Clinical features, management, and therapy of plasma cell neoplasms: What pathologists need to know

Plasma cell neoplasms are characterized by the proliferation of monoclonal plasma cells and include a spectrum of disorders with different clinical manifestations. Multiple myeloma (MM) is the second most common hematological malignancy and recent studies have indicated that almost all cases of MM are preceded by a precursor state of monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SM). The main clinical manifestations of MM are summarized by the CRAB symptoms: hypercalcemia, renal insufficiency, anemia, and bone lesions. Survival of multiple myeloma patients has significantly improved in the last two decades. The clinical benefit has occurred mainly in the younger population with the introduction of high-dose chemotherapy and autologous stem cell transplantation (ASCT) and with the use of novel agents at the time of relapse. The use of novel agents in the elderly population has also resulted in a significant benefit with respect to outcome. Despite the use of these new agents, and the improvement of the median survival from 3 to 6 years in the last 20 years, MM is generally considered an incurable disease and relapse occurs in virtually all patients. Cytogenetic analysis and molecular biology studies indicate that MM is a heterogeneous disease. The non-satisfactory cure rate has been conditioned by intraclonal heterogeneity with branching evolutionary patterns.