Sarcomatoid Carcinoma of the Mandible: A Case Report and Literature Review

Background: Sarcomatoid carcinoma is a rare biphasic malignancy with an epithelial and mesenchymal component. Given its histological particularity, the diagnosis of this tumor still represents a challenge for pathologists and surgeons. Sarcomatoid carcinoma of the mandible is a very rare and aggressive entity. To date, only sporadic cases have been reported in the literature. Aim: To report a rare case of aggressive mandibular sarcomatoid carcinoma treated with radical surgery and adjuvant chemoradiation, and discuss the re-lated literature. Case Report: We introduce a rare case of mandibular sarcomatoid carcinoma occurring in a 34-year-old woman. Treatment consisted of radical surgery and re-excision for positive margins, adjuvant radiation therapy (66 Gy in 33 fractions in simultaneous integrated boost delivered using Volumetric Modulated Arc Therapy) and Cisplatin-based concurrent chemotherapy. The tumor displayed aggressive behavior and high metastatic po-tential, causing tumour recurrence and extensive lung metastasis. Conclu-sion: Sarcomatoid carcinoma of the mandible is an extremely rare malignant entity, with a high tendency for local recurrence, distant metastasis. Treatment involves radical surgery and adjuvant chemoradiation, although the outcome and prognosis might be poor.


Introduction
Sarcomatoid carcinoma is a rare biphasic malignant tumor with both mesenchymal and epithelial components. Given its histological peculiarity, the diagnosis of this tumor always represents a challenge for pathologists and surgeons.
Carcinosarcomas usually occur in the urinary tract and upper respiratory tract in elderly men, and is rarely found in the maxillofacial region. Primary sarcomatoid carcinoma of the mandibular gingiva is extremely rare. Only sporadic cases have been reported so far in the literature, and have mainly focused on the histopathological aspects of this disease. The little data available in the literature have exhibited considerably aggressive clinical behavior, poor prognosis, high rates of recurrence and frequent metastasis. Treatment is primarily surgical resection, though an adjuvant therapy may be necessary [1] [2].
Here, we report a clinically aggressive, recurrent and metastasizing primary sarcomatoid carcinoma of the left mandible in a 34-year-old woman, despite aggressive local treatment with radical surgery and adjuvant chemoradiation. In addition, we present a brief review of the relevant literature and increase our knowledge on this rare entity.

Case Report
A 34-year-old female patient presented to a dental office in December 2017 with a complaint of intermittent chin paresthesia and rapidly growing painless mass on the left mandibular gingiva for one month. The patient did not report a habit of smoking or daily drinking of alcoholic beverages. Medical history was not significant. Oral cavity examination showed a 30 mm × 30 mm irregular, indurated, nonmobile tumor in the left mandibular region both on buccal and lingual gingiva. Patient consent was obtained for taking photograph and using it for study and publication purposes ( Figure 1). Lymphnodes were not palpable.
Speech, swallowing and mouth opening were unimpaired. Clinical examination revealed no extraoral pathological findings.
Panoramic radiography revealed irregular osteolytic bone destruction in the left mandible. DentaScan imaging showed heterogeneous lytic lesion of the left mandibular horizontal branch, destroying the cortical bone, extending to soft tissues and reaching the alveolar rim with loss of teeth 34 to 38. An incisional biopsy was performed. The diagnosis was high grade fibrosarcoma of the jaw.
Computed tomography scans ruled out metastatic disease. Desmin, h-caldesmon, and S100 protein were negative. Based on the histological and immunohistochemical findings, the final diagnosis was corrected to sarcomatoid carcinoma. Multidisciplinary board considered re-excision. However, during this time interval, the patient experienced subsequent tumor progression very shortly after surgery. Re-excision was performed, although clear margins could not be obtained. Given the aggressive and rapidly evolving behavior of the tumor, with positive surgical margins despite re-excision, multidisciplinary board opted for adjuvant treatment. The patient was sent to radiation oncology department for evaluation and was taken up for concomitant chemoradiation with cisplatin-based chemotherapy.
Simulation was performed using the CT simulator (SOMATOM Sensation Open; Siemens). The patient was immobilized in supine position with a 5-point head neck and shoulder thermoplastic mask. An intra-venous iodine contrast enhanced planning CT with 3-mm slice thick reconstruction was obtained. The CT DICOM images were transferred to the Monaco® treatment planning system Version 5.11 (Elekta, Stockholm, Sweden) for target delineation.
The acquired images were co-registered with diagnostic CT images to contour the preoperative gross tumor volume (GTV-T), with the aim of better selecting the clinical target volume (CTV-T). Multiple suspicious cervical lymph nodes were identified on the planning CT scan, in left level II, III, and IVa and right level II and III. The largest node measured 1.5 cm × 2.2 cm. A 5-mm isotropic margin was given around the preoperative GTV to generate high-risk clinical target volume (CTV-T HR), and was adjusted on the planning CT, including the entire surgical bed to consider the microscopic disease. A 5-mm isotropic margin was given around the nodal gross tumor volume (GTV-N) to generate high-risk clinical target volume (CTV-N HR). A low-risk clinical target volume (CTV-LR) was defined as the CTV-T HR with a 5-mm margin, including the drainage lymph nodes starting 3 mm below the skin. The planning target volume (PTV) was created adding a 5 mm expansion around the corresponding CTV, except in the skin direction ( Figure 2). Organs at risk were contoured according to the Radiation Therapy Oncology Group (RTOG) atlas for normal tissue contouring.   The clinical presentation varies from an exophytic, pedunculated, polypoid mass with an ulcerated surface to a frankly infiltrative ulcer [2] [11].

Discussion
The main radiographic and CT appearance of mandibular sarcomatoid carcinoma is diffuse, irregular osteolytic bone destruction with a soft tissue mass [3] [13]. However, these imaging appearances are not unique features of this low-incidence neoplasm. The differential diagnosis includes a number of benign  [2]. Therefore, the diagnosis of mandibular sarcomatoid carcinoma can be challenging for the pathologist and must depend on histopathological and immunohistochemical examinations.
Epithelial differentiation and staining for one or more epithelial markers supports the diagnosis. In most cases (26% -62%) Keratin and cytokeratin are commonly found to be positive. Furthermore, positivity to mesenchymal-type markers is also demonstrated. Almost all of the cases show positivity for vimentin and about a third of them for smooth muscle actin [1] [3].
The optimal treatment of sarcomatoid carcinomas of the head and neck region is not based on high level evidence as this is a rare entity and only retrospective reports have been published. It usually follows the same footsteps as that of squamous cell carcinoma of similar stage. Nevertheless, in comparison to squamous cell carcinoma, within the head and neck region, sarcomatoid carcinoma is considered as a more aggressive tumor, with a tendency to recur and metastasize early [3].
Wide surgical excision, with or without radical neck dissection, is the treatment of choice. It is common for the patients to undergo several surgeries, owing to frequent recurrence. Despite wide-margin surgical resection and improved cooperation between ablative and reconstructive surgeons, the outcome continues to be poor. Currently, there is no literature describing the reconstructive strategies for sarcomatoid carcinomas in the head and neck area. However, caution should be exercised when planning reconstruction after resection. The reconstructive surgeon should take into account the poorer prognosis in such cases and avoid complicated procedures that require long operative time and may increase the rate of perioperative complications, prolong the hospital stay, and potentially delay the initiation of adjuvant therapies [14].
The effectiveness of radiotherapy was suggested by Ballo et al. in 1998, however, more recent studies did not confirm the impact of radiotherapy on survival [13]. Most authors agree that irradiation is ineffective. Radiation therapy is considered an acceptable alternative for inoperable patients. Adjuvant (che-

Conclusions
Sarcomatoid carcinoma is a very rare, aggressive and highly malignant entity with a complex histogenesis making its diagnosis extremely difficult and often misleading and controversial.
The management of sarcomatoid carcinoma remains challenging due to the rarity of this malignancy, high tendency for local recurrence, distant metastasis, and poor outcome. Surgery is considered to be the mainstay in the management of sarcomatoid carcinomas and should be performed as soon as possible with the aim of complete resection. Adjuvant treatment can be of value in high-risk disease, nevertheless the chance for survival might be poor.

Conflicts of Interest
Authors declare having no conflict of interests.