Surgical management of adenoid cystic carcinoma in the parotid gland JOHN D. CASLER, MD, MAJ, MC. and JOHN J. CONLEY. MD. Washington. D.C., and New York, New York
Although ad.nold cy.tlc carcInoma may be found In multIpl••,tes In the head and n.ck a. w.1I a. oth.r glandular slt.s throughout the body, nowh.r.ls manag.m.nt of the dl.ease more controv.rslal than In the parotid gland. Here the facial nerve Is bt rl.k from both the dlsea •• and the treatment. Seventy-five case. of adenoId cystic carcinoma of the parotid w.r. analyzed. Patients were placed In four groups. dep.ndlng on the type of parotid .urgery recelv.d as deflnltlv. th.rapy: (1) lateral 10b.ctomy. (2) total parotld.ctomy, (3) radical parotld.ctomy without preoperative facial weakn and (4) radical parotidectomy with preoperative facial weakn.ss. Pad with regard to .taglng of the Inltlall••lon, the status of surgical tl.nts w.re a margin., ~nd the use of po.top.ratlv. radiotherapy. Th.lncldence of local recurr.nce and dl.tant m.ta.ta••• w.re al.o record.d. Survival .tatlstlcs are presented for .ach group. Though associated with facial nerve sacrifice, radical parotidectomy appears to off.r clear advantages In t.rm. of long-term dl.ea.e-free .urvlvalln patient. with Ta and Ta I.slons. Th. residual facial paralysis may be rehabilitated primarily or secondarily to reduce patl.nt morbidity. Four of 16patl.nt. (25%) with preoperatlv. weakness achl.v.d 10-y.ar .urvlval wh.n radIcal parotidectomy was used. Obtaining clear margIn. at the InItial settIng appears to offer Improved survival. (OTOlAR'r'NGOL HEAD NECK SURG 1992;106:332.)
Adenoid cystic carcinoma (ACC) may have a prolonged clinical course in which many patients are subjected to multiple recurrences and/or distant metastases over the course of 10 or 20 years. The tumor is well known for its tendency to invade perineural lymphatic spaces and to travel along nerve sheaths. In addition, this carcinoma has an unusually high rate of distant metastases. more than 40% in some series.!" In many respects it remains unpredictable and threatening.
From the Otolaryngology Service-Head and Neck Surgery (Dr. Casler), Walter Reed Army Medical Center; the Department of Otolaryngology-Head and Neck Surgery, College of Physicians and Surgeons (Dr. Conley). Columbia University; and the Department of Head and Neck Surgery (Dr. Conley). St. Vincent's Medical Center. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the U.S. Government. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery. San Diego, Calif .• Sept. 913,1990. Received for publication Jan. 7, 1991; revision received Dec. 9. 1991; accepted Dec. 18, 1991. Reprint requests: John D. Casler. MD. Department of Surgery, Walter Reed Army Medical Center, Washington. DC 20307. Z3/1/35696
332
Table 1. Staging of parotid neoplasms Stage
Diameter (em)
0.1 to 2.0 2.1 to 4.0 4,1 to 6.0 6.0
The management of ACC in the parotid gland remains controversial with respect to therapy and the consequences of therapy. The facial nerve is at risk from both the disease and the treatment. The literature is replete with articles that advocate either radical or conservative surgical approaches.':" Facial weakness resulting from nerve invasion is recognized as a very grave prognostic sign. Batsakis" has stated that, in his experience. all ACC more than I em will manifest extension into the perineural spaces. I' Whether radical surgery with facial nerve sacrifice is warranted under such circumstances is open to debate. Facial nerve sacrifice in the absence of facial weakness is an even more controversial issue. One must frequently rely on anecdotal experience in making decisions regarding the facial nerve. In order to provide a scientific basis for decision making in management of this disease, a ret-
Volume 106 Number 4 April 1992
rospective review of ACC arising within the parotid gland was undertaken.
METHODS AND MATERIAL The records of 108 patients who underwent surgical treatment for adenoid cystic carcinoma in the parotid gland were analyzed. Seventy-five charts were selected for comprehensive analysis. Approximately one half of patients were operated on primarily at our institutions. Other patients were referred for treatment after a diagnosis of ACC was made at another institution. In this case, histologic or cytologic slides were reviewed by our pathologists and the diagnosis was confirmed before further surgical treatment. Patients treated primarily underwent fine-needle aspiration. Frozen section control was used intraoperatively. If the diagnosis was equivocal, no radical surgery was performed until the diagnosis was established on permanent sections. There were no cases in which a conclusive frozen section diagnosis of ACC was changed on permanent section. Patients who manifested metastatic disease or who underwent surgery only for diagnosis were eliminated. Patients who were lost to followup before 5 years were eliminated. Patients were grouped according to the type of operation they underwent as the first definitive attempt to cure their disease. Patients who underwent facial nerve sacrifice were further subdivided according to the presence or absence of preoperative facial weakness. Four groups were thus established. Group I (lateral lobectomy with facial nerve preservation) consisted of eight patients. Three patients had T I lesions, whereas five had a T2 lesion. Group JJ (total parotidectomy with facial nerve preservation) consisted of 16 patients. Five patients were staged as T I , seven as Th and four patients had an indeterminate initial stage (T.). Group JJJ (radical parotidectomy with facial nerve sacrifice but without preoperative facial weakness) had 32 patients. Five were T I , fifteen were T2 , four were T 3 , and eight were Tx ' Group IV (radical parotidectomy with facial nerve sacrifice and with preoperative facial weakness) contained 19 patients. Two were T io nine were T 2 , six were T Jo and two were T4 • (No patient in the first three groups had preoperative facial weakness, whereas all 19 patients in group IV had preoperative facial weakness.) Radical partoidectomy was performed with the intent of obtaining at least a 1 em margin around the tumor when possible. This occasionally required including adjacent bone and muscle in the specimen, especially in cases in which surgery was performed for recurrent disease.
Adenoid cysttc carcinoma In the parotid gland 333
In cases in which no palpable neck disease was present, and the primary tumor was a T( or T2 , a sampling of nodes from the upper cervical, postauricular, and superior spinal accessory groups was included with the dissection. Patients with palpable neck disease or large T3 and T41esions received a radical or modified radical neck dissection with preservation of the spinal accessory nerve. The patients in the groups were of similar ages, with a mean age of 44.4 years. There were 29 men and 46 women, and their distribution within treatment groups showed some variation, particularly in groups II and III. Group II had 1 man and 15 women, whereas group III had 16 men and 16 women. Mean followup was 10.2 years (range, 1 to 33 years). Patients with less than a 5-year followup were not analyzed unless they had died of disease. Patients were analyzed for the stage of their initial lesion if known (Table 1), whether surgery achieved microscopically clear margin, or whether they received postoperative radiation therapy. If the "definitive" surgical procedure was performed as a salvage procedure after recurrence of the tumor; this was also noted. Information on the histologic grading of the tumors was available in some cases. The subsequent clinical course was analyzed. Notation was made if the patients had multiple (two or more) recurrences after definitive surgical therapy, and if they developed distant metastatic disease. The clinical status of the patient was ascertained at the end of followup. Patients were either free of disease, living with their disease, had died of their disease, or had died of other causes. An attempt was made to ascertain whether patients who died of their disease died of metastatic disease or from locally uncontrolled disease. The data were analyzed by use of chi-square testing to determine whether clinical outcome was related to the type of surgery performed, and to determine which factors were associated with improved survival. Table 2 shows the compiled data on the patients in the study. Table 3 compares the groups with respect to histology, perineural invasion, and presence of metastases.
RESULTS Clinical status at the end of followup for each group is shown in Table 4. Figure 1 shows actuarial survival percentages for each of the four groups. Information regarding the status of the initial surgical margins was obtainable in 64 cases. The status of surgical margins impacted significantly on disease-free status. Patients with clear surgical margins had a 59.6% disease-free rate as opposed to patients with violated
334
OtolaryngologyHead and Neck Surgery
CASLER and CONLEY
Table 2. Summary of data for patients In the study Followup Patient
no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
30 31 32 33 34 35 36 37 38
Group
I II /I /I /I II II II II II III III III III III III III III III
III III
III III
1/1
Tumor stage
Radiation therapy
Margins clear
Multiple recurrences
T, T, T, T2 T2 T2 T2 T2 T, T, T, T, T, T2 T2 T2 T2 T2 T2 T2 T, T, T, T, T, T, T, T, T, T2 T2 T2 T2 T2 T2 T2 T2 T2
+
+ +
+
+ + + +
+ + + +
?
+
?
+ + +
+
+ + +
+ + +
+ + + +
+ +
+ + + + + + +
+ + + +
Metastases
8
FOD DOD LWDm LWD FOD FOD FOD FOD LWD FOD FOD DOD LWD DOD FOD FOD DOD LWDm LWD FOD DOOm DOD FOD DOD DOD FOD FOD DOD FOD LWD LWDm FOD FOD FOD FOD FOD DODm LWDm
+
18 5 21 12 9 7 10 5 5 19 12 7, 16 5 7 5 16 5 2 11 7 5 9 6 11 4 10 5 11 16 5
+
+ + +
+ +
+
+ +
?
?
Status
3
+ ?
+
Vears
?
+ + +
Salvage surgery
+ +
+ + + + + + + +
11
12 20 6 7
FOD, Free of disease; DOD, died of disease; LWD, living with disease; m (used as in LWDm and DOOm), metastatic disease with local control; +, yes; -, no; 7, not known.
margins who had a disease-free rate of only 11.6% = 0.005). Radiation therapy did not statistically improve survival rates, though it tended to improve local control of disease. Specifically, it did not improve survival when there was a positive (violated) surgical margin. The overall rate of metastases was 50.6%. The rate of metastases to regional lymph nodes was 17.3% (13 of 75 patients). Five of these patients had involvement of periparotid nodes, which was discovered in the processing of the primary specimen. Approximately forty patients underwent local "node sampling" as part of their procedure. Of these. two patients had microscopic (p
foci of tumor noted in their upper cervical nodes. At least twenty-three patients underwent radical or modifled radical neck dissection. Three patients had palpable adenopathy that was confirmed as metastatic nodes through radical or modified radical neck dissection. The type of neck dissection used in the remaining three patients with positive nodes was not made clear in the records. It was also not clear what type of node dissection (if any) was performed in an additional twelve patients. A 33.3% rate of distant metastasis was noted. This consisted of spread to lung, bone, brain, and liver, in that relative frequency. There was a higher incidence of metastatic disease with increasing size of the primary
Volume 106 Number 4 April
Adenoid cystic carcinoma In the parotid gland UI
1992
Table 2. Confd. Patient
no. 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
Group
III III III III III III III III III III III III III III III III III III IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV
Radiation therapy
Tumor stage
T2 T2 T2 T2 T2 T2 T3 T3 T3 T3 T,
Margins clear
Followup
Multiple recurrenc..
+
+
?
+ +
+ +
+
+
+
+
+ +
+
+
+
r,
+ +
?
+
Tx
+ +
? ?
r,
Metasta..s
Salvage surgery
+
T,
r, r, r,
+
+ +
+
T, T, T2 T2 T2 T2 T2 T2 T2 T2 T2 T3 T3 T3 T3 T3 T3 T. T.
+ +
+ +
+ + +
+
+ ?
+ + +
+
+ +
+
+
+
+ +
+
+ + + + + +
+
+
+ + + + + +
+ + ?
+ + +
+ +
+
+
Vears
5 21 21 2 25 18 6 15 1 10 33 22 5 15 8 5 18 16 5 11 5 16 7 10 6 6 12 9 13 1 5 5 5 1 1 2 6
Status
DODm DOD LWDm DODm FaD FaD DOD FOD DOD DODm LWDm FaD FaD FaD FaD LWDm DODm FaD LWDm DODm FOD FaD DOD DODm FaD DODm DOD LWD FaD DOD LWD LWDm LWDm DODm DODm DODm DOD
Table 3. Group characteristics Perineural Invasion
Histology Group
I II III IV
Metasta...
Tubular
CrIbriform
aasalold
Unknown
V..
No
Unknown
Regional
3 3 5
6 8 11 6
2 6 13 19
1 2 4
5 8 15
1
5 1
1 5 13 7
lesion: 33.3% for r., 44.4% for T 2 • 80% for T3 • and 100% for T4 • Although group III had more advanced primary disease than group II. the rate of metastases was the same for the two groups (Table 5).
4
1
Distant
loth
1 6 12 6
6
The incidence of multiple recurrences varied between treatment groups and is shown in Table 5. Group II had a higher incidence of recurrence that was statistically significant at p = 0.005. Multiple recurrence was as-
336
OtolaryngologyHead and Neck Surgery
CASlER and CONLEY
100 90
80 70 60
50 40 30
20
10
o
j-__-'-
.L__ --L__ - L
o
I
5 -
Group I
~
10 Group II
-ljf-
15 Group III
I 20
-e- Group IV
FIg. 1. Actuarial survival of patients In each surgical group, plotted over time (In years).
sociated with disease-free status (Table 6). Only 12.5% of patients who had multiple recurrences were free of disease at the end of followup. Conversely, 65% of patients without multiple recurrences were free of disease at the end of followup (p = 0.005). Ten-year survival averaged 46.6% for patients with multiple recurrences, as opposed to 70.4% (p = 0.05) for patients without multiple recurrences (Table 6). A subgroup of 14 patients in group III underwent radical parotidectomy for salvage of recurrent disease (Table 4). The survival rate was less under these circumstances and reduced overall survival of patients in group III.
DISCUSSION In order to decide whether there is merit to performing radical parotidectomy with facial nerve sacrifice in the absence of preoperative facial weakness, we must focus attention on the differences between groups II and III. Any benefit to be gained from facial nerve sacrifice should be apparent when these two groups are compared. We must remember, however, that group III had patients with somewhat more advanced primary disease. Also, group II contained proportionally more women than group III. Spiro et al.? showed a trend that suggested improved survival for women that was not statistically significant. These two factors would tend to favor improved survival in group II if all other factors were equal; however, patients in group III had longer disease-free survival periods on average than patients in group II (\3.27 vs. 8.25 years). As seen in Fig. I,
patients in group III had better actuarial survival than patients in group II after 10 years. At fifteen years, the patient survival in group III was 60% as opposed to survival of 37% for group II. This was not statistically significant (p = 0.15), however, but strongly suggested a trend. Radical parotidectomy appears to offer improved local control of adenoid cystic carcinoma. This is perhaps a result of the manner in which the procedure is performed. A radical parotidectomy does not attempt to preserve the facial nerve. The specimen in the radical procedure is removed in an "en bloc" fashion, in contrast to a total parotidectomy with nerve preservation in which the individual branches are traced out and the parotid is separated into a lateral and a deep lobe. Total parotidectomy increases the chances of tumor spillage or of amputation of microscopic projections of cancer that will present themselves as subsequent recurrences, which is especially likely when the tumor approximates or abuts the facial nerve (as most of these lesions do). The lower recurrence rate associated with radical parotidectomy appears to be associated with a longer disease-free survival period that translates into improved survival past 10 years. Further evidence of the ability of radical parotidectomy to achieve good local control is seen in patients in group IV. Though the prognosis is certainly poorer when there is preoperative facial weakness, the IO-year survival rate was still 36%. It was interesting to note, however, that of the 10 patients who died of their disease. six of those died of metastatic disease, in spite
Volume 106 Number 4
Adenoid cystic carcinoma In the parotid gland 337
April 1992
Table 5. Incidence of metastases and multiple recurrences by group
Table 4. Clinical outcome of patients at the end of followup No. ot patient. (Ok) Group
No. of patient.
8 II
16
III
32
IV
19
III"
14
FOD
LWD
DOD
Group
Meta.fale' (Ok)
5 (62.5) 6 (37.5) 17 (53.1) 4 (21.0) 4 (29.0)
2 (25.0) 4 (25.0)
1 (12.5) 6 (37.5) 9 (28.1) 10 (53.0) 7 (50.0)
I II III IV
12 50 50 70
6 (18.8) 5 (26.0) 3 (21.0)
Multiple recurrence (Ok) 25 62 12 10
Difference in incidence of multiple recurrences between groups II and III is significant at the p = 0.005 level.
Table 6. Effect of multiple local recurrences on disease-free status and 10-year survival
"After salvage surgery.
FOD. Free of disease; I,.WD. living with disease; DOD. died of disease.
Recurrencaa
of good local control. A similar picture was seen! with patients in group IV who were living with disease at the end of followup. Most of these patients received radiation therapy, which may have contributed to good local control. The data clearly indicate the benefit to be gained from clear surgical margins in terms of disease-free survival. The longest disease-free survival with a violated margin in the current study was 8 years. This patient had a T , lesion, underwent lateral lobectomy, and received postoperative radiation therapy. One might argue that total parotidectomy is quite capable of producing surgically clear margins. In fact, many of the patients in group II had clear margins. However, it is interesting to note that in group II, five of six patients (83.3%) who died of their disease had clear surgical margins. On the other hand, only three of nine patients (33.3%) who died of disease in group III had clear margins initially. Those three patients died of metastatic disease with good local control. Does this mean that a clear margin is better with a radical parotidectomy than with a total parotidectomy with nerve preservation? Support for this concept may be found with Lathrop." who advocated excising a 1 em margin of normal parotid tissue around the tumor specimen, Adenoid cystic carcinoma has been described as being "radio-sensitive," but not "radio-curable." As previously mentioned, radiation therapy did not appear to produce consistent long-term survival in the present study. Cummings" has advocated nerve-sparing procedures followed by radiation therapy in the absence of facial weakness. This approach appears to work well for T) lesions and small T 2 lesions, but survival beyond
Multiple None
Free of dl.eaae(Ok)
Survived 10 years (%)
12.5 65.0 (p = 0.005)
46.6 70.4 (p = 0.05)
15 years was seen in many patients with small lesions who did not receive radiation therapy. Unfortunately, the decision to use radiation therapy was not standardized in our study. In earlier patients it was held in reserve in order to manage the inevitable recurrence(s). In other patients it was used when the surgical margins were not clear, which was generally unsuccessful. A true picture of the benefits of radiotherapy would require a controlled randomized prospective study. The present data appear to show that the rate of metastatic disease may be decreased with radical parotidectomy. This decrease may also be a function of improved local control. If the tumor spends less time in a patient's body, it has less opportunity to gain access to vascular channels. Additionally, an en bloc resection may prevent hematogenous spread by denying the tumor access to open vessels. Embolization of cancer cells at the time of surgery may thus be decreased. A correlate to this principle has been well established in the management of colon cancer. It was striking to note how many patients died of metastatic disease with good local control of their disease, even after 20 years. It seems that good local control could be obtained with an appropriate surgical procedure, but metastatic disease ultimately developed in many patients who ultimately died from it. Prevention of metastatic disease through the routine use of adjunctive chemotherapy may be of some benefit in this disease and should be investigated in further studies.
_
OIoIaryngologyHead and Neck surgery
CASlER and CONlEY
It is not the intent of this report to advocate facial nerve sacrifice in every case of adenoid cystic carcinoma of the parotid gland. As we have seen, small tumors (T, or early T2) may be adequately managed with nerve-sparing procedures, possibly followed by radiation therapy. This assumes that the tumor is not abutting or involving the facial nerve. The practice of stripping tumor off of nerve branches appears to be fraught with hazard in this disease. It is possible that tumors that are found adjacent to the facial nerve have already invadedthe nerve on a microscopic level. Proof of this might have been found through examination of the facial nerves from patients in group III, in which the nerve was sacrificed in the absence of clinical evidence of invasion. This was not done, unfortunately, and the retrospective nature of this study makes it virtually impossible to reconstructthose data. Tumorspillage and embolization are likely to result in multiple recurrences and perhaps an increased likelihood of development of distant metastases. Any surgical procedure should be approached with the intention of obtaining clear surgical margins, preferably with a I em margin of normal parotid tissue surrounding the tumor. Survival of patients with larger tumors appears to be enhancedwith an en bloc resectionthat does not attempt to spare the facial nerve. The potential for improved survival must be balanced against the loss of facial mobility. This undesirablesequelaemay be ameliorated somewhatthrough the use of various reanimation techniques. Though the face is never completely normal even with the best of reconstructive techniques, the patient should not be denied the opportunity for potentially improved survival. Statistical analysis was performed by Virginia Gildengorin, PhD, of the Department of Biostatistics, Letterman Anny Institute of Research, Presidio of San Francisco, California.
REFERENCES 1. Conley J. Dingman D. Adenoid cystic carcinoma in the head
and neck (cylindroma). Arch Otolaryngol 1974;100:81-90. 2. Spiro R.Huvos A, Strong E. Adenoidcystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83. 3. Matsuba HM. Thawley SE. Simpson JR. Levine LA. Mauney M. Adenoidcystic carcinomaof majorand minorsalivarygland origin. Laryngoscope 1984;94:1316-8. 4. Slaughter D, Southwick H, Walter L. The fate of recurrent or persistentparotidtumors. Surg GynecolObstet 1952;96:535-40. 5. Mustard R. Anderson W. Malignant tumorsof the parotid. Ann Surg 1964;159:291-304. 6. LuceioliG. GlementH. PaimerJ. An analysisof fifty carcinomas of the salivary glands. Can J Surg 1965;8:389-98J 7. Beahrs O. Chang G. Management of the facial nerve in parotid gland surgery. Am J Surg 1972;124:473-6. 8. EnerothC. Facialnerve paralysis-a criterionof malignancy in parotid tumors. Arch Otolaryngol 1972;95:300-4. 9. Spiro R, Huvos A. Strong E. Adenoidcystic carcinomaof salivaryorigin-a clinicopathologic studyof 2
Although ad.nold cy.tlc carcInoma may be found In multIpl••,tes In the head and n.ck a. w.1I a. oth.r glandular slt.s throughout the body, nowh.r.ls manag.m.nt of the dl.ease more controv.rslal than In the parotid gland. Here the facial nerve Is bt rl.k from both the dlsea •• and the treatment. Seventy-five case. of adenoId cystic carcinoma of the parotid w.r. analyzed. Patients were placed In four groups. dep.ndlng on the type of parotid .urgery recelv.d as deflnltlv. th.rapy: (1) lateral 10b.ctomy. (2) total parotld.ctomy, (3) radical parotld.ctomy without preoperative facial weakn and (4) radical parotidectomy with preoperative facial weakn.ss. Pad with regard to .taglng of the Inltlall••lon, the status of surgical tl.nts w.re a margin., ~nd the use of po.top.ratlv. radiotherapy. Th.lncldence of local recurr.nce and dl.tant m.ta.ta••• w.re al.o record.d. Survival .tatlstlcs are presented for .ach group. Though associated with facial nerve sacrifice, radical parotidectomy appears to off.r clear advantages In t.rm. of long-term dl.ea.e-free .urvlvalln patient. with Ta and Ta I.slons. Th. residual facial paralysis may be rehabilitated primarily or secondarily to reduce patl.nt morbidity. Four of 16patl.nt. (25%) with preoperatlv. weakness achl.v.d 10-y.ar .urvlval wh.n radIcal parotidectomy was used. Obtaining clear margIn. at the InItial settIng appears to offer Improved survival. (OTOlAR'r'NGOL HEAD NECK SURG 1992;106:332.)
Adenoid cystic carcinoma (ACC) may have a prolonged clinical course in which many patients are subjected to multiple recurrences and/or distant metastases over the course of 10 or 20 years. The tumor is well known for its tendency to invade perineural lymphatic spaces and to travel along nerve sheaths. In addition, this carcinoma has an unusually high rate of distant metastases. more than 40% in some series.!" In many respects it remains unpredictable and threatening.
From the Otolaryngology Service-Head and Neck Surgery (Dr. Casler), Walter Reed Army Medical Center; the Department of Otolaryngology-Head and Neck Surgery, College of Physicians and Surgeons (Dr. Conley). Columbia University; and the Department of Head and Neck Surgery (Dr. Conley). St. Vincent's Medical Center. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, the Department of Defense, or the U.S. Government. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery. San Diego, Calif .• Sept. 913,1990. Received for publication Jan. 7, 1991; revision received Dec. 9. 1991; accepted Dec. 18, 1991. Reprint requests: John D. Casler. MD. Department of Surgery, Walter Reed Army Medical Center, Washington. DC 20307. Z3/1/35696
332
Table 1. Staging of parotid neoplasms Stage
Diameter (em)
0.1 to 2.0 2.1 to 4.0 4,1 to 6.0 6.0
The management of ACC in the parotid gland remains controversial with respect to therapy and the consequences of therapy. The facial nerve is at risk from both the disease and the treatment. The literature is replete with articles that advocate either radical or conservative surgical approaches.':" Facial weakness resulting from nerve invasion is recognized as a very grave prognostic sign. Batsakis" has stated that, in his experience. all ACC more than I em will manifest extension into the perineural spaces. I' Whether radical surgery with facial nerve sacrifice is warranted under such circumstances is open to debate. Facial nerve sacrifice in the absence of facial weakness is an even more controversial issue. One must frequently rely on anecdotal experience in making decisions regarding the facial nerve. In order to provide a scientific basis for decision making in management of this disease, a ret-
Volume 106 Number 4 April 1992
rospective review of ACC arising within the parotid gland was undertaken.
METHODS AND MATERIAL The records of 108 patients who underwent surgical treatment for adenoid cystic carcinoma in the parotid gland were analyzed. Seventy-five charts were selected for comprehensive analysis. Approximately one half of patients were operated on primarily at our institutions. Other patients were referred for treatment after a diagnosis of ACC was made at another institution. In this case, histologic or cytologic slides were reviewed by our pathologists and the diagnosis was confirmed before further surgical treatment. Patients treated primarily underwent fine-needle aspiration. Frozen section control was used intraoperatively. If the diagnosis was equivocal, no radical surgery was performed until the diagnosis was established on permanent sections. There were no cases in which a conclusive frozen section diagnosis of ACC was changed on permanent section. Patients who manifested metastatic disease or who underwent surgery only for diagnosis were eliminated. Patients who were lost to followup before 5 years were eliminated. Patients were grouped according to the type of operation they underwent as the first definitive attempt to cure their disease. Patients who underwent facial nerve sacrifice were further subdivided according to the presence or absence of preoperative facial weakness. Four groups were thus established. Group I (lateral lobectomy with facial nerve preservation) consisted of eight patients. Three patients had T I lesions, whereas five had a T2 lesion. Group JJ (total parotidectomy with facial nerve preservation) consisted of 16 patients. Five patients were staged as T I , seven as Th and four patients had an indeterminate initial stage (T.). Group JJJ (radical parotidectomy with facial nerve sacrifice but without preoperative facial weakness) had 32 patients. Five were T I , fifteen were T2 , four were T 3 , and eight were Tx ' Group IV (radical parotidectomy with facial nerve sacrifice and with preoperative facial weakness) contained 19 patients. Two were T io nine were T 2 , six were T Jo and two were T4 • (No patient in the first three groups had preoperative facial weakness, whereas all 19 patients in group IV had preoperative facial weakness.) Radical partoidectomy was performed with the intent of obtaining at least a 1 em margin around the tumor when possible. This occasionally required including adjacent bone and muscle in the specimen, especially in cases in which surgery was performed for recurrent disease.
Adenoid cysttc carcinoma In the parotid gland 333
In cases in which no palpable neck disease was present, and the primary tumor was a T( or T2 , a sampling of nodes from the upper cervical, postauricular, and superior spinal accessory groups was included with the dissection. Patients with palpable neck disease or large T3 and T41esions received a radical or modified radical neck dissection with preservation of the spinal accessory nerve. The patients in the groups were of similar ages, with a mean age of 44.4 years. There were 29 men and 46 women, and their distribution within treatment groups showed some variation, particularly in groups II and III. Group II had 1 man and 15 women, whereas group III had 16 men and 16 women. Mean followup was 10.2 years (range, 1 to 33 years). Patients with less than a 5-year followup were not analyzed unless they had died of disease. Patients were analyzed for the stage of their initial lesion if known (Table 1), whether surgery achieved microscopically clear margin, or whether they received postoperative radiation therapy. If the "definitive" surgical procedure was performed as a salvage procedure after recurrence of the tumor; this was also noted. Information on the histologic grading of the tumors was available in some cases. The subsequent clinical course was analyzed. Notation was made if the patients had multiple (two or more) recurrences after definitive surgical therapy, and if they developed distant metastatic disease. The clinical status of the patient was ascertained at the end of followup. Patients were either free of disease, living with their disease, had died of their disease, or had died of other causes. An attempt was made to ascertain whether patients who died of their disease died of metastatic disease or from locally uncontrolled disease. The data were analyzed by use of chi-square testing to determine whether clinical outcome was related to the type of surgery performed, and to determine which factors were associated with improved survival. Table 2 shows the compiled data on the patients in the study. Table 3 compares the groups with respect to histology, perineural invasion, and presence of metastases.
RESULTS Clinical status at the end of followup for each group is shown in Table 4. Figure 1 shows actuarial survival percentages for each of the four groups. Information regarding the status of the initial surgical margins was obtainable in 64 cases. The status of surgical margins impacted significantly on disease-free status. Patients with clear surgical margins had a 59.6% disease-free rate as opposed to patients with violated
334
OtolaryngologyHead and Neck Surgery
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Table 2. Summary of data for patients In the study Followup Patient
no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29
30 31 32 33 34 35 36 37 38
Group
I II /I /I /I II II II II II III III III III III III III III III
III III
III III
1/1
Tumor stage
Radiation therapy
Margins clear
Multiple recurrences
T, T, T, T2 T2 T2 T2 T2 T, T, T, T, T, T2 T2 T2 T2 T2 T2 T2 T, T, T, T, T, T, T, T, T, T2 T2 T2 T2 T2 T2 T2 T2 T2
+
+ +
+
+ + + +
+ + + +
?
+
?
+ + +
+
+ + +
+ + +
+ + + +
+ +
+ + + + + + +
+ + + +
Metastases
8
FOD DOD LWDm LWD FOD FOD FOD FOD LWD FOD FOD DOD LWD DOD FOD FOD DOD LWDm LWD FOD DOOm DOD FOD DOD DOD FOD FOD DOD FOD LWD LWDm FOD FOD FOD FOD FOD DODm LWDm
+
18 5 21 12 9 7 10 5 5 19 12 7, 16 5 7 5 16 5 2 11 7 5 9 6 11 4 10 5 11 16 5
+
+ + +
+ +
+
+ +
?
?
Status
3
+ ?
+
Vears
?
+ + +
Salvage surgery
+ +
+ + + + + + + +
11
12 20 6 7
FOD, Free of disease; DOD, died of disease; LWD, living with disease; m (used as in LWDm and DOOm), metastatic disease with local control; +, yes; -, no; 7, not known.
margins who had a disease-free rate of only 11.6% = 0.005). Radiation therapy did not statistically improve survival rates, though it tended to improve local control of disease. Specifically, it did not improve survival when there was a positive (violated) surgical margin. The overall rate of metastases was 50.6%. The rate of metastases to regional lymph nodes was 17.3% (13 of 75 patients). Five of these patients had involvement of periparotid nodes, which was discovered in the processing of the primary specimen. Approximately forty patients underwent local "node sampling" as part of their procedure. Of these. two patients had microscopic (p
foci of tumor noted in their upper cervical nodes. At least twenty-three patients underwent radical or modifled radical neck dissection. Three patients had palpable adenopathy that was confirmed as metastatic nodes through radical or modified radical neck dissection. The type of neck dissection used in the remaining three patients with positive nodes was not made clear in the records. It was also not clear what type of node dissection (if any) was performed in an additional twelve patients. A 33.3% rate of distant metastasis was noted. This consisted of spread to lung, bone, brain, and liver, in that relative frequency. There was a higher incidence of metastatic disease with increasing size of the primary
Volume 106 Number 4 April
Adenoid cystic carcinoma In the parotid gland UI
1992
Table 2. Confd. Patient
no. 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75
Group
III III III III III III III III III III III III III III III III III III IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV IV
Radiation therapy
Tumor stage
T2 T2 T2 T2 T2 T2 T3 T3 T3 T3 T,
Margins clear
Followup
Multiple recurrenc..
+
+
?
+ +
+ +
+
+
+
+
+ +
+
+
+
r,
+ +
?
+
Tx
+ +
? ?
r,
Metasta..s
Salvage surgery
+
T,
r, r, r,
+
+ +
+
T, T, T2 T2 T2 T2 T2 T2 T2 T2 T2 T3 T3 T3 T3 T3 T3 T. T.
+ +
+ +
+ + +
+
+ ?
+ + +
+
+ +
+
+
+
+ +
+
+ + + + + +
+
+
+ + + + + +
+ + ?
+ + +
+ +
+
+
Vears
5 21 21 2 25 18 6 15 1 10 33 22 5 15 8 5 18 16 5 11 5 16 7 10 6 6 12 9 13 1 5 5 5 1 1 2 6
Status
DODm DOD LWDm DODm FaD FaD DOD FOD DOD DODm LWDm FaD FaD FaD FaD LWDm DODm FaD LWDm DODm FOD FaD DOD DODm FaD DODm DOD LWD FaD DOD LWD LWDm LWDm DODm DODm DODm DOD
Table 3. Group characteristics Perineural Invasion
Histology Group
I II III IV
Metasta...
Tubular
CrIbriform
aasalold
Unknown
V..
No
Unknown
Regional
3 3 5
6 8 11 6
2 6 13 19
1 2 4
5 8 15
1
5 1
1 5 13 7
lesion: 33.3% for r., 44.4% for T 2 • 80% for T3 • and 100% for T4 • Although group III had more advanced primary disease than group II. the rate of metastases was the same for the two groups (Table 5).
4
1
Distant
loth
1 6 12 6
6
The incidence of multiple recurrences varied between treatment groups and is shown in Table 5. Group II had a higher incidence of recurrence that was statistically significant at p = 0.005. Multiple recurrence was as-
336
OtolaryngologyHead and Neck Surgery
CASlER and CONLEY
100 90
80 70 60
50 40 30
20
10
o
j-__-'-
.L__ --L__ - L
o
I
5 -
Group I
~
10 Group II
-ljf-
15 Group III
I 20
-e- Group IV
FIg. 1. Actuarial survival of patients In each surgical group, plotted over time (In years).
sociated with disease-free status (Table 6). Only 12.5% of patients who had multiple recurrences were free of disease at the end of followup. Conversely, 65% of patients without multiple recurrences were free of disease at the end of followup (p = 0.005). Ten-year survival averaged 46.6% for patients with multiple recurrences, as opposed to 70.4% (p = 0.05) for patients without multiple recurrences (Table 6). A subgroup of 14 patients in group III underwent radical parotidectomy for salvage of recurrent disease (Table 4). The survival rate was less under these circumstances and reduced overall survival of patients in group III.
DISCUSSION In order to decide whether there is merit to performing radical parotidectomy with facial nerve sacrifice in the absence of preoperative facial weakness, we must focus attention on the differences between groups II and III. Any benefit to be gained from facial nerve sacrifice should be apparent when these two groups are compared. We must remember, however, that group III had patients with somewhat more advanced primary disease. Also, group II contained proportionally more women than group III. Spiro et al.? showed a trend that suggested improved survival for women that was not statistically significant. These two factors would tend to favor improved survival in group II if all other factors were equal; however, patients in group III had longer disease-free survival periods on average than patients in group II (\3.27 vs. 8.25 years). As seen in Fig. I,
patients in group III had better actuarial survival than patients in group II after 10 years. At fifteen years, the patient survival in group III was 60% as opposed to survival of 37% for group II. This was not statistically significant (p = 0.15), however, but strongly suggested a trend. Radical parotidectomy appears to offer improved local control of adenoid cystic carcinoma. This is perhaps a result of the manner in which the procedure is performed. A radical parotidectomy does not attempt to preserve the facial nerve. The specimen in the radical procedure is removed in an "en bloc" fashion, in contrast to a total parotidectomy with nerve preservation in which the individual branches are traced out and the parotid is separated into a lateral and a deep lobe. Total parotidectomy increases the chances of tumor spillage or of amputation of microscopic projections of cancer that will present themselves as subsequent recurrences, which is especially likely when the tumor approximates or abuts the facial nerve (as most of these lesions do). The lower recurrence rate associated with radical parotidectomy appears to be associated with a longer disease-free survival period that translates into improved survival past 10 years. Further evidence of the ability of radical parotidectomy to achieve good local control is seen in patients in group IV. Though the prognosis is certainly poorer when there is preoperative facial weakness, the IO-year survival rate was still 36%. It was interesting to note, however, that of the 10 patients who died of their disease. six of those died of metastatic disease, in spite
Volume 106 Number 4
Adenoid cystic carcinoma In the parotid gland 337
April 1992
Table 5. Incidence of metastases and multiple recurrences by group
Table 4. Clinical outcome of patients at the end of followup No. ot patient. (Ok) Group
No. of patient.
8 II
16
III
32
IV
19
III"
14
FOD
LWD
DOD
Group
Meta.fale' (Ok)
5 (62.5) 6 (37.5) 17 (53.1) 4 (21.0) 4 (29.0)
2 (25.0) 4 (25.0)
1 (12.5) 6 (37.5) 9 (28.1) 10 (53.0) 7 (50.0)
I II III IV
12 50 50 70
6 (18.8) 5 (26.0) 3 (21.0)
Multiple recurrence (Ok) 25 62 12 10
Difference in incidence of multiple recurrences between groups II and III is significant at the p = 0.005 level.
Table 6. Effect of multiple local recurrences on disease-free status and 10-year survival
"After salvage surgery.
FOD. Free of disease; I,.WD. living with disease; DOD. died of disease.
Recurrencaa
of good local control. A similar picture was seen! with patients in group IV who were living with disease at the end of followup. Most of these patients received radiation therapy, which may have contributed to good local control. The data clearly indicate the benefit to be gained from clear surgical margins in terms of disease-free survival. The longest disease-free survival with a violated margin in the current study was 8 years. This patient had a T , lesion, underwent lateral lobectomy, and received postoperative radiation therapy. One might argue that total parotidectomy is quite capable of producing surgically clear margins. In fact, many of the patients in group II had clear margins. However, it is interesting to note that in group II, five of six patients (83.3%) who died of their disease had clear surgical margins. On the other hand, only three of nine patients (33.3%) who died of disease in group III had clear margins initially. Those three patients died of metastatic disease with good local control. Does this mean that a clear margin is better with a radical parotidectomy than with a total parotidectomy with nerve preservation? Support for this concept may be found with Lathrop." who advocated excising a 1 em margin of normal parotid tissue around the tumor specimen, Adenoid cystic carcinoma has been described as being "radio-sensitive," but not "radio-curable." As previously mentioned, radiation therapy did not appear to produce consistent long-term survival in the present study. Cummings" has advocated nerve-sparing procedures followed by radiation therapy in the absence of facial weakness. This approach appears to work well for T) lesions and small T 2 lesions, but survival beyond
Multiple None
Free of dl.eaae(Ok)
Survived 10 years (%)
12.5 65.0 (p = 0.005)
46.6 70.4 (p = 0.05)
15 years was seen in many patients with small lesions who did not receive radiation therapy. Unfortunately, the decision to use radiation therapy was not standardized in our study. In earlier patients it was held in reserve in order to manage the inevitable recurrence(s). In other patients it was used when the surgical margins were not clear, which was generally unsuccessful. A true picture of the benefits of radiotherapy would require a controlled randomized prospective study. The present data appear to show that the rate of metastatic disease may be decreased with radical parotidectomy. This decrease may also be a function of improved local control. If the tumor spends less time in a patient's body, it has less opportunity to gain access to vascular channels. Additionally, an en bloc resection may prevent hematogenous spread by denying the tumor access to open vessels. Embolization of cancer cells at the time of surgery may thus be decreased. A correlate to this principle has been well established in the management of colon cancer. It was striking to note how many patients died of metastatic disease with good local control of their disease, even after 20 years. It seems that good local control could be obtained with an appropriate surgical procedure, but metastatic disease ultimately developed in many patients who ultimately died from it. Prevention of metastatic disease through the routine use of adjunctive chemotherapy may be of some benefit in this disease and should be investigated in further studies.
_
OIoIaryngologyHead and Neck surgery
CASlER and CONlEY
It is not the intent of this report to advocate facial nerve sacrifice in every case of adenoid cystic carcinoma of the parotid gland. As we have seen, small tumors (T, or early T2) may be adequately managed with nerve-sparing procedures, possibly followed by radiation therapy. This assumes that the tumor is not abutting or involving the facial nerve. The practice of stripping tumor off of nerve branches appears to be fraught with hazard in this disease. It is possible that tumors that are found adjacent to the facial nerve have already invadedthe nerve on a microscopic level. Proof of this might have been found through examination of the facial nerves from patients in group III, in which the nerve was sacrificed in the absence of clinical evidence of invasion. This was not done, unfortunately, and the retrospective nature of this study makes it virtually impossible to reconstructthose data. Tumorspillage and embolization are likely to result in multiple recurrences and perhaps an increased likelihood of development of distant metastases. Any surgical procedure should be approached with the intention of obtaining clear surgical margins, preferably with a I em margin of normal parotid tissue surrounding the tumor. Survival of patients with larger tumors appears to be enhancedwith an en bloc resectionthat does not attempt to spare the facial nerve. The potential for improved survival must be balanced against the loss of facial mobility. This undesirablesequelaemay be ameliorated somewhatthrough the use of various reanimation techniques. Though the face is never completely normal even with the best of reconstructive techniques, the patient should not be denied the opportunity for potentially improved survival. Statistical analysis was performed by Virginia Gildengorin, PhD, of the Department of Biostatistics, Letterman Anny Institute of Research, Presidio of San Francisco, California.
REFERENCES 1. Conley J. Dingman D. Adenoid cystic carcinoma in the head
and neck (cylindroma). Arch Otolaryngol 1974;100:81-90. 2. Spiro R.Huvos A, Strong E. Adenoidcystic carcinoma: factors influencing survival. Am J Surg 1979;138:579-83. 3. Matsuba HM. Thawley SE. Simpson JR. Levine LA. Mauney M. Adenoidcystic carcinomaof majorand minorsalivarygland origin. Laryngoscope 1984;94:1316-8. 4. Slaughter D, Southwick H, Walter L. The fate of recurrent or persistentparotidtumors. Surg GynecolObstet 1952;96:535-40. 5. Mustard R. Anderson W. Malignant tumorsof the parotid. Ann Surg 1964;159:291-304. 6. LuceioliG. GlementH. PaimerJ. An analysisof fifty carcinomas of the salivary glands. Can J Surg 1965;8:389-98J 7. Beahrs O. Chang G. Management of the facial nerve in parotid gland surgery. Am J Surg 1972;124:473-6. 8. EnerothC. Facialnerve paralysis-a criterionof malignancy in parotid tumors. Arch Otolaryngol 1972;95:300-4. 9. Spiro R, Huvos A. Strong E. Adenoidcystic carcinomaof salivaryorigin-a clinicopathologic studyof 2
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