This case shows the challenging diagnostic and therapeutic decisions of a low-grade malignant spindle cell tumor with similarities to benign, reactive or other malignant tumors. After clinical and radiological examination, benign and malignant lesions were both possible. The differentials considered were a giant cell lesion of the jaw (GCLJ), a myofibroma, a nodular fasciitis, a squamous cell carcinoma, a lymphoma, or a metastasis. The presence of a rare tumor was also discussed. The quite well demarcated firm soft tissue mass had the appearance of a benign process, whereas its fast growth in conjunction with bony destruction and mobility of a single tooth were typical signs for malignancy. This clinical discrepancy of a possible benign or malignant lesion reinforced the importance of a biopsy. However, the histopathologic diagnosis was particularly difficult in the present case.
A common oral GCLJ is the peripheral giant cell granuloma (PGCG) or so-called giant cell epulis. Trigger factors such as dental trauma or local irritation such as chronic infections, dental plaque or food impaction as well as poorly adapted margins of restorations or orthodontic therapy have been discussed [3, 6]. Erosion of the adjacent alveolar bone has been described, but the presence of a crater-like osteolytic lesion in the radiograph was not typical for a PGCG. After histopathological examination of the first biopsy specimen a GCLJ was ruled out.
Another reactive process is nodular fasciitis, first described by Konwaler in 1955 and often found in the subcutaneous fascia of adults aged between 20 to 40 years [1, 7]. The head and neck region is affected in 20% of all cases, but lesions in the oral cavity are rare. [8]. The histopathology of a nodular fasciitis shows a variably cellular fibroblastic and myofibroblastic proliferation, arranged in short irregular fascicles, growing in a so-called cell culture pattern, sometimes with a high mitotic index. The presence of prominent vasculature and extravasated red blood cells can be helpful in differentiation from other myofibroblastic lesions. Clinically and histologically, nodular fasciitis can be misdiagnosed as a sarcoma. A rearrangement of the USP6 gene is commonly found and can be of great diagnostic help in difficult cases [1, 3]. The clinical context of the case presented here fitted well with a nodular fasciitis: a rapidly growing tumor-like mass, increasing pain and no evidence of systemic disease. The clinical appearance alone was, however, not reliable for diagnosis [9]. Nodular fasciitis is self-limited and often a spontaneous regression can be observed. Incisional biopsy with histopathological examination remains essential for the diagnosis and subsequent procedure.
The myofibroma is a rare benign soft-tissue neoplasm of the head and neck region and affects mostly the mandible, the tongue or the buccal mucosa. A genetic predisposition and factors such as trauma and injury have been discussed in the literature [10, 11]. The myofibroma is a fairly indolent slow-growing firm mass with lobulated surface, but cases with rapid and aggressive growth have also been described. It can present intraosseous as well-defined, unilocular radiolucency, mainly in the posterior mandible [12]. Not in accordance with the present case is that 75% of the patients are younger than 20 years of age [11]. Histopathologically, a myofibroma is an unencapsulated, well-demarcated biphasic lesion composed of myofibroblasts. Tumor cells are spindle shaped with scant cytoplasm and sometimes showing a zoning phenomenon [10].
The most frequent malignant tumor affecting the oral cavity is in 90% of cases a squamous cell carcinoma (SCC) [13, 14]. Predilections sites for SCC in the oral cavity are the tongue and floor of the mouth, but all sites can be involved, including the gingiva and alveolar ridge. The prevalence of SCC on the gingiva has been reported in 14% [15] in a multicenter study including populations from Canada, Korea, Iran, Taiwan and Thailand to 32% [14] in a population from Lagos in Nigeria. The clinical findings of the present case with rapid growth of a tumor mass, superficial ulceration, as well as the infiltration of the alveolar bone were suspicious for an SCC. Atypical, however, was the mesio-distal symmetrical shape of the tumor mass and the intact mucosa to the caudal. The absence of risk factors such as tobacco and alcohol use as well as the age of the patient were also considered as unusual.
Lymphoma are the third most common malignancies in the oral cavity and the diffuse large B cell lymphoma not otherwise specified (DLBCL NOS) is most often diagnosed. DLBCL NOS can arise in patients without risk factors and 40% are extranodal. A rapid growing soft tissue tumor typically located at the palate or the gingiva or alveolar ridge is a typical sign. Some cases involving the alveolar bone have been described in the literature [16, 17].
Another consideration was the presence of an intraoral metastasis. In early stages, mucosal metastases present as exophytic, most often on the gingiva. Jawbone metastases are more frequently found in the mandible than the maxilla and the most common site is the molar area. Overall, metastatic dissemination is rarely found in the oral cavity [18] and the presented patient had no cancer history.
The histopathologic diagnosis was essential, but also difficult in the present case. Potential differential diagnoses like a PCLJ, an SCC or a lymphoma were easily ruled out histopathologically, whereas myofibromas, nodular fasciitis and an LGMS show a significant morphologic overlap. After the first biopsy this overlap and potential differential diagnoses were a challenge for the subsequent treatment approach. In the case of a benign tumor or reactive lesion, a highly invasive therapy should be avoided to minimize the patient’s morbidity and subsequent impact on quality of life. On the other hand, overlooking and not rapidly and adequately treating a malignant tumor can be fatal. Furthermore, there is a lack of immunohistochemical and molecular markers that differentiate a myofibroma from an LGMS with certainty. Chromosomal imbalances have been described in myofibroblastic sarcoma and, in a small case series, these genetic aberrations were occurring more often compared to nodular fasciitis [19]. However, the methods of detection have their limitations and it is not an established method used to identify malignancy of a tumor. The histopathologic resemblance of LGMS to a myofibroma and fibromatosis is often likely a source of diagnostic confusion. Furthermore, the possibility of a lack of experience of the clinician and/or the pathologist due to the rarity of these pathologies further complicates the matter [20].
In the present case, the amount of cellular atypia together with the locally aggressive and symptomatic growth (bone erosion, surface ulceration), were very suspicious for an LGMS. For this reason, a more radical treatment approach with extraction of teeth and adequate bone resection was suggested to the patient and subsequently performed by the maxillofacial surgeon. The histopathological analysis of the resected specimen showed the invasive growth of the tumor into the bone and together with the high mitotic rate confirmed the diagnosis of a LGMS. The margins of resection were tumor free.
The complete clinical picture of LGMS remains unclear. Often LGMS is a slow-growing and indolent tumor [4, 21, 22]. This is in contrast to our case. It is assumed that LGMS occurs far more often than the scarcity of reported cases might portray. While most studies reported the head and neck region, including oral cavity, as predilection sites, the incidence of LGMS in other regions of the body could be higher than expected as shown by one of the latest studies [23].
Wide tumor excision including surrounding tissue is the suggested therapy. A recent case series showed the association between local recurrence and the tissue invasion of LGMS as well as the surgical method. Resection margins > 2 cm are suggested to minimize the risk of recurrence [24]. However, wider safety margins are often more problematic in the oral cavity than in other parts of the body, such as the extremities. A histopathological confirmation of tumor-free margins is requested and ideally already available during the surgery, but does not exclude recurrence [23, 25]. Some authors have recommended an adjuvant chemotherapy and radiotherapy. The latter is controversial as it is supposed to even induce poorer prognosis, with a reported recurrence rate of 18.8% following surgery only and 71.4% after surgery and radiotherapy [2]. Definitive treatment criteria, treatment protocols and requirements are still undetermined and require further research.
While the potential for recurrence of LGMS is high, the risk of metastasis is low [21, 22, 24]. In an earlier case series, only one patient with multiple distant soft-tissue, intraosseous and pulmonary metastases after a long time interval was described. Thus, it seems appropriate to classify these neoplasms as malignancy [22]. However, a more recent case series observed a higher rate of metastasis than earlier studies. It could also be assumed, that recurrent cases are more prone to present as intermediate and high-grade, but this has not been observed [25].
This case shows the diagnostic and therapeutic challenge of a rare low-grade myofibroblastic sarcoma and the team approach of clinicians and pathologists alike in order to achieve state-of-the-art patient management.
