Multiple Myeloma Masquerading as Metastatic Breast Cancer

DAVID SAVAGE, MD, AND T. J. GARRETT, MD

Two women are described in whom, on the basis of prior therapy for breast cancer and the presence of painful, lytic bone lesions, an initial diagnosis of metastatic breast cancer was made. Further evaluation established the diagnosis of multiple myeloma in both patients. Neither had evidence of recurrent breast cancer. These cases indicate that women with a history of breast cancer in whom lytic bone lesions develop without evidence of extraskeletal metastases should have the diagnosis of multiple myeloma excluded.

Cancer 57:923-924, 1986.

REAST CANCER is the most common malignancy in B women, and it frequently metastasizes to bone. In a patient previously treated for breast cancer, the devel- opment of bone pain and lytic skeletal lesions suggests that recurrence has occurred.’ However, as indicated by the two cases described below, a similar picture may result from multiple myeloma, an illness with a different prog- nosis and management.

Case Reports

Patient I A 73-year-old black woman was admitted in September 1979

with a 2-month history of right-sided pleuritic chest pain. In July 1968, she had undergone a right radical mastectomy at another hospital for medullary carcinoma of the breast; meta- static disease was absent from all 14 axillary lymph nodes. No postoperative chemotherapy or radiotherapy was given. She was well from 1968 to 1979. In July 1979 she experienced anorexia and dull right-sided pleuritic chest pain. A technetium 99m (99mT~) phosphate bone scan revealed increased uptake in the ribs of the right lower chest wall. Osteolytic changes were noted in the sixth anterior rib on chest roentgenogram. A presumptive diagnosis of metastatic breast cancer was made, and local ra- diotherapy was begun.

Three days after a fall at home, the patient was hospitalized on the Medical Service for excruciating right-sided chest pain. Physical examination revealed no evidence of local recurrence, lymphadenopathy, or hepatomegaly. The hematocrit value was 32%, the serum calcium level was 1 1.5 mg/dl, the alkaline phos- phatase level was 108 IU/l, and the total protein value was 72

g/l. Results of liver function tests were normal. A chest x-ray showed clear lung fields with pathologic fractures of the right sixth and eighth ribs. Radiographs of the spine, scapulae, pelvis, femurs, and skull demonstrated osteoporosis and multiple os- teolytic lesions. Bone marrow aspiration and biopsy showed large clusters of plasma cells and no adenocarcinoma. Serum protein electrophoresis demonstrated h ypogammaglobulinemia. Kappa light chain proteinuria was shown by urine immunoelectropho- resis. A diagnosis of multiple myeloma was made, and treatment with melphalan and prednisone was begun.

Patient 2

A 56-year-old black woman was admitted November 1984 for low back pain and anemia of 6 months’ duration. She un- derwent a right radical mastectomy for lobular breast cancer in May 1975. No axillary lymph nodes were involved with tumor. In 1978, a modified left radical mastectomy was performed for infiltrating duct carcinoma, and cancer was present in 2 of 16 lymph nodes. No adjuvant chemotherapy or radiotherapy was administered.

She was well until May 1984, when low back pain and anorexia developed. In the next 6 months, her pain increased, and she lost 20 kg. A 99mTc phosphate bone scan was normal. Spine films revealed osteoporosis, several osteolytic lesions, and partial collapse of the first lumbar vertebra.

Because of these findings and marked weakness, bone pain, and anemia, she was referred to the Oncology Service with the diagnosis of breast cancer metastatic to bone. She had no local recurrence of breast cancer, hepatomegaly, or lymphadenopathy. The hematocrit value was 12%, the leukocyte count was 4500/ mm3, the platelet count was 102,000/mm3, the serum calcium level was 8.7 mg/dl, the alkaline phosphatase value was 105 IU/ 1, the albumin level was 32 g/l, the total protein value was 105 g/l, and the erythrocyte sedimentation rate was 139 mm/hour. Liver function test results were normal. Roentgenograms dem- onstrated diffuse osteoporosis and lytic changes in the skull,

From the Hematology-Oncology Service, Department of Medicine, Harlem Hospital Center, Columbia University, college of Physicians and Sureeons. New York. New York.

- j

Address for reprints: David Savage, MD, Department of Medicine,

The authors thank Dr. John Lindenbaum for helpful suggestions in

spine, scapulae, pelvis, left femur, and left humerus. Myelogram

vealed “sheets” of plasma cells and no evidence of metastatic breast cancer. Serum protein electrophoresis and immunoelec- trophoresis demonstrated a monoclonal IgG lambda protein; its

Harlem Hospital Center, 506 Lenox Avenue, New York NY 10037. findings were normal. Bone marrow aspiration and biopsy re- the preparation ofthe manuscript and MS. Gwen Williams for assistance.

Accepted for publication May 20, 1985.

923

924 CANCER March 1 1986 VOl. 57

concentration was 49 g/l. Lambda Bence Jones protein was found in the serum and urine. Multiple myeloma was diagnosed, and therapy with melphalan and prednisone was initiated.

Discussion

These two patients illustrate the importance of exclud- ing the diagnosis of multiple myeloma in patients with a previous history of breast cancer or other malignancies who have lytic bone disease with no evidence of extra- skeletal metastases. In both of these cases, a diagnosis of recurrent breast cancer was assumed on the basis of the history of mastectomy and the roentgenographic findings. As a result, one patient received radiotherapy, and in both cases, there was a delay in beginning chemotherapy for multiple myeloma.

Several clinical features in these patients were more consistent with multiple myeloma than breast cancer, and might have suggested the correct diagnosis. Despite de- structive bone involvement on x-ray, bone scintigraphy was normal in Patient 2 and abnormal in only a single focus in Patient 1; both patients had a normal serum al- kaline phosphatase value. Enhanced uptake on bone scintigraphy occurs in areas of increased osteoblastic ac- tivity and new bone formation2; alkaline phosphatase lev- els increase by the same me~hanism.~ Presumably because of the presence of reactive new bone formation in met- astatic foci, bone scanning is a more sensitive indicator of osseous involvement in metastatic breast cancer than roentgenography. In the presence of radiographically de- monstrable osseous foci, negative scintigraphy would be distinctly unusual in metastatic breast cancer, occurring in 0% to 5% of patients in several large ~ e r i e s . ~ , ~ Approx- imately two thirds of patients with osseous metastatic breast cancer also have an increased level of serum alkaline pho~phatase.~,~ In multiple myeloma, on the other hand, where reactive new bone formation is minimal, bone scans are less reliable than conventional radi~graphy~,~,’; simi- larly, serum alkaline phosphatase values are increased in only 4% to 17% of patients with myel~ma.”~ ,~ In addition,

both patients had evidence of extensive metastatic disease of bone but no extraskeletal involvement, a pattern of spread seen in the great majority of myeloma patients: but found in only 16% of patients with advanced meta- static breast cancer involving bone.’.’0 Finally, although the intervals of 9 and 1 1 years to the development of bony recurrence would not be rare in breast cancer, the long period to relapse should have raised the possibility of a second, unrelated disease.

Because of the differences between multiple myeloma and metastatic breast cancer in prognosis and manage- ment, it is important to differentiate between these two processes. In women with a history of breast cancer who have only lytic skeletal disease, the diagnosis of multiple myeloma must be excluded by bone marrow aspiration and biopsy or electrophoresis of serum and urine. These cases illustrate the importance of making a histologic di- agnosis of new lesions in patients with cancer.

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