Ledderhose’s Disease-What do We Know and What do We not know

Plantar fibromatosis of the foot is a rare benign, hyperproliferative, and local aggressive disease of the plantar aponeurosis (i.e. fascia) (Figure 1A) of unknown etiology and included among the extra-abdominal desmoids tumors, this entity was first described in 1894 bythe German physician Georg Ledderhose (1855-1925), and it is accompanied by a high recurrence rate [1-3]. Regarding etiology, it has been described to be most frequent in patients with diabetes, low body weight, epilepsy, alcohol abuse, and smoking, and a familial history in up to 19.1% of cases is observed as well [2,4]. Occurrence is observed at all ages ranging from 2 to 83 years (N=178), but especially in the 4th and 5th decade of life in the absence of significant sex-related differences (51.7% male vs. 48.3% female in 178 patients), and bilateral involvement is reported to be 20-50% of cases [2,4]. It can be associated in 5-21.3% of cases with the palmar fibromatosis of the hand (Figure 2A-D) first described quite earlier in 1831by the French physician Baron Guillaume Dupuytren (17771835) which can also be associated with the fibrous subcutaneous nodules (i.e. knuckle pads) upon the proximal interphalangeal finger joints (Figure 3) first described in1904 by the British physician SirArchibald Edward Garrod (1857-1936), and in 1-3% of cases with the penile fibromatosis first described substantial quite earlier in 1743 by the French physician François Gigot de la Peyronie (1678-1747) [2,5-12]. Histopathological findings in plantar fibromatosis reveal similar findings to those in palmar fibromatosis [13]. In the literature, it has been proposed for palmar fibromatosis that growth factors, such as platelet-derived growth factor and transforming growth factor-beta, free oxidized radicals, increased levels of plasminogen activator enzymes, and expression of Ki-67 antigen contribute the etiology, and it was found that the number of androgen receptors in specimens of palmar fibromatoses was considerably higher than in normal palmar fascia [14-19]. Noted that expression of the Ki-67 antigen plays an important role in detection of malignancies [20]. For the palmar fibromatosis, family history probably has the strongest influence on the age at time of first surgery compared to environmental factors, followed by male sex, and the percentage of familial cases decreased with age of onset from 55% in patients aged 40-49 years to 17% in patientsaged80 years and older, and men are upto 15 times more likely to suffer from this disease but during the 8th and 9th decade of life the ratio between affected men and women is equal [21,22]. Moreover, palmar fibromatosis is more frequently observed in the white Caucasian and Nordic race than in Africa or Asia [23]. Noted that the incidence of palmar fibromatosis in elderly men is reported to be up to 25.3% in Australia [24], up to 28.9% in Ireland [25], and up to 13.75% in England [26]. The differential diagnosis of plantar fibromatosis should include stenosing tenosynovitis, ganglion cyst of the ankle with medial plantar nerve entrapment (i.e. tarsal tunnel syndrome) (Figure 4A-B), other conditions leading to entrapment of plantar digital nerves such as the primary Morton’s neuroma (Figure 5A-C) or secondary post-traumatic/post-operative neuroma (Figure 6A-C), plantar fasciitis or rupture with or without plantar calacaneal spurs (Figure 7 compared to Figure 8), heel bursitis with or without Haglund’s exostosis (Figure 7 compared to Figure 8), aseptic osteonecrosis such as Köhler’s disease (Figure 9), or other benign or malignant lesions (Figure 10), including fibrosarcoma [27,28]. Mini Review