Primary cases of malignant tumours in the head and neck region treated at the Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, between January, 1995 and December, 2010, were retrospectively investigated. All the cases were biopsied for diagnosis by pathologists and classified according to the World Health Organization guidelines (1). The cases were divided into two groups: SCCs and non-SCCs. Clinicopathological characteristics, including age, gender, primary lesion site, pathological diagnosis, TNM classification, treatment, distant metastasis and outcome were retrospectively analyzed using patient medical records to determine the clinical characteristics of non-SCCs.

The statistical analyses for distant metastasis in cases of ACC or clinical outcome associated with surgery were performed using the Fisher’s exact test. The overall survival rate was assessed using the Kaplan-Meier analysis and the difference was analyzed using the log-rank test. P<0.05 was considered to indicate a statistically significant difference.

A total of 463 patients were included in this study, of whom 266 were men and 197 were women. The average age of the men was 61.6 years (range, 13–85 years) and that of the women 62.1 years (range, 29–94 years). In total, 43 cases (9.3%) were confirmed as non-SCC (Fig. 1A). Of the non-SCC cases, 20 (46.5%) were male (Fig. 1B) and the overall average age at the first visit was 61.8 years (range, 13–92 years). Of the 420 SCC cases, 246 (58.6%) were male (Fig. 1C) and the average age was 66.2 years (range, 21–94 years). The age distribution analysis revealed that a higher number of SCC patients were in the age range of 50–80 years. However, the non-SCC group included younger patients (aged <30 years) as well as older patients (Fig. 2). These data indicate that the non-SCC group included more women compared to the SCC group and that there is a wider age distribution trend in the non-SCC compared to the SCC group.

Among the SCC cases, the tongue was the most frequent primary site, followed by the mandible. However, non-SCCs occurred most frequently in the palate and maxilla (Fig. 3).

The pathological classification revealed that ACC (14 cases) and haematolymphoid tumours (16 cases) were the most frequently encountered malignancies (Table I). Less frequent neoplasms included mucoepidermoid carcinoma (2 cases), basal cell adenocarcinoma (1 case), adenocarcinoma (1 case), malignant ameloblastoma (1 case), small-cell carcinoma (1 case), mucosal malignant melanoma (4 cases), rhabdomyosarcoma (2 cases) and synovial sarcoma (1 case). Patients with haematolymphoid tumours were referred to the Division of Internal Medicine for treatment. Therefore, ACC was the most frequently encountered non-SCC malignancy treated at our Department.

Surgery was mainly selected as the primary treatment, except for malignant lymphoma, with chemotherapy or radiotherapy administered as necessary. Conversely, malignant lymphoma was mainly treated with chemotherapy and/or radiotherapy (Table II). In cases with local recurrence or distant metastasis, additional surgery, chemotherapy and/or radiotherapy were administered.

The correlation between surgical treatment and outcome was analyzed in non-SCC cases, except for malignant lymphoma. Four patients did not undergo surgery and they all succumbed to the disease within 5 years (Table III). Conversely, 14 of the 19 patients (74%) who underwent surgery survived for >5 years. The 5-year survival rate was significantly higher among patients who underwent surgery compared to those who did not (P=0.014) (Table IV).

The 5-year survival rates were ≤50% for patients with adenocarcinoma, small-cell carcinoma, mucosal malignant melanoma, rhabdomyosarcoma and synovial sarcoma (Table I).

One ACC patient refused treatment. The remaining 13 ACC patients underwent surgery and additionally received radiotherapy or chemotherapy, as required. Among the 5 surviving ACC patients, 2 have survived for >5 years, while 6 of the 9 deceased ACC patients survived for >5 years after treatment. Thus, 8 of the 11 cases (73%) remained alive at the 5-year observation time point (Table I). Subsequently, the survival rate decreased significantly, resulting in a 10-year cumulative survival rate of 38% (Fig. 4). The cumulative survival rates at the 5-year observation time point between ACC and SCC patients were similar. However, the subsequent decrease in the ACC was more noticeable compared to the decrease in the SCC survival rate (P=0.004; Fig. 4).

Distant metastasis was not observed in any of the surviving patients. Distant metastases were observed in 9 of the 14 ACC cases, 6 of which occurred within 3 years following primary treatment (Fig. 5). Lung metastasis occurred in all patients with metastasis (Table V). The overall average survival duration following local recurrence or distant metastasis was 4.1 years and the survival duration was 3.4 and 6.4 years when treated with and without radiotherapy, respectively (Fig. 6). Distant metastasis was observed in 22 of the 420 SCC patients; thus, ACC exhibited a significantly higher incidence of distant metastasis compared to SCC (P<0.001) (Table VI). The ACC patient information is summarized in Table VII to clarify the association between clinicopathological factors and distant metastasis. The data demonstrated that the distant metastasis rate was significantly higher in T3+T4 when compared to that in T1+T2 cases (P=0.021). In addition, distant metastasis occurred in all the patients who experienced regional lymph node metastasis. Distant metastasis was frequently observed in the sinus (100%), submandibular gland (100%) and oral floor (75%), but was comparably rare in the palate (33%) (Table VII). There was no significant association between distant metastasis and histological type.

In addition, there were 2 cases of mucoepidermoid carcinoma, 1 advanced case of adenocarcinoma and 1 case of basal cell adenocarcinoma. The 2 cases with mucoepidermoid carcinoma were treated with surgery, including neck dissection, and the patients have remained alive for 7 and 11 years, respectively, with no evidence of recurrence or metastasis (Table VIII). The advanced adenocarcinoma case was staged as T3N2bM0 (Table VI). The patient underwent surgical tumour resection and neck dissection. Additional treatments, such as adjuvant chemotherapy and radiotherapy were planned; however, neither was administered due to the patient’s poor overall condition. After 8 months, multiple lymph node metastases were detected in the neck. The patient did not consent to further treatment and eventually succumbed to the disease 17 months after her first visit.

Three patients underwent surgery, were diagnosed with malignant lymphoma and were referred to the Internal Medicine Department. For the other malignant lymphoma cases, biopsy or image analyses were used for diagnosis and the patients were directly referred to Internal Medicine. All the malignant lymphoma cases were non-Hodgkin lymphomas, with 13 cases of B-cell neoplasms and 3 cases of natural killer or T-cell (NK/T) neoplasms (Table IX). Chemotherapy or radiotherapy was the main therapeutic option for patients with malignant lymphoma (Tables II and IX). At the 5-year observation time point, 5 of the 11 malignant lymphoma cases (45%) had survived (Table I). The median observation period for surviving patients and the survival period for deceased patients were 6.0 and 3.6 years, respectively. Of the NK/T-cell lymphoma patients, 2 succumbed to the disease and 1 has remained alive for 5 years without recurrence. The surviving NK/T-cell lymphoma patient is a 28-year-old woman who was treated with radiotherapy (50 Gy) and 3 courses of dexamethasone, etoposide, ifosfamide and carboplatin (DeVIC).

A case of small-cell carcinoma (neuroendocrine type) was treated by surgery (tumour resection and neck dissection) and concurrent chemoradiotherapy, which comprised 5 courses of cisplatin + etoposide (PE) and 1 course of cisplatin + irinotecan (PI), with 66 Gy of radiotherapy (Table VIII). This malignancy is common in the lung but extremely rare in the head and neck region (11,12). Since PE and PI are considered to be the standard treatment for SCC of the lung, they were selected for this case. However, the patient succumbed to the disease 18 months after his first visit.

In total, 4 cases of malignant melanoma were treated (Table X). All the patients succumbed to the disease at 2, 3, 8 and 10 years after diagnosis. The 2 patients who survived the longest had undergone tumour resection with regional neck dissection, combined with chemotherapy or concurrent chemoradiotherapy. Surgical treatment was suggested to the remaining 2 patients, who experienced a shorter survival. However, both patients refused surgery and opted for chemotherapy or concurrent chemoradiotherapy.

A total of 2 rhabdomyosarcoma patients and 1 synovial sarcoma patient visited our Department (Table XI). The outcomes for the rhabdomyosarcoma cases were poor. The first rhabdomyosarcoma patient was a 13-year-old boy. The CT scan revealed multiple metastases in the lungs, suggesting that surgical treatment was not feasible. Thus, the patient was immediately transferred to the Pediatrics Department for chemotherapy. The patient finally succumbed to respiratory dysfunction 9 months after his first visit. The second rhabdomyosarcoma patient was a 61-year-old woman who was treated with surgery and chemoradiotherapy. The treatment achieved effective control of the local lesion; however, distant lung metastasis occurred and compromised the patient’s general condition. It should be noted that both rhabdomyosarcoma patients succumbed to their disease within 2 years after their first visits.

The synovial sarcoma patient was a 66-year-old man treated with surgery. Although there was no evidence of recurrence, the patient died of hepatocellular carcinoma 2 years after surgery.