Management and prognostic factors of recurrent pleomorphic adenoma of the parotid gland: personal experience and review of the literature

It is generally accepted that the standard treatment of pleomorphic adenoma of the parotid gland is a formal parotidectomy or at least the removal of the tumor with a surrounding cuff of normal parotid tissue after identification, dissection and preservation of the facial nerve [7]. Unfortunately, if the tumor is in contact with the facial nerve, even a total parotidectomy can not guarantee the presence of a cuff of normal tissue, because the surgeon must carry on the dissection between the tumor and the branches of the nerve with the risk of leaving microscopic disease behind or causing microscopic spillage of the tumor. This accounts for 1–4% probability of recurrence [5, 7]. These low percentages, together with the increasing number of institutions that treat parotid neoplasms, have reduced the number of cases of RPA being referred to a single institution; this, in turn, has contributed to a lack of experience in managing these tumors. Moreover, with the number of reported patients usually varying from less than 15 to about 50 [6, 8, 9, 11, 12, 14‐17, 19‐24], and only a few studies reporting about a hundred patients [10, 13, 18, 25], there has been relatively little discussion of the prognostic factors for RPA [13‐18].

Follow-up of parotidectomies is currently performed by ultrasonography, but most patients do not avail themselves of regular follow-up and only 12.1% of our patients with an RPA were diagnosed by routine ultrasonography, while the majority came to our observation for a swelling in the parotid region. In 77.4% of our patients, there was a multinodular lesion (in Stennert et al. [4], 90% were multinodular at pathologic examination), reinforcing the pathogenetic hypothesis of incomplete excision, violation of the pseudocapsule of the tumor, or obvious or underestimated tumor spillage during the first surgery due to the impossibility of obtaining healthy free margins when the lesion is adjacent to the facial nerve.

Delineation of the extension of the RPA is better depicted by MRI, which better demonstrates the multinodular nature of the disease [24] and potential deep-lobe or parapharyngeal extension. Many patients that we treated came from other institutions without clear documentation of their previous treatment(s); in such cases, MRI can also help in determining the amount of parotid gland still present after any previous surgery. The signal and enhancement characteristics of RPA of the parotid gland are nonspecific [26]. The lesions are usually round; they are of low intensity on T1-weighted images and of high intensity on T2-weighted MR images. With contrast administration, the lesions show mild enhancement [26]. However, MRI can also be inadequate for identifying all nodules, and frequently the surgeon’s microscope or the pathologist’s microscope reveals many more nodules than suspected from clinical assessment [4].

Management options for RPA include observation only, localized resection, resection with facial nerve dissection, wide-field resection with facial nerve sacrifice, and radiotherapy [2, 4, 24]. Only observation has been suggested for the elderly or medically infirm patient [2, 4, 24]. When surgical excision is considered, it should be tailored to the individual patient [19, 23]. In general, it is recommended to resect the scars of any previous surgery. Localized resection of the tumor has been employed after multiple recurrences or after previous total parotidectomy when it is the only option to preserve the facial nerve [10, 14]. Superficial or total parotidectomy, depending on the location of the recurrence, has been suggested when the previous operation was a simple local excision [6, 8‐15, 17, 18, 20, 23‐25]. Radical and extended parotidectomies have been considered for patients with infiltration of branches or the main trunk of the facial nerve, and in cases of multinodular recurrences [9, 11‐13, 15, 18, 23‐25]. In particular, facial nerve resection has been suggested for patients with a history of multiple recurrences or failed radiotherapy [24]. In 30.3% of our patients, the resection of at least a branch of the facial nerve was performed (Table 2). Facial nerve dissection and preservation were performed in all cases with still healthy parotid tissue between the nerve and the tumor, and in the case of facial nerve encasement when a patient refused facial nerve resection. The observation of many cases with unexpected multinodularity persuaded Stennert et al. [4] to routinely perform a total parotidectomy for all RPAs. However, such an aggressive policy of treatment does not prevent leaving microscopic residuals; indeed, a recent study by the same group reported a 52% probability of new recurrences [18].

The role of radiotherapy remains questionable [9, 13, 16, 17, 24, 27]. Some authors suggest that radiotherapy should be reserved only for malignant tumors since it carries, especially in young people, a risk of malignant transformation that increases over time [17]. Nonetheless, its use is not infrequent [6, 9, 13‐16, 19, 20, 27]. Jackson et al. [9] used postoperative radiotherapy in patients in whom histology showed that resection margins of the specimen were not free of tumor or in those with intraoperative spillage of tumor. Renehan et al. [13] recommended postoperative radiotherapy in multinodular recurrences. Douglas et al. [16] reported their experience of fast neutron radiotherapy and recommended radiotherapy for selected cases: when complete extirpation is not possible, when sacrifice of the facial nerve is necessary, or after multiple recurrences. Glas et al. [17] suggested postoperative radiotherapy for difficult cases in which further surgical treatment of recurrent disease is not recommended for technical reasons. Kamida et al. [27] suggested the use of stereotactic radiosurgery for difficult selected cases, such as the patient they treated for skull base invasion with no regrowth after 5 years. Our experience, including only nine patients, is too limited to draw any conclusion about indications for radiation therapy.

Complications of treatment of RPA are similar to those for primary surgery for parotid pleomorphic adenoma. The main difference is the higher risk of facial nerve damage in the former, with unexpected permanent facial nerve paralysis in more than 30% of cases [24].

Even though we did not have cases of malignant transformation, a high incidence is expected, especially after multiple recurrences, reaching up to 15% in the experience of Mercante et al. [22].

The main purpose of our study was to analyze risk factors for new recurrence after treatment for RPA. The percentage of new recurrences varies from 10 to 58% [8, 10, 12‐15, 17‐20, 23‐25]. In two surveys of the literature with a 10-year follow-up, the prevalence of a new recurrence was 43 and 45%, respectively [12, 25]. Wittekindt et al. [18] reported a recurrence rate increasing from 42% at 5 years to 75% at 15 years. We observed a prevalence of 33.3% with an estimation of recurrence rate increasing from 14.1 ± 6.6% at 5 years to 31.4 ± 9.4% at 10 years, 43.0 ± 10.8% at 15 years, and 57.2 ± 14.8% at 20 years (Fig. 1).

Among the variables tested with the log-rank test against the estimated new recurrence rate (Table 5), just two were significantly associated with the likelihood of developing a new recurrence: local excision of the RPA instead of a formal parotidectomy and the presence of multinodular disease. To date, no new recurrences have been observed for uninodular recurrences. There was a trend toward increased risk of a new recurrence for deep-lobe localization, although it was not statistically significant.

Few papers have analyzed prognostic factors for RPA [13‐18]. Renehan et al. [13] studied 114 patients with first-recurrence RPA and reported significantly better, new recurrence-free survival for patients treated with postoperative radiotherapy when the RPA was multinodular. Age, gender, time to first recurrence, and the type of prior treatment were all not significant predisposing factors for a new recurrence [13]. Yugueros et al. [14] followed 39 patients treated for RPA at their institution: they found no significant difference in development of another recurrence in relation to gender, time after the previous treatment, size of the tumor, type of resection, and postoperative radiotherapy. Carew et al. [15] analyzed 31 patients treated for RPA and concluded that the extent of the first parotid operation was the only factor with a statistically significant impact on tumor control after resection of the recurrence. Local control was achieved in all patients whose initial procedures involved local excision. Superficial lobe location and postoperative radiotherapy showed better results but were not significant [15]. Fast neutron radiotherapy of 16 patients with residuals of RPA stopped progression of the tumor in patients without gross residuals, without multifocal disease and with an interval from diagnosis of less than 25 years; however, the results were not statistically significant [16]. Glas et al. [17] analyzed 52 patients with RPA, treated after one or more recurrences: no significant influence was seen in the recurrence rate with respect to gender, age at initial treatment, time of first recurrence, and intraoperative tumor spillage. Wittekindt et al. [18], in a group of 108 patients, observed a significantly higher rate of new recurrences in female patients, in younger patients, and in patients treated with a simple enucleation.