Myofibroblast distribution in Dupuytren's cords: correlation with digital contracture.
Verjee LS., Midwood K., Davidson D., Essex D., Sandison A., Nanchahal J.
PURPOSE: Dupuytren's tissue has typically been described as being composed of myofibroblast-rich palmar nodules and relatively acellular tendon-like cords. We aimed to determine myofibroblast distribution (alpha-smooth muscle actin [alpha-SMA] positive cells) within Dupuytren's tissue and to correlate histologically defined alpha-SMA-positive nodules with digital contracture and recurrent disease. METHODS: One hundred and three digital Dupuytren's cords (72 fasciectomy, 31 dermofasciectomy) were stained with anti-alpha-SMA antibody. The presence of alpha-SMA-positive nodules, their surface area, and alpha-SMA-positive cells were quantified throughout excised Dupuytren's tissue. Clinical data on diathesis, flexion deformity, and previous surgeries were collected. RESULTS: Cords were nodular (66%) or non-nodular (34%). Nodular cords contained 1 (55%), 2 (33%), or 3 or more nodules (12%) composed of localized collections of cells. The mean total nodule surface area was 23 mm(2) (range, 1.3-105 mm(2)). Nodules contained the highest number of alpha-SMA-positive cells (mean 97%, 2374 cells/mm(2)) compared to peri-nodular areas (mean 32%, 763 cells/mm(2)), and more distant cord (mean 8%, 495 cells/mm(2)). Non-nodular cords contained 9% to 17% alpha-SMA-positive cells (mean 475-663 cells/mm(2)), with higher numbers distally. There was greater digital contracture in patients with non-nodular cords. Thirty-six of 38 proximal interphalangeal (PIP) joint-marked samples had a nodule that co-localized with the PIP joint. Nodule size did not correlate with flexion deformity or with primary or recurrent disease. CONCLUSIONS: We found that two thirds of digital cords were nodular. Nodules were hypercellular, the majority being alpha-SMA-positive cells. Nodules varied in size and co-localized with the PIP joint. Cord was relatively cellular throughout; a proportion of these cells were alpha-SMA-positive and cells aligned with collagen fibers. Non-nodular cords correlated with significantly greater digital flexion contracture. We propose that cells in nodular cords contract and deposit extracellular matrix components. The matrix is then remodeled in shortened configuration, and as fixed flexion deformity develops, stress shielding eventually leads to myofibroblast apoptosis, and cord becomes less cellular.