Radical excision with wide safety margins in combination with postoperative radiotherapy is the preferred treatment of ACC in the head and neck region. In this study, all intraoperative proximal margin FS specimens had negative surgical margins, and radical surgical excision was successful. Moreover, adjuvant radiotherapy with a total dose of 60 Gy was administered to the patients with stage III–IV disease. The median follow-up duration was 32.9 months, 71.7% of patients survived without evidence of disease recurrence, 15.5% survived with recurrent tumors, and 13.8% died of regional, distant, or multiorgan metastasis. The median OS was 32.5 months, and the median PFS was 32.9 months. All patients died of local (brain), distant (lung), or multiorgan metastasis (lung and liver).
ACC of the minor salivary glands of the palate is a life-threatening malignant tumor due to its high risk of recurrence and multiorgan metastasis. The characteristic biologic features of ACC include local recurrence, perineural spread, and late distant metastasis. Local control of the disease is difficult because of these features, even in patients with clinically clear surgical resection margins. Our study showed that the cervical lymph node metastasis rate of ACC was very low, and only 5.2% was confirmed. It is suggested that the rationality of selective lymph node dissection needs further study.
Spread via the blood to distant sites, particularly the lungs, usually occurs when the primary tumor has been inadequately treated [15]. In this study, that are more linked to the intrinsic malignancy of the tumor [16]. According to our statistical analysis, the rate of survival without disease was significantly higher in patients with low-grade tumor (90.6%) and stage I–II disease (75.9%) than in patients with high-grade tumor (42.3%) and stage III–IV disease (24.1%). The rates of survival with disease recurrence and death were significantly higher in patients with high-grade tumor (34.6 and 23.1%, respectively) and stage III–IV disease (50.0 and 35.7%) than in patients with low-grade tumor (0 and 6.3%) and stage I–II disease (4.5 and 6.8%) (P = 0.0001).
Although radiotherapy is an important adjuvant treatment [17] and we treated 14 patients with stage III–IV disease with surgical excision followed by adjuvant radiotherapy, and the rate of survival without disease was significantly lower among patients who underwent radical excision with radiotherapy (81.8%) than among those who underwent only radical excision (35.7%). Obviously, patients with histopathologic grade I–II tumors or stage I–II disease, but without metastatic tumors, had a better prognosis than those with stage III–IV disease, grade III transformed tumors, or metastatic tumors. In a previous study, patients who received primary treatment with curative intent, mainly surgery, for early stage ACC in the minor salivary glands had a favorable prognosis [18]. Moratin et al. recommend surgical therapy for patients with ACC of the minor salivary glands, including elective neck dissection and microvascular reconstruction, to optimize the planning of adjuvant therapy [19].
Importantly, stage III–IV disease, grade III and transformed tumors, and metastatic tumors indicate advanced disease that warrants aggressive treatment (i.e., local or regional recurrence requires salvage surgery). Early initiation of cyclophosphamide, doxorubicin, and cisplatin chemotherapy may help control metastatic ACC [20]. Chemotherapy can be used to treat patients with brain, lung, or multiorgan metastasis, but such treatment failed in our patients. ACC is an indolent, slow-growing tumor but commonly metastasizes to the lungs and bones. Perineural invasion and bone invasion were noted in 82.8 and 89.7% of patients, respectively; these features can cause local or regional recurrence, hematogenous metastasis, and adverse reactions to radiotherapy or chemotherapy.
Ki-67 expression was significantly higher in the high- than low-grade tumor specimens in this study (P < 0.05). Ki-67 may be a subtype-specific marker of ACC in the minor salivary glands of the palate, and a possible prognostic biomarker for tumor progression.
Radical resection with safety margins is the mainstay of treatment for malignant tumors; however, reconstruction of the palate after tumor ablation can be challenging. ACC of the minor salivary glands can be treated radically with surgery, but reconstruction of the defect is rarely reported [14, 21, 22].
The FSAIF has a lower complication incidence when compared to the radial forearm free flap, while maintaining speech and swallowing function [23], and associated with less operative time, shorter hospitalization, fewer perioperative complications, and potentially similar disease recurrence rates compared to free tissue transfer for the reconstruction of oral cavity defects [24]. FSAIF is a reliable and safe method for reconstruction of Brown class II maxillary defects after cancer ablation [25]. However, the best outcomes for Brown class III maxillary defects are achieved with titanium mesh and a free ALTF, which provides good functional and esthetic outcomes after maxillectomy [26].
ACC is a life-threatening malignant tumor owing to its high risk of recurrence; of the rate of tumor-related death within 30 years after primary treatment is high [27]. In this study, the median follow-up of 30 months seems short for a disease like ACC that tends to recur after several years. It is necessary for these patients to continue follow-up.