Ⅰ.INTRODUCTION
Carcinoma ex pleomorphic adenoma (Ca ex PA) is an uncommon malignant tumor. Ca ex PA arises from a primary or recurrent benign pleomorphic adenoma1,2). Ca ex PA is a rare disease, with a prevalence rate of 5.6 cases per 100,000 malignant neoplasms. The yearly incidence rate is 0.17 tumors per 1 million persons3). Around 25% of pleomorphic adenomas undergo malignant transformation4). Malignant mixed tumors can be divided into three different types: (1) carcinoma ex pleomorphic adenoma; (2) true malignant mixed tumor (carcinosarcoma); (3) metastasizing mixed tumor. Ca ex PA is the most common malignant form5).
In this study, we investigate a case of malignant transformation of a pleomorphic adenoma into a Ca ex PA, following two surgical operations to remove the tumor.
Ⅱ.CASE REPORT RESULTS
A 70-year-old female patient, with no unusual medical history, presented to our department with swelling, pain and palpations at the root of her right ear, which had begun one month previously.
On the first examination, swelling of the right parotid gland area was observed. Three-dimensional (3D) neck computed tomography (CT) was performed. The CT result showed a well-defined soft tissue mass, measuring 2 x 1.5 cm, on the right parotid gland. Bony invasion was not observed. For a more accurate diagnosis, sonography and fine needle aspiration (FNA) were performed. The sonography reading indicated a hypoechoic mass in the right parotid. FNA results suggested the presence of a benign mixed tumor. Based on these readings, the mass was provisionally diagnosed as pleomorphic adenoma. The patient re-visited the clinic four months later. A 3D neck CT was taken showing that the mass had enlarged (Fig. 1A, B). The patient underwent a superficial parotidectomy (Fig. 1C, D). Microscopic examination showed the presence of a pleomorphic adenoma with a well-circumscribed and encapsulated tumor mass. Plasmacytoid myoepithelial cells in a myxoid stroma and ductal structures with an associated mycomatous background were also observed (Fig. 1E, F).
At the 11-month follow-up, a mass measuring 1 cm was observed at the right mandibular angle. A CT scan indicated a relatively well-circumscribed mass on the lateral and anterior part of the right masseter muscle (Fig. 2A, B). A recurrent pleomorphic adenoma was diagnosed and a total parotidectomy was performed. The postoperative tissue specimen revealed a relatively well-circumscribed mass (Fig. 2C, D). Tissue biopsy showed the presence of a pleomorphic adenoma (Fig. 2E, F).
Six months after the second operation, a new mass was found on the lower edge of the patient’s right mandibular angle. FNA was conducted and indicated the presence of a benign salivary gland neoplasm. Further surgery was considered; however, the patient was not followed up for two years, due to her personal circumstances.
Two years later, the patient presented with a large mass located to the posterior of the right ear at the right mandibular lower edge. A CT scan showed a large lesion across the entire right parotid gland. The lesion had invaded the upper portion of the mandible and had abutted the right internal carotid artery (Fig. 3A, B). A malignant transformation was confirmed and positron emission tomography (PET)-CT showed a lung metastasis (Fig. 3C, D). A tissue biopsy demonstrated a high tissue malignancy rate and showed the presence of a clear cell tumor (of the spindle cell subtype), with an increase in tissue shape diversity and atypical mitosis (Fig 3E, F). Based on clinical information, radiological scans and the result of the tissue biopsy, the patient was diagnosed with Ca Ex PA. A salvage operation was considered; however, the patient did not re-attend the clinic.
Ⅲ.DISCUSSION
Pleomorphic adenoma (PA) is the most common benign salivary gland tumor6). PA arises predominantly from the parotid gland, though may arise from the minor salivary glands and the seromucinous glands of other organs (e.g. the oral cavity, trachea and nasal cavity)7). There is a strong correlation between early surgical removal of PA and a reduced recurrence rate8). One study reported that following parotidectomy, PA has the lowest tumor recurrence rate9,10). PA recurs in around 11~18% of cases. A second recurrence occurs in around 20~40% of cases, following which the rate is around 20%11,12). In this study, we witnessed a rare case of a patient with two recurrences of a PA, which at the second recurrence had transformed into a Ca ex PA.
Malignant transformation of PA typically presents as a Ca ex PA, an uncommon and aggressive salivary malignancy, which is hard to diagnose and cure. Ca ex PA has a high propensity for metastatic spread. The malignant mixed tumor area is often small and extensive hyalinization may occur. These factors lead to the high mortality rate seen in the disease13).
The most common clinical presentation of Ca ex PA is a mass in the parotid gland. A study reported the presence of a parotid mass in 86% of cases of Ca ex PA2,13). The majority of Ca ex PA lesions are invasive and have ill-defined borders14). Pain usually arises from the local extension of the neoplasm into adjacent soft and hard tissues. When Ca ex PA involves the facial nerve, the patient presents with facial nerve paresis or palsy13,15). The patient in this study had a large mass on the parotid gland and presented with mild facial nerve paresis after the first and second operations.
A well-constructed clinical history and a pathological biopsy are necessary for making the final diagnosis. Additionally, FNA, sonography, CT scanning, and magnetic resonance imaging can be used for making a diagnosis1). Ca ex PA occasionally arises as a mixture of PA and carcinoma. Benign mixed components may exist close to the malignant area and metastasis can occur to the benign region. However, sometimes it is not easy to FNA to diagnosis Ca ex PA. There is even a report claiming that the sensitivity is less than 30%17). Due to the difficulties in diagnosing a mixed sample, comprehensive testing should be performed to allow for an accurate diagnosis. A rapid growth spurt, in a slow growing parotid mass, should alert the clinician to the possibility of a Ca ex PA. Ca ex PA should be diagnosed differentially with other benign and malignant salivary gland tumors and with subtypes of malignant mixed tumor16).
Treatment for Ca ex PA may involve a parotidectomy. Superficial parotidectomy is used for intracapsular or minimally invasive Ca ex PA localized to the superficial lobe of the parotid gland. Total parotidectomy is used when both the deep and superficial lobes of the parotid are involved. In all cases, every attempt should be made to preserve the facial nerve2,13).
Here we initially performed a superficial parotidectomy Following recurrence of the mass we performed a total parotidectomy. Following this, a second recurrence occurred and the malignant transformation of PA into Ca ex PA was observed.
Ca ex PA is an uncommon malignant tumor, arising from a primary or recurrent, benign pleomorphic adenoma. Here, we reported a rare case of a PA at the second recurrence had transformed into a Ca ex PA. Clinicians should be aware of the potential malignant transformation of PA and understand the need for regular follow-ups. Furthermore, clinicians should always assess for tumor recurrences and long-distance metastases, with regular clinical and radiological follow-ups.
