1. Abstract Carcinosarcoma of the parotid gland is a rare and aggressive malignant mixed tumor in which carcinomatous and sarcomatous elements coexist and metastasize together. The tumor may occur in patients with previous or coexisting pleomorphic adenoma or may arise de novo of the parotid gland. We report the first case with carcinosarcoma of the parotid gland that developed brain metastasis. Our patient underwent the surgical resection of metastatic brain lesion and had adjuvant radiosurgery postoperatively. The prognosis of carcinoma with distant metastasis and the standard treatment have not been established yet. We summarize rare examples of carcinosarcoma of the parotid gland that metastasize to the distant organs.
Keywords: Carcinosarcoma; Parotid gland; Metastasis; Malignant mixed tumor; Brain
2. Background Malignant mixed tumors of the salivary glands are a broad term includes carcinoma ex pleomorphic adenoma (PA), benign metastasizing PA, and true malignant mixed tumor (carcinosarcoma) [1]. Of these tumors, carcinoma ex PA represents approximately 99% of cases [2]. Carcinosarcoma of the parotid gland is a very rare tumor composed of both malignant epithelial (carcinomatous) and malignant mesenchymal (sarcomatous) elements. It represents only 0.04 to 0.16% of salivary gland tumors and 0.4% of malignant salivary gland neoplasm [3,4]. We reviewed cases reported in literatures diagnosed with carcinosarcoma of parotid gland and developed distant metastasis. To our knowledge, this is the first case with carcinosarcoma of the parotid gland that developed brain and lung metastases as well as liver metastases on post mortem examination.
3. Case Presentation A 56-year-old male patient was presented to our department with the left hemiparesis. 16 months ago, he underwent the total parotidectomy on the left side with the sacrifice of the ipsilateral facial nerve. The lesion was 4.7 cm in the greatest dimension and showed both malignant stromal and epithelial components. Histopathological findings were consistent with a carcinosarcoma of the parotid gland. On sectioning, perineuronal invasion was noted. Lymphovascular invasion was not observed. He had adjuvant chemoradiation therapy. Six months later, pleural metastasis was found. The patient underwent stereotactic body radiotherapy to the left lung. On the neurological examination, the motor power of the left extremities was grade 2 and the left facial palsy was noted with grade 2 according to House-Brackmann scale. The brain magnetic resonance images (MRI) showed a huge cystic lesion (44x51x40 mm) with a solid component in the right fronto-temporal region. There was a midline shift and perilesional edema (Figure 1). He underwent craniotomy with tumor removal. After resection, his headache disappeared and the left hemiparesis improved to grade 4. Histopathological evaluation revealed squamous differentiation in the tumor. Highly positive immunostaining of Cam5.2 and p40 showed the evidence of squamous differentiation in this metastatic tumor. Cam5.2 is a low molecular weight cytokeratin and is expressed in a majority of the tumor, meaning that it is purely epithelial. The diffuse nuclear expression of p40 is consistent with the finding of squamous differentiation (Figure 2). The next-generation sequencing based assay identified the amplification of IRS2, CDK4, IGF1R, MDM2 and MYC genes in metastatic brain lesions. In primary parotid lesion, genomic alteration identified amplication of RAF1, CDK4, IGF1R, MDM2 and MYC genes. Postoperative radiosurgery was given to the remaining tumor mass. Three months later, new growth of tumor mass with increased intracranial pressure was noted. He went the second craniotomy for the treatment of growing intracranial lesion and brain edema. Eventually, 8 months after the diagnosis of brain metastasis, the patient died due to the progression of lung metastasis. The patient and his wife donated his body for autopsy (consent signed prior). Autopsy examinations showed postresectional changes in the brain and multiple metastatic lesions in the liver and lung (Figure 3).
4. Discussion There are 3 histologic subtypes of malignant mixed tumors of the parotid gland. Carcinoma ex PA is the most common and consists of only a carcinomatous component. Carcinomatous transformation within a benign mixed tumor in which the initial benign elements are still identifiable is termed carcinoma ex PA. It has been thought to be indolent and slow-growing tumors. Carcinoma ex PA arises as a recurrence in a patient in whom a benign mixed tumor was previously resected. Metastasizing mixed tumor is the most infrequent subtype, occurring years after excision of the primary tumor or with a recurrence. Although no malignant features are identified within a benign mixed tumor, distant metastases occur. The histopathology of these metastatic lesions are also benign [5]. The true malignant mixed tumor, carcinosarcoma was first described in 1951 [6]. Carcinosarcoma is composed of both carcinomatous and sarcomatous elements. This is in contrast to the carcinoma ex PA in which only the epithelial element undergoes malignant transformation. One third of carcinosarcoma occur in patients with previous or coexisting Pas [7]. Hematogenous distant metastases have been reported to occur in as many as 44% of patients with carcinoma ex PA [8]. However, the metastasis to central nervous system (CNS) has been reported only in one case with carcinoma ex PA [9]. A 36-year-old man developed an end stage complication of parotid PA, malignant conversion followed by diffuse CNS metastases. Clinically, carcinosarcomas are very aggressive. Local recurrence and metastasis via both lymphatic and hematologic pathways to local or regional sites are frequently seen in up to 50% of patients [10]. However, the distant metastasis of carcinosarcoma of the parotid gland has little been reported in English literature sources. Clinical manifestations of the patients with carcinosarcom of the parotid gland developing distant metastasis are summarized in Table 1. A 47-year old patient presented with a one-year history of an enlarging mass in the jaw which was then diagnosed with malignant mixed tumor [11]. However, she had the excision from the same area two times when she was 8 years old and 22 years. The possibility of benign PA gave rise to malignant mixed tumor could not be excluded. Other two patients had the history of coexisting PA in the parotid gland and developed pleural and pulmonary metastasis, respectively [12,13]. A 10-yearold boy was simultaneously diagnosed with orbital metastasis and carcinosarcoma of the parotid gland [14]. It is suggested that carcinosarcoma of the parotid gland developed de-novo. Similarly, our case was newly diagnosed with carcinosarcoma of the parotid gland without past history of PA. 16 months later, the metastatic brain lesion developed. He had the resection via craniotomy and adjuvant radiosurgery. Although the follow-up period was short, his neurologic recovery was impressive.
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Jay-Jiguang Zhu. Metastasis to Brain and Lung in Carcinosarcoma of the Parotid Gland - A Case Report and Review of Literatures. Annals of Clinical and Medical Case Reports 2021