Lymphocyte Subset Ratio Cannot Diagnose Immune Failure of a TKA.

BACKGROUND: Up to 20% of patients are dissatisfied following total knee arthroplasty (TKA), most often due to pain and/or stiffness. The differential diagnosis includes immune reaction to the prosthesis. However, there is no consensus on diagnostic criteria for immune failure, an allergic reaction, to a TKA. Histologic evaluation could provide evidence as to whether an allergic reaction caused TKA failure. A recent study showed an increase in CD4+ lymphocytes compared to CD8+ lymphocytes in patients lymphocyte transformation testing (LTT) + for Ni. This finding is consistent with Ni sensitization, but can lymphocyte subsets be used to diagnose immune failure on a case-by-case basis? METHODS: Periprosthetic tissues from 18 revision cases of well-fixed, aseptic, but painful and/or stiff primary TKAs were analyzed. Six patients LTT- for Ni were matched as a cohort for age, sex, and body mass index (BMI), to 12 patients LTT + for Ni. Periprosthetic tissue biopsies underwent immunohistochemical IHC staining for CD4+ and CD8+ lymphocyte subsets and were compared by LTT status. The immunohistochemicalIHC results were also compared with periprosthetic histology. RESULTS: There was no relationship between LTT status and mean CD4+ cells/hpf or CD4+:CD8+ lymphocyte ratio. No relationship was found between LTT stimulation index (continuous or categorical) and CD4+:CD8+ ratio or aseptic lymphocyte-dominant vasculitis-associated lesion ALVAL score. CONCLUSION: Lymphocytes in periprosthetic tissue are highly variable in number, subtype ratio, and location, and have no relationship to LTT result or ALVAL score on a case-by-case basis. Based on these results, lymphocyte subsets cannot diagnose immune failure. Further work is needed to determine criteria for the diagnosis of immune failure of a TKA.

Periprosthetic Tissue Reaction Independent of LTT Result and Implanted Materials in Total Knee Arthroplasty.

BACKGROUND: An allergic reaction may rarely cause a painful or stiff total knee arthroplasty (TKA). However, no consensus diagnostic criteria for TKA immune failure exist. Lymphocyte transformation testing (LTT) measures immune sensitivity to various materials, but its role in diagnosing an allergic reaction to a TKA has not been established. This study compares TKA periprosthetic tissues in a) LTT-positive versus -negative patients and b) patients with conventional CoCrNi versus hypoallergenic implants. METHODS: Periprosthetic tissues from 26 revision cases of well-fixed, aseptic, but painful or stiff TKAs were analyzed. Twelve patients LTT positive for nickel (Ni) were matched as a cohort to 6 LTT-negative patients. In 4 patients LTT positive for Ni, tissue from first revision of CoCrNi implants was compared with tissue from subsequent revision of hypoallergenic implants. Histology was evaluated using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) score. RESULTS: No correlation was found between LTT and any ALVAL score component. The mean total ALVAL score was 3.8 ± 1.5 for LTT-negative patients and 3.3 ± 1.2 for LTT-positive patients (P = .44). The mean total ALVAL score at revision of CoCrNi implants was 3.0 ± 1.8 compared with 5.8 ± 0.5 at rerevision of hypoallergenic implants (P = .053). CONCLUSION: Periprosthetic TKA tissue reactions were indistinguishable between LTT-positive and -negative patients. LTT does not predict the periprosthetic tissue response. ALVAL scores of hypoallergenic revision implant tissue trended higher than primary CoCrNi implant tissue. A positive LTT may not indicate that a periprosthetic immune reaction is the cause of pain and stiffness after TKA. LEVEL OF EVIDENCE: 3, retrospective cohort study.

Lymphocyte Transformation Testing (LTT) in Cases of Pain Following Total Knee Arthroplasty: Little Relationship to Histopathologic Findings and Revision Outcomes.

BACKGROUND: The utilization of lymphocyte transformation testing (LTT) has increased for diagnosing metal sensitivity associated with total knee arthroplasty (TKA), but its validity for the diagnosis of TKA failure due to an immune reaction has not been established. In this study, we sought to characterize the relationship of a positive LTT result to histopathologic findings and clinical and functional outcomes. METHODS: This was a retrospective study of 27 well-fixed, aseptic, primary TKA cases in which the patient had persistent pain and/or stiffness and underwent revision due to a suspected metal allergy to nickel, as determined on the basis of positive LTT. Revision procedures were performed by a single experienced arthroplasty surgeon. Periprosthetic tissue samples obtained at the time of revision surgery were scored using the aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) scoring system. RESULTS: Eight patients were categorized as mildly reactive; 8 patients, moderately reactive; and 11 patients, highly reactive to nickel by LTT. The predominant findings on routine histopathologic analysis were fibrosis and varying degrees of lymphocytic infiltration in 17 (63%) of the 27 cases. The average ALVAL score of the cohort was 3.1 ± 1.9, of a maximum score of 10. Average Knee Society Score (KSS) values improved post-revision, as did range of motion (all p < 0.01). Neither LTT stimulation index as a continuous variable nor as a categorical variable (mildly reactive, moderately reactive, highly reactive) was correlated with ALVAL score, pre-revision function (as assessed by KSS-clinical, KSS-functional, and range of motion), or change in function at the most recent follow-up (0.015 < r < 0.30, 0.13 < p < 0.95). In addition, the ALVAL score did not correlate significantly with either pre-revision or post-revision KSS or range of motion (0.061 < r < 0.365, 0.09 < p < 0.88). CONCLUSIONS: On the basis of this analysis, including histopathologic assessment, LTT results alone were insufficient for the diagnosis of TKA failure due to an immune reaction. A positive LTT may not indicate that an immune reaction is the cause of pain and stiffness post-TKA. The role of LTT in assessing TKA failure from an immune reaction needs further investigation. Diagnostic criteria for such TKA failure need to be established. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Myxopapillary ependymoma with anaplastic features: A case report with review of the literature.

BACKGROUND: Myxopapillary ependymoma (MPE) with anaplastic features is extremely rare, with only three case reports in the literature. CASE DESCRIPTION: We report the case of a MPE with anaplastic features in a 24-year-old female who presented with a dominant lumbar mass along with intracranial and sacral metastases. Upon gross total resection of the dominant tumor located at L2-L3, it appeared to arise from the filum terminale, and had a solid component in addition to soft or necrotic areas. Histologically, the tumor was composed of the two classic components of MPE: (1) low-grade ependymal cells surrounding blood vessels, producing the papillary appearance and (2) perivascular myxoid material between blood vessels and ependymal cells, creating the myxopapillary appearance. The high-grade anaplastic component showed hypercellularity, brisk mitotic rate, and vascular proliferation, with frequent pleomorphic cells and atypical mitotic figures. It was positive for vimentin and glial fibrillary acidic protein (GFAP); negative for epithelial membrane antigen (EMA), CAM5.2, creatine kinase 7 (CK7), CK20; and the MIB-1 index (Ki-67) was 8-38%. Ten months after initial resection, follow-up magnetic resonance imaging revealed new lesions in (1) the hypothalamus, (2) the left pons, and (3) the left medial temporal lobe, which were treated with radiosurgery. Eight months later (18 months from initial surgery), the patient underwent thoracic laminectomy for a large leptomeningeal metastasis at T6 and T8. CONCLUSION: The present case of MPE with anaplastic features is the fourth case on record in the medical literature.