Review Question - QID 220377

This patient's presentation is indicative of a diagnosis of Multiple Myeloma (MM). As such, the next best step in management would be to obtain serum protein electrophoresis (SPEP) and urine protein electrophoresis (UPEP) which would demonstrate 50% IgG, 25% IgA, an M spike with kappa and lambda light chains (Bence Jones proteins), respectively (Answer 3).

MM is a plasma cell malignancy characterized by monoclonal proliferation, leading to bone marrow abnormalities and cytopenias. Radiographs typically reveal lytic lesions, and skeletal surveys are typically preferred for detecting osseous disease as bone scans can be falsely negative in osteolytic processes. As stated above, serum and urine protein electrophoresis can help confirm a diagnosis of MM while a bone marrow biopsy demonstrating greater than 10% monoclonal plasma cells is confirmatory. Pathologic fractures require surgical stabilization while the size, location, and functional limitations associated with the pain of other lytic lesions may warrant prophylactic fixation.

Hideshima et al. review the pathogenesis of MM within marrow elements to help identify therapeutic targets. The authors state that MM is currently an incurable B-cell malignancy characterized by monoclonal plasma cell proliferation with associated excess monoclonal protein in serum or urine. Cytogenetic abnormalities, including hyperdiploidy and IgH translocations, influence prognosis while genomic profiling has identified new therapeutic targets. The bone marrow microenvironment supports myeloma cell survival through adhesion-mediated drug resistance and cytokine-driven proliferation, contributing to chemotherapy resistance. The authors conclude that targeted therapies disrupting tumor–bone marrow interactions, osteoclast activation, and oncogenic pathways offer promising strategies to overcome drug resistance and improve patient outcomes.

Kazandjian et al. review the epidemiology and survival in patients with MM. The authors note that MM is the second most common hematologic malignancy and exists on a spectrum that begins with monoclonal gammopathy of unknown significance (MGUS) to plasma cell leukemia and extramedullary myeloma. It primarily affects older adults, with African Americans having twice the incidence of European Americans. Advances in autologous stem cell transplantation, immunomodulatory drugs, and proteasome inhibitors have significantly improved survival, alongside more sensitive minimal residual disease detection techniques. The authors conclude that as treatment and diagnostics evolve, inclusive clinical trials are crucial to addressing health disparities and ensuring broader applicability of therapeutic advancements.

Scharschmidt et al. review the diagnosis and orthopedic implications of MM. The authors note MM is a hematologic malignancy that frequently leads to pathologic fractures. While primarily managed with chemotherapy and radiation, orthopedic intervention is crucial for pathologic fracture fixation, and prophylactic stabilization of impending fractures, which both help restore function and reduce pain. The incidence of multiple myeloma and associated fractures is rising, necessitating a multidisciplinary approach between orthopedic surgeons and oncology teams. The authors conclude that individualized treatment plans aim to enhance patient quality of life and optimize long-term outcomes.

Figure A is an AP radiograph of a right hip with a pathologic fracture through a lytic lesion that extends toward the subtrochanteric region.

Incorrect answers:
Answers 1,2,4,5: The SPEP findings that are indicative of MM include 50% IgG and 25% IgA with a M spike present. A UPEP with present kappa and lambda light chains, also referred to as Bence Jones proteins, is indicative of MM.