Extensive extramedullary disease in myeloma. An uncommon variant with features of poor prognosis and dedifferentiation.
BACKGROUND: The development of extramedullary plasmacytomas and elevated serum lactic dehydrogenase (LDH) in myeloma indicates poor prognosis. A 75-year-old man was diagnosed with immunoglobulin (Ig) A, lambda myeloma when he developed pathologic rib fractures, hypercalcemia, and anemia. After 6 months of treatment with melphalan and prednisone, he was in complete remission as evidenced by the disappearance of the monoclonal protein in the serum and free light chain in the urine. Eight months after diagnosis, his disease took an unusual course with the simultaneous development of plasmacytomas in the skin, breast, stomach, and pancreatic head, complicated by severe upper gastrointestinal bleeding and obstructive jaundice. METHODS: Immunohistochemical staining of the marrow and breast mass was done using monoclonal antibodies against B-cell and T-cell antigens as well as kappa and lambda light chains. In situ hybridization was performed to detect ras oncogene overexpression in the breast mass. RESULTS: Immunohistochemical staining of the original marrow and breast mass was positive for IgA and lambda, confirming the identical clonal origin of the plasma cells. The disorder expressed elevated serum LDH, both at diagnosis and relapses. Features of dedifferentiation were expressed by the disappearance of myeloma protein in the serum at relapse, absence of marrow plasma cell infiltration, and development of multiple extramedullary plasmacytomas. There was no overexpression of H-ras or N-ras oncogenes by in situ hybridization of the plasmacytoma from the breast. The patient died shortly after the development of the extramedullary plasmacytomas. CONCLUSIONS: The simultaneous appearance of plasmacytomas in multiple extramedullary sites heralds a change of clinical behavior in myeloma. When accompanied by the disappearance of serum myeloma protein, and marrow plasma cell infiltration, and serum LDH elevation, the disorder may follow a fulminant course.