Metastasizing pleomorphic adenoma (MPA), also known as metastasizing mixed tumor or “benign” metastasizing mixed tumor, is a rare salivary tumor that metastasizes despite retaining benign histopathology [1]. MPA clinically presents as a painless mass of the affected site, and typically develops many years after primary excision of a pleomorphic adenoma (PA) [2]. Common initial tumor sites of PA include the parotid, submandibular, and minor salivary glands [3]. Common sites of MPA include bone, lymph nodes, and lung [4]. Unlike carcinoma-ex-pleomorphic adenoma, MPA does not undergo histologically evident malignant transformation before metastasizing [5].
Histologically, MPA is indistinguishable from PA [6–8]. Computerized tomography (CT) findings vary depending on size. Smaller tumors are smooth and homogenous; larger tumors are more lobulated with enhancement and calcifications [6, 9]. On magnetic resonance imaging (MRI), tumors are homogenous with intermediate to low intensity signal on T1-weighted images, and high intensity on T2-weighted images.
The most widely accepted treatment for MPA is complete surgical excision with clear margins [8]. Radiotherapy and chemotherapy may play a complementary role in treatment, but are not proven to effectively reduce disease progression [10, 11]. Local enucleation is not recommended for treatment of MPA as incomplete tumor removal can lead to local recurrence [8, 12].
Several hypotheses have been proposed regarding the etiology of PA metastasis. Surgical intervention of a primary PA may lead to vascular implantation of tumor cells and subsequent metastatic spread [13]. However, MPA has also been rarely reported in patients without surgical treatment of a primary PA [14]. Incomplete surgical excision of PA is also strongly associated with local recurrence and distant metastasis [8]. Although the prognosis of MPA is generally favorable, death after extensive and metastases have been reported [1, 15, 16].
Here we describe the clinical course and surgical outcomes of two patients with MPA, both involving spread to the mandible and scalp. Additionally, we summarize four previously reported cases of MPA involving the mandible, and five involving the scalp (Table 1, Table 2).
Case 1
An otherwise healthy 67-year-old female with a history of a left parotidectomy for PA 23 years prior, presented for evaluation of a new left neck mass. Surgical history was notable for prior removal of a scalp cyst with unknown pathology. The original parotid tumor or the corresponding report was not available for review.
Fine-needle aspiration (FNA) biopsy of the neck mass was suggestive of a reactive level II lymph node, which was thought to be associated with parotid sialadenitis. Subsequent facial CT and MRI demonstrated a lytic and expansile lesion of the left mandibular ramus and the condylar head. The lesion had an intact cortical surface without associated soft tissue mass or extension to the parotid (Fig. 1). An additional hypointense scalp lesion was noted on T1-weighted imaging (Fig. 2). PET-CT demonstrated a hyperintense lesion of the left condyle and the scalp (Fig. 3).
The patient underwent a preauricular open bone biopsy of the left condylar lesion. Biopsy histology revealed bland epithelial cells embedded in a myxoid stroma. Immunohistochemistry expression of AE1/AE3, CAM5.2, S100, SMA, p63, and calponin in tumor cells. A diagnosis of recurrent intraosseous PA was rendered.
Left segmental mandibulectomy, condylectomy, left partial parotidectomy, mandibular reconstruction with an osteocutaneous fibular free flap, and excision of two scalp lesions, were performed. Final surgical pathology confirmed the mandibular condyle lesion and both scalp lesions as MPA (Fig. 4).
Postoperatively, the patient did well without significant complications. The patient underwent consultation with radiation oncology but declined adjuvant therapy. Panoramic X-ray at six months follow-up demonstrated satisfactory mandibular reconstruction (Fig. 5). The patient maintained good functional status with appropriate maxillomandibular occlusal relationships and an excellent oral aperture.
Case 2
A 42-year-old male had a prior history of multiple recurrent MPAs involving the scalp and mandible. His first surgery was performed at age 11 for a right parotid PA. He presented to our clinic 16 years later with a right parotid recurrence requiring a revision parotidectomy. Two years later, he was evaluated for subcutaneous lesions of the forehead and parietal scalp measuring 0.8 and 0.6 cm, respectively. FNA of the right lateral scalp mass demonstrated benign cytology, favoring a diagnosis of PA. Subsequent excision and pathological analysis of both masses revealed benign mixed tumors, consistent with a diagnosis of MPA. He required two subsequent revision surgeries of the parotid and the scalp. Fourteen years after his first scalp metastasis, neck MRI revealed an expansile multilobular lesion of the right mandibular ramus (Fig. 6). On facial CT, a multilobular, lytic, and expansile 3 x 1.5 cm lesion was present at the right proximal mandibular ramus (Fig. 7). The patient subsequently underwent a right segmental mandibulectomy and revision parotidectomy with left fibula free flap reconstruction and neck dissection. The 1.6 cm mass was diagnosed as a metastasizing mixed tumor involving bone on final surgical pathology. The parotid bed contained two additional nodules of recurrent PA. All lymph nodes were negative for metastatic disease.
Final surgical pathology confirmed the diagnosis of recurrent MPA. While some lesions demonstrated increased mitotic activity and/or increased cellularity, overt malignant transformation was not observed. Surveillance imaging four months after his last surgery demonstrated no evidence of persistent or recurrent disease on MRI.