Oncology Case Challenge: A Daily Beer Drinker With Bruises, Back Pain, and Bleeding

Arun Gupta, MD, DNB

Disclosures

July 28, 2022

Discussion

The patient's skull radiograph shows multiple punched-out osteolytic lesions, which are considered a characteristic feature of myeloma. Similar osteolytic lesions were noted on radiographs of the patient's lumbar spine, pelvic bones, and scapula. A bone marrow biopsy revealed sheets of plasmacytoid cells in various stages of development, with marked replacement of normal hematopoietic tissue. More than 90% of these cells were morphologically plasmablasts, whereas the rest were mature plasma cells. These cells were negative for antibodies to leukocyte common antigen, CD117, cytokeratin, carcinoembryonic antigen, and anaplastic lymphoma kinase; however, they were positive for antibodies to CD38, CD138, CD56, and lambda-light chain, thereby confirming the plasmablastic nature and monoclonal origin of these cells. This established the diagnosis of myeloma. The patient did not have hypergammaglobulinemia, a monoclonal spike on serum protein electrophoresis, or Bence-Jones proteins in the urine, indicating the nonsecretory nature of these cells.

Multiple myeloma is a B-cell lymphoid malignancy characterized by malignant clonal proliferation and accumulation of plasma cells in the bone marrow that synthesize abnormal immunoglobulins. It is the most common primary malignant tumor of the bone, accounting for approximately 1% of all bone malignancies and 10% of all hematologic malignancies. The median age at diagnosis is 60-65 years; however, in less than 2% of people it occurs before age 40 years. No risk factors have been established for myeloma, although lifestyle, dietary habits, occupational and environmental agents, chronic immune stimulation, obesity, and lower socioeconomic status have been implicated.[1]

The clinical presentation of myeloma varies, ranging from indolent to a highly aggressive disease. The symptoms are related to tumor mass effects, bone destruction, protein deposition in various organs, and immunosuppression.[2] Among the varied presentations, 10%-40% of patients are asymptomatic. The most common symptoms observed are spine pain (reported in approximately 70% of patients), pathologic fractures, symptoms related to anemia, bleeding tendency, and/or peripheral neuropathy.[3] The patient may also have a history of repeated infections due to hypogammaglobulinemia. The diagnosis of multiple myeloma is based on major and minor criteria, including the presence and number of plasma cells in the bone marrow, quantitation of monoclonal immunoglobulins in serum by protein immunoelectrophoresis, immunofixation, and lytic bone lesions. MRI is useful for detecting thoracic and lumbar spine lesions, paraspinal involvement, and early cord compression; it can detect as many as 40% of spinal abnormalities in patients with asymptomatic gammopathies in whom radiographic studies are normal.[4] Numerous structural and numerical aberrations in chromosomes have been reported, the most common of which is translocation (11;14). The presence of a chromosome 11q13 translocation has been associated with an unfavorable prognosis.[5,6]

Measurement of circulating monoclonal immunoglobulins has been the standard for diagnosis and management of patients with myeloma. However, in about 1%-5% of cases, no protein can be detected in the serum or urine. This variant is known as nonsecretory multiple myeloma (NSMM) and results from either a lack of synthesis by tumor cells or rapid degradation of these proteins in circulation. [7]

Based on the inability of malignant plasma cells to synthesize immunoglobulin or the failure of such components to be exported from the cells, these have been classified into 2 types: the nonproducer type (15%), wherein immunoglobulins are not found in plasma cells, and the producer type (85%), in which the immunoglobulins are demonstrable in plasma cells but not in the blood. In such cases, bone marrow immunostaining positivity for CD38, CD138, and CD56 markers and anti-kappa- or anti-lambda-light chain antibodies are helpful in confirming a diagnosis of nonsecretory myeloma. The introduction of assays to quantitate circulating free kappa and free lambda-light chains has made it possible to reclassify approximately one half to two thirds of patients previously thought to have nonsecretory myeloma.[8]

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