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Parotidectomy in the Treatment of Aggressive Cutaneous Malignancies
Stephen Y. Lai, MD, PhD;
Gregory S. Weinstein, MD;
Ara A. Chalian, MD;
David I. Rosenthal, MD;
Randal S. Weber, MD
Arch Otolaryngol Head Neck Surg. 2002;128:521-526.
ABSTRACT
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Background Aggressive nonmelanoma skin cancer (ANMSC) of the head and neck may
require parotidectomy because of neurotropic spread, direct invasion of the
parotid gland, or parotid metastasis.
Objective To review our experience with parotidectomy in the treatment of these
tumors to examine the indications for this procedure and to analyze treatment
outcomes. We emphasize the importance of early identification of an ANMSC
and a systematic approach to treatment.
Design Review of 23 patients with an ANMSC who required parotidectomy with
or without facial (VII) nerve sacrifice between January 5, 1996, and December
27, 1999. Median follow-up for all patients was 24 months.
Setting Academic tertiary care referral center.
Patients This study focused on 23 (median age, 71 years) of 54 patients treated
for an ANMSC. Most tumors were in the periauricular (n = 9) and the frontozygomatic
(n = 6) areas. Seven patients presented with facial weakness or paralysis.
Three patients had clinically evident parotid metastasis, while 14 patients
had tumors directly invading the parotid gland. Eighteen patients had recurrent
disease that had been treated previously with Mohs micrographic surgery.
Interventions Following wide local excision of the ANMSC, 12 patients had resection
of the lateral parotid lobe with preservation of the nerve, while 11 required
radical parotidectomy with sacrifice of 1 or more branches. Nineteen patients
received cervical lymphadenectomy. Postoperative radiotherapy was administered
in 19 patients.
Main Outcome Measures Tumor pathologic findings (specifically, perineural invasion of the
facial nerve), locoregional control or recurrence, disease-free survival,
disease-specific survival, and overall survival.
Results Neurotropic spread to the facial nerve was present in 6 patients and
was more likely to occur in younger patients (51 vs 75 years, P = .006). Locoregional failures occurred in 9 patients following treatment.
Patients who required parotidectomy in their surgical treatment for an ANMSC
were more likely to have recurrent disease (P = .0002).
Disease-specific and overall survival was 79% and 69%, respectively, at 42
months.
Conclusions Patients with ANMSC may require parotidectomy in the context of neurotropic
spread, regional metastasis, or direct invasion into the parotid gland. Surgery
combined with postoperative radiotherapy is necessary in most patients because
of adverse clinical and pathologic findings. A systematic approach to the
management of the parotid and facial nerve in the presence of these aggressive
tumors is required. Despite comprehensive treatment, local recurrence of ANMSC
and mortality remain high.
INTRODUCTION
NONMELANOMA SKIN cancer (NMSC) is the most common neoplasm affecting
humans. The 2 principal histologic types of NMSC are squamous cell carcinoma
(SCC) and basal cell carcinoma (BCC), with BCC affecting more patients than
SCC by a ratio of nearly 4:1. Approximately 800 000 to 1 million new
cases are diagnosed annually, and the incidence is increasing by 4% to 8%
per year.1-2 Men are affected
by these lesions twice as often as women. Although the head and neck comprises
only 9% of total body surface area, increased actinic exposure to this region
relative to other body surfaces likely accounts for 80% of skin cancers occurring
in this region.3 Despite increasing incidence
of NMSC, the prognosis for patients is typically excellent. Cure rates are
96% to 99%, with mortality often due to metastatic disease in about 1% of
cases.
Although the overall statistics are encouraging, a significant number
of patients present with advanced disease. Features of this aggressive subset
of NMSC include recurrent disease, regional metastasis, large lesions ( 2
cm), rapid growth, and involvement of significant cosmetic and functional
regions of the face (Table 1). 4 The aggressive nature of these lesions increases the
risk for metastasis to regional lymphatics and deep invasion into the parotid
gland. Tumors in the periauricular region may directly invade the facial nerve
(Figure 1). In addition, lesions
with neurotropic capability are likely to spread along the trigeminal and
facial nerves. Because the parotid serves as a watershed for lymphatics of
the scalp and periauricular regions, the facial nerve may be invaded by metastatic
disease to the parotid gland.
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Table 1. Identification of Aggressive Nonmelanoma Skin Cancer
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Figure 1. Invasion of the facial nerve by
an aggressive nonmelanoma skin cancer of the head and neck. The facial nerve
is intimately related to the parotid and is at risk for direct invasion by
any lesion in the periauricular region. In addition, the parotid is a watershed
area for cutaneous lymphatics of the scalp and periauricular region. This
serves as an additional route for tumor to invade the facial nerve.
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These aggressive characteristics result in a poorer prognosis for patients
with advanced lesions. Involvement of the parotid by metastasis or direct
invasion is associated with increased recurrence and mortality.5
In cases of aggressive NMSC (ANMSC) with perineural invasion, the likelihood
of recurrence, local metastasis, and mortality is significantly increased.6 Furthermore, facial nerve invasion by an ANMSC can
lead to devastating physical deformity and dysfunction. The catastrophic potential
of ANMSC demands critical attention to the early identification of these lesions
and to the comprehensive management of the parotid and facial nerve in the
locoregional control of this disease. We reviewed our experience with parotidectomy
in the treatment of ANMSC to examine the indications to perform this procedure
and to evaluate treatment outcomes.
PATIENTS AND METHODS
A retrospective review of 54 patients with ANMSC treated by the Department
of Otorhinolaryngology–Head and Neck Surgery at the University of Pennsylvania
Medical Center, between January 5, 1996, and December 27, 1999, was undertaken.
Of this group of patients, 23 required parotidectomy with facial nerve dissection
or sacrifice.
Variables examined included the primary site, size, and facial pain
or paralysis. In addition, imaging studies, history of prior disease, previous
treatment, evidence of regional metastasis, predisposing factors (eg, immunocompromised
host), and biopsy data were obtained. Treatment and reconstructive strategies,
including facial nerve repair, were recorded. Pathologic information included
lesion size, depth, histologic type, differentiation, margins, cervical node
status, and evidence of perineural invasion. Postoperative treatment with
radiotherapy and chemotherapy was noted. Outcome measures included site(s)
of disease recurrence and survival.
Statistical analysis was performed using commercially available software
(SPSS/PC+, version 2.0; SPSS Inc, Chicago, Ill). To determine statistical
significance for factors relative to regional metastasis, perineural invasion,
and disease recurrence, univariate analysis of the continuous variable was
done using the Mann-Whitney U test. Categorical variables
were analyzed using the Pearson  2 test, with Yates correction
where applicable. Survival analysis was done using the Kaplan-Meier survival
method, with log-rank analysis to compare groups.7-8
RESULTS
CLINICAL PRESENTATION
The median age of the patients was 71 years, and 21 of the 23 patients
were men (Table 2). Most patients
presented with primary lesions in the periauricular (n = 9) and the frontozygomatic
(n = 6) areas. Two patients presented with nasal lesions, and 4 patients presented
with primary disease of the neck skin. In addition, 1 patient had a lip lesion,
and 1 patient presented with posterior scalp disease. Seven patients presented
with facial weakness or paralysis, and 10 of the patients had clinical evidence
of metastasis to the parotid gland or the neck. Eighteen of the 23 patients
presented with recurrent disease, and all of these patients had Mohs micrographic
surgery as part of their prior treatment.
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Table 2. Clinical Presentation in 23 Patients*
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TREATMENT
In addition to wide local excision of the primary lesion, surgical treatment
of an ANMSC included parotidectomy with facial nerve dissection, cervical
lymphadenectomy, or facial nerve resection. Twelve patients required superficial
parotidectomy, while 11 required radical parotidectomy with sacrifice of 1
or more facial nerve branches. The facial nerve was completely resected in
8 patients and partially resected in 4 others. Nineteen patients received
cervical lymphadenectomy. In addition, 2 of 23 patients had bony invasion,
requiring lateral temporal bone resection in 1 patient and segmental mandibulectomy
in the other. Reconstruction of the facial defect required primary closure
in 8 patients, split-thickness skin grafts in 5, locoregional flaps in 9,
and free tissue transfer in 4. Facial nerve reconstruction was achieved with
a cable graft in 8 patients. In 4 patients who presented with facial weakness
or paralysis, no attempt was made to reconstruct the facial nerve. Following
surgical treatment, 18 patients received radiotherapy, and 1 patient received
combination radiotherapy and chemotherapy (mean dosage, 62.1 Gy; range, 51.0-74.0
Gy).
TUMOR PATHOLOGIC FINDINGS
Pathologic findings are listed in Table 3. The primary lesion was SCC in 18 patients and BCC in only
5. Twelve of the 18 squamous cell lesions were poorly differentiated. Seventeen
of the 23 lesions were 2 cm or larger in diameter, with a mean area of 18.8
cm2 (range, 1.0-89.6 cm2). Mean tumor depth was 1.5
cm (range, 0.3-4.0 cm). Margins were negative in 17 of the 23 patients, close
in 4, microscopically positive in 1, and grossly positive in 1 patient. In
the treatment of regional metastasis by parotidectomy and cervical lymphadenectomy
(mean number of nodes removed, 23; range, 1-60), 10 patients had regional
metastasis, with positive neck nodes in 6 patients and positive parotid nodes
in 9 patients (mean number of positive nodes, 4.8; range, 1-22). Extracapsular
spread was present in 6 patients.
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Table 3. Tumor Pathologic Findings*
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In 12 patients, the facial nerve was partially or totally resected because
of gross tumor involvement or preoperative facial paralysis. Perineural invasion
was histologically identified in 6 cases. In addition, 2 patients had perineural
invasion of the ophthalmic division of the trigeminal nerve (V1).
Interestingly, younger patients with an ANMSC were more likely to have perineural
invasion of the facial nerve (51 vs 75 years, P =
.006).
RECURRENCE AND OUTCOME
Following our treatment, 12 patients had recurrent disease. In 9 patients,
locoregional failures occurred. One patient had local recurrence and distant
metastases, while 2 patients with auricular primary lesions had distant metastases
alone. The 23 patients who received parotidectomy for locoregional control
were a subset of the entire population of 54 patients treated for ANMSC by
our department. Despite the inclusion of parotidectomy in their surgical treatment,
these patients were more likely to have disease recurrence (P = .0002) than those patients whose disease treatment did not require
parotidectomy. Except for cases of facial nerve involvement by an ANMSC that
required nerve resection, management of the facial nerve did not result in
facial weakness or paralysis in any patients with normal preoperative nerve
function. Median follow-up was 24 months (range, 5-43 months). Disease-specific
and overall survival was 79% and 69%, respectively, at 42 months (Figure 2).
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Figure 2. Survival plot. Calculation of
survival analysis was done by the Kaplan-Meier survival method, with log-rank
analysis to compare groups. Overall and disease-specific survival was 79%
and 69%, respectively, at 42 months. Disease-free survival at 42 months was
30%.
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COMMENT
Despite efforts to improve early detection of skin cancer through public
education, a significant number of patients present with advanced ANMSC. These
lesions are difficult to eradicate and often result in severe functional and
cosmetic sequelae. Rowe et al4 identified several
common features of ANMSC. These lesions grow rapidly and are often greater
than 2 cm in diameter. Histologically, they are often poorly differentiated
SCC, spindle cell SCC, or basosquamous or morpheaform BCC. In addition, they
frequently occur in the midface "H-zone" that encompasses the medial canthus,
glabella, posterolateral nares, alar rims, nasolabial sulcus, columella labial
junction, and auricular regions, including the tragus and antitragus.9 This region of embryonic fusion planes may provide
avenues for deeper tumor invasion.10 These
features contribute to the difficulties encountered in the management of these
lesions and their increased likelihood of recurrence following surgical resection.
The increased incidence of regional metastasis and perineural invasion
by ANMSC also contributes to the higher recurrence rate and poorer prognosis
associated with this lesion. In our patients, 10 (43%) of 23 had regional
metastasis, and 12 (52%) of 23 had some form of facial nerve involvement.
Parotid metastasis of ANMSC is associated with poorer patient outcomes.5 In addition, perineural invasion is associated with
increased local recurrence, regional metastasis, and mortality.6, 11
Although perineural invasion as a means of tumor spread has been well documented,
accurate diagnostic methods and basic pathogenic mechanisms remain poorly
defined.
Cosmetic and functional sequelae following surgical resection complicate
the management of these patients. Although the first priority of the surgeon
should be disease eradication, Wentzell and Robinson12
have suggested that surgeons frequently underestimate the depth of invasion
of an ANMSC and that the potential cosmetic and functional results of surgical
resection may lead to less aggressive excision of these tumors. Our experience
with ANMSC involved many patients who presented with recurrent disease that
had been previously treated with Mohs micrographic surgery. Although Mohs
micrographic surgery has proven effective in the control of NMSC, particularly
aggressive forms of skin cancer may demand a more radical resection, complex
reconstruction, and radiotherapy. Physicians need to remain cognizant of the
features of ANMSC during the initial evaluation of an NMSC. When an aggressive
lesion is suspected, comprehensive treatment may require consultation with
other specialists. This is best achieved through a multidisciplinary approach,
with collaboration among the head and neck surgeon, the dermatologic surgeon,
and the radiation oncologist.
We reviewed the clinical course of patients with ANMSC who required
parotidectomy to identify common disease characteristics and to analyze treatment
outcomes. Most patients presented to us with recurrent disease (18/23 [78%]).
Twenty-one (91%) of the 23 patients were men, and 18 (78%) of the 23 lesions
were SCC, although BCC tends to be more common in patients with NMSC. Younger
patients (51 vs 75 years) were more likely to have lesions with perineural
invasion (P = .006). Variables such as location,
size, and depth of invasion did not predict increased potential for perineural
invasion or regional metastasis in ANMSC. The small patient population of
this study may have affected the ability to demonstrate the statistical significance
of these variables. In addition, this population already represented an aggressive
subset of NMSC.
Our experience demonstrates that a systematic approach is required to
ensure proper understanding of disease extent and definitive management of
NMSC with aggressive features. On clinical presentation, these patients may
have facial muscle twitching or facial paresis or paralysis. The primary lesions
may be fixed to deep structures within the pretragal region (eg, the parotid
gland). Unfortunately, approximately 60% of patients with ANMSC involvement
of the facial nerve may present asymptomatically.6, 13-14
In our series, 7 of 23 patients presented with facial weakness or paralysis,
although facial nerve dissection was performed in all of the patients, and
surgical resection of the facial nerve was required in 12.
When these situations are not clinically obvious, but suspected, radiographic
studies should be obtained. Computed tomographic scans and magnetic resonance
imaging studies are critical for delineating the size and invasive nature
of an ANMSC.15 In this study, parotid metastasis
was clinically appreciated in only 3 of 9 patients, and parotid invasion was
recognized in only 3 of 14 patients. The remaining cases of parotid involvement
were identified by imaging studies or surgical exploration. Furthermore, findings
of facial nerve enhancement or thickening provide evidence for perineural
invasion. Although they cannot substitute for intraoperative assessment, imaging
studies should be routinely included in the preoperative assessment of an
ANMSC.
As the parotid serves as a watershed for lymphatics of the anteroparietal
scalp, forehead, temple, ear, eyelids, and zygomatic area, management of the
parotid is a critical consideration in the locoregional control of an ANMSC.
The intimate relationship of the facial nerve with the parotid also demands
critical attention to this region to maintain the integrity of the nerve.
There are 4 primary indications for parotidectomy in cases of ANMSC: parotid
metastasis, invasion of the parotid capsule, facial nerve invasion, and temporal
bone invasion. Our approach to management of the parotid is detailed in Table 4. Depending on the depth of the
primary lesion, especially in the preauricular region, local control may require
superficial parotidectomy and facial nerve dissection. Similarly, facial nerve
dissection is requisite in superficial parotidectomy for nodal involvement
or deep invasion from preauricular primary lesions. As the facial nerve is
identified, areas of gross tumor involvement may necessitate partial or total
facial nerve resection. Histologic evaluation for perineural invasion of the
nerve branches resected would provide guidance for further nerve excision.
Most important, resection must lead to disease control proximally and distally
along the course of the facial nerve. As with one of our patients, mastoidectomy
may be required for local disease extirpation and facial nerve resection.
Finally, reconstruction of the facial nerve is usually performed immediately,
with cable grafting of all resected branches.
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Table 4. Management of the Facial Nerve in Aggressive Nonmelanoma Skin
Cancer of the Head and Neck*
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Given the devastating potential of this disease, our approach to patients
with ANMSC includes postoperative radiotherapy. The value of this combined
approach has been well documented in cases of parotid invasion by skin cancers.16 In that study, Taylor et al demonstrated that ultimate
control of disease was 62.5% with surgical treatment and 46% with radiation
therapy, but improved to 89% when both forms of treatment were used. Indications
for postoperative radiotherapy include the following: a large or recurrent
primary lesion, close or positive tumor margins, perineural invasion, and
poorly differentiated or spindle cell SCC. In addition, radiotherapy may improve
regional control in patients with lymph node metastases at multiple neck levels
or extracapsular spread of metastatic disease.
Despite the comprehensive treatment that our patients received for ANMSC,
the tenacious nature of this disease is obvious. Twelve (52%) of 23 patients
had locoregional recurrent disease, and 4 patients (17%) died following distant
metastasis of their disease. Compared with the entire population treated for
ANMSC by our department, patients whose disease had progressed to the point
of requiring a parotidectomy were more likely to have disease recurrence (P = .0002). This may have been because of the advanced
state of their disease at the time of presentation for treatment.
Conservative treatment of an NMSC with aggressive features may contribute
to a high local recurrence rate. Despite comprehensive surgical treatment
and postoperative radiotherapy, the prognosis for recurrent and extensive
ANMSC remains grim. Therefore, physicians must remain aware of the features
of an ANMSC and attempt to identify these lesions at earlier stages or in
their initial presentation. Younger patients and those presenting with SCC
are more likely to have tumors with aggressive behavior and to require definitive
treatment to prevent complications and future recurrence.
CONCLUSIONS
Definitive treatment of ANMSC in the head and neck remains a challenging
problem. Identification of these high-risk lesions at initial presentation
provides the best opportunity to eradicate disease and to prevent the deleterious
effects of facial nerve invasion. Although Mohs micrographic surgery remains
valuable for most NMSC, treatment of ANMSC requires a multidisciplinary approach.
A review of our experience with these patients demonstrates the importance
of parotidectomy in cases of ANMSC with parotid metastasis, invasion of the
parotid capsule, and facial nerve invasion. Despite aggressive treatment of
this disease, disease recurrence and mortality remain high. Future efforts
should be directed toward the earlier detection of lesions with aggressive
characteristics and the development of more effective adjuvant therapies.
AUTHOR INFORMATION
Accepted for publication October 26, 2001.
We thank Pat Wolf, BS, for the compilation of the database and statistical
analysis and Devin M. Cunning, MD, for his medical illustration.
This study was presented at the Fifth International Conference on Head
and Neck Cancer, San Francisco, Calif, July 31, 2000.
Corresponding author and reprints: Randal S. Weber, MD, Department
of Otorhinolaryngology–Head and Neck Surgery, University of Pennsylvania
Medical Center, 5 Silverstein/Ravdin, 3400 Spruce St, Philadelphia, PA 19104
(e-mail: randal.weber{at}uphs.upenn.edu).
From the Departments of Otorhinolaryngology–Head and Neck Surgery
(Drs Lai, Weinstein, Chalian, and Weber) and Radiation Oncology (Dr Rosenthal),
University of Pennsylvania Medical Center, Philadelphia.
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