- Email: [email protected]
Pseudotumor With Dominant B-Lymphocyte Infiltration After Metal-On-Metal Total Hip Arthroplasty With a Modular Cup
The Journal of Arthroplasty Vol. 27 No. 3 2012
Case Report
Pseudotumor With Dominant B-Lymphocyte Infiltration After Metal-On-Metal Total Hip Arthroplasty With a Modular Cup Masahiro Hasegawa, MD, PhD, Kakunoshin Yoshida, MD, Hiroki Wakabayashi, MD, PhD, and Akihiro Sudo, MD, PhD
Abstract: We report a case of a patient who underwent metal-on-metal total hip arthroplasty with a modular cup and developed a pseudotumor 5 years postoperatively. Immunohistochemistry showed dominant B-lymphocyte infiltration in the periprosthetic tissue. Keywords: pseudotumor, metal on metal, total hip arthroplasty, B lymphocyte, immunohistochemistry. © 2012 Elsevier Inc. All rights reserved.
Second-generation metal-on-metal (MoM) hip resurfacing is a recent development in hip arthroplasty. Although early clinical results were encouraging, several complications have been reported, including femoral neck fracture, avascular necrosis of the femoral head, implant loosening, metal ion release, metal hypersensitivity, and the formation of pseudotumor [1-3]. Pseudotumor also occurs after MoM total hip arthroplasty (THA) [3]. We report a case of a patient who underwent MoM THA with a modular cup and developed a pseudotumor 5 years postoperatively. The patient was informed that data concerning her case would be submitted for publication, and she consented.
Case Report A 66-year-old woman without major medical comorbidities was referred to our institution in July 2005 for evaluation and treatment of right hip pain. Her body mass index was 21.8 kg/m2. She had undergone an uncomplicated primary MoM THA for end-stage osteoarthritis in September 2005. The arthroplasty was done
From the Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan. Submitted December 31, 2010; accepted May 5, 2011. The Conflict of Interest statement associated with this article can be found at doi:10.1016/j.arth.2011.05.005. Reprint requests: Masahiro Hasegawa, MD, PhD, Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan. © 2012 Elsevier Inc. All rights reserved. 0883-5403/2703-0027$36.00/0 doi:10.1016/j.arth.2011.05.005
with a 54-mm M2a-Taper acetabular cup, a 32-mm metal head, and a proximally coated Bimetric stem (Biomet, Warsaw, Ind). The postoperative recovery was uneventful, and the patient was without symptoms until 2 years postoperatively. The patient then began to develop pain in her right groin, buttock, and thigh. Radiograph and computed tomographic (CT) scan revealed well-seated cementless prostheses without evidence of loosening, osteolysis, implant failure, or pseudotumor. The abduction angle of the acetabular cup was 48°; and the anteversion of the cup, which was measured via CT, was 10°. The patient underwent conservative treatment including physiotherapy and administration of nonsteroidal anti-inflammatory drugs. The pain continued for 3 more years (total, 5 years after THA). At that point, the patient developed worsening groin and buttock pain with inability to bear weight. The patient had no history of allergy to metal jewelry. Radiograph revealed no evidence of loosening. Magnetic resonance image (Fig. 1) as well as CT scan revealed pseudotumor. Blood tests revealed a white blood cell count of 5600 cells/mm3, and a C-reactive protein was 1.35 mg/dL (normal, b0.3 mg/dL). Serum Co and Cr levels were elevated to 2.0 and 3.2 μg/L, respectively (normal, b1.0 μg/L). A diagnosis of pseudotumor was considered, and the patient underwent revision surgery during which a lot of “milk-stained” fluid was obtained from the capsule. There was a large thick-walled cyst, consistent with pseudotumor, which communicated with the joint. Cultures of fluid and cyst wall failed to grow bacteria. Although both the acetabular shell and femoral stem were well fixed, the acetabular shell was removed; and the new Trilogy acetabular shell with a highly cross-
493.e5
493.e6 The Journal of Arthroplasty Vol. 27 No. 3 March 2012
Fig. 1. Magnetic resonance image showing a large cystic mass extending from the posterosuperior aspect of the joint. Coronal T2-weighted image showing a high intensity mass.
linked polyethylene liner (Zimmer, Warsaw, Ind) was implanted. The femoral stem was retained, and the head was exchanged for a new metal head. Macroscopic appearance failed to detect any surface damage on the retrieved metal liner and head. The modular head-neck junction showed no metal debris. All samples of pseudotumor were fixed in 10% neutralbuffered formalin before processing and embedding in paraffin wax. Five-micrometer-thick sample sections were stained with hematoxylin and eosin and examined by light microscopy. Sections of the pseudotumor were also analyzed by immunohistochemistry using antibodies to T lymphocytes (CD3; DAKO, Glostrup, Denmark), B lymphocytes (CD20; DAKO), and macrophages (CD68; DAKO) to characterize the immunophenotype. Histology showed extensive necrosis and lymphocytic infiltration in periprosthetic tissues of the hip. We identified perivascular lymphocytes and diffusely distributed lymphocytes. The immunohistochemical methods suggested more CD20positive B lymphocytes (Fig. 2) than CD3-positive T lymphocytes. CD68-positive macrophage infiltration was also found. Scattered tiny black particles, presumed aggregates of metallic wear particles, were seen. Postrevision serum Co and Cr levels dropped to 0.7 and 0.9 μg/L, respectively. C-reactive protein dropped to 0.03 mg/dL. One month postoperatively, lymphocyte transformation test showed no reactivity to Ni, Co, or Cr. Six months postoperatively, the patient reported substantial resolution of pain, and she walks without a limp. Radiographs reveal no evidence of loosening or osteolysis.
Discussion The etiology of pseudotumor has not been established. Pandit et al [1] reported 17 patients (20 hips) with a soft tissue mass that they termed a pseudotumor. The pre-
Fig. 2. Immunohistochemical staining showing numerous CD20-positive B-lymphocyte infiltration in periprosthetic tissue (original magnification ×200).
valence of pseudotumor was reported to be 1.8% based on the number of revised cases within 8 years [2]. The prevalence was reported to be 4% including asymptomatic patients [4]. Risk factors for pseudotumor include female sex, hip dysplasia, age younger than 40 years, and small acetabular components [2,5]. Lymphocyte infiltration and extensive necrosis seen in pseudotumors are similar to a characteristic histologic pattern of tissue reactions to MoM bearings, previously described as aseptic lymphocyte-dominated vasculitisassociated lesion [6]. Aseptic lymphocyte-dominated vasculitis-associated lesion is also known as adverse reactions to metal debris [7]. This histologic feature is thought to represent a metal-induced systemic T lymphocyte–mediated hypersensitivity reaction of type IV (delayed-type hypersensitivity). Systemic hypersensitivity reactions would, in part, explain the high prevalence in women, which could possibly be related to previous exposure to jewelry, which is more likely to be worn by women. Therefore, a delayed hypersensitivity reaction to Co and Cr or Ni has been suggested to play a role in the etiology of pseudotumor [8]. In immunohistochemical study of the periprosthetic retrievals in THA with MoM bearings, Aroukatos et al [9] reported that there was an excess of T cells over B cells in 65% of the revised hips, whereas 35% of the hips showed dominant B cells, as in the present case. The increased incidence of T cells over B cells in the periprosthetic retrievals in THA with MoM bearings could be considered consistent with a delayed-type hypersensitivity. Kwon et al [10] investigated metal sensitivity in patients with MoM hip resurfacing arthroplasty both with and without pseudotumor, by lymphocyte transformation test instead of skin patch testing. In type IV delayed hypersensitivity reaction, activated T lymphocytes are responsible for sustaining the chronic inflammatory response and providing a mechanism for memory of the specific antigen.
Pseudotumor following Metal-On-Metal Total Hip Arthroplasty Hasegawa et al
The lymphocyte transformation test measures the proliferative response of lymphocytes after activation. Lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumor compared with patients without pseudotumor. This finding suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biologic reaction involved in the occurrence of the soft tissue pseudotumor. Patients with pseudotumor were shown to have significantly higher serum Co and Cr concentrations compared with patients without pseudotumor [11]. Langton et al [7] performed metal allergy testing and found that none of the adverse reactions to metal debris samples showed increased lymphocyte reactivity to Co or Cr. A recent study quantified the wear of in vivo of implants revised because of pseudotumor after MoM hip resurfacing, and greater linear wear of both the femoral and acetabular components was observed. Wear of the acetabular component in the hips with pseudotumor always involves the edge of the implant, indicating that edge loading had occurred [11]. This supports the in vivo findings of elevated concentrations of metal ions in patients with pseudotumor. The presence of extensive necrosis and macrophage infiltrate seen histologically would be in keeping with a metalinduced cytotoxic effect. An in vitro study showed a dose-dependent cytotoxicity of clinically relevant Co nanoparticles on macrophages. Thus, metal debris cytotoxicity may be an important biologic reaction involved in pseudotumor [4]. The necrotic and inflammatory changes seen in periimplant tissues in response to Co-Cr metal wear debris are thought to be due to either cytotoxicity or to a delayed hypersensitivity reaction [6]. In conclusions, B cells predominate in the histology of the pseudotumor in this report; and this response is not a hypersensitivity (as indicated by the prevalence of B cells), but rather, a cytotoxicity response to metal wear debris.
493.e7
References 1. Pandit H, Glyn-Jones S, McLardy-Smith P, et al. Pseudotumours associated with metal-on-metal hip resurfacings. J Bone Joint Surg [Br] 2008;90:847. 2. Glyn-Jones S, Pandit H, Kwon YM, et al. Risk factors for inflammatory pseudotumour formation following hip resurfacing. J Bone Joint Surg [Br] 2009;91:1566. 3. Shahrdar C. Pseudotumor in large-diameter metal-onmetal total hip articulation. J Arthroplasty 2010 [Epub ahead of print]. 4. Kwon YM, Ostlere SJ, McLardy-Smith P, et al. “Asymptomatic” pseudotumors after metal-on-metal hip resurfacing arthroplasty prevalence and metal ion study. J Arthroplasty 2010 [Epub ahead of print]. 5. Grammatopoulos G, Pandit H, Oxford Hip and Knee Group, et al. The relationship between head-neck ratio and pseudotumour formation in metal-on-metal resurfacing arthroplasty of the hip. J Bone Joint Surg [Br] 2010; 92:1527. 6. Willert HG, Buchhorn GH, Fayyazi A, et al. Metal-onmetal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study. J Bone Joint Surg [Am] 2005;87:28. 7. Langton DJ, Jameson SS, Joyce TJ, et al. Early failure of metal-on-metal bearings in hip resurfacing and largediameter total hip replacement: a consequence of excess wear. J Bone Joint Surg [Br] 2010;92:38. 8. Mahendra G, Pandit H, Kliskey K, et al. Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties. Acta Orthop 2009;80:653. 9. Aroukatos P, Repanti M, Repantis T, et al. Immunologic adverse reaction associated with low-carbide metal-onmetal bearings in total hip arthroplasty. Clin Orthop Relat Res 2010;2135:468. 10. Kwon YM, Thomas P, Summer B, et al. Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010;28:444. 11. Kwon YM, Glyn-Jones S, Simpson DJ, et al. Analysis of wear of retrieved metal-on-metal hip resurfacing implants revised due to pseudotumours. J Bone Joint Surg [Br] 2010;92:356.
Case Report
Pseudotumor With Dominant B-Lymphocyte Infiltration After Metal-On-Metal Total Hip Arthroplasty With a Modular Cup Masahiro Hasegawa, MD, PhD, Kakunoshin Yoshida, MD, Hiroki Wakabayashi, MD, PhD, and Akihiro Sudo, MD, PhD
Abstract: We report a case of a patient who underwent metal-on-metal total hip arthroplasty with a modular cup and developed a pseudotumor 5 years postoperatively. Immunohistochemistry showed dominant B-lymphocyte infiltration in the periprosthetic tissue. Keywords: pseudotumor, metal on metal, total hip arthroplasty, B lymphocyte, immunohistochemistry. © 2012 Elsevier Inc. All rights reserved.
Second-generation metal-on-metal (MoM) hip resurfacing is a recent development in hip arthroplasty. Although early clinical results were encouraging, several complications have been reported, including femoral neck fracture, avascular necrosis of the femoral head, implant loosening, metal ion release, metal hypersensitivity, and the formation of pseudotumor [1-3]. Pseudotumor also occurs after MoM total hip arthroplasty (THA) [3]. We report a case of a patient who underwent MoM THA with a modular cup and developed a pseudotumor 5 years postoperatively. The patient was informed that data concerning her case would be submitted for publication, and she consented.
Case Report A 66-year-old woman without major medical comorbidities was referred to our institution in July 2005 for evaluation and treatment of right hip pain. Her body mass index was 21.8 kg/m2. She had undergone an uncomplicated primary MoM THA for end-stage osteoarthritis in September 2005. The arthroplasty was done
From the Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Mie, Japan. Submitted December 31, 2010; accepted May 5, 2011. The Conflict of Interest statement associated with this article can be found at doi:10.1016/j.arth.2011.05.005. Reprint requests: Masahiro Hasegawa, MD, PhD, Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan. © 2012 Elsevier Inc. All rights reserved. 0883-5403/2703-0027$36.00/0 doi:10.1016/j.arth.2011.05.005
with a 54-mm M2a-Taper acetabular cup, a 32-mm metal head, and a proximally coated Bimetric stem (Biomet, Warsaw, Ind). The postoperative recovery was uneventful, and the patient was without symptoms until 2 years postoperatively. The patient then began to develop pain in her right groin, buttock, and thigh. Radiograph and computed tomographic (CT) scan revealed well-seated cementless prostheses without evidence of loosening, osteolysis, implant failure, or pseudotumor. The abduction angle of the acetabular cup was 48°; and the anteversion of the cup, which was measured via CT, was 10°. The patient underwent conservative treatment including physiotherapy and administration of nonsteroidal anti-inflammatory drugs. The pain continued for 3 more years (total, 5 years after THA). At that point, the patient developed worsening groin and buttock pain with inability to bear weight. The patient had no history of allergy to metal jewelry. Radiograph revealed no evidence of loosening. Magnetic resonance image (Fig. 1) as well as CT scan revealed pseudotumor. Blood tests revealed a white blood cell count of 5600 cells/mm3, and a C-reactive protein was 1.35 mg/dL (normal, b0.3 mg/dL). Serum Co and Cr levels were elevated to 2.0 and 3.2 μg/L, respectively (normal, b1.0 μg/L). A diagnosis of pseudotumor was considered, and the patient underwent revision surgery during which a lot of “milk-stained” fluid was obtained from the capsule. There was a large thick-walled cyst, consistent with pseudotumor, which communicated with the joint. Cultures of fluid and cyst wall failed to grow bacteria. Although both the acetabular shell and femoral stem were well fixed, the acetabular shell was removed; and the new Trilogy acetabular shell with a highly cross-
493.e5
493.e6 The Journal of Arthroplasty Vol. 27 No. 3 March 2012
Fig. 1. Magnetic resonance image showing a large cystic mass extending from the posterosuperior aspect of the joint. Coronal T2-weighted image showing a high intensity mass.
linked polyethylene liner (Zimmer, Warsaw, Ind) was implanted. The femoral stem was retained, and the head was exchanged for a new metal head. Macroscopic appearance failed to detect any surface damage on the retrieved metal liner and head. The modular head-neck junction showed no metal debris. All samples of pseudotumor were fixed in 10% neutralbuffered formalin before processing and embedding in paraffin wax. Five-micrometer-thick sample sections were stained with hematoxylin and eosin and examined by light microscopy. Sections of the pseudotumor were also analyzed by immunohistochemistry using antibodies to T lymphocytes (CD3; DAKO, Glostrup, Denmark), B lymphocytes (CD20; DAKO), and macrophages (CD68; DAKO) to characterize the immunophenotype. Histology showed extensive necrosis and lymphocytic infiltration in periprosthetic tissues of the hip. We identified perivascular lymphocytes and diffusely distributed lymphocytes. The immunohistochemical methods suggested more CD20positive B lymphocytes (Fig. 2) than CD3-positive T lymphocytes. CD68-positive macrophage infiltration was also found. Scattered tiny black particles, presumed aggregates of metallic wear particles, were seen. Postrevision serum Co and Cr levels dropped to 0.7 and 0.9 μg/L, respectively. C-reactive protein dropped to 0.03 mg/dL. One month postoperatively, lymphocyte transformation test showed no reactivity to Ni, Co, or Cr. Six months postoperatively, the patient reported substantial resolution of pain, and she walks without a limp. Radiographs reveal no evidence of loosening or osteolysis.
Discussion The etiology of pseudotumor has not been established. Pandit et al [1] reported 17 patients (20 hips) with a soft tissue mass that they termed a pseudotumor. The pre-
Fig. 2. Immunohistochemical staining showing numerous CD20-positive B-lymphocyte infiltration in periprosthetic tissue (original magnification ×200).
valence of pseudotumor was reported to be 1.8% based on the number of revised cases within 8 years [2]. The prevalence was reported to be 4% including asymptomatic patients [4]. Risk factors for pseudotumor include female sex, hip dysplasia, age younger than 40 years, and small acetabular components [2,5]. Lymphocyte infiltration and extensive necrosis seen in pseudotumors are similar to a characteristic histologic pattern of tissue reactions to MoM bearings, previously described as aseptic lymphocyte-dominated vasculitisassociated lesion [6]. Aseptic lymphocyte-dominated vasculitis-associated lesion is also known as adverse reactions to metal debris [7]. This histologic feature is thought to represent a metal-induced systemic T lymphocyte–mediated hypersensitivity reaction of type IV (delayed-type hypersensitivity). Systemic hypersensitivity reactions would, in part, explain the high prevalence in women, which could possibly be related to previous exposure to jewelry, which is more likely to be worn by women. Therefore, a delayed hypersensitivity reaction to Co and Cr or Ni has been suggested to play a role in the etiology of pseudotumor [8]. In immunohistochemical study of the periprosthetic retrievals in THA with MoM bearings, Aroukatos et al [9] reported that there was an excess of T cells over B cells in 65% of the revised hips, whereas 35% of the hips showed dominant B cells, as in the present case. The increased incidence of T cells over B cells in the periprosthetic retrievals in THA with MoM bearings could be considered consistent with a delayed-type hypersensitivity. Kwon et al [10] investigated metal sensitivity in patients with MoM hip resurfacing arthroplasty both with and without pseudotumor, by lymphocyte transformation test instead of skin patch testing. In type IV delayed hypersensitivity reaction, activated T lymphocytes are responsible for sustaining the chronic inflammatory response and providing a mechanism for memory of the specific antigen.
Pseudotumor following Metal-On-Metal Total Hip Arthroplasty Hasegawa et al
The lymphocyte transformation test measures the proliferative response of lymphocytes after activation. Lymphocyte reactivity to Co, Cr, and Ni did not significantly differ in patients with pseudotumor compared with patients without pseudotumor. This finding suggests that systemic hypersensitivity type IV reactions, as measured by lymphocyte proliferation response to these metals, may not be the dominant biologic reaction involved in the occurrence of the soft tissue pseudotumor. Patients with pseudotumor were shown to have significantly higher serum Co and Cr concentrations compared with patients without pseudotumor [11]. Langton et al [7] performed metal allergy testing and found that none of the adverse reactions to metal debris samples showed increased lymphocyte reactivity to Co or Cr. A recent study quantified the wear of in vivo of implants revised because of pseudotumor after MoM hip resurfacing, and greater linear wear of both the femoral and acetabular components was observed. Wear of the acetabular component in the hips with pseudotumor always involves the edge of the implant, indicating that edge loading had occurred [11]. This supports the in vivo findings of elevated concentrations of metal ions in patients with pseudotumor. The presence of extensive necrosis and macrophage infiltrate seen histologically would be in keeping with a metalinduced cytotoxic effect. An in vitro study showed a dose-dependent cytotoxicity of clinically relevant Co nanoparticles on macrophages. Thus, metal debris cytotoxicity may be an important biologic reaction involved in pseudotumor [4]. The necrotic and inflammatory changes seen in periimplant tissues in response to Co-Cr metal wear debris are thought to be due to either cytotoxicity or to a delayed hypersensitivity reaction [6]. In conclusions, B cells predominate in the histology of the pseudotumor in this report; and this response is not a hypersensitivity (as indicated by the prevalence of B cells), but rather, a cytotoxicity response to metal wear debris.
493.e7
References 1. Pandit H, Glyn-Jones S, McLardy-Smith P, et al. Pseudotumours associated with metal-on-metal hip resurfacings. J Bone Joint Surg [Br] 2008;90:847. 2. Glyn-Jones S, Pandit H, Kwon YM, et al. Risk factors for inflammatory pseudotumour formation following hip resurfacing. J Bone Joint Surg [Br] 2009;91:1566. 3. Shahrdar C. Pseudotumor in large-diameter metal-onmetal total hip articulation. J Arthroplasty 2010 [Epub ahead of print]. 4. Kwon YM, Ostlere SJ, McLardy-Smith P, et al. “Asymptomatic” pseudotumors after metal-on-metal hip resurfacing arthroplasty prevalence and metal ion study. J Arthroplasty 2010 [Epub ahead of print]. 5. Grammatopoulos G, Pandit H, Oxford Hip and Knee Group, et al. The relationship between head-neck ratio and pseudotumour formation in metal-on-metal resurfacing arthroplasty of the hip. J Bone Joint Surg [Br] 2010; 92:1527. 6. Willert HG, Buchhorn GH, Fayyazi A, et al. Metal-onmetal bearings and hypersensitivity in patients with artificial hip joints. A clinical and histomorphological study. J Bone Joint Surg [Am] 2005;87:28. 7. Langton DJ, Jameson SS, Joyce TJ, et al. Early failure of metal-on-metal bearings in hip resurfacing and largediameter total hip replacement: a consequence of excess wear. J Bone Joint Surg [Br] 2010;92:38. 8. Mahendra G, Pandit H, Kliskey K, et al. Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties. Acta Orthop 2009;80:653. 9. Aroukatos P, Repanti M, Repantis T, et al. Immunologic adverse reaction associated with low-carbide metal-onmetal bearings in total hip arthroplasty. Clin Orthop Relat Res 2010;2135:468. 10. Kwon YM, Thomas P, Summer B, et al. Lymphocyte proliferation responses in patients with pseudotumors following metal-on-metal hip resurfacing arthroplasty. J Orthop Res 2010;28:444. 11. Kwon YM, Glyn-Jones S, Simpson DJ, et al. Analysis of wear of retrieved metal-on-metal hip resurfacing implants revised due to pseudotumours. J Bone Joint Surg [Br] 2010;92:356.