Plantar Fibromatosis

The fibromatoses represents a wide spectrum of locally infiltrative clinicopathologic processes characterized by the proliferation of generally mature fibroblasts associated with mature collagen. Some of these entities are present at birth or develop in early childhood (eg, juvenile fibromatosis [JF]). Others may appear in adulthood.[1]

The term plantar fibromatosis (PF) is used for different conditions, as follows: (1) a relatively common plantar equivalent of Dupuytren palmar contracture most commonly termed Ledderhose disease (LD), but also referred to as morbus Ledderhose; (2) a more uncommon plantar superficial fibromatosis that unlike deep fibromatosis (eg, abdominal, extra-abdominal, and visceral fibromatosis), generally has a less aggressive and recurrent tendency; and (3) an extremely rare, benign cerebriform mesodermal hamartomatous proliferation that in a plantar location, appears to be a clinicopathologic marker of Proteus syndrome (PS).

Juvenile aponeurotic fibroma (JAF) and aggressive infantile fibromatosis (AIF) can also be considered to be in the plantar fibromatosis group when lesions are present on the sole of the foot.

Plantar fibromatosis represents not a single entity, but rather, a heterogeneous group of conditions with the common characteristics of plantar location and histologic features of mature collagen and fibroblasts with no malignant cytologic features.

In Ledderhose disease (described in 1897), as in Dupuytren contracture (DC) (first reported in 1831), repeated trauma, long-term alcohol consumption, chronic liver disease, diabetes, and epilepsy have been reported in association with the development of the lesions in middle-aged or elderly people. The development of clinically apparent disease actually occurs later in the condition’s development as the initial stages are clinically imperceptible and involve a reduction in existing collagen networks with a corresponding increase in fibroblast activity. Clinical manifestations appear during the “active” or “involution” stage as fibroblast maturation leads to increased collagen synthesis and the beginnings of the characteristic nodule formation, usually in the medial plantar aponeurosis. This active phase also derives its namesake from the active contraction of the plantar aponeurosis by differentiated myofibroblasts within the tissue.[2] Patients with Ledderhose disease often also have other fibrosing conditions such as Dupuytren contracture, knuckle pads, or induratio penis plastica (ie, Peyronie disease, first reported in 1743 by François de la Peyronie, physician of Louis XV of France). In fact, literature has shown that concurrence of Ledderhose disease and Peyronie disease to Dupuytren contracture ranges from 9% to 25% and 4%, respectively.[2] This indicates that heredity is a likely factor for the development in patients, and work by Hu et al has suggested the relatively high concurrence frequency is suggestive of a commonly shared defect in wound repair, as Ledderhose disease can develop secondary to repetitive trauma.[3]

Superficial fibromatosis (SF) in a plantar location includes a variety of soft-tissue tumoral proliferations of fibroblasts. However, it has been shown that some forms are not due to fibroblast overgrowth but to myofibroblast proliferation; superficial fibromatosis is more common in children and young adults than in older people.

Cerebriform mesodermic hamartomas on the soles represent a kind of mesodermal nevus and are usually associated with Proteus syndrome. This syndrome was named after the Greek god Proteus, the "Old Man of the Sea" and son of Poseidon who was able to change his shape to protect himself. Proteus syndrome is a complex malformative or asymmetric hypertrophic syndrome born from of an activating mutation within the oncogene AKT1.[4] The syndrome is associated with multiple cutaneous and musculoskeletal manifestations such as epidermal verrucous nevus, vascular hamartomas, and exophytic cerebriform fibrolipomata and scoliosis, kyphosis, and exostosis, respectively.[5] Hamartomatous cerebriform plantar fibromatosis may develop on the soles before other manifestations of Proteus syndrome appear, and it is considered a marker for Proteus syndrome.

Fibromas and desmoid tumors (eg, intestinal polyps, osteomas, soft-tissue tumors, epidermal cysts) are common in Gardner syndrome, which was described in 1950. These tumors often arise over previous surgical scars. By means of direct DNA sequencing, recent studies show that somatic beta-catenin or adenomatous polyposis coli (APC) gene mutations are present in virtually 100% of cases of Gardner syndrome–associated fibromatosis (GAF), as well as most cases of deep fibromatosis (DF). On the other hand, no somatic mutations were identified in beta-catenin or APC genes in superficial fibromatosis. Therefore, the divergent behaviors of superficial fibromatosis in relation to deep fibromatosis and Gardner syndrome–associated fibromatosis, despite their similar clinical and histologic morphologic features, are based on genetic differences.[6]

As with many tumors, the causes are not known. As previously stated, owing to the high concurrence rate with Dupuytren contracture, there is suspicion that a shared defect in wound repair could be to blame, but no definitive etiology has been elucidated to date.[3]

Frequency

Ledderhose disease is relatively common, and plantar contracture develops in approximately 25% of middle-aged or elderly individuals (1 of every 4 with Dupuytren contracture). Superficial plantar fibromatosis (SPF) is uncommon, and the hamartomatous form associated with Proteus syndrome is rare. The exact incidences of superficial plantar fibromatosis and the hamartomatous form associated with Proteus syndrome are unknown.

Race

Whites are affected more often than other groups.[2]

Sex

Ledderhose disease affects men approximately 10 times more often than it affects women. Juvenile aponeurotic fibroma is more common in boys than in girls. No sex predilection is evident for the other forms of plantar fibromatosis.

Age

Ledderhose disease is seen in middle-aged and elderly individuals. Superficial plantar fibromatosis and juvenile aponeurotic fibroma are most common in children and youths when compared with adults. The exceptional aggressive infantile fibromatosis begins in an infant's first year of life. The rare hamartomatous variety also develops in infants.

The different varieties of plantar fibromatosis may be asymptomatic. However, the feeling of a mass in the foot, difficulty fitting in shoes, and pain with weight bearing often affect patients' ability to stand or walk.

Only aggressive infantile fibromatosis has an invasive course, as does fibrosarcoma; however, it does not metastasize.

Ledderhose disease has a favorable prognosis, although slow progression is not uncommon. Patients who undergo plantar fasciectomy have been shown to have a lower recurrence rate.

Superficial plantar fibromatosis is usually benign and may regress spontaneously. Rare cases that are relatively progressive and recurrent occur. The hamartomatous form is also benign, and problems are related to difficulties in standing or walking or to associated Proteus syndrome.

Juvenile aponeurotic fibroma is benign, but recurrences are common.

Patients with Ledderhose disease have a range of presentations that can span from unawareness of their condition owing to lack of pain to painful nodules that impair proper ambulation.[7]

Likewise, patients with other forms of plantar fibromatosis may not be aware of their disease; however, they may notice difficulty in standing, walking, or wearing shoes when nodules or bumps become large enough.

Ledderhose disease is typically bilateral and progresses slowly but not indefinitely.

Superficial plantar fibromatosis may grow gradually, and, in most cases, self-involution occurs. In some cases, superficial plantar fibromatosis lesions enlarge and persist; if excised, they recur iteratively.

Juvenile aponeurotic fibroma can spontaneously regress or persist. Recurrences after excision are common.

Ledderhose disease consists of one or more small, asymptomatic, round or flattened, hard nodules that are generally located on the medial side of the sole. Flexion deformities usually do not occur in opposition to Dupuytren contracture.

Superficial plantar fibromatosis appears as one or more asymptomatic, bad limited, flat nodules of fibrous consistency and variable size. They are most commonly located on the plantar aspect of the anteromedial portion of the heel pad (see the image below).

Juvenile aponeurotic fibroma may appear as a localized form affecting adults or a diffuse variety observed in children. It is more common in males than in females, and the hard nodules grow slowly and adhere to deep structures (see the image below).

Aggressive infantile fibromatosis is rare and ordinarily begins in the patient's first year of life. It grows rapidly and infiltrates the subcutaneous tissue, aponeurosis, and muscles with an expansive or infiltrative course like a fibrosarcoma. However, metastasis does not occur.

Hamartomatous plantar fibromatosis lesions look like raised cerebriform soft-to-firm exophytic masses on any plantar area, where they are covered by pink, lightly dark, or normal-colored skin (see the image below). They can become large enough to cause disability.

In patients with Ledderhose disease, the presence of other fibrosing conditions (eg, Dupuytren contracture, knuckle pads, Peyronie disease in men) must be checked.

In superficial plantar fibromatosis, Gardner syndrome must be ruled out.

In the presence of cerebriform fibrous exophytic plantar lesions, Proteus syndrome must be considered.

MRI is a useful primary step in differentiating plantar fibromatosis from surrounding tissue. Images show some signal intensity heterogeneity and, usually, infiltrative margins.[8] MRI can show the degree of deep invasion of the plantar fibromatosis, which often reaches the aponeurosis.[9]

The MRI signal intensity and the consistency of the clinical location of Ledderhose disease enable the diagnosis to be made with reasonable confidence. However, one must consider the diagnosis of clear cell sarcoma in the differential. In effect, the 2 entities can have similar MRI findings and clinical locations.

For fluorine-18 fluorodeoxyglucose (FDG) imaging, see Scheler et al.[10]

All types of plantar fibromatosis have a dense fibrocellular tissue with mature collagen and fibrocytes in various stages of maturation, but they do not have prominent atypical features or abnormal mitotic activity. The overlying epidermis and superficial dermal tissue are usually normal, but the neoformation, which grows upward and downward, generally replaces the adipose tissue. The proliferation often involves many cellular foci surrounded by fibrous scarlike connective tracts.

In superficial plantar fibromatosis, the limits are usually undefined. Some areas may be almost acellular, with a scarlike appearance. In other areas, or in the most active early cases, the fibrocytic component can be dense, with cells closely packed together; the differential diagnosis with fibrosarcoma can be difficult in these cases. The reticulin network is often prominent. Usually, inflammation-associated infiltrate is not present. The connective stroma may involve various aspects. The stroma may be dense and fibrous; less commonly, it is loose. Sometimes, myxoid or chondroid areas can be seen. Vascularization is not a prominent feature. Local nerves and Vater-Pacini corpuscles can seem to be increased in number or size.

In juvenile aponeurotic fibroma, the cells are round or oat-shaped, and the stroma is chondroid (cartilage analogue fibromatosis). Aggressive forms are usually more cellular and have increased mitotic activity. Peripherally, the proliferation is poorly limited and penetrates the neighboring structures. Hamartomatous cerebriform plantar fibromatosis has a variable fibromalike, lipomatous, angiolipomatous, or combined structure.

The myofibroblast is the key proliferative cell in some so-called fibromatoses; therefore, these might be better named myofibromatoses. In these fibromatoses, results of tests for cytologic markers in muscle cells are positive.

In recurrent plantar fibromatosis, as in aggressive fibromatosis, tumoral cells express platelet-derived growth factor-B (PDGF-B) proto-oncogene.[11] This proto-oncogene encodes the B chain of PDGF-B, a mitogen for fibrocytes, whereas normal plantar fascia, nonrecurrent plantar fibromatosis, and scars do not. Thus, the detection of PDGF-B may be a useful adjunct to the pathologic evaluation of invasive plantar fibromatosis for prognostic purposes.

Osseous metaplasia and distinct multinucleate giant cells have been reported in Ledderhose disease.[12, 13]

No medical care is effective in plantar fibromatosis, and reported success probably is due to the possible spontaneous involution of superficial plantar fibromatosis. Early treatments have included anti-inflammatory medication, orthotics, and physical therapy. Other modalities have included methotrexate and radiation after surgery.

For Ledderhose disease, the conservative treatment options are numerous, including offloading pads, radiation, extracorporeal shockwave, antiestrogens, verapamil, collagenase injection, colchicine, and 5-fluorouracil injection. Offloading pads as well as extracorporeal shockwave have been shown only to provide symptomatic relief, with the latter providing some softening of lesions. Ionizing radiation and intralesional injections of corticosteroids have been shown to reduce the size of lesions. It is important to note that the remaining treatments have no in vivo data demonstrating efficacy (antiestrogens), have only been shown to be efficacious in similar disorders like Dupuytren contracture or Peyronie disease (verapamil, collagenase), or require additional study to demonstrate efficacy (colchicine). In summary, conservative treatment certainly requires more study to determine the most efficacious modality, but collagenase, corticosteroids, and 5-fluorouracil injections are being used with variable success. However, pain associated with the injections can be a limiting factor in their use.[7]

For Ledderhose disease, fasciectomy and excision of the fibrous tissue can represent either an initial option for patients with symptomatic lesions or a choice decided upon after conservative treatment fails. Fasciectomy has been shown to reduce the rate of recurrences and can be of the local, wide, or radical complete plantar variety.[7, 14] The choice of type of fasciectomy must be weighed with the risk of complications, especially recurrence, which can be 57-100%, less than 50%, and 0-50%, for local, wide, and complete plantar fasciotomies, respectively.[14] In order to better guide treatment decisions with regard to surgery, Sammarco and Mangone have developed preoperative and intraoperative staging criteria based on a retrospective study of 18 patients and the corresponding lesion propagation and soft-tissue infiltration seen during subtotal plantar fasciotomy. While their study involved a small cohort of patients, Sammarco and Mangone’s criteria have shown promise at predicting delayed wound healing and may be of use when advising patients in the postoperative period.[15]

For the other forms of plantar fibromatosis, surgery is the only therapeutic alternative. However, in infantile forms, physicians should evaluate the need for surgery before performing it.[16]

Many juvenile fibromatoses spontaneously regress, and biopsy may be performed to induce their involution. Some lesions can grow, and others can recur after excision that appears complete. Because tumor growth characteristics may be relatively important before surgery, physicians should consider the possibility of an expectant control.

Hamartomatous plantar fibromatosis does not regress spontaneously; therefore, surgical removal is appropriate.

Modification of activity, the use of orthotics, and physical therapy have been used as therapeutic modalities for the treatment of plantar fibromatosis.

Ledderhose disease treatment complications, whether medical or surgical, often involve recurrence or incomplete treatment of the primary lesion. Following surgery, complications can include painful scars, wound dehiscence, nerve entrapment, and loss of arch height. Recurrence of the primary lesion is arguably the most damaging of surgical complications, often necessitating wider and more radical excisions, which presumably raise the risk of those complications previously mentioned.[7]