Hindawi Publishing Corporation

Journal of Skin Cancer

Volume 2011, Article ID 972497, 6 pages
doi:10.1155/2011/972497

Clinical Study
Outcomes of Recurrent Head and Neck Cutaneous
Squamous Cell Carcinoma

Nichole R. Dean,1 Larissa Sweeny,1 J. Scott Magnuson,1 William R. Carroll,1

Daniel Robinson,1 Renee A. Desmond,2 and Eben L. Rosenthal1
1 Division of Otolaryngology, Head and Neck Surgery, Department of Surgery, The University of Alabama at Birmingham,
Volker Hall G082,1670 University Boulevard, Birmingham, AL 35233, USA
2 Division of Preventive Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 25294, USA

Correspondence should be addressed to Eben L. Rosenthal, oto@uab.edu

Received 10 March 2011; Accepted 18 April 2011

Academic Editor: S. Ugurel

Copyright © 2011 Nichole R. Dean et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.

Recurrent, advanced stage cutaneous squamous cell carcinoma (cSCC) is uncommon with limited publications on patient
outcomes. A retrospective study including patients who underwent surgical resection for recurrent, advanced stage cSCC of the
head and neck was performed (n = 72). Data regarding tumor site, stage, treatment, parotid involvement, perineural invasion,
positive margins, metastasis, and disease-free survival was analyzed. The majority of patients were male (85%) and presented with
recurrent stage III (89%) cSCC. Two-year disease-free survival was 62% and decreased to 47% at 5 years. Parotid involvement,
positive margins, nodal metastasis, or the presence of perineural invasion did not correlate with decreased survival (P > .05).
Distant metastasis was a strong indicator of poor overall survival (P < .001). Adjuvant postoperative radiotherapy did not improve
overall survival (P = .42). Overall survival was poor for patients with advanced recurrent cSCC despite the combined treatment
with surgery and radiotherapy.

1. Introduction factors can be applied to determine prognosis in patients

with recurrent disease.
Nonmelanoma skin cancer (NMSC) is the most common In the present study, we evaluate outcomes in patients
diagnosed malignancy in the United States with more than with advanced, recurrent cSCC of the head and neck. In the
one million new cases reported each year [1]. Basal cell majority of cases, the treatment recommendations for this
(BCC) and cutaneous squamous cell carcinoma (cSCC) patient population are surgery and adjuvant radiotherapy
comprise nearly all of the NMSCs. The majority of lesions [7]. Although no single variable can dictate treatment,
(80–90%) arise in the sun exposed areas of the head and this study sought to identify further predictive factors and
neck [2] and are successfully treated by complete tumor provide guidance for counseling patients with aggressive
excision. A small percentage of NMSCs, mostly cSCCs, head and neck cSCC.
are refractory to standard surgical resection [1, 3]. Several
outpatient-based studies have demonstrated a low incidence 2. Materials and Methods
of nodal metastasis (2-3%) in patients with cSCC [4, 5].
Most tertiary care center-referred patients, however, present A retrospective review of all patients (n = 72) who presented
with recurrent disease and are at increased risk for neck with recurrent, advanced stage (III or IV) cSCC of the
metastasis, poor local control, and further cancer recurrence. head and neck between June 1998 and December 2007 was
High risk prognostic indicators include size, anatomic site, performed at The University of Alabama at Birmingham
recurrence, history of radiation, immunosuppression, and following Institutional Review Board approval. Tumors were
perineural invasion [6]. It is unknown whether the same risk staged according to the American Joint Committee on
2 Journal of Skin Cancer

Cancer (AJCC) guidelines, and histology was confirmed by Table 1: Patient characteristics.
pathology. Tumors were divided into 5 different anatomic Characteristic n (%)
sites: face, neck, ear, periauricular area, and scalp. Lesions
Age-years
occurring on the face included forehead, periorbital, nose,
lip, and chin. Periauricular lesions were defined as lesions Mean (range) 71 (42–93)
occurring on the temple, cheek, or postauricular area. Gender
All patients underwent aggressive surgical resection. This Male 61 (85)
included parotidectomy for cases in which parotid involve- Female 11 (15)
ment was suspected on preoperative imaging or clinical Tumor subsite
exam. Parotidectomy ranged from superficial to radical Face 19 (27)
parotidectomy with sacrifice of the facial nerve. The major- Forehead 5
ity of patients required neck dissection and postoperative Periorbital 4
radiation. Selective, modified, or radical neck dissection was Nose 8
performed at the time of resection or in a staged procedure.
Chin 1
Neck dissection was indicated when nodal metastasis was
Lip 1
suspected on preoperative imaging or when the patient
presented with an advanced T classification of their lesion. Periauricular 34 (47)
Postoperative radiation was recommended for patients with Cheek 13
large cutaneous malignancies when more than one positive Temple 18
node was identified on neck dissection, when negative Postauricular 3
surgical margins could not be obtained, or in the presence of Ear 13 (18)
perineural or lymphovascular invasion. Histological margins Scalp 3 (4)
were defined as negative if the advancing tumor edge was Anterior 2
≥4 mm from the line of surgical excision and positive if less Posterior 1
than 4 mm. All cutaneous defects were repaired either by
Neck 3 (4)
primary closure, split thickness skin graft, local or regional
T classification
flap coverage, or free tissue transfer.
Demographic characteristics, including patient age, gen- T1 1 (1)
der, a history of immunosuppression, previous treatment, T2 5 (7)
and time to recurrence, were recorded. Prognostic indicators T3 4 (6)
including tumor site, size, perineural invasion, positive mar- T4 60 (83)
gins, or histologic grade were reviewed. Outcomes measured Tx 2 (3)
consisted of disease-free survival and cancer recurrence. TMN Stage
Descriptive variables are reported as means (±SD) and III 64 (89)
categorical variables as percentages. Descriptive statistics IV 8 (11)
were compared by general linear models for normally
distributed variables or the Kruskal-Wallis test for otherwise.
The relationship between patient clinical and treatment
factors and disease-specific survival was calculated using the of immune suppression due to lymphoma or leukemia
Kaplan-Meier method. Survival time was calculated as the (n = 6), rheumatoid arthritis (n = 1) or were currently
interval from date of surgery to date of death or date of maintained on immunosuppressive medications due to prior
last followup. Deaths due to other causes were censored for transplant (n = 3).
these analyses. A P-value of <.05 was considered statistically No difference in margin status was observed between the
significant. Statistical analysis was performed using SAS various tumor sites (P = .48). Perineural invasion, a known
Version 9.2 software (SAS Institute Inc., Cary, NC). risk factor for recurrence and metastasis, occurred in 36.9%
of patients. Patients with cSCC of the ear and periauricular
3. Results area were more likely to demonstrate perineural invasion on
surgical pathology in comparison to all other sites (P = .06).
Between 1998 and 2007, there were 72 patients identified Although perineural invasion did not significantly correlate
who underwent surgical resection for recurrent, advanced with tumor site or size, patients with this finding were more
stage cSCC. The majority of patients were male (84.7%), likely to have parotid involvement (P = .04). A total of
presented with stage III disease (88.8%), and had undergone 39 patients (54.1%) underwent superficial (n = 16), total
previous surgical resection (76.5%). Median time from pre- (n = 11) or radical (n = 12) parotidectomy. Four patients
vious skin cancer diagnosis to presentation with recurrence had undergone previous parotidectomy for positive nodal
was 5.7 months (range, 1–41 months). Mean tumor size was metastasis. Parotid involvement, either by direct extension
3.4 cm in largest dimension (±SD 2.07). The majority of or nodal metastasis, was confirmed by surgical pathology in
lesions occurred on the ear or periauricular area (65.2%) 92.3% of cases (n = 36).
and were classified as T4 lesions (83.3%) invading into deep The majority of patients with parotid involvement
extradermal structures (Table 1). Ten patients had a history underwent neck dissection (92.3%). Neck dissection was
Journal of Skin Cancer 3

performed in 66.7% of all patients. The majority (64.5%) Table 2: Free flaps used for cutaneous defect reconstruction.
underwent selective (n = 31) or modified radical (n =
Flap type n
14) neck dissection. One patient required a radical neck
dissection. Another patient with a posterior scalp lesion ALT 12
had previously undergone an extended posterior triangle Latissimus 3
dissection. Three patients had undergone previous neck Rectus 8
dissections. Positive nodal metastasis occurred in 43.7% RFFF 13
(n = 21/48) of patients, and nearly all cases occurred in Fibula 2
patients with advanced T classification (83.3%) and those OCRFFF 4
with parotid involvement (85.7%, n = 18/21). The majority ALT: anterolateral thigh; RFFF: radial forearm free flap; OCRFFF: osteocu-
of nodes were located in levels I–III (95%). No positive taneous radial forearm free flap.
nodes were identified in level IV, and one case of nodal
metastasis occurred in level V (Table 3). Nodal metastasis Table 3: Patterns of cervical lymph node metastasis.
did not correlate with tumor size, though a larger percentage
of patients with cSCC of the ear demonstrated neck disease Level n (%)
(66.7%) in comparison to other sites (P = .14). Eight I 6 (25)
patients had evidence of distant metastasis at the time of II 12 (50)
surgical resection. Distant metastasis did not correlate with III 5 (20)
perineural invasion, original tumor site, size, or parotid IV 0 (0)
involvement at the time of surgical resection (P > .05). The V 1 (5)
histologic grades of the tumors consisted of 19% (n = 14)
well differentiated, 56% (n = 40) moderately differentiated,
8% (n = 6) moderate-poorly differentiated, and 17% (P = .18). Margin status, a history of immunosuppression,
(n = 12) poorly differentiated. There was not a statistically and perineural invasion did not predict cancer recurrence.
significant relationship found between histologic grade and Two-year disease-free survival was 62.2% and was
survival (data not shown). reduced to 47.2% at 5 years (Figure 1). Age greater than
All defects were closed either by primary closure or split 65 (P = .34), male gender (P = .06), immunosup-
thickness skin graft (n = 23), local or regional flap (n = 7), pression (P = .22), and patients with a previous history
or free tissue transfer (n = 42). One patient underwent of radiation (P = .4) tended towards worse survival
pectoralis major myocutaneous flap reconstruction, and 6 outcomes. Surprisingly, tumor characteristics including site,
patients required local cervicofacial flap coverage. Patients size (greater than 3.4 cm), parotid involvement, perineural
with larger defects typically required free flap reconstruction. invasion, or positive margins following resection had no
The radial forearm free flap (n = 13) and anterolateral influence on disease-free survival. Two-year disease-free
thigh (n = 12) were most commonly utilized for soft tissue survival for patients with positive nodal metastasis was
coverage. In cases in which bony reconstruction was also 47.7% versus 72.9% for those without neck disease (P =
required, the osteocutaneous radial forearm free flap (n = 4) .14) (Figure 2). Although locoregional metastasis was not
and fibula (n = 2) were employed (Table 2). a significant predictor of survival, distant metastasis noted
The majority of patients underwent postoperative radi- within 30 days of surgical resection was associated with poor
ation (66.7%) as a result of advanced stage disease. Fifteen prognosis (P < .001). No patient with distant metastasis
patients had undergone previous radiotherapy, and 3 under- survived beyond 13 months. Most patients required free
went both pre- and postoperative radiation. The majority flap reconstruction and postoperative radiation for advanced
of patients with positive margins underwent postoperative disease. Patients who underwent free flap reconstruction
radiation. Three patients had prior radiation therapy and tended towards worse survival outcomes (P = .24). Despite
were unable to tolerate the cytotoxic effects of a second aggressive surgical resection, postoperative radiation was not
course of radiation, and two electively declined further ther- shown to affect long term disease-free survival (P = .42)
apy. Three patients with perineural invasion did not undergo or repeat cancer recurrence (P = .85) for this patient pop-
postoperative radiotherapy based on personal preference. ulation. Although not statistically significant, patients with
Mean time to follow up was 18.5 months. Forty percent cervical metastasis who underwent postoperative radiation
of patients (n = 28) developed local (67.8%, n = 19), had improved locoregional control (68% versus 25%, P =
regional (25%, n = 7) or distant metastasis (14.2%; n = 4) .14) when compared to those who underwent surgery alone.
during the followup period. Median time to cancer recur-
rence was less than 7 months (6.5, range 1–41 months). One
patient had local recurrence and developed lung metastasis 4. Discussion
while another patient developed both recurrent neck disease Nonmelanoma skin cancer is the most common malignancy
and lung metastasis. Although not statistically significant, worldwide with over 140,000 cases of cSCC diagnosed each
patients were more likely to recur if they presented with cSCC year in the United States alone [8]. The incidence of regional
of the ear or periauricular area (P = .06), demonstrated metastasis among patients with cSCC ranges from 0.5 to 16%
positive nodal metastasis at the time of neck dissection [4] and can result in potentially fatal consequences. Although
(P = .14), or did not undergo postoperative radiotherapy a number of factors have been identified as high risk
4 Journal of Skin Cancer

1 series, 5-year disease-free survival was significantly improved

for patients undergoing adjuvant radiotherapy following
0.8 surgical resection (73% versus 18%, P = .001), and
locoregional control was maintained in 77% of patients
Survival probability

[11]. Both studies included patients with parotid or cervical

0.6 metastasis. Nearly 50% of all patients in this study presented
with parotid involvement, and 30% had cervical metastasis.
0.4 All patients underwent surgical resection, and most (66.7%)
had postoperative radiation. Postoperative radiation did not
have an impact on overall disease-free survival (P = .42)
0.2 or cancer recurrence (P = .85). Although not statistically
significant, patients who presented with cervical metastasis
0 and received adjuvant radiotherapy in addition to surgical
0 2 4 6 resection had improved locoregional control when compared
(years) to those who underwent surgery alone (68% versus 25%,
P = .14). Adjuvant radiotherapy appears to provide some
Figure 1: Overall disease-free survival for patients with advanced benefit in patients with advanced, recurrent cSCC though
recurrent cutaneous squamous cell carcinoma. the risk for repeat recurrence is high given the aggressive
nature of these neoplasms. The role for systemic therapy in
1
the treatment of recurrent, advanced stage cSCC remains
unknown. Although there have been some case reports citing
improved outcomes with the addition of cetuximab [12–14],
0.8 the majority of publications on targeted therapies against
Survival probability

EGFR and its tyrosine kinase have demonstrated limited

0.6 No regional Dz improvement in the mortality of patients with advanced
disease when used as monotherapy [15–19].
0.4
The median time from previous skin cancer diagno-
Regional Dz sis to presentation with initial recurrence was only 5.7
months (range, 1–41 months). This is likely due to the
0.2 patient population being comprised of advanced, recurrent
cutaneous squamous cell carcinomas, and as a result, this
0 cohort of patients had very aggressive disease. The rapid
0 2 4 6 recurrence of the disease reflects the malignant biology of
(years) late stage cSCC. In addition, nearly 40% of patients in
this series developed a second recurrence with the majority
Figure 2: Disease-free survival for patients with and without occurring locally (68%). Distant metastasis noted in the
positive nodal metastasis. Two-year disease-free survival for patients immediate postoperative period was associated with poor
with regional disease was 47.7% versus 72.9% for those without prognosis (P < .001). Median time to cancer recurrence
regional metastasis (P = .14). was 6.5 months, and overall 2-year disease-free survival was
62%. Although not statistically significant, patients from the
present study were more likely to recur if they had cSCC
prognostic indicators for cancer recurrence and metastasis, of the ear or periauricular area (P = .06), demonstrated
most studies to date have only evaluated primary cSCC. In cervical metastasis on surgical pathology (P = .14), or
contrast, the majority of patients presenting to a tertiary care did not undergo postoperative radiotherapy (P = .18).
center have undergone previous skin cancer treatment and Previous studies have demonstrated a higher incidence of
subsequently developed a second primary or recurrence. A nodal metastasis among patients with lesions located on
diagnosis of recurrent cSCC alone confers a more aggressive or around the ear as a result of lymphatic drainage to the
tumor subtype [9], yet identifying factors associated with parotid gland [20, 21]. In the present study, nearly half
poor outcome is essential for patient management and of all patients with parotid involvement either by direct
decision making. extension or nodal metastasis also demonstrated cervical
In the present study, we review tumor characteristics, disease. Multiple studies have demonstrated that patients
prior treatment, and outcomes in patients with recurrent, with parotid involvement are at a high risk for cervical
advanced stage cSCC and evaluate the role of postopera- metastasis [9, 22]. In a study by Ying et al., 44% of patients
tive radiotherapy. Surgery combined with radiation is the with parotid metastasis also had positive cervical nodes [23].
recommended treatment in most cases of advanced disease Therefore it is recommended that all patients with parotid
[7]. In a study by Veness et al., improved locoregional metastasis undergo selective neck dissection.
control and disease-free survival (73% versus 54%, P = The majority of patients in this series underwent selective
.004) were achieved in patients who received adjuvant neck dissection which included levels I–III. Fifty percent of
radiotherapy compared to surgery alone [10]. In another the nodal metastasis were located in level II. This finding is
Journal of Skin Cancer 5

similar to what a recent article published, where nearly 80% Acknowledgments

of all positive nodal metastasis from cSCC were located in
level II [24]. Although parotid involvement did not have an This work was supported by Grants from the National Insti-
influence on disease-free survival in this patient population, tute of Health (NCI K08CA102154 and 2T32 CA091078-06).
the 2-year disease-free survival for patients with cervical
metastasis was 48% versus 73% for those without neck References
disease (P = .14). In the study by Clayman et al., 3-year
disease-free survival was 69% for patients with lymph node [1] M. Alam and D. Ratner, “Cutaneous squamous-cell carci-
involvement versus 87% for those without nodal disease noma,” New England Journal of Medicine, vol. 344, no. 13, pp.
(P = .09) [25]. Cervical metastasis seemingly confers a worse 975–983, 2001.
prognosis for patients with recurrent disease. Appropriate [2] R. T. Greenlee, M. B. Hill-Harmon, T. Murray, and M. Thun,
neck dissection should be employed in patients with evidence “Cancer statistics, 2001,” CA: A Cancer Journal for Clinicians,
of cervical metastasis or in the presence of parotid involve- vol. 51, no. 1, pp. 15–36, 2001.
ment. If parotid involvement occurs and a neck dissection is [3] A. K. Joseph, T. L. Mark, and C. Mueller, “The period
not performed then radiation should also be directed at the prevalence and costs of treating nonmelanoma skin cancers
neck due to the high risk of cervical metastasis in patients in patients over 65 years of age covered by medicare,”
with both primary and recurrent disease. Dermatologic Surgery, vol. 27, no. 11, pp. 955–959, 2001.
Perineural invasion and tumor size have been considered [4] M. G. Joseph, W. P. Zulueta, and P. J. Kennedy, “Squamous cell
high risk factors in patients with primary disease [9]. In a carcinoma of the skin of the trunk and limbs: the incidence of
study by Clayman et al., patients with recurrent carcinoma metastases and their outcome,” Australian and New Zealand
Journal of Surgery, vol. 62, no. 9, pp. 697–701, 1992.
were more likely to present with larger tumors which invaded
beyond subcutaneous tissues and which demonstrated per- [5] D. Czarnecki, M. Staples, A. Mar, G. Giles, and C. Meehan,
“Metastases from squamous cell carcinoma of the skin in
ineural (24%) and lymphovascular invasion [25]. Mean
southern Australia,” Dermatology, vol. 189, no. 1, pp. 52–54,
tumor size for patients presenting with recurrent disease 1994.
in our study was 3.6 cm, and the majority were T4 lesions
[6] M. J. Veness, “Treatment recommendations in patients diag-
(83%). In addition, perineural invasion occurred in 37% of nosed with high-risk cutaneous squamous cell carcinoma,”
patients. Patients with cSCC of the ear and periauricular Australasian Radiology, vol. 49, no. 5, pp. 365–376, 2005.
area were more likely to demonstrate perineural invasion on [7] C. J. O’Brien, E. B. McNeil, J. D. McMahon, I. Pathak, C. S.
surgical pathology in comparison to all other sites (P = .06), Lauer, and M. A. Jackson, “Significance of clinical stage, extent
and patients with perineural invasion were more likely to of surgery, and pathologic findings in metastatic cutaneous
have parotid involvement (P = .04). It has previously been squamous carcinoma of the parotid gland,” Head and Neck,
demonstrated that there is a significant increase in both vol. 24, no. 5, pp. 417–422, 2002.
nodal and distant metastasis for patients with perineural [8] B. S. Cherpelis, C. Marcusen, and P. G. Lang, “Prognostic
invasion when compared to those without [26]. Similarly, factors for metastasis in squamous cell carcinoma of the skin,”
tumor size has been associated with an increased risk of Dermatologic Surgery, vol. 28, no. 3, pp. 268–273, 2002.
metastasis: 30% for tumors >2 cm versus 9% for those <2 cm [9] M. J. Veness, S. Porceddu, C. E. Palme, and G. J. Mor-
[27]. Perineural invasion and tumor size did not influence gan, “Cutaneous head and neck squamous cell carcinoma
survival rates in this patient population. These results may metastatic to parotid and cervical lymph nodes,” Head and
be related to the fact that all these patients had high Neck, vol. 29, no. 7, pp. 621–631, 2007.
risk prognostic factors and received postoperative radiation [10] M. J. Veness, G. J. Morgan, C. E. Palme, and V. Gebski,
which resulted in some improvement in locoregional control. “Surgery and adjuvant radiotherapy in patients with cuta-
It could also be that recurrent cSCC represents a more neous head and neck squamous cell carcinoma metastatic to
aggressive tumor subtype, and these patients all presented lymph nodes: combined treatment should be considered best
with advanced disease. practice,” Laryngoscope, vol. 115, no. 5, pp. 870–875, 2005.
[11] M. J. Veness, C. E. Palme, M. Smith, B. Cakir, G. J. Morgan,
and I. Kalnins, “Cutaneous head and neck squamous cell
5. Conclusions carcinoma metastatic to cervical lymph nodes (nonparotid):
a better outcome with surgery and adjuvant radiotherapy,”
Recurrent advanced stage cSCC confers a poor prognosis Laryngoscope, vol. 113, no. 10, pp. 1827–1833, 2003.
with an increased risk for parotid involvement, nodal
[12] S. Kim, M. Eleff, and N. Nicolaou, “Cetuximab as primary
metastasis, and poor locoregional control. Despite aggressive treatment for cutaneous squamous cell carcinoma to the
surgical resection including parotidectomy and neck dissec- neck,” Head and Neck, vol. 33, no. 2, pp. 286–288, 2011.
tion followed by postoperative radiotherapy, 5-year disease- [13] J. K. Suen, L. Bressler, S. S. Shord, M. Warso, and J. L. Villano,
free survival rates are less than 50%. Patients presenting with “Cutaneous squamous cell carcinoma responding serially to
recurrent disease should be appropriately counseled with single-agent cetuximab,” Anti-Cancer Drugs, vol. 18, no. 7, pp.
regards to outcome and treatment recommendations. 827–829, 2007.
[14] J. E. Bauman, K. D. Eaton, and R. G. Martins, “Treatment
Conflicts of Interest of recurrent squamous cell carcinoma of the skin with
cetuximab,” Archives of Dermatology, vol. 143, no. 7, pp. 889–
The authors declare that there is no conflicts of interests. 892, 2007.
6 Journal of Skin Cancer

[15] E. E. Cohen, D. W. Davis, T. G. Karrison et al., “Erlotinib

and bevacizumab in patients with recurrent or metastatic
squamous-cell carcinoma of the head and neck: a phase I/II
study,” The Lancet Oncology, vol. 10, no. 3, pp. 247–257, 2009.
[16] E. E. W. Cohen, F. Rosen, W. M. Stadler et al., “Phase II trial of
ZD1839 in recurrent or metastatic squamous cell carcinoma
of the head and neck,” Journal of Clinical Oncology, vol. 21, no.
10, pp. 1980–1987, 2003.
[17] J. S. W. Stewart, E. E. W. Cohen, L. Licitra et al., “Phase III
study of gefitinib 250 compared with intravenous methotrex-
ate for recurrent squamous cell carcinoma of the head and
neck,” Journal of Clinical Oncology, vol. 27, no. 11, pp. 1864–
1871, 2009.
[18] K. A. Gold, H. Y. Lee, and E. S. Kim, “Targeted therapies in
squamous cell carcinoma of the head and neck,” Cancer, vol.
115, no. 5, pp. 922–935, 2009.
[19] D. Soulieres, N. N. Senzer, E. E. Vokes, M. Hidalgo, S.
S. Agarvala, and L. L. Siu, “Multicenter phase II study of
erlotinib, an oral epidermal growth factor receptor tyrosine
kinase inhibitor, in patients with recurrent or metastatic
squamous cell cancer of the head and neck,” Journal of Clinical
Oncology, vol. 22, no. 1, pp. 77–85, 2004.
[20] D. Lee, M. Nash, and G. Har-El, “Regional spread of auricular
and periauricular cutaneous malignancies,” Laryngoscope, vol.
106, no. 8, pp. 998–1001, 1996.
[21] L. E. Afzelius, M. Gunnarsson, and H. Nordgren, “Guidelines
for prophylactic radical lymph node dissection in cases of
carcinoma of the external ear,” Head and Neck Surgery, vol. 2,
no. 5, pp. 361–365, 1980.
[22] C. J. O’Brien, E. B. McNeil, J. D. McMahon, I. Pathak, and C.
S. Lauer, “Incidence of cervical node involvement in metastatic
cutaneous malignancy involving the parotid gland,” Head and
Neck, vol. 23, no. 9, pp. 744–748, 2001.
[23] Y. L. M. Ying, J. T. Johnson, and E. N. Myers, “Squamous cell
carcinoma of the parotid gland,” Head and Neck, vol. 28, no. 7,
pp. 626–632, 2006.
[24] T. J. Vauterin, M. J. Veness, G. J. Morgan, M. G. Poulsen, and
C. J. O’Brien, “Patterns of lymph node spread of cutaneous
squamous cell carcinoma of the head and neck,” Head and
Neck, vol. 28, no. 9, pp. 785–791, 2006.
[25] G. L. Clayman, J. J. Lee, F. C. Holsinger et al., “Mortality risk
from squamous cell skin cancer,” Journal of Clinical Oncology,
vol. 23, no. 4, pp. 759–765, 2005.
[26] H. Goepfert, W. J. Dichtel, J. E. Medina, R. D. Lindberg, and M.
D. Luna, “Perineural invasion in squamous cell skin carcinoma
of the head and neck,” The American Journal of Surgery, vol.
148, no. 4, pp. 542–547, 1984.
[27] D. E. Rowe, R. J. Carroll, and C. L. Day, “Prognostic
factors for local recurrence, metastasis, and survival rates in
squamous cell carcinoma of the skin, ear, and lip: implications
for treatment modality selection,” Journal of the American
Academy of Dermatology, vol. 26, no. 6, pp. 976–990, 1992.
 MEDIATORS of

INFLAMMATION

The Scientific Gastroenterology Journal of

World Journal
Hindawi Publishing Corporation
Research and Practice
Hindawi Publishing Corporation
Hindawi Publishing Corporation
Diabetes Research
Hindawi Publishing Corporation
Disease Markers
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Journal of International Journal of

Immunology Research
Hindawi Publishing Corporation
Endocrinology
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Submit your manuscripts at

http://www.hindawi.com

BioMed
PPAR Research
Hindawi Publishing Corporation
Research International
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Journal of
Obesity

Evidence-Based
Journal of Stem Cells Complementary and Journal of
Ophthalmology
Hindawi Publishing Corporation
International
Hindawi Publishing Corporation
Alternative Medicine
Hindawi Publishing Corporation Hindawi Publishing Corporation
Oncology
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014

Parkinson’s
Disease

Computational and
Mathematical Methods
in Medicine
Behavioural
Neurology
AIDS
Research and Treatment
Oxidative Medicine and
Cellular Longevity
Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014