Eur J Cardiothorac Surg 2008;33:790-793. doi:10.1016/j.ejcts.2007.12.057
Copyright © 2008, European Association for Cardio-thoracic Surgery. Published by Elsevier. All rights reserved.
Lung metastasis resection of adenoid cystic carcinoma of salivary glands
Antonio Bobbioa,*,
Chiara Copellib,
Luca Ampollinia,
Bernardo Bianchib,
Paolo Carbognania,
Stefano Bettatic,
Enrico Sesennab,
Michele Ruscaa
a Unit of Thoracic Surgery, Department of Surgical Science, University of Parma, Italy
b Unit of Maxillo-Facial Surgery, Head and Neck Department, University of Parma, Italy
c Department of Biochemistry and Molecular Biology, University of Parma, Italy
Received 5 September 2007;
received in revised form 20 November 2007;
accepted 10 December 2007.
* Corresponding author. Address: U.O. Chirurgia Toracica, Università di Parma, Azienda Ospedaliera di Parma, Viale Gramsci 14, 43100 Parma, Italy. Tel.: +39 03406874733; fax: +39 0521 992019. (Email: antonio.bobbio{at}unipr.it; antonboa{at}hotmail.com).
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Abstract
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Background: Adenoid cystic carcinoma is a rare tumour originating from the exocrine mucous glands, known for its high propensity for distant metastases. The value of lung metastasis resection from adenoid cystic carcinoma of salivary glands origin is evaluated. Methods: A retrospective study was conducted on patients undergoing surgery for primary adenoid cystic carcinoma of the salivary glands between 1982 and 2006. Patients were excluded who had primary tumour macroscopic incomplete resection or were lost at follow-up. From a database of 50 eligible patients, 27 were identified as having presented a tumour recurrence during follow-up; in 20 it was first diagnosed in the form of distant metastases, and in 7 in the form of loco-regional recurrence. Nine patients who presented isolated lung recurrence underwent complete lung metastasectomy. Demographic data, pathologic characteristics and operative and postoperative record were reviewed, as well as updated survival. Results: Twenty-six men and 24 women with a median age of 57 years (range 33–79) underwent radical surgery for adenoid cystic carcinoma during the study period. In 20 patients, at a median free interval time of 3 years (range 1–12), a distant metastasis relapse was observed. Nine patients with a median free interval time of 5 years (range 1–12) underwent lung metastasectomy: five had single metastasis resection, one multiple mono-pulmonary and three multiple and bilateral. In six of these patients a new disease recurrence was noted: four patients underwent further lung metastasectomy, but in all of them progression of the disease was observed. Mean survival of the population as a whole resulted as being 16 years (SE = 1.4) with an actuarial survival of 77% at 5 years, 66% at 10 years and 56% at 15 years. Mean survival of patients having presented with distant metastases resulted as being 11 years (SE = 2.2). Mean survival after appearance of distant metastases resulted as being 72 months (SE = 15.8) in the 9 patients treated by metastasectomy, and 62 months (SE = 15.1) in the 11 who did not have metastasis resection. Conclusions: Patients with adenoid cystic carcinoma could be frequently encountered with disease recurrence confined to the lung. The impact of complete lung metastasis resection on the course of the disease, however, is yet to be determined.
Key Words: Adenoid cystic carcinoma • Lung metastasectomy
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1. Introduction
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Adenoid cystic carcinoma (ACC) is a rare malignant tumour first reported in 1856 as ‘cylindroma’ by Theodor Bilroth (1829–1894) [1]. Surgery is the treatment of choice, although ACC is known for its propensity to late and multiple distant metastases, with the lung being the most commonly involved organ [2]. Because of the relative rarity of the disease, however, and because of its slow growth pattern, the impact of ACC lung metastasis resection on the course of the disease has previously been scantily explored [3–5].
In this study we analysed the effects on survival of complete resection of isolated lung deposit of ACC. For this purpose, the data of patients operated on during a 26-year period for a primary ACC of the head and neck were retrospectively reviewed and follow-up was updated; those patients who presented a disease relapse in the form of distant metastases were analysed, and the survival of patients in whom a complete lung metastasectomy was performed was compared to that of patients in whom the surgical clearance of metastatic disease was not done.
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2. Materials and methods
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The records of all patients undergoing surgery for a primary ACC of the head and neck at the Unit of Maxillo-Facial Surgery of the University of Parma from January 1982 to December 2006 were retrospectively reviewed. After having excluded those patients who underwent a macroscopic incomplete resection and those in whom follow-up could not be established, a population study of 50 patients resulted for analysis. Demographic data, tumour characteristics such as origin from major or minor salivary glands, histological type, size (diameter >3 cm), and the presence of microscopic infiltrated margins and of perineuronal infiltration, were collected; pathologic staging was undertaken in accordance with the rule regarding squamous carcinoma at similar sites, and the histology was established of the major relative proportion of tubular, cribriform and solid pattern. Postoperative radiotherapy was delivered in pathological stage III or IV and in the presence of microscopic infiltrated surgical margins. Twenty-seven patients among the study population were diagnosed with disease recurrence during follow-up, 20 in the form of distant metastases and 7 in the form of loco-regional recurrence. In those cases in which distant metastasis was diagnosed in the form of lung deposit, an indication for surgical therapy was established at the Unit of Thoracic Surgery of the University Hospital of Parma. The criteria used to undergo lung metastasectomy were: (a) the absence of any other site of tumour recurrence, (b) the possibility to accomplish a complete resection of the lung nodules and (c) a sufficient pulmonary functional reserve to undergo the planned lung parenchymal resection. In those patients in whom a new disease recurrence was diagnosed after lung metastasectomy, the same criteria were applied to undergo new surgical resection. At the end of the study period nine patients underwent complete lung metastasectomy. Out of those 11 patients in whom a diagnosis of distant metastases was established but who did not undergo metastasectomy, there were 7 who had multiple sites of disease relapse, three who had lung deposit judged as not amenable to complete resection (one exploratory thoracotomy) and one with operable lung metastatic deposit who refused intervention.
2.1 Statistical analysis
Actuarial survival was calculated according to the method of Kaplan–Meier; the influence of variables on survival was analysed by the log-rank test. Chi square was used in univariate analysis; multivariate analysis was carried out by binomial linear regression model.
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3. Results
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The demographic data and pathologic records of the 50 eligible patients operated on for a primary ACC of the salivary glands during the study period are listed in Table 1
. Mean survival for the population as a whole resulted as being 16 years (SE = 1.4) with an actuarial survival of 77% at 5 years, 66% at 10 years and 56% at 15 years (Fig. 1
). During follow-up a diagnosis of distant metastasis was established in 20 patients at a median disease-free interval of 3 years (range 1–12). Mean survival of these 20 patients resulted as being 11 years (SE = 2.2), and the actuarial survival was 69% at 5 years, 50% at 10 years and 20% at 15 years (Fig. 2
).
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Fig. 2. Cumulative survival of 20 patients who presented with distant metastases during follow-up after surgery for adenoid cystic carcinoma.
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By univariate analysis the occurrence of distant metastases resulted as being significantly associated to the solid and cribriform histological type of the primary tumour (p
= 0.048), to an advanced pathological stage (stage III and IV vs stage I and II: p
= 0.012), and to a tumour diameter larger than 3 cm (p
= 0.002). On the other hand no correlation was found with regard to sex, age, origin from major or minor salivary glands, or the presence of microscopic infiltration on surgical margins or of perineuronal infiltration. By multivariate analysis, the size of the primary tumour resulted as being the strongest predictor of distant metastases (p
= 0.002).
Eight men and 1 woman, with a median age of 59 years (range 47–78) at a median disease-free interval of 5 years (range 1–12) from the time of primary tumour resection, fulfilled the inclusion criteria and underwent complete lung metastasectomy. In these patients the primary tumour originated from the parotid gland in three cases, the palate in four and the tongue and jowl in one case, respectively. In five patients a single metastasis resection was performed, in one patient the resection of four metastatic nodules in the same lung and in three patients the metastasectomy consisted of multiple and bilateral nodule resection. In six of these patients tumour relapse was recorded during follow-up, and in four cases a new lung metastasectomy was performed. However, in all of the latter patients a new relapse occurred. Those three patients in whom no progression of the disease was established all had single metastasis resection, all are alive at the completion of follow-up, the highest score being obtained by a patient with no sign of disease 7 years after lung metastasectomy. Mean survival of nine patients after metastasectomy resulted as being 72 months (SE = 15.8). The one patient who presented a diagnosis of distant metastases and who did not undergo lung metastasectomy had a mean age of 60 years (41–71), and the disease-free interval after primary tumour resection resulted as being 2 years (range 0–6). Mean survival after the diagnosis of distant metastases was 62 months (SE = 15.1). The Kaplan–Meier survival curves of these two groups of patients are shown in Fig. 3
and appear not to be significantly different (p
= 0.81).
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Fig. 3. Cumulative survival since diagnosis of distant metastases of patients who underwent metastasectomy (linear) versus non-operated patients (dots).
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4. Discussion
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ACC exhibits a unique malignant profile characterised by slow growth and high propensity to systemic metastases. In the study of Spiro, with a minimum follow-up of 10 years, the overall incidence of distant metastases was 38% [2].
Few studies report the results of lung metastasectomy for ACC: the largest one is from the Memorial Sloan Kettering of New York, published in 1999 by Lieu: the author found no disease-free survivors among 14 patients undergoing lung metastasectomy after 14 years of follow-up [3]. Another report is the one by Locati in which 11 patients who had a complete lung metastasis resection were found to have a similar survival to that of patients having undergone non-radical lung metastasis surgery [4].
In our study we first analysed the course of the disease after radical surgery of the primary tumour, and this allowed us to observe the long-term survival of patients operated on even in the presence of disease progression. On the other hand, in those patients in whom a complete lung metastasis resection was performed, the cumulative survival from the time of lung surgery resulted as being no different from that observed among patients in whom distant metastasis was diagnosed but the deposit not extirpated. Despite the methodology study limitations and the small number of patients involved, these results are in line with those previously mentioned, and appear to indicate that surgery for ACC lung metastasis does not seem to alter the survival of patients; it is worth noting that, in our study, in all four patients undergoing re-metastasectomy a progression of the disease was observed.
In conclusion, although the progression of salivary gland ACC could be observed in the form of isolated lung deposit and a complete lung metastasectomy could be envisaged, the potential effect of radical metastasectomy in the control of the disease has not yet been assessed.
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Appendix A
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Conference discussion
Dr L. Lang-Lazdunski (London, United Kingdom): I’d like to make a comment. It seems that in your series you had three patients who had a single metastasis.
Dr Bobbio: Five.
Dr Lang-Lazdunski: Five, okay. The long-term survivors are mainly the ones who had one single metastasis excised, but the other ones did have relapse subsequently.
Dr Bobbio: Five patients had single metastasis resection. And three of these patients are free of disease and alive. But the longest follow-up is in one of these three patients, free of disease, at 7 years. So is short follow-up.
Dr R. Stanbridge (London, United Kingdom): Do you have a maximum number of metastases which you are prepared to resect? And if there are lots of them and bilateral, which may require further lung resection, what is the long-term outcome?
Dr Bobbio: Well, this study has a long latency status, so I cannot answer for all the period long. I resume that resectability was based upon the preoperative imaging exploration and the possibility to resect all visible deposit.
Dr Stanbridge: So no maximum?
Dr Bobbio: I have no answer.
Dr H.-B. Ris (Lausanne, Switzerland): You had 9 patients who underwent metastasectomy and 11 patients who did not?
Dr Bobbio: Yes.
Dr Ris: How did you make the choice for offering metastasectomy in your patients? What were the selection criteria to do metastasectomy in 9 patients and in the other 11 patients not?
Dr Bobbio: In the group of control, there are different patients: one patient who refused intervention and one who had thoracotomy and no resection of all metastases. And there were two patients with isolated lung metastasis. Seven patients, we say there was disease that was not isolated to lung. So mainly bone metastases discovered during the follow-up.
Dr Ris: If I understand well, the two groups were not really comparable?
Dr Bobbio: Not really, they had only systemic disease recurrences after radical operation in the head and neck compartment.
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Footnotes
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Presented at the 21st Annual Meeting of the European Association for Cardio-thoracic Surgery, Geneva, Switzerland, September 16–19, 2007.
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References
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- Bilroth T. Die cylindergeschwulst, Untersuchungen uber die Entwicklung der Blutgefasse, nebst Beobachtungen aus der koniglichen chirugischen Universtats-Klink zu Berlin, Berlin, G. Riemer, Germany, 1856, p. 55–69.
- Spiro RH. Distant metastases in adenoid cystic carcinoma of salivary origin. Am J Surg 1997;174:495-498.[CrossRef][Medline]
- Liu D, Labow DM, Dang N, Martini N, Bains M, Murt M, Downey R, Rusch V, Shah J, Ginsberg RJ. Pulmonary metastasectomy for head and neck cancers. Ann Surg Oncol 1999;6:572-578.[Abstract]
- Locati LD, Guzzo M, Bossi P, Brega Massone PP, Conti B, Fumagalli E, Bareggi C, Cantù G, Licitra L. Lung metastasectomy in adenoid cystic carcinoma of salivary gland. Oral Oncol 2005;41:890-894.[CrossRef][Medline]
- Mazer TM, Robbins KT, McMurtrey MJ, Byers RM. Resection of pulmonary metastases from squamous carcinoma of the head and neck. Am J Surg 1988;156:238-242.[CrossRef][Medline]
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Abstract
1. Introduction
