Introduction: Pseudotumors (PT) are aseptic lesions in the periprosthetic tissues that destroy soft tissues generating pain and discomfort[1]. They are histologically characterized by the disappearance of the synovial epithelium, variable degree of necrosis in the underlying connective tissue and lymphocyte infiltration, within a thickened synovial membrane[2]. They were firstly described in patients with Metal on Metal (MoM) systems[3], but recently they have been observed in Metal on Polyethylene (MoP) implants, which are the most used prosthesis now days[4]. This work aimed to describe the pseudotumors in MoP implants and compare them with those in MoM to determine their etiological similarities. For this reason a histological study and cytokine analysis was performed.
Methods: Patients with PT related to MoM (n=20), MoP (n=17) and control patients (n=10) with no PT were included. Histological sections from biopsies were assessed for necrosis and the ALVAL score was assigned by an experienced pathologist.
Tissue slides were incubated in specific antibodies against CD20, CD3, Pro-Collagen I, aSMA and Ky 67. The peroxidase reaction or the incubation of fluorescent antibodies was performed in the samples to observe the immunoreaction under light or fluorescence microscopy.
Tissue sections were mechanically pulverized under liquid nitrogen, resuspended in buffer and clarified by centrifugation. Aliquots of 100 µg of total protein were used to assess the presence of 120 human cytokines using a sandwich-ELISA antibody array. The arrays were read in a laser scanner with a wavelength of 532 nm. T-test for independent samples was applied to determine statistical differences between the groups.
Results: The pseudotumors in MoM showed to be a cystic cavity surrounded by a thin wall, composed by inflammatory connective tissue with different degrees of necrosis in the synovial surface. However MoP pseudotumors are thick solid structures composed by extensive areas of necrotic dense connective tissue up to 8 cm thick, in which scare viable cells can be observed in the most external part of the tissue. The ALVAL score and necrosis measurement were significantly higher in MoP than in MoM.
The immunohistochemistry revealed that the cells in the viable connective tissue in MoP are mostly myofibroblasts (a-SMA+).
The cytokine analysis, showed elevated levels of pro-inflammatory cytokines in MoMs, however MoPs didn’t show any significant increase in cytokine secretion compared to controls.
Discussion: Our observations showed that MoM PTs are mostly inflammatory, while MoPs are fibro-necrotic lesions. The presence of myofibroblsats could reveal an unresolved reparation process in the tissues, which can explain the significant increase in thickness of the connective tissue in the joint capsule. The mechanisms of this proliferation of fibroblasts and the subsequent cell death are not clear. The used methodology didn’t show any difference in cytokine secretion that could explain that process, but some of them can be responsble of macrophage recruitment and differentiation in MoM pseudotumors.
Manju Sharma; Robert Bell
References:
[1] Matthies A, et al. Clin Orthop Relat Res. 2012;470(7):1895-906.
[2] Natu S, et al. J Clin Pathol. 2012; 65(5):409-418.
[3] Pandit H, et al. J Bone Joint Surg Br. 2008;90(7):847-51.
[4] Cooper, J, et al. Bone Joint Surg Am, 2012; 94:1655-61.
[5] Perino G, et al. BMC Clin Pathol. 2014; 14: 39.