Carcinosarcoma of the parotid gland is extremely rare and is first reported in 1951 by Kirklin et al [4]. The term malignant mixed tumor was coined in 1976 by King Jr [5] and less than 100 cases reported to date in literature [6]. Carcinosarcomas can arise from a pre-existing pleomorphic adenoma (PA) or may occur de novo [7]. These are high-grade tumors with an aggressive clinical course with distant metastases being reported in 54% of cases [8].
Gupta et al reviewed 66 cases of carcinosarcomas in the salivary glands over 42 years (1973–2015) and found that these tumors most commonly occur in the sixth to seventh decade of life with a male preponderance. The parotid was the most common location (78%) and the mean size of the tumor at presentation was more than 4 cm with extra-parenchymal extension in 43.9% of cases [9].
There are two theories postulating the origin of these tumors. The convergence hypothesis suggests these tumors to be arising from two or more polyclonal stem cells while the divergent theory proposes they arise from a totipotent stem cell and differentiate into distinct epithelial and mesenchymal elements [10]. The genomic profile of the carcinomatous and sarcomatous elements was studied by Vekony et al using oligonucleotide microarray-based comparative genomic hybridization. 75% homology was seen between the two components suggesting the divergent hypothesis that these components are clonally related [11].
The most common sarcomatous element is chondrosarcoma as was seen in our case, followed by fibrosarcoma, leiomyosarcoma, osteosarcoma, and liposarcoma [12]. The most common carcinomatous elements seen are adenocarcinoma, undifferentiated carcinoma, and squamous cell carcinoma [3]. Myoepithelial carcinoma and epithelial-myoepithelial carcinoma have also been reported [13]. The adenoid cystic carcinoma seen in our case was predominant tubular and cribriform growth patterns and focal solid growth patterns. On histomorphology, a diagnosis of carcinoma ex-pleomorphic adenoma, a sarcomatoid variant of salivary duct carcinoma, and myoepithelial carcinoma were considered. Immunohistochemistry is helpful in the diagnosis of such lesions. The adenoid cystic carcinoma was stained for both ductal (CK7, CAM 5.2) and myoepithelial (p63, p40, cytokeratin, SMMH) markers and CD117. The sarcomatous component was negative for all epithelial markers, CD57, AR, and calponin. It was positive for vimentin and showed focal S-100 positivity in the chondroid component. This immunohistochemical profile in the absence of any history of pre-existing parotid lesion and absence of histological evidence of pleomorphic adenoma was suggestive of primary carcinosarcoma of the parotid gland.
Fine needle aspiration cytology has not been extensively studied in these tumors. Previously cases have been reported as suspicious and atypical on cytology and a final diagnosis was given based on resection specimens [3, 14]. In our case, cellular atypia and hyperchromasia in a background of necrosis prompted the lesion to be classified as Milan 3.
Fowler et al studied tumor suppressor genes (3p, 5q, 9p, 17p, and 18q) for loss of heterozygosity in malignant mixed tumors of the salivary gland. It was noted that loss of heterozygosity of 17q21 and 9p21 was seen only in carcinosarcomas de novo as compared to carcinoma ex pleomorphic adenoma. The sarcomatous areas had a higher mean fractional allelic loss as compared to the carcinomatous areas suggesting additional mutations in those areas [13]. Katsakhyan et al reported a case of carcinosarcoma harboring PLAG1 translocation with an adjacent PA with an HMGA2 translocation [15]. As these translocations are mutually exclusive, it was concluded that the carcinosarcoma most likely came from another PA with PLAG1 mutation or originated de novo, thereby suggesting that the presence of PA is not conclusive of carcinosarcoma ex pleomorphic adenoma.
The imaging modality of choice is Magnetic Resonance Imaging as it helps determine the involvement of the deep lobe, facial nerve, and surrounding soft tissues [16]. These tumors have a poor prognosis with overall 2-year and 5-year survival having been reported as 68.1% and 37.2% respectively. The median survival reported by Gupta et al was 38 months while some studies have reported medical survival as low as 10 months. Distant metastases have been reported in up to 54% of cases and are an independent predictor of poor survival [8, 9]. The treatment of choice is radical parotidectomy followed by postoperative radiotherapy. Staffieri et al demonstrated a significant decrease in recurrence rate following surgery followed by radiotherapy as compared to surgery alone. The most common site for metastases is the lungs followed by hilar and cervical lymph nodes and is mostly hematogenous [9].