Histology of Joint Implant Failures and Bone Graft Materials
Histology of Joint Implant Failures and Bone Graft Materials
By Thomas W. Bauer, MD, PhD
Featured in Pathology Today: Winter/Spring 2017 Edition
Total joint replacement surgery is a common and generally successful procedure, with nearly 7 million people in the United States living with a hip or knee replacement.1 However, prosthetic failures occur in approximately 1-2% of arthroplasty cases, and can be associated with damage to periprosthetic tissues and inflammation.2 Similarly, material from bone grafts and synthetic bone graft substitutes can result in histological abnormalities that pathologists either may not recognize or may misinterpret as necrotic lesion tissue. In both cases, recognition of characteristic histological reactions caused by implant failures can help guide clinical diagnosis and treatment, provide information for improved device manufacture, and maintain compliance with federal reporting policies.
There are many potential mechanisms of arthroplasty failure, but those of most interest to pathologists include: insufficient osseointegration, osteolysis, periprosthetic joint infection (PJI), aseptic lymphocyte dominant vasculitis-associated lesion (ALVAL), and pseudotumors.
If an implanted device does not adequately bond with the bone, then micromotion may induce a fibrous membrane or granulation tissue. Imaging reveals a linear radiolucency around the implant, and histology of the peri-implant tissue shows a fibrous membrane with no neutrophils and relatively few macrophages. Particles of wear debris, giant cells, lymphocytes, and plasma cells are also rare.
A macrophage and giant cell reaction to implant wear debris particles can induce osteoclasts to resorb bone (“osteolysis”), contributing to implant loosening and pain. Biopsies show sheets of macrophages with a foamy or granular-appearing cytoplasm created by debris particles (Figure 1). Necrosis can be prominent but with relatively few lymphocytes.3,4 Debris particles from arthroplasty wear or failure may also be observed in regional or distant lymph nodes due to migration of the particles via the lymphatic system.5,6
Periprosthetic joint infection (PJI)
Infection around the joint implant, or periprosthetic joint infection (PJI), is one of the most common and serious complications of total joint replacement, and it can result in considerable healthcare costs and patient distress. Diagnostic guidelines from the American Academy of Orthopedic Surgeons (AAOS) recommend intraoperative consultations (frozen sections) in cases where periprosthetic infection has been neither diagnosed nor excluded. The AAOS found adequate literature to support two different thresholds for diagnosing infection: (1) a maximum tissue concentration of 5 neutrophils in each of five, ×400 high power fields (hpf), or (2) 10 neutrophils in each of 5 hpf.7 Cleveland Clinic looks for a more sensitive reading of at least 5 neutrophils in each of 3 hpf.
Neutrophils beneath the surface of the membrane are suggestive of infection (Figure 2), but neutrophils entrapped in superficial fibrin, blood clot, bone marrow, or within vessels are not considered to be diagnostic. Additionally, lymphocytes and plasma cells are not considered indicative of PJI. Frozen sections can be more difficult to interpret and diagnose due to cauterization from surgery, or inflammation from other conditions such as rheumatoid arthritis.8-10
Figure 3: This tissue was adjacent to a failed metal-on-metal hip arthroplasty and shows features typical of aseptic lymphocyte-dominant vasculitis associated lesion (ALVAL). Although not a true vasculitis, it has a laminated appearance with a hyalinized surface and deeper diffuse and perivascular chronic inflammation.
Aseptic lymphocyte dominant vasculitis-associated lesion (ALVAL)
An unusual pattern of inflammation associated with failures of metal-on-metal implants and devices with corrosion at modular interfaces has been termed “aseptic lymphocyte dominant vasculitis-associated lesion” (ALVAL), and consists of a laminated fibrous membrane with superficial necrosis, a hyalinized layer of collagen just beneath the surface, and deeper perivascular and diffusely distributed chronic inflammation (Figure 3).11,12 Particles in macrophages may have a green, grey-green, or brown appearance. Despite its name, ALVAL is not a true vasculitis; the inflammation is thought by many investigators to reflect an immune reaction to metal particles or ions.
Solid or cystic mass lesions around the hip may be observed with failed metal-on-metal implants or devices with corrosion at modular junctions.13-17 Sometimes referred to as “pseudotumors,” such lesions may be associated with inflammation similar to ALVAL. Additional studies are needed to establish more rigorous criteria for this designation as well as the mechanism causing the lesions.
Bone Graft Materials
Bone grafts used to replace bone tissue around sites of previously failed implants, fracture repair, or other orthopedic procedures employ a variety of materials that may not be recognized if observed in tissue sampled during subsequent operations.
Bone graft preparations
Autograft and allograft preparations can consist of bone fragments, bone marrow, stem cells, or connective tissue precursors, all of which can be misinterpreted as necrotic host tissue. Tissue that appears necrotic at the site of a previous orthopedic operation may in fact be bone fragments from bone graft used in the previous operation.
Demineralized bone matrix (DBM)
Commercially produced demineralized bone matrix (DBM) is used to induce bone formation, and in histology sections it can be recognized as shavings of cortical bone with empty osteocyte lacunae (Figure 4), sometimes associated with endochondral or intramembranous bone formation.
Figure 4: This biopsy is from the site of a previously treated non-union contains shavings of necrotic bone surrounded by fibrous tissue. This is not necrotic host bone, but instead represents a commercially processed, demineralized allograft bone product. It is sometimes associated with endochondral or intramembranous new bone.
Synthetic calcium compounds
Compounds containing calcium and phosphate or sulphate used in bone graft substitutes may dissolve in specimen processing if subjected to decalcification, leaving observable voids in the section (Figure 5).18 The rate at which the compounds dissolve depends on their composition, with calcium sulphates generally dissolving faster than calcium phosphates.
Bone graft materials should not induce acute inflammation, so a high concentration of neutrophils associated with a bone graft material suggests the possibility of infection.
Figure 5: This is a biopsy from a mandibular bone defect that had previously been treated with a synthetic bone graft substitute composed of hydroxyapatite (HA). The HA dissolved during tissue processing, leaving spaces occupied by acellular protein. Small foci of bone formation can be seen around the periphery of some of the HA granules.
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About the Author
Dr. Bauer specializes in orthopaedic pathology, especially biomaterials, and in that context has published more than 245 peer-reviewed publications and 32 book chapters. He is the deputy editor for research for the Journal of Bone and Joint Surgery, is the co-editor-in-chief of JBJS Case Connector, has been a consultant to orthopaedic device manufacturers, and is a frequent speaker at orthopaedic and biomedical engineering meetings.
In his spare time during the last 10 years, he has completed more than 40 marathon races, five 50K races, six 50-mile and nine 100-mile ultramarathons.
Thomas W. Bauer, MD, PhD
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