768051
research-article2018
FAIXXX10.1177/1071100718768051Foot & Ankle InternationalEspert et al
Current Concepts Review
Current Concepts Review: Plantar
Fibromatosis
Melissa Espert, BA, MS1, Michael R. Anderson, DO2 ,
and Judith F. Baumhauer, MD, MPH3
Level of Evidence: Level V, Expert Opinion
Keywords: plantar fibromatosis, hyperproliferation, plantar foot, Ledderhose, morbus Ledderhose, plantar fascia
Plantar fibromatosis (PF) is an uncommon benign, hyperp-
roliferative disease of the superficial plantar aponeurosis.
PF is frequently bilateral and multinodular and occurs in the
central medial, nonweightbearing areas of the plantar foot.11
PF is also known as Ledderhose syndrome, morbus
Ledderhose, and Dupuytren’s disease of the plantar fascia
and was initially described by George Ledderhose in 1897.25
This condition belongs to a family of fibroblastic prolifera-
tive diseases first described by Plater in 1610 and later
named after Baron Guillaume Dupuytren, who described
procedures to correct the disease in the hand.11 PF is associ-
ated with Dupuytren’s disease of the palmar fascia (palmar
fibromatosis) and Peyronie’s disease (penile fibromatosis).
Cooccurrence of PF and Dupuytren’s disease is 9% to 25%,
while cooccurrence of PF and Peyronie’s disease is 4%.10,13
Histologic evaluation of PF reveals a characteristic over-
production of fibroblasts, which are responsible for nodule
formation (Figure 1). The fibroblastic cells are randomly
arranged but uniform in size and surrounded by a vascular
poor matrix. It has been shown that the overproduction of
fibroblasts occurs adjacent to hypocellularized areas of the
plantar fascia where there is less collagen network.6,19,25
Myofibroblasts and fibronectin are also present in high
quantities in the cytoskeleton and extracellular matrix
respectively.6
PF is divided into 3 stages that follow the progression,
activity, and severity of disease.25 The proliferative stage is
first and characterized by increased fibroblastic activity and
reduced collagen network. This stage occurs early in the dis-
ease process and therefore does not result in the clinical man-
ifestation of symptoms. Stage 2, also known as the active
stage or involution stage, histologically shows fibroblast
maturation, myofibroblast differentiation, and increased col-
lagen synthesis.13 This stage can be the start of contraction of
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the plantar aponeurosis because of myofibroblasts’ contrac-
tile nature. Thick bundles of collagen fibers begin to domi-
nate the fibroblasts. At this stage, nodular formation appears
along the plantar fascia. Stage 3, the residual stage, displays
both reduced fibroblast maturation and reduced collagen
maturation. This stage is also susceptible to scar contracture
formation.6,13,25
The exact etiology is not well established, but various
studies have deduced that the onset of PF is typically in mid-
dle-aged patients8 and that the involvement of growth fac-
tors, including insulin-like growth factor, basic fibroblast
growth factor, connective tissue growth factor, platelet-
derived growth factor, and transforming growth factor beta
(TGFB) all play a major role in fibromatosis diseases.9,13 PF
is most common in Caucasians and has a predilection for
males.13,19 There is believed to be a hereditary component to
PF. Other contributing factors include repetitive trauma,
long-term alcohol consumption, chronic liver disease, diabe-
tes mellitus, and epilepsy.16
Clinical Presentation
PF is characterized by slow-growing nodules that accumu-
late in the medial plantar aponeurosis due to local prolifera-
tion of abnormal fibrous tissue within the plantar fascia.9
The aponeurosis is replaced by locally invasive tissue that
1
SUNY Upstate Medical University, Syracuse, NY, USA
2
Summit Orthopedics, St. Paul, MN, USA
3
University of Rochester Medical Center, Rochester, NY, USA
Corresponding Author:
Judith F. Baumhauer, MD, MPH, University of Rochester Medical Center,
601 Elmwood Avenue, Box 665, Rochester, NY 14642, USA.
Email: judy_baumhauer@urmc.rochester.edu
2 Foot & Ankle International 00(0)
Figure 1.  Histologic slides demonstrating an overabundance of disorganized fibroblasts.
forms a thickened fascia and subsequently progresses to
nodules ranging from 0.3 to 5.0 cm.8 Although uncommon,
severe hyperproliferation of the nodules can progress and
lead to contractures of the toes. The symptoms range from
painless nodules to markedly tender, erythematous lesions
that can result in difficulty walking. The nodules may be
found subcutaneously, buried within the fascia, or intra-apo-
neurotic.9 PF does not typically affect smooth muscle tissue
or skin, which accounts for the relative rarity of contractures
seen in PF compared with palmar fibromatosis.8,13
Diagnosis and Diagnostic Imaging
The differential diagnosis of a mass in the medial plantar
aponeurosis includes leiomyoma, simple fibroma, rhabdo-
myosarcoma, neurofibroma, and liposarcoma.19 A detailed
history and clinical examination coupled with radiographic
imaging and histological analysis, when necessary, guides
the diagnosis.5 Radiographs are used to rule out bone dis-
ease and to evaluate for soft tissue calcifications seen in
malignant conditions.25 Ultrasound can demonstrate single
or multiple areas of hypoechoic thickening of the plantar
fascia and is useful in providing measurements of depth
and size of the nodules.21 Magnetic resonance imaging
(MRI) with contrast is helpful in cases with an equivocal
diagnosis or there is a concern of malignancy.18 MRI pro-
vides the most accurate measurements of the lesion, and it
allows clear visualization of the extent to which the nod-
ules have invaded the neighboring tissue.18,26 On MRI, the
lesions shows heterogeneous signaling, ranging from
isointense to hypointense.26 T1-weighted images show
hypointense areas within the nodule itself, and T2-weighted
images show hypointense to medium signal intensity areas
(Figure 2). The T2-weighted signal increases as the nod-
ules become more cellular and the collagen content
decreases.26 MRI can be limited by its inability to differen-
tiate between invasive malignancies and more advanced
stages of PF, such as the maturation stage. MRI with con-
trast can aid in distinguishing between malignancy and
advanced stage PF, but MRI is most sensitive when applied
to early stages of PF.18,26 Finally, biopsy is used to exclude
malignancies in cases where the diagnosis remains unclear
following imaging.25
Nonoperative Treatment
High-level studies on the effectiveness of orthotics and shoe
modifications for PF are lacking, but many authors have
provided expert opinion (Level V evidence) advocating for
these as the initial treatment, resulting in a Grade C recom-
mendation.2,16,21,25 Table 1 summarizes levels of evidence
and grade of recommendation for all treatments described.
Authors advocate for over-the-counter or custom orthotics,
activity modification to avoid jumping sports, and soft-
soled shoes to provide additional shock absorption.
Orthotics are intended to offload the painful lesion and
cushion the foot. When this cannot be achieved with over-
the-counter orthotics, custom orthotics can be attempted.
Additional options include a carbon foot plate underneath
the orthotic, which may decrease strain on the plantar fas-
cia. A rocker-bottom shoe may further decrease strain on
the plantar fascia by rolling the foot through the stance
phase of gait. If these simple measures do not improve the
patient’s pain symptoms, alternative options for treatment
Espert et al 3
Figure 2.  Characteristic magnetic resonance image demonstrating lesions (arrows) with heterogenous signal in the plantar foot.
(A) Lesions tend to be hypointense on T1-weighted images. (B) Increased signal is seen on T2-weighted images.
Table 1.  Levels of Evidence and Grades of Recommendation.
Levels of evidence
  Level I: High-Quality, Randomized Prospective Clinical Trial
  Level II: Prospective Comparative Study
  Level III: Retrospective Case-Control Study
  Level IV: Case Series or Case Study
  Level V: Expert Opinion
Grades of recommendation
  Grade A: Treatment options are supported by strong
evidence (Level I and Level II studies)
  Grade B: Treatment options are supported by fair evidence
(Level III and Level IV studies)
  Grade C: Treatment options are supported by either
conflicting or poor-quality evidence (Level IV studies)
  Grade I: Insufficient evidence exists to make a
recommendation
include cortisone injections, hormonal therapy, radiation
treatment, and surgery (Table 2).
Hormonal Therapy
Hormonal therapy is an active area of research in fibroma-
tosis disease. Multiple hormonal targets have been identi-
fied, including the TGFB superfamily and tumor necrosis
factor. Both TGFB2 and tumor necrosis factor are cytokines
that are responsible for the maturation of fibroblasts and the
differentiation of myofibroblasts.4,12,15 Overexpression of
these factors potentially increases fibroblast production and
resultant contracture. Suppression therefore may decrease
contraction in fibromatosis disease, including PF.
Antiestrogen therapy is an experimental, noninvasive,
treatment that has been shown to be successful in decreasing
contractures in a basic science model.15 Kuhn et al15 cultured
fibroblasts from a Dupuytren’s disease–affected sample and
fibroblasts from a carpal tunnel syndrome–affected sample
in a collagen lattice. Contraction was measured daily for 5
days. The collagen lattices cultured with Dupuytren’s dis-
ease–affected fibroblasts were found to contract signifi-
cantly more than the control sample. Furthermore, the
palmar fibromatosis lattices expressed increased TGFB2.
Tamoxifen is a synthetic nonsteroidal estrogen modulator
that downregulates TGFB2. Tamoxifen is used mainly in the
treatment of breast cancer, but in the lattices that were treated
with tamoxifen, downregulation of TGFB2 was noted.15
In a clinical study by Degreef et al,7 preoperative and
postoperative tamoxifen was shown to result in decreased
contractures compared with a control group in Dupuytren’s
disease (Level III study). However, the clinical difference
deteriorated over time, and by 2-year follow-up, no differ-
ence could be seen between groups. Nevertheless, tamoxi-
fen has shown promise in the treatment of Dupuytren’s
disease in both basic science and clinical studies.
Much of the research performed on hormonal therapy
has been done in the basic science model or in Dupuytren’s
disease, and therefore the effects on PF are unknown, lead-
ing to a Grade I recommendation.
Radiotherapy
Two studies support electron-beam radiotherapy (RT) and
orthovoltage x-ray RT as effective treatment for PF.13,22 RT
reduces fibroblast activity and therefore is most effective in
stage 1 of PF.13,25
Multiple authors have presented RT protocols with vary-
ing results. In a case series of 24 patients (Level IV study),
Heyd et al13 reported that 33.3% and 54.5% of patients
experienced complete or partial remission of nodules,
respectively, when treated with RT. Decrease in nodule
number and size translated to 60.4% of patients experienc-
ing complete pain remission. Furthermore, gait abnormali-
ties were observed to improve by 73.3% in these patients.
The patients’ subjective satisfaction with their functional
outcomes increased to 91.6% at an average follow-up of
22.5 months. In a later study combining PF and Dupuytren’s
4 Foot & Ankle International 00(0)

Table 2.  Summary of Treatment Options for Plantar Fibromatosis.

Treatment Recurrence Rate Description Adverse Events

Corticosteroid injection
Radiation therapy
Local excision
Wide excision
Complete plantar fasciectomy
Unknown in the foot Intralesional injections
monthly for 3–5 mo
Unknown; overall 60%–90% Direct radiation to lesion;
improvement various protocols described
57%–100% Marginal resection of lesion
8%–20% Removal of lesion with clean
margin
9.5%–25% Radical resection
Depigmentation of skin, fat atrophy
Skin tenderness, erythema, blistering
and thickening; neurosensory
changes
Wound-healing problems, recurrence
Wound-healing problems, neuroma,
recurrence
Wound-healing problems, skin
necrosis, recurrence, neuroma,
potential pes planus

patients, Schuster et al22 demonstrated 94% satisfaction in
33 patients at an average of 31 months following treatment
(Level IV study). Four patients required repeat radiation,
but radiation toxicity was not observed in any patients
regardless of repeat radiation.22 RT use has been historically
relegated to Europe and remains underused in the United
States. Despite 2 studies demonstrating success, additional
and higher level of evidence studies with comparison
groups, randomization and blinding are needed for RT
(Grade C recommendation).
Corticosteroid Injections
Corticosteroid injections have not been studied in PF, and
knowledge of the effect of corticosteroids on fibroblastic
cells comes from studies of Dupuytren’s disease and basic
science literature. Corticosteroid injections target the prolif-
erative stage by decreasing fibroblastic activity and increas-
ing the rate of fibroblast apoptosis.9,25 More specifically,
triamcinolone is known to degrade insoluble collagen in scar
contractures and keloids to a salt-soluble collagen that is
subsequently excreted.14 Following a series of injections for
palmar fibromatosis, Ketchum et al14 demonstrated soften-
ing and flattening of lesions that occurred after the second or
third injection and that 73 of 75 patients had reductions in
nodular size and pain (Level IV study). Importantly, adverse
effects were reported in 50% of patients following injection,
and recurrence was noted between 1 and 3 years in half of
the study participants.14 The 2 most common adverse events
were skin depigmentation and temporary subcutaneous fat
atrophy.14 Although the study demonstrated success in pal-
mar fibromatosis, the use of steroid injections in PF has not
been studied, and its use may be limited by the potential for
fat atrophy which could be a serious issue in the foot (Grade
I recommendation).
Collagenase Injections
Collagenase Clostridium histolyctium (Xiaflex, Endo
Pharmaceuticals) injections gained US Food and Drug
Administration (FDA) approval for the treatment of
Dupuytren’s and Peyronie’s disease in 2010 and 2013,
respectively12; however, they have been inadequately stud-
ied in PF and receive a Grade I recommendation. Collagenase
injections are an active area of research in the treatment of
PF, but reports in the current literature are limited to case
reports with mixed success. Hammoudeh12 (Level IV study)
demonstrated a failure of collagenase to resolve a plantar
fibroma that had previously been recalcitrant to other treat-
ments. Despite the mixed results, collagenase may be prom-
ising in the treatment of PF, but further research is needed to
identify the optimal patients for this treatment.
Percutaneous Ultrasonic Treatment
Percutaneous ultrasonic treatment (Tenex Health) is a
recently developed modality whereby an ultrasound tip is
inserted directed into an area of diseased tissue through a
small incision. The device then delivers pulsed ultrasonic
energy, resulting in emulsification of local tissue, which is
evacuated by the device tip. Tenex is FDA approved only
for use in tendons and has not gained approval for the treat-
ment of fascia or fibrous tissue. To date, this technology has
been primarily studied in the treatment of chronic tendinop-
athy, which is reflective of its limited FDA approval. Barnes
et al3 performed a prospective case series (Level IV evi-
dence) which is the highest quality study of percutaneous
ultrasonic treatment to date. They demonstrated a visual
analog scale score improvement from a mean of 6.4 to 0.7
following percutaneous ultrasonic treatment in 19 cases of
refractory tendinopathy about the elbow 1 year following
the procedure. Patel et al20 recently completed a retrospec-
tive case series (Level IV study) evaluating percutaneous
ultrasonic treatment in 8 patients with refractory PF.
American Orthopaedic Foot & Ankle Society scores
improved from an average of 30.8 before the procedure to
90.1 following the procedure, with an average follow-up of
2.5 years. No complications were reported. Although
encouraging, percutaneous ultrasonic treatment receives a
Grade I recommendation because of a paucity of data and
Espert et al 5
Figure 3.  (A) Intraoperative photograph demonstrating wide excision of a large, recalcitrant plantar fibroma (marked by arrows).
(B) Gross specimen following excision. This specimen was sent to pathology for definitive histological analysis. Photographs courtesy
of Keith Wapner, MD.
lack of high-quality studies, including randomization and
comparison groups.
Operative Treatment
Operative treatment is indicated in cases refractory to com-
prehensive nonoperative care with the presence of debilitat-
ing pain and receives a Grade B recommendation on the
basis of current literature.17 Three operative procedures have
been described: (1) local excision of the nodule, (2) wide
excision of the nodule including a minimum of 2 cm margin
(Figure 3), and (3) complete plantar fasciectomy.25 Studies
have demonstrated that subtotal plantar fasciectomy has the
lowest recurrence rate because of its radical resection.1,23
Van der Veer et al24 performed a single-center long term
retrospective study of 27 patients (33 feet) demonstrating
among the 3 operative procedures, the overall recurrence
rate was 60% (Level III study). A total plantar fasciectomy
had the lowest recurrence at 25%, while the local excision
had the highest recurrence rate of 100%. Results also dem-
onstrated a positive correlation between the number of
nodules and the recurrence rate: the more nodules, the
higher the recurrence rate with resection. The authors noted
that risk factors that contributed to recurrence of PF were
the presence of bilateral lesions, multiple lesions in the
involved foot, and a positive family history of PF.24 There
is a high recurrence rate in local excision procedures
because of the residual microscopic diseased tissue being
left behind, specifically located in the invaded fascia. Wide
excision procedures result in lower recurrence rate because
normal-appearing fascia and wide margins also removed
along with the lesion.24
Residual diseased tissue is thought to result in recurrence
of PF following isolated nodule resection.2 Wapner et al27
demonstrated that revision surgery using a wide resection
with delayed skin grafting could lead to success in instances
of recurrence following the index procedure (Level IV
study). In this series of 7 patients with revision surgery for
nodule recurrence, the disease was irradiated, but outcomes
in 2 patients were compromised by the formation of postop-
erative neuromas. The potential morbidity and technical
demand of the described wide resection revision technique
must be considered when counseling patients with recur-
rence following nodule resection.
A case series by de Bree et al5 (Level IV study) reported
that plantar fasciectomy combined with postoperative RT
has a lower recurrence rate compared with other operative
procedures, but the lack of high-level studies results in a
Grade I recommendation. Although promising, adjuvant
RT has known side effects, such delayed wound healing,
fractures, lymph edema, and dystrophic foot with impaired
foot function. When severe, these side effects can lead to
potential amputation, which has stifled the adoption of
adjuvant RT.
Summary of Graded Evidence
•• Orthotics and shoe modifications are advocated
by many authors as the preferred initial treatment
for PF, but the lack of studies demonstrating the
efficacy of these options results in a Grade I
recommendation.
•• Hormones, including TGFB and tumor necrosis fac-
tor, have been identified and implicated in the matu-
ration of fibroblasts and the differentiation of
myofibroblasts. Targeting these cytokines is an
area of active basic science research and has been
clinically studied in Dupuytren’s disease. Lack of
6 Foot & Ankle International 00(0)
study in PF, however, results in a Grade I recommen-
dation.
•• RT has been used in Europe, with multiple Level IV
studies supporting its use in PF. Specific RT proto-
cols and high-level studies are lacking, resulting in a
Grade C recommendation.
•• Corticosteroid injections have been shown to
degrade fibroblastic cells in the basic science
model and demonstrated mixed results in the treat-
ment of Dupuytren’s disease; however, efficacy
remains unknown in the treatment of PF (Grade I
recommendation).
•• Collagenase injections have shown promise in the
treatment of Dupuytren’s disease but remain unproven
for use in PF, with only 1 case report in PF demon-
strating poor results (Grade I recommendation).
•• Percutaneous ultrasonic treatment is a new technique
with demonstrated efficacy in the treatment of PF in
a single Level IV study (Grade I recommendation).
•• Operative treatment is reserved for recalcitrant and
debilitating cases of PF (Grade B recommendation).
Local excision of PF lesions results in a high rate of
recurrence, while complete plantar fasciectomy
results in the lowest rate of recurrence at about 25%.
•• RT following operative treatment is an option but
lacks strong literature and receives a Grade I
recommendation.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this arti-
cle. ICMJE forms for all authors are available online.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
ORCID iD
Michael R. Anderson, DO https://orcid.org/0000-0003-1791-2770
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