Abstract
This is a retrospective study of 11 patients treated for sinonasal adenoid cystic carcinomas (ACCs) between 1989 and 2008. The authors statistically analysed the epidemiological, clinical, histological and therapeutic aspects of this series of patients with sinonasal ACCs and their impact in terms of overall and disease-free survival established using the Kaplan–Meier method. A search for prognostic factors was made using a log-rank test. There were 5 women (45.4%) and 6 men (54.6%). Average age at diagnosis was 52.2 years (24–75 years). Mean follow-up of patients was 63 months (11–142 months). Tumours were classified as T1 in 9%, T2 in 45.4% and T4 in 45.4% of cases. Disease-free survival rates at 1, 5 and 10 years were 83%, 41% and 18%, respectively, and overall survival rates were 100%, 64% and 35%, respectively. Surgery followed or not by radiotherapy resulted in better survival than other treatment, regardless of tumour stage. Better disease-free survival with postoperative radiotherapy was not found. These tumours should be treated by surgical resection with clear margins followed by adjuvant radiotherapy.
Adenoid cystic carcinoma (ACC), first described in 1856 and originally called cylindroma, is a rare tumour of the accessory and principal salivary glands. Sinonasal ACC represents 10–25% of all head and neck ACC. Sinonasal cancers often present nonspecific symptoms and mimic inflammatory or infectious diseases. Most sinonasal ACCs are diagnosed only at an advanced stage (invasion of the skull base, or even the brain due to its neurotropism). The aim of this study was to statistically analyse the epidemiological, clinical, histological and therapeutic aspects of this series of patients with sinonasal ACC and their impact in terms of overall and disease-free survival.
Materials and methods
This is a retrospective study of 11 consecutive patients treated in the authors’ institution for sinonasal ACC between November 1989 and June 2008. Epidemiological, clinical, radiological, histological features, treatment modalities and the outcome of the patients were studied. To ensure the homogeneity of the series, the 2009 AJCC TNM classification was applied retrospectively to all patients. The database was created in FileMaker Pro ® (version 5). Overall and disease-free survival were established using the Kaplan–Meier method. A search for prognostic factors was performed using a log-rank test. All statistical tests were conducted using SPSS version 17.0 software (SPSS Inc., Chicago, IL, USA).
Results
There were 5 women (45.4%) and 6 men (54.6%) (ratio 1.2). The average age at diagnosis was 52.2 years (24–75 years). The tumour was on the right side in 6 cases (54.6) and on the left in 5 cases (45.4%). No risk factors for tumour occurrence were detected. Mean follow-up was 63 months (11–177 months).
Clinical presentation
Clinical data were usable for 11 patients (100%). Initial symptoms were always unilateral, the most frequent being nasal obstruction (70.6%) and epistaxis (58.8%). Other symptoms included rhinorrhea (29.4%), neurological signs (17.6%), eye signs (11.7%), pain (11.7%), trismus (11.7%) and skin damage (5.8%).
Location, extension and TNM
Radiological investigation in all cases included: a sinus computed tomography (CT) image for local staging; a neck and thorax CT for regional and remote staging. A sinus magnetic resonance image (MRI) completed this assessment in 10 patients (90%). Image analysis was used to study primary tumour sites and their modes of propagation and to define TNM staging. Tumour locations were: nasal cavity in 3 cases (27.3%), ethmoid in 3 cases (27.3%) and maxillary sinus in 5 cases (45.4%).
There was a breach of key structures such as the infratemporal fossa in 4 cases (36.4%), skull base in 3 cases (27.3%), orbit in 3 cases (27.3%), sphenoid bone in 2 cases (18.2%), the dura mater in 1 case (9.1%), skin in 1 case (9.1%) and the cavernous sinus in 1 case (9.1%). Involvement of the infratemporal fossa was associated with lysis of the pterygoid in 2 cases. The tumour was classified as T1 in 1 case (9.2%), T2 in 5 cases (45.4%) and T4 in 5 cases (45.4% of cases). The 5 tumours classified T4 were divided into T4a (4 cases) and T4b (1 case). There was no T3 in this series. All patients were N0 at the time of initial diagnosis. Only one metastatic patient (9.1%) (lung) was classified T4aN0M1.
Histological data
Of the 11 cases of histologically proven ACC, the exact subtype was noted in 7 cases (63.6%). It was an ACC of cribriform type in 2 cases, of tubular type in 1 cases, of solid type in 1 case and a mixed pattern (cribriform and solid) in 3 cases. The authors found no dedifferentiated type. The proliferation index was never specified.
Treatment
Four types of initial treatment were used: surgery alone in 4 cases (36.4%); surgery followed by radiotherapy in 5 cases (45.4%); concurrent radio-chemotherapy in 1 case (9.1%); and chemotherapy in one case (9.1%) classified as T4a with pterygoid lysis.
9 patients (81.8%) underwent surgery. The quality of excision margins was identified in 11 cases (100%). All patients (20%) showed clear margins on final histological analysis.
For radiotherapy, using an unfractionated protocol, the authors delivered doses ranging from 45 to 70 Gy to the tumour site.
Recurrence and survival
Disease-free survival rates at 1, 5 and 10 years were 83%, 41% and 18%, respectively ( Fig. 1 ). The overall survival rates at 1, 5 and 10 years were 100%, 64% and 35%, respectively ( Fig. 2 ).
Seven treatment failures (63.6%) were observed. Of these 7 patients, two patients classified as T4a (18.2% of all cases) evolved further after initial treatment. The remaining 5 had recurrences and were classified as T2 in 3 cases, T4a in 1 case and T4b in 1 case. The results in terms of local and remote occurrence depending on tumour location, TNM status and initial treatment are shown in Table 1 .
| Localization | Tumoural staging | First treatment | Number of patients | Local | Remote |
|---|---|---|---|---|---|
| Nasal fossa and ethmoid | T1 | S + RT | 1 | 0 | 0 |
| T2 | S + RT | 2 | 2 | 0 | |
| T4a | S | 1 | 1 | 0 | |
| T4a | S + RT | 2 | 0 | 1 | |
| Maxillary sinus | T2 | S | 3 | 1 | 0 |
| T4a | C | 1 | 1 | 0 | |
| T4b | C + RT | 1 | 1 | 0 | |
| Total | 11 | 6 | 1 | ||
Median time to recurrence was 43.5 months. There was local recurrence in 6 cases (54.5%) and distant recurrence (lung) without local recurrence in 1 case (9.1%).
Patients with local recurrence were treated by further surgery in 3 cases classified as T2N0 (27.3%). These were located in the infrastructure of the maxilla in 2 cases and in the nasal cavity in 1 case. The other 3 patients were treated with chemotherapy in 4 cases (one T2 and one T4a of the nasal cavity, one T4b of the maxillary sinus). 6 of the 11 patients (54.5%) died of their malignant disease (two T2, three T4a and one T4b).
Factors influencing survival
Surgery followed or not by radiotherapy resulted in better survival than other treatment, regardless of tumour stage. The authors did not find better disease-free survival with postoperative radiotherapy. There was no significant difference between the different treatment modalities in terms of overall survival.
The recurrence-free survival rates at 1, 5 and 10 years, depending on the treatment modality (surgery followed by radiotherapy versus surgery alone) are presented in Table 2 . Gender, age and site of the lesion did not appear to affect overall or relapse-free survival. Similar results were observed for tumour stage and the involvement of key structures.
| Author (year published) | Patients | 5 y DFS | 10 y DFS | 5 y OS | 10 y OS | Rate of adjuvant RT |
|---|---|---|---|---|---|---|
| Tran et al. (1989) | 24 | – | – | 82% | 50% | – |
| Harrison et al. (1998) | 49 | – | – | 53% | 24% | – |
| Chummum et al. (2001) * | 45 ( 14 ) | 63% ( 50% ) | – | 65% ( 50% ) | – | 67% |
| Wiseman et al. (2002) | 35 | – | – | 65% | 55% | 57% |
| Lupinetti et al. (2006) | 105 | 70.9% | – | 62.9% | – | 84.5% |
| Gomez et al. (2008) | 110 ( 30 ) | 76% | 40% | 87% | 65% | 63% |
| Oplatek et al. (2009) * | 113 ( 35 ) | – | – | 78% | 55% | – |
| Wei et al. (2009) | 40 | 44.2% | 23% | 76.9% | 61.6% | – |
| Present series | 11 | 41% | 18% | 64% | 35% | 50% |
* Series with sinonasal and salivary glands ACC. The figure in italics shows the number of sinonasal ACC.
Results
There were 5 women (45.4%) and 6 men (54.6%) (ratio 1.2). The average age at diagnosis was 52.2 years (24–75 years). The tumour was on the right side in 6 cases (54.6) and on the left in 5 cases (45.4%). No risk factors for tumour occurrence were detected. Mean follow-up was 63 months (11–177 months).
Clinical presentation
Clinical data were usable for 11 patients (100%). Initial symptoms were always unilateral, the most frequent being nasal obstruction (70.6%) and epistaxis (58.8%). Other symptoms included rhinorrhea (29.4%), neurological signs (17.6%), eye signs (11.7%), pain (11.7%), trismus (11.7%) and skin damage (5.8%).
Location, extension and TNM
Radiological investigation in all cases included: a sinus computed tomography (CT) image for local staging; a neck and thorax CT for regional and remote staging. A sinus magnetic resonance image (MRI) completed this assessment in 10 patients (90%). Image analysis was used to study primary tumour sites and their modes of propagation and to define TNM staging. Tumour locations were: nasal cavity in 3 cases (27.3%), ethmoid in 3 cases (27.3%) and maxillary sinus in 5 cases (45.4%).
There was a breach of key structures such as the infratemporal fossa in 4 cases (36.4%), skull base in 3 cases (27.3%), orbit in 3 cases (27.3%), sphenoid bone in 2 cases (18.2%), the dura mater in 1 case (9.1%), skin in 1 case (9.1%) and the cavernous sinus in 1 case (9.1%). Involvement of the infratemporal fossa was associated with lysis of the pterygoid in 2 cases. The tumour was classified as T1 in 1 case (9.2%), T2 in 5 cases (45.4%) and T4 in 5 cases (45.4% of cases). The 5 tumours classified T4 were divided into T4a (4 cases) and T4b (1 case). There was no T3 in this series. All patients were N0 at the time of initial diagnosis. Only one metastatic patient (9.1%) (lung) was classified T4aN0M1.
Histological data
Of the 11 cases of histologically proven ACC, the exact subtype was noted in 7 cases (63.6%). It was an ACC of cribriform type in 2 cases, of tubular type in 1 cases, of solid type in 1 case and a mixed pattern (cribriform and solid) in 3 cases. The authors found no dedifferentiated type. The proliferation index was never specified.
Treatment
Four types of initial treatment were used: surgery alone in 4 cases (36.4%); surgery followed by radiotherapy in 5 cases (45.4%); concurrent radio-chemotherapy in 1 case (9.1%); and chemotherapy in one case (9.1%) classified as T4a with pterygoid lysis.
9 patients (81.8%) underwent surgery. The quality of excision margins was identified in 11 cases (100%). All patients (20%) showed clear margins on final histological analysis.
For radiotherapy, using an unfractionated protocol, the authors delivered doses ranging from 45 to 70 Gy to the tumour site.
Recurrence and survival
Disease-free survival rates at 1, 5 and 10 years were 83%, 41% and 18%, respectively ( Fig. 1 ). The overall survival rates at 1, 5 and 10 years were 100%, 64% and 35%, respectively ( Fig. 2 ).
