1. health and fitness
2. disease
3. cancer

Good oncological control
and excellent outcomes
are possible in cases of
cutaneous leiomyosarcoma.
Tenzin Norbu Lama. Building the Temple.
Cutaneous Leiomyosarcoma: Treatment and Outcomes
With a Standardized Margin of Resection
Jeremiah L. Deneve, DO, Jane L. Messina, MD, Marilyn M. Bui, MD, PhD,
Suroosh S. Marzban, MS, G. Douglas Letson, MD, David Cheong, MD,
Ricardo J. Gonzalez, MD, Vernon K. Sondak, MD, and Jonathan S. Zager, MD
Background: Cutaneous leiomyosarcoma is primarily a low-grade malignancy that affects elderly male
Caucasians. It is a rare dermal-based tumor for which treatment algorithms have been poorly defined.
Methods: We retrospectively reviewed the use of a median 1-cm margin for resection to treat patients with
cutaneous leiomyosarcoma referred for treatment between 2005 and 2010.
Results: Thirty-three patients with cutaneous leiomyosarcoma were treated. Of these, 76% were male, 97% were
Caucasian (median age: 63.5 years), and 67% of tumors were located on the extremities. Preoperative staging
was negative for distant metastasis in all patients. A majority of the tumors (88%) were low grade (median
size: 1.3 cm). All of the tumors were positive for smooth-muscle actin. A total of 94% of patients underwent
primary surgical resection with a median margin of 1 cm. Final resection margin was negative in 97% of
patients. Adjuvant radiotherapy was used in 15%. No metastatic spread or recurrences were present, and
100% of patients were alive at last follow-up (median: 15.5 months).
Conclusions: Good oncological control and excellent outcomes are possible with a 1-cm resection margin in
most cases of cutaneous leiomyosarcoma.
From the Departments of Cutaneous Oncology (JLD, JLM, SSM,
RJG, VKS, JSZ), Anatomic Pathology (JLM, MMB), and Sarcoma
(MMB, GDL, DC) at the H. Lee Moffitt Cancer Center & Research
Institute, Tampa, Florida. Dr Deneve is now with the Division of
Surgical Oncology (JLD) at the University of Tennessee Health Science Center, Memphis, Tennessee.
Submitted November 4, 2012; accepted January 31, 2013.
Address correspondence to Jonathan S. Zager, MD, FACS, Department of Cutaneous Oncology, Moffitt Cancer Center, 12902 Magnolia Drive, Tampa, FL 33612. E-mail: [email protected]
No significant relationship exists between the authors and the
companies/organizations whose products or services may be referenced in this article.
Presented in part at the Society of Melanoma Research Annual
Meeting in Tampa, Florida, November 9-13, 2011.
October 2013, Vol. 20, No. 4
Introduction
Cutaneous leiomyosarcoma (LMS) is a rare soft-tissue tumor believed to arise from the arrector pili
muscle of the hair follicles and accounts for 1% to
3% of all soft-tissue sarcomas.1,2 Although cutaneous LMS originates within the dermis of the skin,
occasional extension into the subcutaneous tissue
may be present. Histologically, LMS is characterized
by a dermal-based proliferation of spindle cells with
blunt-ended, “cigar-shaped” nuclei and increased mitotic figures.3 Immunohistochemical staining using
vimentin, smooth-muscle actin, and desmin often aids
in the diagnosis of cutaneous LMS and excludes other
cutaneous spindle-cell proliferations.3,4
Cancer Control 307
The clinical behavior of cutaneous LMS is difficult
to establish because most retrospective series do not
separately distinguish these tumors from soft-tissue
LMS. However, cutaneous LMS is thought to have an
indolent course and a better prognosis than those of
subcutaneous and deeper origins.5 Cutaneous LMS
has a risk of local recurrence as high as 40% in some
earlier series.6 Massi et al7 reported a 6% recurrence
for cutaneous LMS confined to the dermis but an
18.1% incidence of recurrence for cutaneous LMS
with a subcutaneous extension. Distant metastases
are more commonly associated with subcutaneous
LMS, whereas those with cutaneous LMS do not have
the same risk of metastasis. Moreover, subcutaneous
LMS, which is thought to arise from smooth muscle
of the small vessels, may metastasize earlier and have
a worse prognosis.5,8 By contrast, findings from the
Scandinavian Sarcoma Group,9 which reviewed 225
patients with nonvisceral soft-tissue LMS, revealed no
patients with strictly cutaneous LMS whose cancer
metastasized or who died of tumor-related causes.
Some treatment-related issues remain unresolved
for cutaneous LMS. For instance, although many published series recommend wide excision, few specify
the actual surgical margin used. A variety of margins
have been described as appropriate for resection in
the medical literature, including narrow excision, wide
excision, and Mohs micrographic surgery.10-14 However, no consensus currently exists with regard to the
most appropriate margin of resection. We have found
that standardization of the surgical margin of resection
is useful when treating other rare soft-tissue tumors
(eg, dermatofibrosarcoma protuberans).15,16 This article explores our experience at a single institution
in the diagnosis and management of cutaneous LMS
using a median of 1 cm for a margin of resection.
Methods
This study was an Institutional Review Board approved, single-institution, retrospective review of patients who underwent resection for cutaneous LMS at
the Moffitt Cancer Center in Tampa, Florida, from 2005
to 2010. Patients with insufficient data for analysis,
LMS of a visceral origin (gastrointestinal, gynecological, or retroperitoneal), atypical fibroxanthoma, dermatofibrosarcoma protuberans, or other noncutaneous LMS were excluded. Patients with cutaneous LMS
arising from the dermis were further analyzed. Those
with cutaneous or dermal LMS with a subcutaneous
extension were included in the study, while those with
LMS originating in the subcutaneous tissues or from
a blood vessel were excluded from analysis.
Preoperative staging evaluation, method of biopsy, and treatment were determined from the electronic medical record or outside documents when
patients were referred to the Moffitt Cancer Center
308 Cancer Control
for consultation or further treatment. The margin of
resection was recorded as follows: < 1 cm, 1.0 cm,
1.1–1.5 cm, 1.6–2 cm, or other as determined from
the dictated operative note when available.
Tumor size was recorded in centimeters with mitotic figures noted when present. The diagnosis of
cutaneous LMS was verified by a sarcoma pathologist (M.M.B.) or a dermatopathologist ( J.L.M.), and
immunohistochemistry was performed when necessary to support or confirm the diagnosis of cutaneous LMS or exclude other entities. Smooth-muscle
tumors with evidence of nuclear pleomorphism and
a greater than 1 mitosis/10 high-power field (HPF)
were diagnosed as LMS. Tumors were evaluated for
nuclear atypia (mild, moderate, or severe), French
Fédération Nationale des Centres de Lutte Contre
le Cancer grade (1, 2, or 3), mitotic activity (count
of the most mitotically active area in 10 consecutive
HPFs, ie, × 400), and presence (and/or percentage)
of tumor necrosis. Immunohistochemical results and
morphology were recorded with immunoreactivity to
smooth-muscle actin and/or desmin as confirmation
of smooth-muscle origin.
Adjuvant treatment, when administered, was
noted. Recurrence and length of follow-up were recorded in months from the date of original diagnosis.
Follow-up status was defined as no evidence of disease, alive with disease, or dead of disease or other
causes. Descriptive statistics were measured using
SPSS 19.0 software (IBM Software, Cary, NC).
Results
Patient Demographics
Of 33 patients who underwent evaluation and treatment for cutaneous LMS between 2005 and 2010
(Table 1), 32 (97%) were Caucasian and 25 (76%)
were men. The median age of the patients was 63.5
years (range, 20–91 years). Primary tumor location
involved the lower extremities in 15 patients (46%),
the head and neck in 9 (27%), the upper extremities
in 7 (21%), and the trunk in 2 (6%). Shave biopsy
was the most frequent method of diagnosis, followed
by excision and punch biopsy.
Preoperative staging studies, which were performed at the discretion of the treating physician,
included chest computed tomography (CT) in 14 patients (42%), diagnostic chest radiography in 13 (39%),
and whole-body positron emission tomography (PET)
imaging in 4 (12%), all of whom were negative for
metastatic disease. No patient received radiation to
the primary tumor site prior to surgical resection.
Primary Tumor Characteristics
All tumors were cutaneous or dermal LMS in origin.
The median tumor size was 1.3 cm (range, 0.4–3.5
cm), with a majority of tumors having low-grade
October 2013, Vol. 20, No. 4
Table 1. — Clinical Characteristics of 33 Patients:
Results of a Single-Institution Study
Variable
No. of Patients (%)
Age (yrs)
63.5 (range, 20–91)
Caucasian
32 (97)
Sex
Female
Male
8 (24)
25 (76)
Location
Head and neck
Trunk
Upper extremities
Lower extremities
9
2
7
15
Biopsy method
Shave
Excision
Punch
16 (49)
11 (33)
6 (18)
Preoperative staging method
Chest radiography
Computed tomography
Positron emission tomography
Magnetic resonance imaging of the brain
Magnetic resonance imaging of the extremity
13
14
4
3
5
(27)
(6)
(21)
(46)
(39)
(42)
(12)
(9)
(15)
histology (88%; Figs 1 and 2). The remaining were
higher-grade tumors. Mitoses were recorded in 76%
of patients (range, 1–58/10 HPF; Table 2). Immunohistochemistry was performed in 27 patients (82%).
Smooth-muscle actin was positive in all tumors tested.
Desmin was tested in 20 patients (61%), with expression present in 14 (42%). S100 was tested in 24 patients
(73%) and was negative in 23 (96%; Fig 3).
Primary Tumor Resection
The definitive margin of resection used following referral to the Moffitt Cancer Center was 1 cm in the
majority of patients (22 of 33; 67%). One patient (3%)
underwent resection with a 1.2-cm margin, 4 patients
(12%) with a 1.5-cm margin, and 4 patients (12%) with
a 2-cm surgical margin. Two patients (6%) underwent
resection with a margin smaller than 1 cm (Fig 4).
One of the patients who underwent resection with
an initial 1-cm margin required temporary regenerative tissue matrix coverage of the scalp defect. Once
negative margins were confirmed, we performed a
planned extirpation of the temporary biological dressing with definitive skin graft coverage. We have used
this technique for other pathologies prior to definitive
coverage while awaiting permanent pathological margin assessment in situations in which further resection
may be required.17
Two patients (6%) had a positive margin following initial resection using a 1-cm margin (Table 3).
Table 2. — Histological Characteristics of the Tumors
in 33 Patients: Results of a Single-Institution Study
Fig 1. — Cutaneous leiomyosarcoma showing fascicular growth of ovoid
spindle cells with mild nuclear pleomorphism and mitotic activity (hematoxylin-eosin stain, × 200).
Variable
No. of Patients (%)
Median tumor size, cm
1.30 (range, 0.4–3.5)
Tumor grade
Low
High
29
4
(88)
(12)
Recorded mitotic activity
25
(76)
Median no. of mitoses (range)
10 (1–58)
Atypical mitotic figures
Fig 2. — Cutaneous leiomyosarcoma demonstrating diffuse positivity for
desmin (× 200).
October 2013, Vol. 20, No. 4
8
(24)
Residual tumor after biopsy
20
(61)
Re-excision
Planned re-excision with
regenerative tissue matrix
Positive margin after
initial excision
Unknown resection margin
at outside
3
1
(9)
Final margin
Negative
Positive
1
1
32
1
(97)
(3)
Cancer Control 309
Immunohistochemistry
Number of Cutaneous LMS Patients
30
25
Negative
20
Positive
15
10
5
Pankeratin
Cytokeratin-903
Cytokeratin
CK34
Melan-A
HMB45
Mart-1
S100
Factor XII
CD68
CD34
CD31
CD10
Pro-collagen
Caldesmon
Vimentin
Desmin
Myosin
SM Actin
0
Fig 3. — Immunohistochemical profile of the tumor. LMS = leiomyosarcoma, SM = smooth muscle.
The first patient underwent re-excision to negative
margins using an additional 1-cm margin, while the
second patient had a 1-cm tumor located at the nasolabial fold. A 1-cm margin was used and the area
was covered with a rotational cheek flap. On final
pathological analysis, the nasal mucosal margin was
microscopically positive. This patient did not undergo
further resection but was instead treated with adjuvant
radiation. Therefore, the final margin of resection was
negative in 32 patients (97%).
Adjuvant Therapy
Adjuvant radiation was administered to 5 patients
(15%) following resection. All of the patients received
radiation therapy based on recommendations from a
multidisciplinary tumor board. One patient received
adjuvant radiation for the presence of a subcutaneMargin of Resection
12%
6%
12%
< 1.0 cm
1.0 cm
1.1 cm
1.5 cm
2.0 cm
3%
67%
Table 3. — Treatment Outcomes of 33 Patients:
Results of a Single-Institution Study
Variable
No. of Patients (%)
Surgical margin (cm)
< 1.0 (0.6 and 0.4)
1.0
1.1
1.5
2.0
2 (6)
22 (67)
1 (3)
4 (12)
4 (12)
Autologous skin graft
Full thickness
Split thickness
Regenerative tissue matrix
10 (30)
5 (15)
3 (9)
2 (6)
Adjuvant radiation
Positive margin (initial/final)
Multidisciplinary recommendation
Cutaneous leiomyosarcoma with
subcutaneous extension
5 (15)
2
2
1
Adjuvant chemotherapy
0
Recurrence
0
Complication
Nonhealing wound
Cellulitis
Self-limiting facial asymmetry
after resection
3
1
1
1
(9)
Length of follow-up, mos (median)
15.5 (range, 2–49)
No evidence of disease at follow-up
33 (100)
Fig 4. — Surgical margin of resection for cutaneous leiomyosarcoma.
310 Cancer Control
October 2013, Vol. 20, No. 4
ous extension of cutaneous LMS on final pathology.
Two patients with positive margins following tumor
resection (one of whom underwent re-excision) received adjuvant radiation therapy. Per recommendations from the multidisciplinary tumor board, 2
patients received radiation therapy, neither of whom
had high-grade tumors nor positive margins. These
two patients were treated earlier in the current series.
No patient received adjuvant chemotherapy.
Complications and Outcomes
Complications were observed in 3 patients (9%).
One patient with a nasolabial fold tumor underwent
rotational flap advancement with a positive mucosal margin and then subsequently developed facial
asymmetry following resection. It was self-limiting
and resolved after 3 months. One patient developed
cellulitis and responded to oral antibiotics. The remaining patient developed a nonhealing scalp wound
that required serial office debridement that healed by
secondary intention.
No locoregional recurrences or distant metastases
were present, and no deaths were observed during
the treatment period (median follow-up, 15.5 months;
range, 2–49 months). All patients were without disease at the last follow-up.
Discussion
Cutaneous soft-tissue sarcomas are rare tumors and
account for fewer than 1% of all soft-tissue malignancies.2,9,18 They most commonly affect Caucasian men,
with a peak incidence in the 5th and 6th decades of
life.7,19 These tumors present as solitary, erythematous, or brownish well-circumscribed dermal nodules
ranging in size from 0.5 to 3 cm. Because they are
dermal-based tumors, they may appear fixed to the
epidermis and ulceration may be present.20 The lower
extremities and head and neck locations are the most
common sites of involvement as identified in the literature.3,14,21 Preoperative staging with cross-sectional
imaging (CT of the thorax, PET imaging, or both) appeared to add minimal clinical impact as more than
one-half of the patients in this series underwent imaging. Imaging results for all patients were negative.
The utility of preoperative staging for cutaneous LMS
has not been previously described in the literature.
Multiple institutions have helped describe the behavioral and outcome differences between cutaneous
and subcutaneous LMS.5,6,22 Pijpe et al22 and others23,24
identified that more superficial tumors may have a
better prognosis than those with a deeper origin. In
the Pijpe series, deeper LMS had a significantly larger
tumor size, which may explain the worse outcome
observed with the deeper tumors. Massi et al7 noted
the impact of tumor grade on outcome; the cases of
cutaneous LMS that recurred or metastasized in their
October 2013, Vol. 20, No. 4
series were all high-grade tumors. Other prognostic
variables, such as DNA ploidy,25 Ki-67 proliferative
index,26,27 and mitotic figures,1,4 have also been identified as markers of worse outcome. However, the
optimal width and impact of the margin of resection
on outcome are not as well defined. Moreover, the
majority of publications concerning cutaneous LMS
have made little or no comment regarding the margin
of resection performed at the time of excision.
Although negative margins are the optimal management for these tumors, no specific consensus statement exists regarding the preferred or most appropriate margin. Retrospective, single-center series and
collective reviews have provided some insight into
this matter. Bernstein and Roenigk14 recommended
a wide margin excision when reporting their experience with 34 patients whom they followed for more
than 30 years. Others have suggested using a 3- to
5-cm margin of excision because of the potential risk
of local recurrence and distant metastasis.20 Narrow
margin excision and Mohs micrographic surgery have
also been used.10,11,13,28 Although several small case
series using Mohs resection have been described,
recurrences have been reported with long-term follow-up. Huether et al12 reported a 14% incidence of
recurrence when treating spindle-cell neoplasms of
the skin (eg, cutaneous LMS) using the Mohs micrographic technique.
Standardizing an appropriate margin of resection
for cutaneous LMS should be a priority. For example, in an analysis of 84 cases of atypical intradermal
smooth-muscle neoplasms, Kraft and Fletcher19 identified margin status as the most important predictor of
recurrence. In that series, 18 local recurrences (21%)
were observed following the initial excision (12 with
positive margins, 1 with a close [< 0.2 cm] margin,
and 5 with unknown margins). No recurrences were
observed when the initial excisions were performed
with negative margins. At the Moffitt Cancer Center,
we attempted to standardize the surgical margin by
taking at least a 1-cm margin at the time of resection. Early in the study period (2006–2009), resection
margins were more variable, ranging from 0.4 to 2
cm. Since 2010, we have more consistently utilized a
resection margin of 1 cm for cutaneous LMS, including
patients who undergo an initial excision at another
facility with unknown margins and subsequent reexcision with a 1-cm margin following a referral to
the Moffitt Cancer Center. Two of the 33 patients in
this series had microscopic positive margins following a 1-cm resection. One patient underwent further
re-excision with an additional 1-cm margin to obtain
negative margins, and another patient received adjuvant radiation. Although the follow-up period was
short for our study, no local recurrences were reported
during the trial period.
Cancer Control 311
The role of adjuvant therapy for cutaneous LMS
has similarly remained nonstandardized and largely
anecdotal. Most institutions reserve the use of adjuvant
radiation, chemotherapy, or both for the development
of recurrence or distant metastasis.6,7 Local recurrence
reports following excision of cutaneous LMS range
from 6% to 40%.6,7,12,19 Furthermore, many series have
included both cutaneous and subcutaneous LMS in
their descriptions, confounding this issue further and
making the interpretation of these recurrence rate results less clear. Jensen et al5 reported no incidences
of recurrence after 5 years of follow-up for intradermal
LMS, but 41% of those patients with subcutaneous
LMS had tumors that metastasized, and these patients
ultimately died of pulmonary metastases. Fields and
Helwig6 similarly reported no distant metastases for
those with cutaneous LMS, whereas 4 of 12 patients
with subcutaneous LMS eventually developed metastases and progressed to tumor-related death. We did
not observe distant metastases in any patient, and no
patient received adjuvant chemotherapy. We administered adjuvant radiation on an individualized basis,
such as in situations in which positive margins were
present on final pathology but limited options existed
for further resection or those who had larger cutaneous LMS with an extensive subcutaneous extension. In
situations of local recurrence development, some have
suggested that simple re-excision is sufficient therapy.
Kraft and Fletcher19 noted that 10 of 18 tumors studied
with local recurrence could be re-excised to negative
margins without additional recurrence or metastasis.
Because many of the patients treated in that series
underwent initial excision at outside institutions and
were referred to their center after the development
of recurrence, they further surmised that appropriate local therapy is most likely sufficient therapy to
prevent recurrence.
Conclusions
Cutaneous leiomyosarcoma is a low-grade malignancy
predominantly affecting elderly male Caucasians in the
lower extremities and the head and neck. Immunohistochemistry may be utilized to confirm cutaneous
leiomyosarcoma or rule out other spindle-cell proliferations. Good oncological local control and favorable
overall outcomes are possible with a standardized, 1-cm
surgical margin of resection. The benefit of preoperative chest imaging and/or adjuvant radiation to the
primary tumor site remains unknown within the setting
of negative margins. The choice for adjuvant radiation
should be individualized; therefore, we recommend a
multidisciplinary discussion of the need for adjuvant
radiation in patients with larger tumors, persistently
positive margins following multiple resections, or those
patients who have cutaneous leiomyosarcoma tumors
with an extensive subcutaneous extension.
312 Cancer Control
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