Non-neoplastic Orthopedic Pathology Updates: Common Problems and Pitfalls and How to Avoid Them

Despite representing <1% of all musculoskeletal surgical pathology cases, primary musculoskeletal neoplasms are disproportionately emphasized in the surgical pathology literature, compared with non-neoplastic orthopedic pathology. Yet, there remains significant interest among practicing pathologists and their clinical colleagues to maintain expertise in the non-neoplastic arena, as evidenced by increasing volumes of non-neoplastic orthopedic diseases, often reflected in consult cases. Recent literature has renewed the discussion of arthroplasty, emphasized the clinical importance of pathologic examination, and provided updated diagnostic clarification for separating avascular necrosis from degenerative joint disease (DJD)/osteoarthritis (OA) with secondary osteonecrosis, acute infectious osteomyelitis from pseudoabscesses of DJD/OA, and revisited the diagnoses of subchondral insufficiency fracture and rapidly destructive arthropathy. Providing accurate neutrophil counts to help determine periprosthetic joint infection has rapidly become one of the most common sources of frozen section evaluation in the United States. Distinguishing periprosthetic joint infection from aseptic loosening has significant intraoperative implications. In addition to acute arthritis and mass effect, calcium pyrophosphate dihydrate (CPPD) deposition disease may lead to DJD/OA. However, most histologically confirmed examples of CPPD, involving the large extremity joints, are not identified preoperatively or radiologically, requiring pathologic evaluation to reliably establish the diagnosis. The incidence of CPPD deposits appears highest in the humeral head/shoulder, followed by the knees and hips/femoral head. Recent evidence has documented infrequent examples of combined gout and CPPD/pseudogout within the same tophi, associated with unique clinicopathologic features compared with those with gout alone. Carpal tunnel syndrome, trigger finger, and lumbar stenosis represent potential early red flags for the development of transthyretin (TR) cardiac amyloidosis. Although previously discarded at many institutions, excised tissue removed from such specimens, particularly tenosynovium from the carpal tunnel flexor retinaculum, are now routinely evaluated histologically with Congo red staining and, when positive, followed by mass spectrometry for confirmatory amyloid subtyping. With the use of a recently developed TR stabilizer, such as tafamidis, early histologic detection and treatment of TR cardiac amyloidosis has improved clinical outcomes. Herein is a summary of recent relevant developments in non-neoplastic orthopedic surgical pathology, updated diagnostic criteria and pitfalls, and the resulting clinical impact, where applicable.