UPS that had occurred in the left mandible, followed by immunohistochemical staining of the resected tissue. The resected tissue showed reactivity to vimentin, unlike the tumor in the present study. While the origin of the tumor in this study could not be identified, it could be deduced that the aforementioned tumor originated from mesenchymal cells. A possible reason for the difference in the results of the first histological examination, and those of the final histological examination performed postoperatively, is that in the first examination, the tissue samples were collected from areas exhibiting some characteristics of a benign tumor only and, therefore, the results were considered to apply to the entire tumor. In a case report by Tanaka et al. [14], an 80-year-old male patient underwent an excisional biopsy for a tumor that had developed in the right mandible, and the patient was eventually diagnosed with a benign fibrous histiocytoma. However, a second surgery was performed due to recurrence 6 months postoperatively, and the patient was diagnosed with UPS after a final biopsy. The recurrent lesion showed reactivity to CD68, alpha-1-antitrypsin, alpha-1-antichymotrypsin, and vimentin. This supports the view that DBFH can change to UPS, and therefore, a lesion can demonstrate characteristics of both DBFH and UPS concurrently. In this study, the tumor was found to be included in the resection site after the first surgery, and radiotherapy was performed accordingly to reduce the risk of local recurrence, and prevent an increase in the extent of surgery [15]. It is controversial whether chemotherapy is necessary for UPS. In this study, chemotherapy was not undertaken as clear therapeutic benefits were difficult to determine. However, studies have recently reported that chemotherapy can be effective in the treatment of UPS [5, 16]. However, UPS recurred at the same site within three years post-treatment. In this study, the first surgery was performed conservatively, and the second surgery involved extensive resection of the lesion and surrounding tissues (Fig. 5A). The tumor showed even clearer characteristics of malignancy in the biopsy performed after the second surgery. Clear signs of bone invasion were observed on hematoxylin and eosin (H&E) staining slides, and the tumor exhibited abnormal mitosis and moderate pleomorphism (Figs. 5D,5E). Signs of tumor invasion in the mandibular cortical bone were observed, as well as invasion in the lateral pterygoid muscle. The tumor signs indicated a grade 2/3 tumor, using the FNCLCC grading system. No metastases in the lymph nodes were observed and the resection margin was clear. DBFH and UPS are both rarely located in the oral and maxillofacial area. Identification of UPS in the mandible is common among men over the aged of 50 years; however, it can also occur in young women. Often, DBFH can become malignant, and early histological examinations of UPS can exhibit signs of a benign tumor. Therefore, it is necessary to refer to medical images and clinical progress, as well as pay close attention to diagnosis and treatment methods, and thoroughly and consistently monitor the treatment process.