Download Squamous cell carcinoma of the parotid gland

ORIGINAL ARTICLE
SQUAMOUS CELL CARCINOMA OF THE PAROTID GLAND
Yu-Lan Mary Ying, MD, Jonas T. Johnson, MD, Eugene N. Myers, MD
Department of Otolaryngology-Head and Neck Surgery, University of Pittsburgh, Eye & Ear Institute;
203 Lothrop Street, Suite 500, Pittsburgh, PA 15213
Accepted 24 August 2005
Published online 10 February 2006 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/hed.20360
Abstract: Background. Our objective was to evaluate the
outcome of patients treated for squamous cell carcinoma (SCC)
of the parotid gland.
Methods. We conducted a retrospective chart review of the
tumor registry from 1982 through 2003 at a tertiary referral medical center. Patients with SCC of the parotid gland were identified
and followed for a minimum of 2 years after therapy.
Results. SCC involving the parotid was identified in 66
patients. The tumor was a metastasis from a known primary site
in 41 patients (62%). In 16 patients (24%), no other primary site
was identified, and the tumor may have originated in the parotid
gland. Nine patients (14%) were undetermined. Therapy frequently included surgery. The integrity of the facial nerve was
preserved in 92% of surgical patients. Only eight patients initially had clinical evidence of cervical metastasis; however, cervical metastasis was identified in 25 patients (44%), changing
the course of therapy.
Conclusion. SCC of the parotid gland was metastatic from a
known primary tumor in more than half of the patients. The most
common site of the primary tumor was a cutaneous malignancy
of the head and neck. The high incidence of cervical lymph node
involvement underscores the diagnostic and therapeutic imporC
tance of neck dissection with parotidectomy. V
2006 Wiley
Periodicals, Inc. Head Neck 28: 626–632, 2006
Keywords: squamous cell carcinoma; parotid gland; parotidectomy; primary; metastasis
Correspondence to: J. T. Johnson
C
V
2006 Wiley Periodicals, Inc.
626
Squamous Carcinoma of Parotid
Tumors of the parotid gland are a histologically
diverse group of neoplasms that exhibit a wide
spectrum of biologic behaviors. Primary squamous cell carcinoma (SCC) originating in the
parotid is rare. The reported incidence of SCC of
the salivary gland is only 0.3% to 1.5%.1 More
commonly, SCC is metastatic to the intraparotid
and periparotid lymph nodes from cutaneous
malignancy of the face and scalp. In patients with
SCC of the skin, the overall risk of metastasis to
regional lymph nodes is reported to be 1% to 2%.2
Direct invasion of the parotid gland from carcinoma of the external ear or preauricular skin also
occurs. Metastatic cancer accounts for less than
10% of the malignancies found in the parotid
gland. Of these metastases to the parotid lymph
nodes, 40% are SCC.3 The purpose of this report
is to review our experience in the management of
primary and metastatic SCC of the parotid gland.
PATIENTS AND METHODS
This study is a retrospective analysis of all
patients treated by the Department of Otolaryngology at University of Pittsburgh between 1982
and 2003. A total of 224 patients with cancer of
the parotid were identified. Of these, 66 patients
(29%) had SCC. Patients ranged in age from 41 to
96 years (mean, of 71.3 years; median, 73 years).
HEAD & NECK—DOI 10.1002/hed
July 2006
There were 49 men and 17 women. Overall, all
patients except for one patient were white.
Metastasis to the parotid gland from a known
primary site was identified in 41 of 66 patients
(62%). In 37 of these patients, the metastasis
came from cutaneous malignancy. The most commonly identified site was the skin of the auricle.
Four patients had a history of multiple cutaneous
cancers on the head, but the actual primary site
was unknown. There were also four patients with
a mucosal primary tumor.
Sixteen of the 66 patients (24%) had SCC of
the parotid gland without a known primary lesion.
In these patients, the cancer may have been primary in the parotid gland or may have been a metastasis from an unknown primary site. However,
after careful review of the charts and pathology
reports, it was convincing that they were primary
SCC of the parotid gland. These patients had
tumors in the parotid parenchyma, in contrast to
intraparotid nodal disease alone, and did not have
another tumor site.
The remaining nine of 66 patients (14%) were
undetermined to have either metastatic or primary
SCC of the parotid gland despite careful review.
For the purpose of this study, they were not included in the data analysis.
All patients were treated and followed for a
minimum of 2 years or until recurrence or death
from the date of primary treatment.
Statistical analysis was carried out using Statistix software for Windows.
Statistical comparisons were made using the twosample t test for age and the chi-square method
for the remainder variables. Two by two table test
was also performed when appropriate. The following assumptions were made to simply the data.
For disease status, patients with no evidence of
disease were grouped with those who died of other
conditions, and patients alive with disease were
grouped with those dead of disease. A p value of
less than .05 was considered to be statistically significant.
Statistical Methods.
was surgery only (25 of 32, 71%); some patients
received both surgery and radiotherapy (7 of 32,
22%). In each case, cancer of the parotid gland
was identified as a metastasis. At the initial presentation, one patient had palpable metastasis in
the neck only (the parotid metastasis was occult),
35 patients had parotid gland metastasis only,
and five patients had metastases to both the parotid gland and the neck.
Treatment prescribed for the 41 patients were
surgery alone in 14 patients (34%), surgery plus
adjuvant therapy, including postoperative radiation, brachytherapy and/or chemotherapy in 25
patients (61%), radiotherapy only in one patient
(2.4%), and one untreated patient (2.4%) who
died of disease shortly after discovery of SCC metastasis to the parotid gland (Table 1). Parotidectomy alone was carried out in six patients, and parotidectomy plus neck dissection was carried out
in 33 patients.
Disease status was determined by following
the patient for a minimum of 2 years after treatment. One patient treated only with surgery died
of other causes before the minimum of 2 years and
was excluded from analysis. The adjusted survival
rates were 62% for surgery only and 64% for surgery plus adjuvant therapy (Table 1).
In 16
patients with primary SCC of the parotid gland,
three patients (19%) underwent surgery only; 11
patients (63%) were treated with surgery plus adjuvant therapies, including radiation, brachytherapy and/or chemotherapy; and two patients (10%)
were treated nonsurgically with radiotherapy
only (Table 2). Parotidectomy alone was carried
out in five patients, and nine patients had parotidectomy and neck dissection.
Patients with Primary Squamous Cell Cancer.
Table 1. Metastatic squamous cell cancer to the parotid gland.
Treatment
Surgery
Initial
control
Salvaged/
attempted
Lost
FU or
DOC
Adjusted
survival–
cured
Adjusted
survival–
DOD
8/14
0/1
1
16/25
0/2
0
8/13
(62%)
16/25
(64%)
5/13
(38%)
8/25
(32%)
0/1
0
0
0
1/1
(100%)
RESULTS
In
41 patients with metastatic SCC to the parotid
gland, 32 of 41 patients (78%) had undergone
prior treatment for cutaneous SCC. Among these
patients, the most common previous treatment
Patients with Metastatic Squamous Cell Cancer.
Squamous Carcinoma of Parotid
Surgery þ
adjuvant
therapy
Radiation
only
Abbreviations: FU, follow-up; DOC, died of other causes; DOD, died of
disease.
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627
Table 2. Primary squamous cell cancer of parotid gland.
Treatment
Surgery
Surgery þ
adjuvant
therapy
Radiation
only
Lost
Initial Salvaged/ FU or
control attempted DOC
Adjusted
survival–
cured
Adjusted
survival–
DOD
2/3
6/11
0
0/1
0
2
2/3 (67%) 1/3 (33%)
6/9 (67%) 3/9 (33%)
1/2
0
0
1/2 (50%) 1/2 (50%)
Abbreviations: FU, follow-up; DOC, died of other causes; DOD, died of
disease.
Eighteen of 41 patients (44%), including those
previously mentioned who were initially seen
with a mass in the neck, were identified as having
positive nodes on histologic examination. The clinical outcomes were as follows: eight patients died
of disease, eight patients without evidence of disease, and two patients died of another condition.
Seven of the eight patients without evidence of
disease had received postoperative adjuvant therapy. Recurrence in the neck was observed in two
patients within 5 months after parotidectomy and
neck dissection (Table 3).
Patients with Primary Squamous Cell Cancer.
Two patients were treated with surgery and
postoperative adjuvant therapy, and they died of
other conditions in less than the 2-year follow-up
period. The adjusted 2-year disease control rate
was identical at 67% for surgery alone and for surgery plus adjuvant therapies (Table 2).
No statistically significant difference was found
in local control when comparing the different
treatments with surgery alone, surgery plus adjuvant therapies, or radiation therapy and chemotherapy in either patient group. Salvage surgery
was attempted for some patients in both groups,
but the results were dismal (Tables 1 and 2).
Overall, 53 of 57 patients (93%) underwent parotidectomy and three of
57 patients (5%) were treated with nonsurgical
modalities because of their poor general medical
condition. As part of their surgical therapy, 49
(92%) had facial nerve preservation. Two patients
(3.8%) in the surgical group had a biopsy of the facial nerve. Sacrifice of the entire facial nerve was
required in four of 53 patients (8%), with most
patients (75%) in the metastatic SCC group.
Nerve reconstruction was performed in two
patients. The 2-year disease control rate with facial nerve preservation was 61%.
Facial Nerve Preservation.
In patients
with primary SCC of the parotid gland, two of 16
patients (13%) initially were seen with cancer in
the parotid gland and metastases to the neck. One
patient was treated with surgery only and was
disease free at the 2-year follow-up. The other
patient received radiotherapy only but died of disease a year after starting treatment.
Occult cervical metastasis was observed in
seven other patients. Overall, nine of 16 patients
(56%) had regional neck metastases. The clinical
outcomes were as follows: four patients died
of disease and five patients without evidence of
disease. Three of the five (60%) patients free of
disease had received postoperative adjuvant
therapy. Recurrence in the neck was observed in
two patients from the group of 16 patients
within an average of 5 months after treatment
(Table 3).
Site of Recurrent Cancer.
Patients with Metastatic Squamous Cell Cancer.
In the
group of patients with metastatic SCC to the parotid gland, 12 patients had documented local or
regional recurrences and/or distant metastases.
Four patients had multiple (>1) sites of local
recurrences, regional recurrences, and/or distant
metastases. Specifically, there were three local
recurrences, nine regional recurrences, and four
distant metastases. The median times for local/
Cervical Node Involvement.
Patients with Metastatic Squamous Cell Cancer.
In patients
with SCC metastases to the parotid gland, six of
41 patients (15%) were initially seen with a clinically palpable mass in the neck. All six patients
underwent parotidectomy and neck dissection and
postoperative radiation therapy. Four patients had
good disease control. Two patients succumbed to
distant metastasis.
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Squamous Carcinoma of Parotid
Table 3. Cervical nodal involvement.
Group
Metastatic
Primary
On
presentation
Occult
nodes
Neck
metastasis/
recurrence
Total
regional
disease
6
2
12
7
2
2
20/41 (49%)
11/16 (69%)
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Table 4. Site of disease recurrence in metastatic squamous
cell cancer to parotid gland.
Table 6. P values for disease outcome.
Disease outcome (NED/DOD)
On presentation
Recurrent site
No. of patients
Neck and parotid
Local
Regional
Distant
Multiple sites
Local
Regional
Distant
Multiple sites
0
1
1
1 (RþD)
0
5
1
3 (LþR, LþR, LþD)
Parotid
Abbreviations: R, regional (head and neck); D, distant (beyond head
and neck, ie, lungs); L, local (parotid gland).
Multiple refers to >1 site of concurrent cancer recurrences.
regional recurrence and distant metastasis were
7.5 months and 5 years, respectively (Table 4).
p value
Age
Tumor group
Sex
Distant metastasis
Treatment group (S vs S þ adj)
Perineural involvement
Margins
Lymph node involvement
Cranial nerve VII preservation
.79
1.0
.51
.001
.75
.76
.13
.14
1.0
Abbreviations: NED, no evidence of disease; DOD, died of disease; S,
surgery; S þ adj, surgery þ postoperative adjuvant therapy.
SCC of the parotid gland, no variable was found to
be statistically significant between the two tumor
groups (Table 7).
Patients with Primary Squamous Cell Cancer.
In the group
with primary SCC of the parotid, five patients
had documented local recurrences, regional recurrences, and/or distant metastases. Two patients
had multiple (>1) sites of local recurrences, regional recurrences, and/or distant metastases.
Specifically, there was one local recurrence, five regional recurrences only, and one distant metastasis. The median time for local/regional recurrence
metastasis was 7 months. This observed local recurrence rate is similar to the findings of Lee et al4
for primary SCC of the parotid gland to occur
within 8 months of definitive treatment (Table 5).
Variables found to be clinically significant to disease outcome were surgical
margins of the parotidectomy and lymph node
involvement. However, only the presence of distant
metastasis was found to be a statistically significant (p .05) poor prognostic factor in the disease
outcome for these patients (Table 6). Comparing
the groups of metastatic SCC to unknown primary
Statistical Analysis.
Table 5. Site of recurrence in primary squamous cell cancer
of parotid gland.
On presentation
Recurrent site
No. of patients
Neck and parotid
Parotid
None
Local
Regional
Distant
Multiple sites
0
0
3
0
2 (LþR, RþD)
Abbreviations: L, local (parotid gland); R, regional (head and neck); D
distant (beyond head and neck, ie, lungs).
Multiple refers to >1 site of concurrent cancer recurrences.
Squamous Carcinoma of Parotid
DISCUSSION
When SCC is identified in the parotid gland, an
effort must be made to identify the etiology. When
no other primary lesion exists, it seems logical to
consider the cancer a primary tumor in the parotid gland. Primary SCC of the parotid gland is
unusual. Therefore, when SCC is identified in the
parotid gland, one must consider all possibilities
so that the proper treatment plan for a particular
setting is selected. After therapy, all patients
require lifelong follow-up.
In both metastatic and primary SCC of the parotid, near total parotidectomy with facial nerve
dissection and preservation was the operation performed most commonly at our institution. The
number of patients with cancer in the parotid gland
and concurrent palpable metastasis to the neck at
initial presentation was low for both groups: five
and two patients in metastatic and primary SCC
group, respectively. Others have reported that elective neck dissection is not routinely recommended
for primary cancer of the parotid gland.5 In our series, 33 of 41 patients (80%) with metastatic cutaneous SCC and nine of 16 patients (56%) with primary SCC underwent neck dissection, irrespective
of the physical finding at presentation. Of the 42
patients who had neck dissections, 25 patients
(60%) had positive occult lymph nodes. The rationale for doing neck dissection is based on the observation that most patients with SCC in the parotid
gland do, in fact, have metastatic disease to the
neck and that the lymph nodes in the parotid area
represent just one metastatic site for cutaneous
SCC of the head and neck region. When the parotid
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Table 7. Variable distribution frequency and p values comparing the two tumor groups: metastatic versus primary
squamous cell carcinoma of the parotid gland.
Age
Sex, M:F
Distant metastasis, Y:N
Treatment group, S:SþAdj
Perineural involvement, Y:N
Margin involvement, Y:N
Lymph node involvement, Y:N
Cranial nerve VII preservation, Y:N
Disease outcome, NED:DOD
Metastatic
Primary
p value
2.9:1
1 (30.8%):2.3 (69.2%)
1 (35.9%): 1.8 (64.1%)
1 (35.9%): 1.8 (64.1%)
1 (35.9%): 1.8 (64.1%)
1 (43.6%): 1.3 (56.4%)
37.5 (97.4%):1 (2.6%)
2.3 (69.2%):1 (30.8%)
2.5:1
1 (28.6%):2.5 (71.4%)
1 (21.4%):3.7 (78.6%)
1 (50%): 1 (50%)
1 (50%): 1 (50%)
1 (50%): 1 (50%)
13 (92.9%): 1 (7.1%)
2.5 (71.4%): 1 (28.6%)
.79
1.00
1.00
.51
.53
.53
.76
1.0
1.0
Abbreviations: M, male; F, female; Y, yes; N, no; S, surgery; SþAdj, surgery plus postoperative adjuvant therapy; NED, no evidence of disease; DOD,
died of disease.
gland is clinically involved, other nodes in the neck
at risk should also be removed.2 Our data only verify the potential metastatic sites of head and neck
cutaneous SCC.
The incidence of occult metastases in the neck,
as supported by positive histologic findings of
lymph nodes and/or extracapsular spread, was observed in 18 of 44 patients (44%) with metastatic
SCC and in seven of 16 patients (44%) with primary SCC of the parotid. The percentage of
patients with metastases to the neck was similar
in both groups, despite the worse disease status
often observed in patients with metastatic cutaneous SCC to the parotid gland. This seems to suggest that patients in whom no other primary site
was found may, in fact, have primary cancer arising in the parotid gland. The incidence of distant
metastasis is increased in patients with metastasis to the neck compared with those with parotid
gland SCC alone.6
The clinical outcome was similar between patients
with metastatic SCC and primary SCC of the parotid gland, regardless of the treatment plan.
Death from cancer occurred in 14 of 40 patients
(35%) and five of 14 patients (36%) in the metastatic and primary SCC patient groups, respectively. In our relatively small group of patients
with primary SCC of the parotid gland, follow-up
visits failed to reveal new primary tumors.
The disease control rate for patients with metastatic SCC to the parotid gland or primary SCC
of the parotid gland treated with surgery alone
was not statistically different from those treated
with surgery and postoperative radiotherapy. This
finding is consistent with the results of Khurana
et al.6 In a retrospective study such as this, treat-
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Squamous Carcinoma of Parotid
ment bias is to be expected, because patients with
the worst prognosis were treated with postoperative radiation. No comparison of efficacy is possible
on the basis of our data. A prospective randomized
trial would be required to address this issue.
Past studies have shown
that involvement of clinically palpable nodes in
the neck worsened prognosis in the primary SCC
of the parotid gland. In our sample, an equally
sensitive negative prognostic factor in both groups
is the histologic evidence of occult metastasis in
the neck. Positive occult lymph nodes on histologic
examination were found in 60% of patients who
underwent neck dissection. Although by statistical analysis only distant metastasis was identified
as a statistically significant variable, lymph node
involvement and surgical margin are important
clinical prognostic factors that are present in
cases with distant metastasis.
Prognostic Factors.
The goal of any treatment is to cure with the least morbidity. In the
setting of parotidectomy, this implies an
attempt to preserve the facial nerve in resection
of the parotid gland. In our experience of 53
parotidectomies, there were only four patients
whose facial nerve had to be resected. Resection
of the facial nerve did not result in improved
outcome. Similarly, preservation of the nerve
with close margins, including peeling the nerve
off tumor, did not result in increased recurrence. Of those patients who underwent facial
nerve preservation in both primary and metastatic SCC of parotid gland, 61% was the 2-year
disease control rate. The extent of parotidecFacial Nerve Function.
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July 2006
tomy (ie, partial vs total) or sacrificing the facial
nerve for better disease control did not seem to
make any significant difference in either patient
group. Therefore, we concur with Audet et al7 that
the treatment approach in patients with metastatic cutaneous SCC to the parotid gland is a
nerve-sparing parotidectomy when possible; although in cases with evidence of facial nerve involvement, a radical parotidectomy with facial
nerve sacrifice is usually necessary despite the
similar disease state outcome found in our study.
The retrospective nature of these data introduces
physician bias that cannot be eliminated.
The number of patients with either
local recurrence, regional recurrence, or distant
metastasis was higher in the group with metastatic SCC (12 patients) than in the group with
primary SCC of the parotid (five patients). The
percentage of recurrent and distant metastatic
rates (31%) for primary SCC of the parotid gland
are in accordance with the recurrence rates
reported in the literature, ranging from 8% to
55% for similarly treated patients with primary
parotid cancer.8–11 In our series, local/regional
recurrences were more commonly encountered
than development of distant metastases during
the follow-up period for both patient groups.
Local recurrence in the area of the parotid
gland was the most important site of failure in
both groups of patients with SCC of the parotid.
Among patients with primary SCC of the parotid
gland, the skin of the auricle was the most common site of local recurrence. The neck and lungs
were the sites for regional and distant metastases,
respectively, common to both primary and metastatic SCC patient groups.
Despite the comprehensive treatments received
or the origin of SCC in the parotid, patients who
had local or regional recurrence and distant metastases all died of disease. In our series, the average
median time of local and regional recurrences for
both patient groups averaged 7 months. On the basis of prior studies, the tendency for primary SCC
of the parotid gland for distant spread has generally been low compared with cervical neck metastases.12 Our data supported this finding, with only
one patient in the primary SCC of the parotid gland
group who had distant metastasis.
Recurrence.
CONCLUSIONS
This review of 57 patients with either primary or
metastatic SCC to the parotid gland suggests that
Squamous Carcinoma of Parotid
an effective treatment is available for approximately 58% of patients with SCC in the parotid
gland. A comprehensive treatment approach consisting of surgery and adjuvant therapy may
increase disease control in those individuals with
metastatic SCC to the parotid gland. The similar
clinical course between the two groups of patients
in our series leads us to hypothesize that some of
the patients with primary SCC of the parotid gland
may have had metastatic SCC to the parotid gland.
Elderly patients are potentially poor historians,
and it could be a challenge for them to recount all of
their cutaneous lesions and treatments.
The pattern of disease failure was dependent
on neck metastasis associated with local recurrence and distant metastases, even when postoperative radiation was administered. Occult
metastases to the cervical nodes are frequently
encountered, suggesting that treatment should
include neck dissection, as well as the excision
of the parotid mass. Elective neck dissection has
the benefit of providing additional pathologic information with low morbidity that will direct
the physician regarding management of the disease and is also an effective treatment for limited metastatic cancer in the neck.
The aggressive clinical behavior of metastatic
cutaneous SCC underscores the importance of
elective treatment of regional lymphatics, including the parotid gland. The goal is a greater chance
of cure with a conservative approach to the parotid gland.
Acknowledgments. We thank the Tumor
Registry Staff, Dr. Carl H. Snyderman for statistical analysis, and Stout Family Fund for Head and
Neck Cancer Research at the Eye & Ear Foundation of Pittsburgh.
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