Adult-acquired flatfoot deformity can cause significant morbidity. Its etiology remains obscure although the condition has been associated with disturbances of the posterior tibial tendon including inflammatory tendinitis,8,16 traumatic rupture,8-10,15,20 ischemia within a 14-mm hypovascular zone distal to the medial malleolus,7 anatomic abnormalities such as an accessory navicular,28 presence of a tight flexor retinaculum,9 shallow medial malleolar groove,24 congenital pes planus,20 and mechanical disturbances.30 Pathologic changes such as increased vascularity, increased fibroblast cellularity, and increased mucin content in the tendon have been described,12,13,21,22 but there is no unifying thesis accommodating these changes.
We think that a clinically triggered event, such as a repetitive mechanical insult causing stretching or tension of the tendon, should be reflected by changes in the histopathologic features of the posterior tibial tendon. Therefore, we examined the pathologic features microscopically, including the degrees of angiogenesis and cellular hyperplasia, and postulate that this repetitive mechanical insult may be related to tendon cell hyperplasia linked to angiogenesis of the the subtenosynovial lining cell layer.
MATERIALS AND METHODS
We obtained 28 posterior tibial tendon specimens from patients who had surgery for clinical Stage II or III posterior tibial tendon insufficiency. There were 19 women and nine men with an average age of 50 years (range, 18-77 years). We based staging on the systems of Johnson and Strom11 who classified posterior tibial tendon insufficiency into three clinical stages, and Myerson23 who added a fourth stage. Johnson and Strom defined Stage I as a normal tendon length with pain along the tendon's course, Stage II as an elongated tendon while the hindfoot remains mobile, and Stage III as an elongated tendon with a stiff hindfoot. Myerson added Stage IV, classified as Stage III disease with valgus angulation of the talus in the tibiotalar joint. Twenty patients were classified as having Stage II disease (14 women, six men). They had reconstructive procedures involving double calcaneus osteotomy, flexor digitorum longus to posterior tibialis transfer, and tendo Achillis lengthening. The remaining eight patients were classified as having Stage III disease (five women, three men). They had triple arthrodeses and tendo Achillis lengthening.
Each specimen was retrieved from the identical site at the insertion into the navicular and extending 3 cm proximally. All specimens were fixed in 10% buffered formalin. The specimens were incised longitudinally, embedded in paraffin, and sectioned for microscopic examination in longitudinal and cross-sectional fashions. Histologic sections were stained with hematoxylin and eosin and Masson trichrome, and viewed in plain and polarized light. For each case, five longitudinal and five cross-sectional sections were analyzed for the degree of vascularization, the presence of mucoid change and chondroid metaplasia, the degree of tenocyte cellularity, and layer thickness. We divided the tendon into three zones: the tenosynovial lining cell layer, the subtenosynovial lining cell layer (defined as the layer immediately below the surface layer of lining cells), and the tendon proper. The degree of vascularization was recorded as present or absent and graded as 1-3 (1 = present in an isolated microscopic field; 2 = present in more than one field; 3 = present in a more diffuse fashion). Mucoid change and chondroid metaplasia were identified as previously described.31 Mucoid change was recorded and graded (1 = one focal microscopic field; 2 = more than one focal microscopic field) if the tendon showed pools of mucinous material in an otherwise normal tendon. Chondroid metaplasia was recorded and graded when patchy chondrocyte hyperplasia was evident (1 = for an isolated microscopic field; 2 = for more than one microscopic field). The presence of tissue calcification (calcific tendinopathy) was recorded when present. The tenosynovial lining layer was evaluated and graded for thickness (1 = if there was a layer of at least two cells in thickness; 2 = if the layer was greater than two cells in thickness), for hypercellularity (1 = if tenocytes were slightly enlarged or increased in number; 2 = if moderately or markedly increased in number), and for neovascularity (1 = for a focal increase in vessels; 2 = if vascularity was diffusely increased and penetrating into the tendon proper). As a reference point for the pathologic findings, the specimens were scored against the known pathologic features of tendon in cadaveric tissue.31 All specimens were reviewed together by the lead author (VAF) and an experienced musculoskeletal pathologist (VJV).
All specimens were grossly abnormal. The tendon sheaths were thickened, and the tendons were enlarged in a bulbous fashion. They appeared dull white without the normal color and sheen. All specimens had several common pathologic processes that varied in degree of severity in each tendon and between specimens. Tenocyte layer thickening, neovascularization, and angiogenic tissue infiltration were present and graded in 75% of specimens (Table 1). The overall microscopic appearance of each tendon showed longitudinally oriented fingerlike projections of neovascular infiltration (Fig. 1) that caused disruption of the collagen fibrils in all specimens. This was quite pronounced, with at least 50% involvement of the tendon in 14 (50%) specimens. Neovascularization was present in all specimens. It was graded as 1 in nine specimens, 2 in 10 specimens, and 3 in nine specimens. Increased mucoid change was seen in eight specimens (28%) (Grade 1 in three specimens and Grade 2 in five specimens) and chondroid metaplasia (Fig. 2) in 10 (36%) specimens (Grade 1 in six specimens and Grade 2 in four specimens). The tenosynovial lining cell layer (Zone 1) showed hyperplasia in nine (32%) specimens (Grade 1 in four specimens and Grade 2 in five specimens) (Fig. 3). The subtenosynovial lining cell layer showed thickening and neovascularization in 22 (79%) specimens (Grade 1 in 11 specimens and Grade 2 in 11 specimens) (Fig. 4), and appeared to be the source for the diffuse neovascular infiltrative process. Although higher grades of neovascularity were observed more commonly in specimens with Stage II disease, there were no clear histologic differences between Stages II and III disease (Table 2). Calcific tendinopathy was seen only in one specimen. Inflammatory cells were found in only one specimen. Tendon bundles on cross-section often revealed bands of neovascular fibrosis (Fig. 5).
Histopathologic alterations in specimens from patients with various tendinosis syndromes compared with cadaveric control specimens include hypoxic degenerative tendinopathy (collagen fiber splitting, variation in size, and deformation), mucoid degeneration (vacuoles consisting of proteoglycans and glycosaminoglycans between collagen fibers), tendolipomatosis (presence of lipocytes in tendon fascicles), and calcifying tendinopathy (large calcium deposits between collagen fibrils).12,13 Mosier et al21,22 compared 15 posterior tibial tendon surgical specimens with 15 cadaveric control specimens. They observed that all diseased specimens had degenerative tendinosis with varying degrees of increased mucin content, fibroblast hypercellularity, chondroid metaplasia, and/or neovascularization resulting in disruption of linear orientation of the collagen fibers in the tendon.21,22 We found similar results, but we also linked neoangiogenesis to the tenosynovial lining cell layer.
A study limitation was that we examined histopathologic findings in specimens from patients with late-stage disease. Etiology may be difficult to ascertain from latestage disease, but doing a biopsy during early-stage disease would be clinically and surgically inappropriate. However, we think our findings are consistent with a tissue response to a repetitive mechanical insult and/or injury.
Neovascular infiltration into the tendon was the most dramatic and prevalent finding (Fig. 1), as all specimens showed some degree of involvement. The grossly abnormal specimens appeared to have a diffuse neovascular infiltrative process that originated from the tenosynovial proliferation (Fig. 4) and then penetrated the collagen bundles, leading to disruption of their orientation. This infiltrative process seemed to be associated with one of two additional findings: (1) scarring with fibrosis and circumscription of the collagen bundles (all specimens) (Fig. 5), and/or (2) degeneration with increased mucin content and chondroid metaplasia (one of three specimens) (Fig. 2).10,14,18 Our findings may be related to a reparative and/or a degenerative process. We found no consistent evidence of ischemic change, and only one patient showed a mild inflammatory process. The lack of inflammatory findings was consistent with similar findings in other tendinosis syndromes including chronic Achilles tendinopathy.25 The presence of mucoid degeneration and chondroid metaplasia was consistent with a corollary degenerative component seen in other connective tissue disorders29 such as the traumatized meniscus,31 Achilles tendinopathy,19,25 degenerating intervertebral discs,14 patella tendinosis,6 and in posterior cruciate ligaments with degenerative joint disease.1,17 It has been suggested that mucoid changes are more common in older patients.19,29
Can these degenerative changes and neovascularity be related? For disc degeneration in an experimental mouse model, Kato et al14 proposed that neovascularization (as observed in our specimens) followed disc herniation, and accompanying matrix degradation (mucoid degeneration in our specimens) was the result of macrophage-generated proinflammatory cytokines and matrix metalloproteinases. In chronic Achilles tendinopathy, the local release of cytokines without inflammation observed on biopsy specimens has been postulated.25
From a mechanical standpoint, electromyographic studies have shown the posterior tibialis to be the primary stabilizer of the medial longitudinal arch.2,30 During the stance phase, the posterior tibialis limits hindfoot eversion eccentrically during heelstrike, then contracts to invert the subtalar joint during midstance. This locks the hindfoot/midfoot joints to provide a rigid lever for forward propulsion. At toe-off it assists in heel-lift (subtalar supination). Dysfunction leads to greater hindfoot eversion with further tensioning and stretching of the tendon. Sutherland30 showed that a 1-cm elongation decreased the tendon's efficacy.
Our findings confirm angiogenesis as the predominant pathologic event. One possible scenario is an obscure event such as tension or stretching leading to alteration in the tendon (Fig. 6), leading to dysfunction. Attempts at adjustment would stimulate the tenosynovial lining cell layer, leading to a cycle of damage and repair marked by prominent neoangiogenesis. This is consistent with previous observations implicating neoangiogenesis in tendon healing,29 remodeling of autologous tendon grafts,27 and even as a vascular response in adjacent supporting ligaments.3 Our findings of mucoid change and chondroid metaplasia are well-documented markers of nonspecific aging and/or degenerative and/or traumatic damage in tendons and related structures.
At the time of operative treatment for Stage II or III posterior tibial tendon insufficiency, there is little histopathologic evidence to support an inflammatory etiology to the posterior tibial tendon in acquired flatfoot deformity. Inflammation was not present and was consistent with the lack of inflammation in another tendinopathy syndrome involving the Achilles tendon.19,25 An obscure ischemic event remains a possibility, and has been proposed as a mechanism for angiogenesis via upregulation of platelet-derived growth factor treatment.5 An inflammatory or ischemic event, now obscure, remains possible. An attractive hypothesis consistent with our histologic findings is that a damaging event such as overuse or stretching of the posterior tibial tendon activates the tenocytes of the tendon lining. This triggers an angiogenic response, a finding consistent with observations of tendinosis initiated by tenocyte cellular activation in asymptomatic athletes,4 spontaneous Achilles tendon rupture,26 expression of vascular endothelial growth factor in tendon fibroblasts subjected to cyclical strain,27 and production of autocrine mediators in repetitively stretched tendon fibroblast.32
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