A 43-year-old female with multiple plasmacytomas

A 43-year-old female presented to the hospital with back pain in October 2010.

Her back pain was chronic but had worsened 2 weeks before admission.

Her past medical history is significant for chronic obstructive pulmonary disease, depression, hyperlipidemia, morbid obesity, obstructive sleep apnea, stage I cervical cancer (status post-hysterectomy) in 2009, sick sinus syndrome (status post-pacemaker placement) and chronic lumbar back pain.

She has had several discectomies in the past. She did not have any motor or sensory dysfunction on examination. She had a CT scan of her thoracic spine that showed degenerative changes and a small T11 lytic lesion. A PET scan showed increased uptake in the corresponding area, and hence, a biopsy was attempted. It was, however, nondiagnostic.

Because the lesion was small, it was felt that a repeat biopsy was not going to be successful and an open biopsy was recommended. Neurosurgery was consulted, but the patient refused open surgery.

Ramya Varadarajan

She also had a myeloma workup, including serum electrophoresis with immunofixation and 24-hour urine protein electrophoresis with immune fixation, all of which did not show a monoclonal protein.

Her CBC, serum creatinine, serum calcium, beta-2 microglobulin and serum free light chains were normal. Interestingly, her skeletal survey was negative at that time. She had a CT of the chest, abdomen and pelvis that did not show lymphadenopathy or abnormal masses in other areas. It was decided to monitor her closely.

A few months later, she was readmitted with back pain. This time, she had a bone scan that was positive in the T11 area and also in the left ninth rib area.

After adequate pain control, she was discharged home. She was supposed to follow up on the abnormal bone scan as an outpatient, but unfortunately, she was lost to follow up. She presented to the hospital 6 months later in August 2011 with inability to walk.

She could not get an MRI because of the pacemaker. She underwent a myelogram that showed progression of the osteolytic lesion involving the T11 area with prominent epidural extension that caused severe spinal canal stenosis and cord compression. There also was interval progression of osteolytic destructive process at the posterolateral left ninth rib with a prominent soft tissue component.

She underwent emergent decompression, and the final pathology was consistent with plasmacytoma. She had a repeat myeloma workup, including serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), 24-hour urine test for urine protein electrophoresis (UPEP) and IFE, and a free light chain assay. All were normal.

She underwent a bone marrow biopsy, which surprisingly was negative for involvement with myeloma. Her beta-2 microglobulin was normal. She did not have anemia or hypercalcemia.

After the surgery, she completed a course of radiation to her T11 region and left ninth rib. She underwent rehabilitation and currently is able to walk with a walker.

She presents with several treatment challenges:

• Her bone marrow biopsy was negative. Does she have a nonsecretory myeloma or multiple plasmacytomas?
• She is truly nonsecretory. The lytic lesions were picked up by CT scans, but her skeletal survey was negative. How would you monitor her?
• She does not have any other lesions, and the two lesions that were identified were treated with definitive radiation. Does she need treatment at this time?

Case Discussion

Approximately 3% of patients with multiple myeloma have no M protein in the serum or urine on immunofixation at the time of diagnosis.

In approximately 60% of patients with myeloma who have a normal serum and urine immunofixation, monoclonal free light chains can be detected in the serum using free light chain assays.

Patients with myeloma who have normal serum and urine immunofixation, as well as normal serum free light chain assay, are considered to have nonsecretory myeloma.

Among these patients, 85% will have M protein that can be detected in the cytoplasm of the neoplastic plasma cells by immunochemistry but will have impaired secretion of this protein. The other 15% do not have detectable immunoglobulin in the plasma cells (ie, non-producer myeloma).

Plasma cells do not secrete heavy or light chains due to a defect in the assembly or secretion of immunoglobulins, or from rapid destruction of the secreted proteins. Nonsecretory myeloma remains nonsecretory in three-fourths of patients, even with extended follow-up. Patients with nonsecretory multiple myeloma are not at risk for myeloma kidney as long as light chains cannot be detected in the urine, but they are at risk for other complications of multiple myeloma.

The International Myeloma Working Group developed the following working criteria for nonsecretory myeloma:

• No M protein in serum and/or urine seen by immunofixation.
• Bone marrow clonal plasmacytosis of more than 10% or plasmacytoma.
• Related organ or tissue impairment, including bone lesions.

Although bone marrow involvement is almost always present, it is not necessary for diagnosis of nonsecretory myeloma if the patient has multiple bone lesions. Although the current case had no evidence of end-organ damage and no involvement of marrow, she has more than one osteolytic lesion and, thus, can be considered to have nonsecretory myeloma.

Patients with nonsecretory myeloma must be monitored mainly on the basis of imaging tests and bone marrow studies, as they tend to remain nonsecretory with time. However, in this case, she does not have bone marrow involvement.

It also is interesting to note that her lesions did not show on a skeletal survey, but they did show up in a bone scan. Because bone involvement in myeloma is osteolytic rather than osteoblastic, lesions usually are seen on X-rays rather than a bone scan.

Routine monitoring with periodic bone scan or CAT scan will put her at increased risk of exposure to radiation. However, given her chronic lumbar pain, it would be difficult to interpret progression of disease with clinical judgment alone.

The next important question is whether this patient needs treatment. The T11 lesion and the ninth rib lesion were treated with definitive radiation. She does not have additional bone lesions. She does not have end-organ damage and her bone marrow biopsy is negative.

She was presented at the lymphoma conference, and the consensus was to monitor her without any treatment at this juncture. However, it was recommended that she might benefit from bisphosphonate therapy.

To conclude, a high index of suspicion is needed in patients with nonsecretory myeloma. Nonspecific clinical presentation and normal laboratory findings can cause a delay in diagnosis.

Ramya Varadarajan, MD, is a consultant at Regional Hematology and Oncology PA at Helen Graham Cancer Center in Newark, Del. She is a member of the HemOnc Today Editorial Board. Disclosure: Dr. Varadarajan reports no relevant financial disclosures.

For more information:

• Hamidah NH. Clin Ter. 2010;161:445-448.
• Ranasinghe KN. Ceylon Med J. 2003;48:63.
• Song YS. Pathol Int. 2011;61:390-393.