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Recurrent pleomorphic adenoma of the parotid gland
The American Journal of Surgery 189 (2005) 203–207
Scientific paper
Recurrent pleomorphic adenoma of the parotid gland Peter Zbären, M.D.a,*, Isabelle Tschumi, M.D.a, Michel Nuyens, M.D.a, Edouard Stauffer, M.D.b a
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Berne, CH-3010 Berne, Switzerland b Department of Pathology, University Hospital, University of Berne, CH-3000 Berne, Switzerland Manuscript received November 7, 2003; revised manuscript April 15, 2004
Abstract Background: Surgery of recurrent pleomorphic adenoma presents an increased risk of facial nerve injury and a considerable re-recurrence rate. Methods: A series of 33 patients with first recurrence of pleomorphic adenoma of the parotid gland was analyzed. The data were derived from medical records as well as from interviews and clinical examinations of all living patients. Histologic material of the initial and recurrent tumor were reviewed. Results: Multifocal recurrence and carcinoma in pleomorphic adenoma were observed in 73% and 9% of patients, respectively. The incidence of permanent partial facial nerve injury after surgery was 23% in patients with initial enucleation and 14% in those with initial superficial parotidectomy (including 1 patient with facial nerve resection and 1 patient with a partial facial paresis before recurrence surgery). A subsequent recurrence occurred in 6 patients, all with initial enucleation after a mean time interval of 9 years. Conclusions: The preservation of the facial nerve was possible in all but 1 patient treated for the first recurrence with a relatively low rate of permanent partial facial paresis because of the use of the operating microscope and facial nerve monitor. To evaluate the re-recurrence rate, a follow-up of at least 10 years is necessary. © 2005 Excerpta Medica Inc. All rights reserved. Keywords: Facial damage; Parotid gland; Recurrent pleomorphic adenoma; Re-recurrence
Pleomorphic adenoma is the most common type of salivary gland tumor and accounts for approximately 60% of all parotid tumors. It has a natural history of slow growth during a long period of time. It generates considerable interest for 2 reasons: the relatively high recurrence rate reported to be between 4% and 45%, depending to a great extent on the initial surgical technique used [1– 4], and the potential for malignant degeneration, which ranges from 2% to 24% [5,6]. The treatment of recurrent pleomorphic adenoma is a challenge. On the one hand, revision surgery is less likely to control the tumor than the initial surgery; on the other hand, facial nerve damage is increased because of a scarred operative field. In the present study, we reviewed our institutional experience with the treatment and outcome of recurrent pleomorphic adenoma of the parotid gland. Furthermore, we evaluated the initial treatment and its impact for further recurrences. * Corresponding author. Tel.: ⫹41-31-632-9633; Fax: ⫹41-31-632-8809. E-mail address: [email protected]
Patients and Methods From 1983 to 2001, 42 surgical parotid procedures were performed at our institution for recurrent pleomorphic adenoma after previous surgery: 33 patients had a single previous surgery, whereas 2, 3, and 4 previous operations had been performed in 5, 2, and 2 patients, respectively. Thirtythree patients with a single previous surgery represent the basis of this report. Patients referred after primary surgery with incomplete excision were categorized as having residual disease and excluded from the study. The data—such as clinical and pathologic features, types of initial surgery and surgery of the recurrence, complications, and local control—were derived from medical records, interviews, and physical examinations of all living patients (N ⫽ 27). All 33 surgical specimens of recurrences and 25 of 33 primary tumors were histopathologically reviewed by one of the investigators (E. S.). The histologic slices of the primary tumor were not available for 8 patients, but the original histologic report of the initial tumor was present for 5 of them. In 3 patients, neither the histologic
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slices nor the original pathologic report of the primary tumor were available, but anamnestic data and the multicentricity of the first recurrence in these 3 patients suggested the initial tumor was a pleomorphic adenoma. All tumors were classified according to the 1991 World Health Organization histologic classification for salivary gland tumors [7]. The follow-up period varied from 15 to 224 months (average 100). The study population comprised 18 women and 15 men with an average age of 49 years (range 24 to 81) at the time of the first recurrence. Nomenclature of parotid surgical techniques Enucleation consists of the resection of a parotid tumor without previous identification of the facial nerve and its branches. The tumor is approached directly and resected with or without a cuff of normal parotid tissue. It was the original technique for removal of benign parotid tumors [8]. Superficial parotidectomy involves the ablation of the parotid tissue superficial to the facial nerve and its branches after identification and dissection of the facial nerve branches [9,10]. Total parotidectomy starts with a superficial parotidectomy followed by the dissection of the facial nerve from the underlying parotid tissue, which is then removed. In this operation, the entire parotid gland is supposed to be removed, and the facial nerve is preserved. Klopp and Winship [11] used subtotal parotidectomy for the first time in 1950. They stated that the parotid gland has numerous extensions that make total removal of the gland difficult and that it is preferable to refer to the procedure as subtotal rather than total parotidectomy. This statement is quite realistic— especially for surgery of recurrent tumors— and has been used by other investigators [12,13].
Results Clinicopathologic characteristic of primary pleomorphic adenoma Average age at the time of surgery of the initial tumor was 34 years (range 17 to 64). Twenty-six patients received their primary treatment elsewhere. Seven patients underwent superficial parotidectomy, and 26 patients underwent enucleation as the initial treatment. In 25 patients, the histologic slices of the initial pleomorphic adenoma were available, and the tumor type was re-evaluated and classified as cellular type (cell rich) in 6 patients (24%), as hypocellular type (mixoid or stroma rich) in 4 patients (16%), and as classical type in 15 patients (60%). Clinicopathologic characteristic of first recurrence Treatment modalities and clinicopathologic findings of the recurrences are listed in Table 1. The overall average
interval between initial surgery and recurrence was 181 months (range 24 to 606). At the time of admission for treatment of the first recurrence, 1 of 33 patients presented a slight partial facial weakness. In all but 1 patient the facial nerve was preserved during recurrence surgery. One patient with an initial enucleation required resection of the facial nerve and reconstruction with a suralis nerve graft. Recurrence—a movable nodule in the cervical part of the scar— was treated by local resection in 1 patient and by subtotal parotidectomy in 6 patients. None of the patients underwent postoperative radiotherapy. Multifocal recurrence was observed on histologic analysis in 24 of 33 patients (73%). Two to 5 nodules in 7 specimens, 6 to 20 nodules in 11 specimens, and ⬎20 nodules in 6 specimens (Fig. 1) were observed. Multifocal recurrence was observed in all 3 patients without histologic slices and histologic report of the initial pleomorphic adenoma, 6 to 20 nodules in 1 patient and ⬎20 nodules in the other 2 patients. The nodule size varied from 0.2 to 30 mm. Seven of 33 recurrent tumors presented with hypocellular pleomorphic, 6 with hypercellular, and 20 with classicaltype adenoma. In 14 of 25 patients with available histologic slices of the primary tumor, the recurrent tumors presented as the same histologic type as the initial pleomorphic adenoma; in 11 patients, the recurrent tumors did not present as the same histologic type. Three patients (9%) had malignant tumor transformation 24, 25, and 30 years, respectively, after the initial treatment of the pleomorphic adenoma. In 2 of these patients, ⬎20 nodules of recurrent pleomorphic adenoma were present; in the third patient, a unique nodule with the carcinoma was found on histologic analysis. Postoperative facial nerve status and follow-up During follow-up after the surgical procedure for the first recurrence, complete facial paresis was observed in none of the patients. Permanent partial facial paresis occurred in 7 of
Table 1 Treatment modalities and clinicopathologic findings of recurrent tumors Findings
Treatment Local resection Superficial parotidectomy Subtotal parotidectomy Histopathology Uninodular recurrence Mutlinodular recurrence Malignant transformation Follow-up Permanent facial paresis Subsequent recurrence
Recurrences after initial enucleation (N ⫽ 26)
Recurrences after initial superficial parotidectomy (N ⫽ 7) 1
11 15
6
7 10 3
2 5
6 6
1
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number of patients even a superficial or total parotidectomy with facial nerve preservation incorporates the principle of limited enucleation or capsular dissection at some point in the technique [5]. Intraoperative tumor spill during parotidectomy, when properly managed, did not seem to be associated with an increased rate of tumor recurrence [20,21]. For some surgeons, a partial superficial parotidectomy has evolved as an ideal procedure [18,22]. However, most—as we do—prefer a superficial parotidectomy to maximize safety in both excision and nerve preservation while also providing a clear view of the whole operative field [17,19] and advocate that enucleation for pleomorphic adenoma should no longer be performed. Age at first presentation and recurrence interval Fig. 1. Recurrent pleomorphic adenoma: multiple tumor nodules in the periglandular fat tissue.
33 patients (21%). The marginal mandibular branch was the most commonly injured division of the facial nerve. A subsequent tumor recurrence occurred in 6 of 33 (18%) patients after a mean interval between the first and second recurrence of 105 months (range 46 to 192). One patient developed a third recurrence 14 years later. The re-recurrence rate of our 11 patients with at least 10 years follow-up after the first recurrence is 5 of 11 (45%).
Discussion Initial treatment The technique of enucleation of primary pleomorphic adenoma was based on the idea that these tumors were encased in a firm capsule. However, recurrence rates after enucleation were as high as 45% [2,4]. Microscopic anatomic studies showed that pleomorphic adenoma presents often with a focal absence of a capsule; furthermore, capsular herniation, pseudopodia, and satellite nodules are frequently observed [3,14 –17]. During surgery, especially with the enucleation technique, small lobulations or pseudopodia of tumor outside the presumed capsule can be detached and left within the normal salivary gland tissue [3,14,16] (Fig. 2). The high recurrence rate after enucleation led to a change in treatment philosophy. The enucleation technique was replaced by a superficial parotidectomy for tumors in the superficial lobe. Since the introduction of this technique, the recurrence rate decreased to 2% to 5% in the last decades [15]. However, several investigators have reported that the recurrence rate after extracapsular dissection of pleomorphic adenoma is the same as that after superficial parotidectomy [18,19]. They advocated that a few millimeters of surrounding parotid tissue might be sufficient for complete resection of a pleomorphic adenoma. In addition, in a large
Several investigators have reported that the mean age of initial presentation of pleomorphic adenoma among patients who later developed recurrence was significantly lower than the mean age of those who remained free of disease on long-term follow-up [4,23]. We can confirm this observation because the mean age at the initial presentation of our patients with recurrence was 34 years, whereas the mean age of patients remaining free of disease according to the literature is 42 to 48 years [19,22,23]. The median interval between the initial surgery and tumor recurrence is reported to be between 3 and 15 years [3,24,25]. Surgical treatment of recurrent pleomorphic adenoma The surgical treatment of recurrent pleomorphic adenoma is a challenge and has never been standardized. Of the different surgical procedures described in the literature, no procedure seems to be superior to another [1,26]. Recurrences after enucleation are more likely treated by superficial parotidectomy or total parotidectomy, a uninodular recurrence after superficial parotidectomy by local excision,
Fig. 2. Tumor bud of a pleomorphic adenoma bound by a fibrous capsule (arrows).
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and a multinodular recurrence by total parotidectomy [1,25]. The type of surgery applied in our series was based on the extent and location of the recurrence as well as the type of surgical procedure done initially. Most investigators agree that the type of surgery used to treat recurrent pleomorphic adenoma must be individualized [24,25,27] to consider the extent of the previous surgery, the type of recurrence, and the patient’s age. Dealing with the facial nerve Permanent partial facial nerve injury is a pertinent risk when treating recurrent parotid pleomorphic adenoma. The incidence in this series was 21%, which is comparable with the incidence of 15% to 29% published elsewhere [1]. The facial nerve can be very difficult to identify because of the presence of scar tissue, especially after an initial superficial or total parotidectomy. In older series, a radical resection of recurrent tumor, sacrificing even the facial nerve, was reported [14,28]. Conley and Clairmont [14] estimated the necessity of having to sacrifice the facial nerve during surgery of recurrent pleomorphic adenoma in 14% of patients. Nevertheless, total parotidectomy with facial nerve sacrifice does not prevent a further recurrence in all patients [26,29]. Most investigators express reservation about sacrificing the facial nerve for a benign tumor [26,27]. Currently, and related to the use of an operating microscope and intraoperative facial nerve monitoring, nerve dissection and preservation is possible in most cases of first recurrence surgery as shown in our series. However, only a few published reports exist on facial nerve monitoring during parotid surgery [30 –34]. Although most investigators suggest that facial nerve monitoring during primary parotidectomy decreases the incidence of postoperative facial paresis [30 – 32], Witt [33] concluded in his study that “intraoperative facial nerve monitoring for a mobile parotid mass of the superficial lobe is not the standard of care.” In fact, only a prospective randomized study, which according to Dulgerov et al [30] might be unethical, could settle the role of routine facial nerve monitoring in parotid surgery. Olsen and Daube [34] used facial nerve monitoring in 7 patients operated on for recurrent pleomorphic adenoma and concluded that “facial nerve monitoring is not a replacement for an experienced surgeon“ but “as an adjunct, it has proved extremely beneficial.” Adjuvant radiotherapy Radiation has been proposed as adjuvant therapy after primary surgery–most often after enucleations–in view of the high recurrence rate of pleomorphic adenomas in earlier series [8]. Most investigators are reticent about postoperative radiotherapy [25,35–37]. Watkin et al [38] stated that, “it is difficult to justify irradiating this region in an attempt to prevent recurrence of a benign tumor when a safer and
probably superior treatment—formal parotidectomy—is so well documented.” The role of adjuvant radiation therapy after surgical treatment of recurrent pleomorphic adenoma is still debated. Renehan et al [1] suggested adjuvant radiotherapy for multinodular recurrences, whereas Glas et al [27] stated that radiation therapy should be reserved for difficult patients in whom further surgical treatment is not recommended for technical reasons. According to Dawson [36], radiation therapy should be considered after piecemeal removal or residual disease or for a second or subsequent recurrent tumor. Some investigators advocate radiation, preferring to leave microscopic disease rather than sacrificing the nerve [39], although others opt against it [20,38]. The major risk of adjuvant radiotherapy is the development of a secondary malignancy, which may occur 20 to 30 years after treatment. Pleomorphic adenoma often presents in young people, as in our series, with an average age of 49 years at the time of first recurrence. Therefore, we do not include radiotherapy in the treatment modality for a first recurrence in those relatively young patients. Characteristics of recurrent tumors Whereas primary tumors are extremely rarely multifocal [16,17], 33% to 98% of recurrent pleomorphic adenomas are multifocal [1,21,24,27,40 – 42], thus rendering radical treatment difficult. According to the literature, hypocellular pleomorphic adenomas with abundant chondromyxoid stroma tend to recur more often than hypercellular tumor types. They present more frequently with focal absence of the pseudocapsule and with pseudopodia and satellite nodules than the other histologic subtypes [3,4,23]. In our series, in contrast, 15 and 6 of 25 recurrent tumors with available slices of primary pleomorphic adenoma presented initially with a classical and cell-rich histologic type, respectively. Furthermore, the histologic subtype of the initial and the recurrent pleomorphic adenoma were not identical in 11 patients. The de novo malignant transformation of recurrent pleomorphic adenoma is reported in 1.5% to 23% [5,6,29]. The risk appears to increase with time and with the number of recurrences. Follow-up The recurrence rate for patients who were operated on for a first re-recurrence has been reported as 15% to 35% [1,6,21,25,27]. Yugueros et al [25] observed re-recurrences only in patients with an initial formal parotidectomy, whereas in the current series all 6 patients with recurrence were treated initially by enucleation. Taking into consideration only patients with at least a 10 year follow-up, the re-recurrence rate in our study was 45% and in the study by Phillips and Olsen [6] was 43%. In conclusion, recurrent pleomorphic adenoma occurs frequently in young patients with initial pleomorphic ade-
P. Zbären et al. / The American Journal of Surgery 189 (2005) 203–207
noma treated by enucleation; therefore, a pleomorphic adenoma in the lateral lobe, especially in young persons, should be treated by superficial parotidectomy. The preservation of the facial nerve was possible in all but 1 patient treated for the first recurrence. Revision surgery is challenging, time consuming, and difficult. An operating microscope and a facial nerve monitor should be available. The mean interval between the first recurrence and re-recurrence was 9 years. To evaluate the re-recurrence rate accurately, a follow-up of at least 10 years is necessary. In contrast to the literature, most of the recurrent pleomorphic adenomas in the current series initially did not present with the hypocellular type, but with the classical type. In approximately half of the patients, the histologic subtype of the initial and recurrent pleomorphic adenoma were not identical.
References [1] Renehan A, Gleave EN, McGurk M. An analysis of the treatment of 114 patients with recurrent pleomorphic adenomas of the parotid gland. Am J Surg 1996;172:710 –14. [2] Donovan DT, Conley JJ. Capsular significance in parotid tumor surgery: reality and myths of lateral lobectomy. Laryngoscope 1984; 94:324 –9. [3] Naeim F, Forsberg MI, Waisman J, et al. Mixed tumors of the salivary glands. Growth pattern and recurrence. Arch Pathol Lab Med 1976;100:271–5. [4] Krolls SO, Boyers RC. Mixed tumors of salivary glands. Long-term follow-up. Cancer 1972;30:276 – 81. [5] Gunn A, Parrott NR. Parotid tumours: a review of parotid tumour surgery in the Northern Regional Health Authority of the United Kingdom 1978 –1982. Br J Surg 1988;75:1144 – 6. [6] Phillips PP, Olsen KD. Recurrent pleomorphic adenoma of the parotid gland: report of 126 cases and a review of the literature. Ann Otol Rhinol Laryngol 1995;104:100 – 4. [7] Seifert G, Sobin LH. Histological typing of salivary gland tumors. Berlin, Germany: Springer Verlag; 1997. [8] Patey DH. The treatment of mixed tumours of the parotid gland. Br J Surg 1940;28:29 –38 [9] Patey DH, Ranger I. Some points in the surgical anatomy of the parotid gland. Br J Surg 1957;45:250 – 8. [10] Sistrunk WE. Mixed tumours of the parotid gland. Minn Med 1921; 4:155– 60 [11] Klopp CT, Winship T. Treatment of mixed tumors of the parotid gland by subtotal parotidectomy. Arch Surg 1950;61:477– 86. [12] Rodriguez-Bigas MA, Sako K, Razack MS, et al. Benign parotid tumors: a 24-year experience. J Surg Oncol 1991;46:159 – 61. [13] Zoa Chang E, Lee WL. Surgical treatment of pleomorphic adenoma of the parotid gland: report of 110 cases. J Oral Maxillofac Surg 1985;43:680 –2. [14] Conley J, Clairmont AA. Facial nerve in recurrent benign pleomorphic adenoma. Arch Otolaryngol 1979;105:247–51. [15] Henrikkson G, Westrin KM, Carlsöö B, et al. Recurrent primary pleomorphic adenomas of salivary gland origin. Intrasurgical rupture, histopathologic features, and pseudopodia. Cancer 1998;82:617–20. [16] Webb AJ, Eveson JW. Pleomorphic adenomas of the major salivary glands: a study of the capsular form in relation to surgical management. Clin Otolaryngol 2001;26:134 – 42. [17] Stennert E, Guntinas-Lichius O, Klussmann JP, et al. Histopathology of pleomorphic adenoma in the parotid gland: a prospective unselected series of 100 cases. Laryngoscope 2001;111:2195–200.
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[18] Iizuka K, Ishikawa K. Surgical techniques for benign parotid tumors: segmental resection vs extracapsular lumpectomy. Acta Otolaryngol 1998;537:75– 81. [19] Witt RL. The significance of the margin in parotid surgery for pleomorphic adenoma. Laryngoscope 2002;112:2141–54. [20] Buchman C, Stringer SP, Mendenhall WM, et al. Pleomorphic adenoma: effect of tumor spill and inadequate resection on tumor recurrence. Laryngoscope 1994;104:1231– 4. [21] Natvig K, Soberg R. Relationship of intraoperative rupture of pleomorphic adenomas to recurrence: an 11–25 year follow-up study. Head Neck 1994;16:213–7. [22] Liu FF, Rotstein L, Davison JA, et al. Benign parotid adenomas: a review of the Princess Margaret Hospital experience. Head Neck 1995;17:177– 83. [23] McGregor AD, Burgoyne M, Tan KC. Recurrent pleomorphic salivary adenoma–the relevance of age at first presentation. Br J Plast Surg 1988;41:177– 81. [24] Leverstein H, Tiwari RM, Snow GB, et al. The surgical management of recurrent or residual pleomorphic adenomas of the parotid gland. Analysis and results in 40 patients. Eur Arch Otorhinolaryngol 1997; 254:313–7. [25] Yugueros P, Goellner JR, Petty PM, et al. Treating recurrence of parotid benign pleomorphic adenomas. Ann Plast Surg 1998;40:573– 6. [26] Piorkowski RJ, Guillamondegui OM. Is aggressive surgical treatment indicated for recurrent benign mixed tumors of the parotid gland? Am J Surg 1981;142:434 – 6. [27] Glas AS, Vermey A, Hollema H, et al. Surgical treatment of recurrent pleomorphic adenoma of the parotid gland: a clinical analysis of 52 patients. Head Neck 2001;23:311– 6. [28] Work WP, Batsakis JG, Bailey DG. Recurrent benign mixed tumor and the facial nerve. Arch Otolaryngol 1976;102:15–9. [29] Niparko JK, Beauchamp ML, Krause CJ, et al. Surgical treatment of recurrent pleomorphic adenoma of the parotid gland. Arch Otolaryngol Head Neck Surg 1986;112:1180 – 4. [30] Dulgerov P, Marchal F, Lehmann W. Post parotidectomy facial nerve paralysis: possible etiologic factors and results with routine facial nerve monitoring. Laryngoscope 1999;105:754 – 62. [31] Terrel JE, Kileny PR, Yian C, et al. Clinical outcome of continuous facial nerve monitoring during primary parotidectomy. Arch Otolaryngol Head Neck Surg 1997;123:1081–7. [32] Wolf SR, Schneider W, Suchy B, et al. Intraoperative facial nerve monitoring in parotid gland surgery. HNO 1995;43:294 – 8. [33] Witt RL. Facial nerve monitoring in parotid surgery: the standard care? Otorhinolaryngol Head Neck Surg 1997;119:468 –70. [34] Olsen KD, Daube JR. Intraoperative monitoring of the facial nerve: an aid in the management of parotid gland recurrent pleomorphic adenomas. Laryngoscope 1994;104:229 –32. [35] Schot LJ, Hilgers FJM, Keers RB, et al. Late effects of radiotherapy on hearing. Eur Arch Otorhinolaryngol 1992;249:305– 8. [36] Dawson AK. Radiation therapy in recurrent pleomorphic adenoma of the parotid. Int J Radiat Oncol Biol Phys 1989;16:819 –21. [37] Fleming WB. Recurrent pleomorphic adenoma of the parotid. Aust N Z J Surg 1987;57:173– 6. [38] Watkin GT, Hobsley M. Influence of local surgery and radiotherapy on the natural history of pleomorphic adenomas. Br J Surg 1986;73:74 – 6. [39] Samson MJ, Metson R, Wang CC, et al. Preservation of the facial nerve in the management of recurrent pleomorphic adenoma. Laryngoscope 1991;101:1060 –2. [40] Stennert E, Wittekindt C, Klussmann P et al. Recurrent pleomorphic adenoma of the parotid gland: a prospective histopathological and immunohistochemical study. Laryngoscope 2004;114:158 – 63. [41] Bradley PJ. Recurrent salivay gland pleomorphic adenoma: etiology, management, and results. Curr Opin Otolaryngol Head Neck Surg 2001;9:100 – 8. [42] Carew JF, Spiro RH, Singh B, et al. Treatment of recurrent pleomorphic adenomas of the parotid gland. Otolaryngol Head Neck Surg 1999;121:539 – 42.
Scientific paper
Recurrent pleomorphic adenoma of the parotid gland Peter Zbären, M.D.a,*, Isabelle Tschumi, M.D.a, Michel Nuyens, M.D.a, Edouard Stauffer, M.D.b a
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital, University of Berne, CH-3010 Berne, Switzerland b Department of Pathology, University Hospital, University of Berne, CH-3000 Berne, Switzerland Manuscript received November 7, 2003; revised manuscript April 15, 2004
Abstract Background: Surgery of recurrent pleomorphic adenoma presents an increased risk of facial nerve injury and a considerable re-recurrence rate. Methods: A series of 33 patients with first recurrence of pleomorphic adenoma of the parotid gland was analyzed. The data were derived from medical records as well as from interviews and clinical examinations of all living patients. Histologic material of the initial and recurrent tumor were reviewed. Results: Multifocal recurrence and carcinoma in pleomorphic adenoma were observed in 73% and 9% of patients, respectively. The incidence of permanent partial facial nerve injury after surgery was 23% in patients with initial enucleation and 14% in those with initial superficial parotidectomy (including 1 patient with facial nerve resection and 1 patient with a partial facial paresis before recurrence surgery). A subsequent recurrence occurred in 6 patients, all with initial enucleation after a mean time interval of 9 years. Conclusions: The preservation of the facial nerve was possible in all but 1 patient treated for the first recurrence with a relatively low rate of permanent partial facial paresis because of the use of the operating microscope and facial nerve monitor. To evaluate the re-recurrence rate, a follow-up of at least 10 years is necessary. © 2005 Excerpta Medica Inc. All rights reserved. Keywords: Facial damage; Parotid gland; Recurrent pleomorphic adenoma; Re-recurrence
Pleomorphic adenoma is the most common type of salivary gland tumor and accounts for approximately 60% of all parotid tumors. It has a natural history of slow growth during a long period of time. It generates considerable interest for 2 reasons: the relatively high recurrence rate reported to be between 4% and 45%, depending to a great extent on the initial surgical technique used [1– 4], and the potential for malignant degeneration, which ranges from 2% to 24% [5,6]. The treatment of recurrent pleomorphic adenoma is a challenge. On the one hand, revision surgery is less likely to control the tumor than the initial surgery; on the other hand, facial nerve damage is increased because of a scarred operative field. In the present study, we reviewed our institutional experience with the treatment and outcome of recurrent pleomorphic adenoma of the parotid gland. Furthermore, we evaluated the initial treatment and its impact for further recurrences. * Corresponding author. Tel.: ⫹41-31-632-9633; Fax: ⫹41-31-632-8809. E-mail address: [email protected]
Patients and Methods From 1983 to 2001, 42 surgical parotid procedures were performed at our institution for recurrent pleomorphic adenoma after previous surgery: 33 patients had a single previous surgery, whereas 2, 3, and 4 previous operations had been performed in 5, 2, and 2 patients, respectively. Thirtythree patients with a single previous surgery represent the basis of this report. Patients referred after primary surgery with incomplete excision were categorized as having residual disease and excluded from the study. The data—such as clinical and pathologic features, types of initial surgery and surgery of the recurrence, complications, and local control—were derived from medical records, interviews, and physical examinations of all living patients (N ⫽ 27). All 33 surgical specimens of recurrences and 25 of 33 primary tumors were histopathologically reviewed by one of the investigators (E. S.). The histologic slices of the primary tumor were not available for 8 patients, but the original histologic report of the initial tumor was present for 5 of them. In 3 patients, neither the histologic
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slices nor the original pathologic report of the primary tumor were available, but anamnestic data and the multicentricity of the first recurrence in these 3 patients suggested the initial tumor was a pleomorphic adenoma. All tumors were classified according to the 1991 World Health Organization histologic classification for salivary gland tumors [7]. The follow-up period varied from 15 to 224 months (average 100). The study population comprised 18 women and 15 men with an average age of 49 years (range 24 to 81) at the time of the first recurrence. Nomenclature of parotid surgical techniques Enucleation consists of the resection of a parotid tumor without previous identification of the facial nerve and its branches. The tumor is approached directly and resected with or without a cuff of normal parotid tissue. It was the original technique for removal of benign parotid tumors [8]. Superficial parotidectomy involves the ablation of the parotid tissue superficial to the facial nerve and its branches after identification and dissection of the facial nerve branches [9,10]. Total parotidectomy starts with a superficial parotidectomy followed by the dissection of the facial nerve from the underlying parotid tissue, which is then removed. In this operation, the entire parotid gland is supposed to be removed, and the facial nerve is preserved. Klopp and Winship [11] used subtotal parotidectomy for the first time in 1950. They stated that the parotid gland has numerous extensions that make total removal of the gland difficult and that it is preferable to refer to the procedure as subtotal rather than total parotidectomy. This statement is quite realistic— especially for surgery of recurrent tumors— and has been used by other investigators [12,13].
Results Clinicopathologic characteristic of primary pleomorphic adenoma Average age at the time of surgery of the initial tumor was 34 years (range 17 to 64). Twenty-six patients received their primary treatment elsewhere. Seven patients underwent superficial parotidectomy, and 26 patients underwent enucleation as the initial treatment. In 25 patients, the histologic slices of the initial pleomorphic adenoma were available, and the tumor type was re-evaluated and classified as cellular type (cell rich) in 6 patients (24%), as hypocellular type (mixoid or stroma rich) in 4 patients (16%), and as classical type in 15 patients (60%). Clinicopathologic characteristic of first recurrence Treatment modalities and clinicopathologic findings of the recurrences are listed in Table 1. The overall average
interval between initial surgery and recurrence was 181 months (range 24 to 606). At the time of admission for treatment of the first recurrence, 1 of 33 patients presented a slight partial facial weakness. In all but 1 patient the facial nerve was preserved during recurrence surgery. One patient with an initial enucleation required resection of the facial nerve and reconstruction with a suralis nerve graft. Recurrence—a movable nodule in the cervical part of the scar— was treated by local resection in 1 patient and by subtotal parotidectomy in 6 patients. None of the patients underwent postoperative radiotherapy. Multifocal recurrence was observed on histologic analysis in 24 of 33 patients (73%). Two to 5 nodules in 7 specimens, 6 to 20 nodules in 11 specimens, and ⬎20 nodules in 6 specimens (Fig. 1) were observed. Multifocal recurrence was observed in all 3 patients without histologic slices and histologic report of the initial pleomorphic adenoma, 6 to 20 nodules in 1 patient and ⬎20 nodules in the other 2 patients. The nodule size varied from 0.2 to 30 mm. Seven of 33 recurrent tumors presented with hypocellular pleomorphic, 6 with hypercellular, and 20 with classicaltype adenoma. In 14 of 25 patients with available histologic slices of the primary tumor, the recurrent tumors presented as the same histologic type as the initial pleomorphic adenoma; in 11 patients, the recurrent tumors did not present as the same histologic type. Three patients (9%) had malignant tumor transformation 24, 25, and 30 years, respectively, after the initial treatment of the pleomorphic adenoma. In 2 of these patients, ⬎20 nodules of recurrent pleomorphic adenoma were present; in the third patient, a unique nodule with the carcinoma was found on histologic analysis. Postoperative facial nerve status and follow-up During follow-up after the surgical procedure for the first recurrence, complete facial paresis was observed in none of the patients. Permanent partial facial paresis occurred in 7 of
Table 1 Treatment modalities and clinicopathologic findings of recurrent tumors Findings
Treatment Local resection Superficial parotidectomy Subtotal parotidectomy Histopathology Uninodular recurrence Mutlinodular recurrence Malignant transformation Follow-up Permanent facial paresis Subsequent recurrence
Recurrences after initial enucleation (N ⫽ 26)
Recurrences after initial superficial parotidectomy (N ⫽ 7) 1
11 15
6
7 10 3
2 5
6 6
1
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number of patients even a superficial or total parotidectomy with facial nerve preservation incorporates the principle of limited enucleation or capsular dissection at some point in the technique [5]. Intraoperative tumor spill during parotidectomy, when properly managed, did not seem to be associated with an increased rate of tumor recurrence [20,21]. For some surgeons, a partial superficial parotidectomy has evolved as an ideal procedure [18,22]. However, most—as we do—prefer a superficial parotidectomy to maximize safety in both excision and nerve preservation while also providing a clear view of the whole operative field [17,19] and advocate that enucleation for pleomorphic adenoma should no longer be performed. Age at first presentation and recurrence interval Fig. 1. Recurrent pleomorphic adenoma: multiple tumor nodules in the periglandular fat tissue.
33 patients (21%). The marginal mandibular branch was the most commonly injured division of the facial nerve. A subsequent tumor recurrence occurred in 6 of 33 (18%) patients after a mean interval between the first and second recurrence of 105 months (range 46 to 192). One patient developed a third recurrence 14 years later. The re-recurrence rate of our 11 patients with at least 10 years follow-up after the first recurrence is 5 of 11 (45%).
Discussion Initial treatment The technique of enucleation of primary pleomorphic adenoma was based on the idea that these tumors were encased in a firm capsule. However, recurrence rates after enucleation were as high as 45% [2,4]. Microscopic anatomic studies showed that pleomorphic adenoma presents often with a focal absence of a capsule; furthermore, capsular herniation, pseudopodia, and satellite nodules are frequently observed [3,14 –17]. During surgery, especially with the enucleation technique, small lobulations or pseudopodia of tumor outside the presumed capsule can be detached and left within the normal salivary gland tissue [3,14,16] (Fig. 2). The high recurrence rate after enucleation led to a change in treatment philosophy. The enucleation technique was replaced by a superficial parotidectomy for tumors in the superficial lobe. Since the introduction of this technique, the recurrence rate decreased to 2% to 5% in the last decades [15]. However, several investigators have reported that the recurrence rate after extracapsular dissection of pleomorphic adenoma is the same as that after superficial parotidectomy [18,19]. They advocated that a few millimeters of surrounding parotid tissue might be sufficient for complete resection of a pleomorphic adenoma. In addition, in a large
Several investigators have reported that the mean age of initial presentation of pleomorphic adenoma among patients who later developed recurrence was significantly lower than the mean age of those who remained free of disease on long-term follow-up [4,23]. We can confirm this observation because the mean age at the initial presentation of our patients with recurrence was 34 years, whereas the mean age of patients remaining free of disease according to the literature is 42 to 48 years [19,22,23]. The median interval between the initial surgery and tumor recurrence is reported to be between 3 and 15 years [3,24,25]. Surgical treatment of recurrent pleomorphic adenoma The surgical treatment of recurrent pleomorphic adenoma is a challenge and has never been standardized. Of the different surgical procedures described in the literature, no procedure seems to be superior to another [1,26]. Recurrences after enucleation are more likely treated by superficial parotidectomy or total parotidectomy, a uninodular recurrence after superficial parotidectomy by local excision,
Fig. 2. Tumor bud of a pleomorphic adenoma bound by a fibrous capsule (arrows).
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and a multinodular recurrence by total parotidectomy [1,25]. The type of surgery applied in our series was based on the extent and location of the recurrence as well as the type of surgical procedure done initially. Most investigators agree that the type of surgery used to treat recurrent pleomorphic adenoma must be individualized [24,25,27] to consider the extent of the previous surgery, the type of recurrence, and the patient’s age. Dealing with the facial nerve Permanent partial facial nerve injury is a pertinent risk when treating recurrent parotid pleomorphic adenoma. The incidence in this series was 21%, which is comparable with the incidence of 15% to 29% published elsewhere [1]. The facial nerve can be very difficult to identify because of the presence of scar tissue, especially after an initial superficial or total parotidectomy. In older series, a radical resection of recurrent tumor, sacrificing even the facial nerve, was reported [14,28]. Conley and Clairmont [14] estimated the necessity of having to sacrifice the facial nerve during surgery of recurrent pleomorphic adenoma in 14% of patients. Nevertheless, total parotidectomy with facial nerve sacrifice does not prevent a further recurrence in all patients [26,29]. Most investigators express reservation about sacrificing the facial nerve for a benign tumor [26,27]. Currently, and related to the use of an operating microscope and intraoperative facial nerve monitoring, nerve dissection and preservation is possible in most cases of first recurrence surgery as shown in our series. However, only a few published reports exist on facial nerve monitoring during parotid surgery [30 –34]. Although most investigators suggest that facial nerve monitoring during primary parotidectomy decreases the incidence of postoperative facial paresis [30 – 32], Witt [33] concluded in his study that “intraoperative facial nerve monitoring for a mobile parotid mass of the superficial lobe is not the standard of care.” In fact, only a prospective randomized study, which according to Dulgerov et al [30] might be unethical, could settle the role of routine facial nerve monitoring in parotid surgery. Olsen and Daube [34] used facial nerve monitoring in 7 patients operated on for recurrent pleomorphic adenoma and concluded that “facial nerve monitoring is not a replacement for an experienced surgeon“ but “as an adjunct, it has proved extremely beneficial.” Adjuvant radiotherapy Radiation has been proposed as adjuvant therapy after primary surgery–most often after enucleations–in view of the high recurrence rate of pleomorphic adenomas in earlier series [8]. Most investigators are reticent about postoperative radiotherapy [25,35–37]. Watkin et al [38] stated that, “it is difficult to justify irradiating this region in an attempt to prevent recurrence of a benign tumor when a safer and
probably superior treatment—formal parotidectomy—is so well documented.” The role of adjuvant radiation therapy after surgical treatment of recurrent pleomorphic adenoma is still debated. Renehan et al [1] suggested adjuvant radiotherapy for multinodular recurrences, whereas Glas et al [27] stated that radiation therapy should be reserved for difficult patients in whom further surgical treatment is not recommended for technical reasons. According to Dawson [36], radiation therapy should be considered after piecemeal removal or residual disease or for a second or subsequent recurrent tumor. Some investigators advocate radiation, preferring to leave microscopic disease rather than sacrificing the nerve [39], although others opt against it [20,38]. The major risk of adjuvant radiotherapy is the development of a secondary malignancy, which may occur 20 to 30 years after treatment. Pleomorphic adenoma often presents in young people, as in our series, with an average age of 49 years at the time of first recurrence. Therefore, we do not include radiotherapy in the treatment modality for a first recurrence in those relatively young patients. Characteristics of recurrent tumors Whereas primary tumors are extremely rarely multifocal [16,17], 33% to 98% of recurrent pleomorphic adenomas are multifocal [1,21,24,27,40 – 42], thus rendering radical treatment difficult. According to the literature, hypocellular pleomorphic adenomas with abundant chondromyxoid stroma tend to recur more often than hypercellular tumor types. They present more frequently with focal absence of the pseudocapsule and with pseudopodia and satellite nodules than the other histologic subtypes [3,4,23]. In our series, in contrast, 15 and 6 of 25 recurrent tumors with available slices of primary pleomorphic adenoma presented initially with a classical and cell-rich histologic type, respectively. Furthermore, the histologic subtype of the initial and the recurrent pleomorphic adenoma were not identical in 11 patients. The de novo malignant transformation of recurrent pleomorphic adenoma is reported in 1.5% to 23% [5,6,29]. The risk appears to increase with time and with the number of recurrences. Follow-up The recurrence rate for patients who were operated on for a first re-recurrence has been reported as 15% to 35% [1,6,21,25,27]. Yugueros et al [25] observed re-recurrences only in patients with an initial formal parotidectomy, whereas in the current series all 6 patients with recurrence were treated initially by enucleation. Taking into consideration only patients with at least a 10 year follow-up, the re-recurrence rate in our study was 45% and in the study by Phillips and Olsen [6] was 43%. In conclusion, recurrent pleomorphic adenoma occurs frequently in young patients with initial pleomorphic ade-
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noma treated by enucleation; therefore, a pleomorphic adenoma in the lateral lobe, especially in young persons, should be treated by superficial parotidectomy. The preservation of the facial nerve was possible in all but 1 patient treated for the first recurrence. Revision surgery is challenging, time consuming, and difficult. An operating microscope and a facial nerve monitor should be available. The mean interval between the first recurrence and re-recurrence was 9 years. To evaluate the re-recurrence rate accurately, a follow-up of at least 10 years is necessary. In contrast to the literature, most of the recurrent pleomorphic adenomas in the current series initially did not present with the hypocellular type, but with the classical type. In approximately half of the patients, the histologic subtype of the initial and recurrent pleomorphic adenoma were not identical.
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