REVIEWS

A new evidence-based risk stratification

system for cutaneous squamous cell
carcinoma into low, intermediate, and
high risk groups with implications
for management
Christian L. Baum, MS, MD,a Adam C. Wright, MD,b Juan-Carlos Martinez, MD,c Christopher J. Arpey, MD,a
Jerry D. Brewer, MD,a Randall K. Roenigk, MD,a and Clark C. Otley, MDa
Rochester, Minnesota; Jacksonville, Florida; and Knoxville, Tennessee

Most primary cutaneous squamous cell carcinomas are cured with surgery. A subset, however, may
develop local and nodal metastasis that may eventuate in disease-specific; death. This subset has been
variably termed high risk. Herein, we review; an emerging body of data on the risks of these outcomes and
propose an evidence-based; risk stratification for low-, intermediate-, and high-risk tumors that takes into;
account both tumor and patient characteristics. Finally, we discuss a framework for; management of these
tumors on the basis of data, when available, and our; recommendations when data are sparse. ( J Am Acad
Dermatol 2018;78:141-7.)

Key words: cutaneous squamous cell carcinoma; immunosuppression; management; radiotherapy; risk
stratification; sentinel lymph node biopsy; staging.

C utaneous squamous cell carcinoma (cSCC)

has an incidence of 180,000 to 520,000
tumors per year in the United States1-3 and
a metastasis rate of 2% to 5%.4-6 The prevalence of
Abbreviations used:
ART:
BWH:
CLL:
adjuvant radiotherapy
Brigham and Women’s Hospital
chronic lymphocytic leukemia
nodal metastasis (NM) from cSCC in the United States cSCC: cutaneous squamous cell carcinoma
is estimated at 5604 to 12,572 cases per year,3 CT: computed tomography
DSD: disease-specific death
whereas the number of deaths is estimated at 3932 HRcSCC: high-risk cutaneous squamous cell
to 8791, with the upper limit of this range carcinoma
approximating the number of melanoma-related IRcSCC: intermediate-risk cutaneous squamous
cell carcinoma
deaths per year.3,7 The progression of cSCC appears LR: local recurrence
to be stepwise from local recurrence (LR) to regional LRcSCC: low-risk cutaneous squamous cell
spread and then distant metastasis.8 Most disease- carcinoma
MMS: Mohs micrographic surgery
specific deaths are preceded by regional recurrence,9 NM: nodal metastasis
and most regional recurrences involve the head and PNI: perineural invasion
neck region.10 Furthermore, in patients treated with SLNB: sentinel lymph node biopsy
surgery for nodal disease, a relatively low burden of
disease is correlated with lower recurrence rates and
higher overall survival.9 These data indicate that identifying cohorts with elevated and actionable
controlling morbidity and mortality from cSCC is risks for LR and NM may focus efforts intended to
predicated on locoregional control. Therefore, decrease cSCC-associated morbidity and mortality.

From the Department of Dermatology, Mayo Clinic, Rochestera;
Anderson and Rahman Dermatology, Knoxvilleb; and
Department of Dermatology, Mayo Clinic, Jacksonville.c
Funding sources: Dr Baum has a Career Development Award in
Dermatologic Surgery from the Dermatology Foundation.
Conflicts of interest: None declared.
Accepted for publication July 24, 2017.
Reprints not available from the authors.
Correspondence to: Christian L. Baum, MS, MD, Department of
Dermatology, Mayo Clinic, 200 First St SW, Rochester,
Minnesota 55905. E-mail: baum.christian@mayo.edu.
Published online September 13, 2017.
0190-9622/$36.00
Ó 2017 by the American Academy of Dermatology, Inc.
http://dx.doi.org/10.1016/j.jaad.2017.07.031

141
142 Baum et al J AM ACAD DERMATOL
JANUARY 2018

The term high-risk squamous cell carcinoma has
been variably defined in prior publications.11-15
However, a unified, evidence-based definition of
high-risk cSCC (HRcSCC) is absent. Although a
distinction between HRcSCC and low-risk cSCC
(LRcSCC) provides a simple binary classification
system, it does not adequately account for the risk
spectrum that reflects the
biology of individual tumors.
In recent years, sufficient CAPSULE SUMMARY
outcomes data have been
A small subset of cutaneous squamous
d
lymph node biopsy (SLNB). Data from the
Multicenter Selective Lymphadenectomy Trial
demonstrated that SLNB provides valuable risk
stratification into a low-risk, negative SLNB cohort
compared with the high-risk, positive SLNB cohort,
with 85% and 62% 10-year melanoma-specific
survival rates, respectively.17 These results further
refine the cohort with a 10%
or higher risk of occult
nodal disease into sub-
groups for which focused

published to allow stratifica- interventions such as inten-

tion of cSCC along a risk
spectrum based on tumor
staging and independent
risk factors, including some
forms of immunosuppres-
sion. The purpose of this re-
view is to propose an
evidence-based risk stratifi-
cation of cSCC into LRcSCC,
intermediate-risk cSCC
(IRcSCC), and HRcSCC on
the basis of the most contem-
porary data. We will also
discuss a framework for management based on these
risk levels.
cell carcinomas are associated with local
sive follow-up, imaging,
recurrence, nodal metastasis, and death.
therapeutic lymph node
An evidence-based risk stratification
d
dissection, and adjuvant
system that consists of tumor staging systemic therapy may be
and patient characteristics is proposed considered. Although the
for low-, intermediate-, and high-risk biologic progression pattern
tumors. of cSCC appears more pre-
This risk stratification system may
d dictable than that of mela-
optimize patient management and lead noma, the data for cSCC
to better outcomes. outcomes are less mature
than those for melanoma.
Therefore, we propose that
an absolute risk of 20% or
higher for LR and NM constitutes a reasonable
action threshold for defining HRcSCC.

WHAT ARE REASONABLE THRESHOLDS WHAT ARE THE EVIDENCE-BASED

FOR RISK STRATIFCIATION OF cSCC?
The risk stratification of cSCC is inherently arbi-
trary, although reasonable reference points exist
within cutaneous oncology. Furthermore, despite
its arbitrary nature, risk stratification offers value
because it has the potential to incorporate data, such
as immunosuppression data, that are currently ab-
sent from any staging systems. At the same time,
stratification may guide management decisions that
are presently based on predominantly empirical
data, including considerations of the associated risks
and costs of various options, as well as more unified
research efforts regarding cohorts that have histori-
cally been ill defined or not defined at all.
First, the risks of LR and NM for the entire
cohort of patients with cSCC are each approxi-
mately 2% to 5%.4,16 Given this baseline risk for all
patients with cSCC, we propose an upper limit of
5% for the LRcSCC cohort. The next level of
distinction lies between the IRcSCC and HRcSCC
cohorts. We believe that this threshold may be
extrapolated from other cutaneous malignancies,
and melanoma is the most thoroughly studied. In
the case of melanoma, a 10% or higher risk for
occult nodal disease is the standard accepted
action threshold for consideration of a sentinel
PATIENT AND TUMOR CHARACTERISTICS
THAT DEFINE LRcSCC, IRcSCC, AND
HRcSCC?
The Brigham and Women’s Hospital (BWH) stag-
ing system (Table I) is derived from a single-
institution cohort of approximately 1800 tumors.
Not only does the cohort represent the data set for
cSCC that has most robust outcomes, but the BWH
staging system also currently appears to be the most
precise. BWH T2b/T3 tumors represented 5% of the
cohort but the majority of NMs (70%) and disease-
specific deaths (DSDs) (83%). In contrast, NM and
DSD were reported in T2a tumors, albeit at a much
lower rate.16 Thus, tumors with a single risk factor
have the potential to develop adverse outcomes. A
recent meta-analysis analyzed more than 23,000
tumors and is the most comprehensive analysis of
single risk factors for cSCC outcomes to date.18 That
study quantified data that supplement BWH risk
stratification of T2a tumors. The application of meta-
analysis data requires consideration of relative risk
and heterogeneity of data, the latter of which is
quantified with the I2 statistic. Values of 0% and 100%
are associated with low and high levels of
heterogeneity, respectively.19 Values of 30% to 60%
may represent moderate heterogeneity,20 and given
J AM ACAD DERMATOL Baum et al 143
VOLUME 78, NUMBER 1

Table I. Brigham and Women’s Hospital staging Table III. Follow-up recommendations
system Risk category Follow-up frequency
Tumor stage Definition Low-risk cSCC Annually
T1 0 risk factors Intermediate-risk cSCC 6-12 mo for 2 y, then annually
T2a 1 risk factor High-risk cSCC 2-4 mo for 2 y, then annually;
T2b 2-3 risk factors consider repeating imaging
T3 $4 risk factors OR bone invasion yearly for 2 y

Risk factors are diameter of $2 cm, poorly differentiated histologic cSCC, Cutaneous squamous cell carcinoma.
findings, perineural invasion of at least 0.1 mm, and invasion
beyond subcutaneous fat. adjuvant radiation for cSCC.10 Currently, the immu-
Adapted from Karia et al.16 nosuppressed population with the most robust out-
comes data is the cohort with chronic lymphocytic
Table II. Risk stratification of primary cSCC and leukemia (CLL) or non-Hodgkin’s lymphoma. Not
associated absolute risks for outcomes only do they have an increased risk for cSCC, but also
the LR rates after Mohs micrographic surgery (MMS)
Risk category and risk factors
Absolute risk
for LR
Absolute risk
for NM
are reported at 13.4%.23 Furthermore, 1 study, which
included 377 tumors in 133 patients, demonstrated
Low-risk cSCC
that Rai stage24 (low stage, I-II; high stage, III-IV) is an
BWH T1 0.6% 0.1%
BWH T2a 5% 3%
independent risk factor in cSCC outcomes stratified by
Intermediate-risk cSCC BWH staging.25 Specifically, BWH T1/T2a tumors
BWH T2a with 6% 12% with a high Rai stage had a higher rate (16.9%) of
diameter [2 cm LR, NM, and DSD than BWH T1/T2a tumors with a
BWH T2a with depth 14% d low Rai stage (5.3%). For patients with BWH T2/T3
beyond SC fat tumors, LR, NM, and DSD were increased for patients
High-risk cSCC with a low (27.3%) or high (50%) Rai stage. Therefore,
BWH T2b/T3 21% 67% we believe that another significant and well-
BWH T2a with depth d 22% documented prognostic factor is CLL with Rai stage
beyond SC fat III or IV.
BWH T2a AND CLL with 25% 37%
On the basis of the best available current data, we
Rai stage III or IV
propose that the criteria outlined in Table II16,18,25 be
BWH, Brigham and Women’s Hospital; CLL, chronic lymphocytic used to define primary LRcSCC, IRcSCC, and HRcSCC
leukemia; cSCC, cutaneous squamous cell carcinoma; LR, local for the outcomes of LR and NM.
recurrence; NM, nodal metastasis; SC, subcutaneous.
Adapted from Thompson et al,18 Karia et al,16 and Velez et al.25
A FRAMEWORK FOR MANAGEMENT OF
HRcSCC
As the risk for tumors increases, so too
the heterogeneous nature of cSCC data, an upper should consideration of a multidisciplinary
limit of 60% for I2 is a reasonable cutoff. When a approach. All patients with cSCC should be
relative risk of 5 or higher (as discussed earlier) and educated on self-examination, encouraged to follow
an I2 less than 60% are applied to cSCC, the 2 risk sun-protective measures, and educated on the
factors that qualify are tumor invasion beyond importance of recommended follow-up. There are
subcutaneous fat and diameter larger than 2 cm. no data on the correlation between follow-up times
Current staging systems for cSCC do not and outcomes. However, we recommend that
include immunosuppression as an independent risk follow-up intervals be based on the risk stratification
factor.16,21,22 There is a paucity of outcomes data that of the tumor (Table III) and that each follow-up visit
adjust for staging of primary cSCC across the various include a thorough palpation and visualization for
types of immunosuppression. A recent study of 205 cutaneous and nodal recurrence.
patients, including 58% with recurrent tumors,
demonstrated an increased risk of locoregional recur- Radiologic and surgical staging for occult
rence (hazard ratio, 5.0; P = .0025) in a heterogeneous nodal metastases
group of immunosuppressed patients (including or- All patients with cSCC should have a thorough
gan transplant recipients, patients with hematologic examination of the draining nodal beds at the time of
malignancies, and patients with HIV) compared with definitive treatment for the tumor. Additional staging
immunocompetent patients treated with surgery and is not recommended for LRcSCC. For IRcSCC and
144 Baum et al J AM ACAD DERMATOL
JANUARY 2018

Table IV. Considerations for staging options and adjuvant therapy for HRcSCC
Local Adjuvant therapy for local Nodal Positive Adjuvant therapy for nodal
BWH Disease-specific recurrence recurrence: ‘‘safety margin,’’ metastasis SLNB metastasis: SLNB, imaging,
stage death rate, % rate, % immunostains, radiotherapy rate, % rate, % and radiotherapy
T1 0 0.6 None 0.1 0 None
T2a 1 5 Consider ‘‘safety margin’’ and/ 3 7 None
or immunostains if PNI or
poor tumor differentiation
T2b 10 21 Encourage ‘‘safety margin’’ 21 29 Consider imaging; consider
and/or immunostains; SLNB or radiotherapy to
consider radiotherapy to nodal basin
primary site especially if PNI
or poor tumor differentiation
T3 100 67 Encourage ‘‘safety margin’’ 67 50 Recommend imaging;
excision, immunostaining, encourage SLNB or
and radiotherapy radiotherapy to nodal basin

Data derived from Karia et al,16 Thompson et al,18 and Schmitt et al.26
BWH, Brigham and Women’s Hospital; HRcSCC, high-risk cutaneous squamous cell carcinoma; PNI, perineural invasion; SLNB, sentinel lymph
node biopsy.

Table V. Advantages and disadvantages of staging options and adjuvant therapy, stratified by type of
recurrence
SO or AT Advantage Disadvantage
Local recurrence
‘‘Safety margin’’ (AT) Removal of discontiguous tumor Tissue loss; complexity of repair
Immunostains (AT) Detection of subtle tumor Time (h); technical expertise
Radiotherapy to primary site (AT) Destruction of discontiguous tumor Time (wk); morbidity, logistics
Nodal metastasis
Imaging (SO) Noninvasive; detection of subclinical Relatively low sensitivity
nodal disease
Sentinel lymph node biopsy (SO) Early detection of microscopic disease General anesthesia; surgical morbidity
and removal of metastasis
Radiotherapy to nodal basin (AT) Destruction of micrometastatic tumor Time (wk); high morbidity

AT, Adjuvant therapy; SO, staging option.

HRcSCC, however, additional staging may be
considered. A summary of the staging recommenda-
tions, considerations, advantages, and disadvantages
is presented in Table IV16,18,26 and Table V. The
purpose of staging for occult nodal metastases in
these cohorts is to decrease the morbidity and
mortality related to macroscopic nodal disease.
Ultrasonography has been suggested in the
evaluation of clinically node-negative patients with
oral squamous cell carcinoma,27,28 as well as for
patients with melanoma and occult NM.29,30
Although ultrasonography is an intriguing option,
we are unaware of any data related to detection of
occult nodal disease from cSCC. Other forms of
imaging, especially computed tomography (CT),
have been more extensively analyzed. In the largest
retrospective study to date (N = 98), patients with
BWH T2b/T3 tumors and imaging (79% had CT) had
50% fewer disease-related outcomes (LR, NM, or
DSD) compared with those who did not have
imaging. The authors attributed these results to
earlier intervention of advanced disease.31 Positron
emission tomographyeCT, although not as well
described, has demonstrated particular utility in
patients with cSCC and CLL and may be attributable
to more intense uptake from cSCC than background
nodal involvement of CLL.32 There are no
prospective studies describing the sensitivity,
specificity, or survival benefit of radiologic staging
for cSCC.
SLNB is also an option for staging cSCC. SLNB is a
safe14 and feasible15 method for identifying a
sentinel lymph node in cSCC, including tumors of
the head and neck. A 2014 meta-analysis reported
that BWH T2b and T3 tumors are associated with
positive SLNB rates of 29.4% and 50%, respectively.26
Subsequent studies have demonstrated a positive
SLNB rate in variably defined cohorts ranging from
J AM ACAD DERMATOL
VOLUME 78, NUMBER 1
12.3%14 to 15.1%15 and negative predictive values of
98% after a median follow-up of 19.4 months (range,
2.4-41).14 Recent data have emphasized the
importance of serial step sectioning of lymph node
specimens with immunohistochemical staining to
minimize false-negative results.15 Although the
impact of SLNB on outcomes of cSCC requires
further study, current data suggest that SLNB may
be considered in practice and should be studied
further in comparison with imaging modalities in
properly selected, high-risk populations, such as the
HRcSCC cohort. Within a multidisciplinary
approach, we consider SLNB for all BWH T2b/T3
tumors and T2a tumors that are larger than 2 cm in
diameter. If SLNB is not performed, then either CT or
positron emission tomographyeCT is recommen-
ded. Rigorous clinical follow-up remains a critical
component in all patients with HRcSCC and may be a
reasonable strategy alone for patients who will
reliably return to the clinic.
Locoregional disease control
LRcSCC can be effectively and efficiently
managed by a variety of options, such as superficial
destruction, wide local excision, and MMS. The
primary intervention for locoregional control of
IRcSCC and HRcSCC is surgery with negative
margins. The efficacy of MMS was demonstrated in
260 patients with cSCC with multiple risk factors
($1 of the following: tumor [2 cm, perineural
invasion [PNI], ear/lip location, temple location in
elderly men, and immunosuppression). After a mean
follow-up of 3.9 years, the LR was 1.2% and the
metastasis rate was 2.3%.11 An LR rate of 13.4% has
been reported after MMS for SCC in patients with
CLL, which may be attributed, in part, to the
significant subclinical extension of tumors in these
patients.23 To optimize peripheral margin control
and to immediately characterize residual tumor, we
recommend MMS as the preferred primary surgical
intervention for IRcSCC and HRcSCC. Multikeratin
immunostains may be included during MMS, and if
there is uncertainty in interpretation of the histology
or if the tumor appears discontiguous, an
additional margin (ie, ‘‘safety margin’’) of normal
tissue may be resected and submitted for review of
paraffin-embedded formalin-fixed tissue. Currently,
there are no data on the efficacy of a safety margin or
immunostains, although such data would be
highly desirable. The risks and benefits of multi-
cytokeratin immunostains and safety margins are
reviewed in Table V. A prospective study is under
way in our institution to evaluate the utility of
multikeratin immunostains for detection of occult
Baum et al 145
cSCC in negative surgical margins in patients with
cSCC and CLL or non-Hodgkin’s lymphoma.
Despite meticulous surgical technique and
microscopic scrutiny of margins, LR may occur after
margins are interpreted as negative.11,16,23 Data on
adjuvant options for HRcSCC in this setting are
sparse, and adjuvant radiotherapy (ART) is
the most commonly described option. Generally,
reports of radiotherapy for cSCC are retrospective;
are underpowered; describe concomitant chemo-
therapy; are frequently missing data regarding
surgical margin status; and are enriched for patients
with recurrent disease, perineural invasion, and/or
NM.10,33,34 To date, it appears that radiotherapy after
surgery may offer improved rates of locoregional
recurrence in immunocompetent patients compared
with in immunosuppressed patients10 and improved
local disease control in patients with PNI,35,36
particularly in those with extensive microscopic
PNI but not in those with focal microscopic PNI.37
There are no prospective studies to date on the safety
and efficacy of ART after negative surgical margins
for HRcSCC. We conducted a retrospective analysis
of 32 patients treated with ART to the primary site
after negative MMS margins. After a median
follow-up time of 3.9 years,38 the LR rate was 3.8%
for BWH T2b/T3 tumors (n = 26) and the NM rates
were 0% for BWH T2b tumors (n = 20) and 17% for
BWH T3 tumors (n = 6). Because the morbidity of
radiotherapy is higher than that of any other option
considered in this discussion, we reserve
consideration of ART to the primary site after
negative surgical margins only for HRcSCC.
CONCLUSION
In this manuscript we have attempted to define
thresholds for LRcSCC, IRcSCC, and HRcSCC in the
context of existing data and the risk factors that
constitute each risk level. We expect that this
three-tiered stratification will be refined in the future
and that the associated management should
continue to evolve. We look forward to
well-designed prospective efforts in this evolution
that will ultimately lead to improved patient
outcomes.
REFERENCES
1. Rogers HW, Weinstock MA, Harris AR, et al. Incidence estimate
of nonmelanoma skin cancer in the United States, 2006. Arch
Dermatol. 2010;146(3):283-287.
2. Muzic JG, Schmitt AR, Wright AC, et al. Incidence and trends of
basal cell carcinoma and cutaneous squamous cell carcinoma:
a population-based study in Olmsted County, Minnesota, 2000
to 2010. Mayo Clin Proc. 2017;92(6):890-898.
3. Karia PS, Han J, Schmults CD. Cutaneous squamous cell
carcinoma: estimated incidence of disease, nodal metastasis,
146 Baum et al
and deaths from disease in the United States, 2012. J Am Acad
Dermatol. 2013;68(6):957-966.
4. Brantsch KD, Meisner C, Schonfisch B, et al. Analysis of risk
factors determining prognosis of cutaneous squamous-cell
carcinoma: a prospective study. Lancet Oncol. 2008;9(8):
713-720.
5. Moore BA, Weber RS, Prieto V, et al. Lymph node metastases
from cutaneous squamous cell carcinoma of the head and
neck. Laryngoscope. 2005;115(9):1561-1567.
6. Brougham ND, Dennett ER, Cameron R, Tan ST. The incidence
of metastasis from cutaneous squamous cell carcinoma and
the impact of its risk factors. J Surg Oncol. 2012;106(7):811-815.
7. Guy GP Jr, Machlin SR, Ekwueme DU, Yabroff KR. Prevalence
and costs of skin cancer treatment in the U.S., 2002-2006 and
2007-2011. Am J Prev Med. 2015;48(2):183-187.
8. Martinez JC, Cook JL. High-risk cutaneous squamous cell
carcinoma without palpable lymphadenopathy: is there a
therapeutic role for elective neck dissection? Dermatol Surg.
2007;33(4):410-420.
9. Tseros EA, Gebski V, Morgan GJ, Veness MJ. Prognostic
significance of lymph node ratio in metastatic cutaneous
squamous cell carcinoma of the head and neck. Ann Surg
Oncol. 2016;23(5):1693-1698.
10. Manyam BV, Garsa AA, Chin RI, et al. A multi-institutional
comparison of outcomes of immunosuppressed and
immunocompetent patients treated with surgery and
radiation therapy for cutaneous squamous cell carcinoma of
the head and neck. Cancer. 2017;123(11):2054-2060.
11. Pugliano-Mauro M, Goldman G. Mohs surgery is effective for
high-risk cutaneous squamous cell carcinoma. Dermatol Surg.
2010;36(10):1544-1553.
12. O’Bryan K, Sherman W, Niedt GW, et al. An evolving paradigm
for the workup and management of high-risk cutaneous
squamous cell carcinoma. J Am Acad Dermatol. 2013;69(4):
595-602.e591.
13. Cheng J, Yan S. Prognostic variables in high-risk cutaneous
squamous cell carcinoma: a review. J Cutan Pathol. 2016;
43(11):994-1004.
14. Gore SM, Shaw D, Martin RC, et al. Prospective study of
sentinel node biopsy for high-risk cutaneous squamous cell
carcinoma of the head and neck. Head Neck. 2016;38(suppl 1):
E884-E889.
15. Durham AB, Lowe L, Malloy KM, et al. Sentinel lymph node
biopsy for cutaneous squamous cell carcinoma on the head
and neck. JAMA Otolaryngol Head Neck Surg. 2016;142(12):
1171-1176.
16. Karia PS, Jambusaria-Pahlajani A, Harrington DP, Murphy GF,
Qureshi AA, Schmults CD. Evaluation of American Joint
Committee on Cancer, International Union Against Cancer,
and Brigham and Women’s Hospital tumor staging for
cutaneous squamous cell carcinoma. J Clin Oncol. 2014;32(4):
327-334.
17. Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of
sentinel-node biopsy versus nodal observation in melanoma.
N Engl J Med. 2014;370(7):599-609.
18. Thompson AK, Kelley BF, Prokop LJ, Murad MH, Baum CL. Risk
factors for cutaneous squamous cell carcinoma recurrence,
metastasis, and disease-specific death: a systematic review
and meta-analysis. JAMA Dermatol. 2016;152(4):419-428.
19. Higgins JP, Thompson SG. Quantifying heterogeneity in a
meta-analysis. Stat Med. 2002;21(11):1539-1558.
20. Higgins JPT, Green S. Cochrane Handbook for Systematic
Reviews of Interventions Version 5.1.0 (updated March 2011).
London: The Cochrane Collaboration; 2011.
J AM ACAD DERMATOL
JANUARY 2018
21. Edge S, Byrd DR, Compton CC, Fritz AG, Greene F, Trotti A, eds.
AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer;
2010.
22. Brierley JD, Gospodarowicz MK, Wittekind C, eds. TNM
Classification of Malignant Tumours. 8th ed. Hoboken, NJ:
Wiley; 2017.
23. Brewer JD, Shanafelt TD, Khezri F, et al. Increased incidence
and recurrence rates of nonmelanoma skin cancer in patients
with non-Hodgkin lymphoma: a Rochester Epidemiology
Project population-based study in Minnesota. J Am Acad
Dermatol. 2015;72(2):302-309.
24. Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN,
Pasternack BS. Clinical staging of chronic lymphocytic
leukemia. Blood. 1975;46(2):219-234.
25. Velez NF, Karia PS, Vartanov AR, Davids MS, Brown JR,
Schmults CD. Association of advanced leukemic stage and
skin cancer tumor stage with poor skin cancer outcomes in
patients with chronic lymphocytic leukemia. JAMA Dermatol.
2014;150(3):280-287.
26. Schmitt AR, Brewer JD, Bordeaux JS, Baum CL. Staging for
cutaneous squamous cell carcinoma as a predictor of sentinel
lymph node biopsy results: meta-analysis of American Joint
Committee on Cancer criteria and a proposed alternative
system. JAMA Dermatol. 2014;150(1):19-24.
27. Norling R, Buron BM, Therkildsen MH, Henriksen BM, von
Buchwald C, Nielsen MB. Staging of cervical lymph nodes in
oral squamous cell carcinoma: adding ultrasound in clinically
lymph node negative patients may improve diagnostic
work-up. PLoS One. 2014;9(3):e90360.
28. van den Brekel MW, Castelijns JA, Stel HV, et al. Occult
metastatic neck disease: detection with US and US-guided
fine-needle aspiration cytology. Radiology. 1991;180(2):
457-461.
29. De Giorgi V, Gori A, Grazzini M, et al. Contrast-enhanced
ultrasound: a filter role in AJCC stage I/II melanoma patients.
Oncology. 2010;79(5-6):370-375.
30. Catalano O, Siani A. Cutaneous melanoma: role of ultrasound
in the assessment of locoregional spread. Curr Probl Diagn
Radiol. 2010;39(1):30-36.
31. Ruiz ES, Karia PS, Morgan FC, Schmults CD. The positive
impact of radiologic imaging on high-stage cutaneous
squamous cell carcinoma management. J Am Acad Dermatol.
2017;76(2):217-225.
32. Tomaszewski JM, Lau E, Corry J. Utility of positron
emission tomography/computed tomography for nodal
staging of cutaneous squamous cell carcinoma in patients
with chronic lymphocytic leukemia. Am J Otolaryngol.
2014;35(1):66-69.
33. Wang JT, Palme CE, Morgan GJ, Gebski V, Wang AY,
Veness MJ. Predictors of outcome in patients with metastatic
cutaneous head and neck squamous cell carcinoma
involving cervical lymph nodes: improved survival with the
addition of adjuvant radiotherapy. Head Neck. 2012;34(11):
1524-1528.
34. Mendenhall WM, Amdur RJ, Hinerman RW, Cognetta AB,
Mendenhall NP. Radiotherapy for cutaneous squamous and
basal cell carcinomas of the head and neck. Laryngoscope.
2009;119(10):1994-1999.
35. Han A, Ratner D. What is the role of adjuvant radio-
therapy in the treatment of cutaneous squamous cell
carcinoma with perineural invasion? Cancer. 2007;109(6):
1053-1059.
36. Kropp L, Balamucki CJ, Morris CG, et al. Mohs resection and
postoperative radiotherapy for head and neck cancers with
J AM ACAD DERMATOL
VOLUME 78, NUMBER 1
incidental perineural invasion. Am J Otolaryngol. 2013;34(5):
373-377.
37. Sapir E, Tolpadi A, McHugh J, et al. Skin cancer of the head and
neck with gross or microscopic perineural involvement:
patterns of failure. Radiother Oncol. 2016;120(1):81-86.
Baum et al 147
38. Chang T, Schwartz DJ, Hochwalt PC, et al. Outcomes of
adjuvant radiotherapy following negative surgical margins for
cutaneous squamous cell carcinoma. Paper presented at: 48th
Meeting of the American College of Mohs Surgery. April
28-May 1, 2016; Orlando, Florida.