Bone Scintigraphy in Multiple Myeloma

David A. Bader MD

J. Stevan Nagel MD

January 17, 1995

Case Presentation:

A 48 year old male with no significant past medical history fell onto his right shoulder at home. A radiograph was obtained and revealed a pathologic fracture of the proximal humerus through a lytic lesion. A bone scan was requested to evaluate for fibrous dysplasia.

Findings:

Bone scan (63k bytes) revealed no significant activity corresponding to the known fracture site. There were several foci of anterior rib activity and an additional focus of mild to moderate increased activity in the left distal medial femur.

Plain films of the ribs (95k bytes) and left femur (41k bytes) were obtained for comparison at the time of the nuclear medicine study and revealed a diffuse lytic process involving essentially all of the visible bones. The mild increased activity in the left femur (arrow, 63k bytes) on bone scintigraphy activity was noted to correspond to periosteal reaction (arrow, 41k bytes) at a site of pathologic fracture. All of the above imaging findings were consistent with the diagnosis of multiple myeloma.

Imaging Technique:

A whole body bone scan was performed following the administration of 25 mCi of Tc-99m MDP utilizing 3 hour delayed regional planar images on a Siemens body scan (dual head) with a low energy high resolution collimator.

Course:

A bone marrow biopsy and aspirate performed at an outside institution revealed markedly hypercellular marrow with increased numbers of plasma cells, including atypical forms, consistent with multiple myeloma.

Discussion:

Bone scintigraphy is a sensitive and efficient method of measuring metabolic activity of the entire skeleton. Tc-99m labeled diphosphonates are well established in screening for most bony metastatic disease. Bone scanning makes up greater than 1/3 of the procedure volume in most nuclear medicine departments, a large proportion of which is screening for metastatic disease. The role of scintigraphy in evaluation of the patient with multiple myeloma is less well defined. Recent developments which necessitate reevaluation of the role of scintigraphy in multiple myeloma with respect to treatment.

Bone scan mechanism of uptake is directly related to blood flow and degree of osteoblastic activity. Autoradiographic studies have shown the deposition of radiolabeled phosphates at sites of osteoid mineralization with Tc-99m labeled bone tracers exchanging with ions in the actively forming hydroxyapatite complex. Bony metastatic disease results in carcinomatous osteodysplasia which refers to a histologic alteration resulting in a variable increase in osteoblasts, osteoclasts, blood vessels, and other stromal tissues. More often than not this will result in increased activity on a bone scan. Over 80% of bony metastases originate from breast, prostate, lung and, much less frequently, thyroid and kidney. The osteoblastic response is less likely with the round cell group of tumors (lymphomas, leukemias, myeloma) and with highly vascular or anaplastic tumors (thyroid and kidney often placed in this category). The round cell group of tumors have been shown to produce osteoclast-activating and osteoblast-inhibiting factors. The highly vascular or anaplastic tumors are associated with very little osteoblastic activity. However, thyroid and renal cell cancer often present with solitary metatases, rapid progression and associated soft tissue masses. Although scintigraphy may be false negative, these tend not to be clinically occult lesions. In addition, one study demonstrated that 42% of radiographically occult renal cell metastases were scintigraphically positive (Cole). Renal cell cancer also has been shown to not uncommonly present as a cortical metastasis, usually scintigraphically positive (Hendrix).

Multiple myeloma is the most common primary bone tumor. It is of plasma cell origin, most commonly presents in the 40-70 year age group, female more frequently than male. The radiographic findings are characterized by round, punched out, clean cut areas of destruction with no surrounding sclerosis. However, radiographs may be normal or show only diffuse osteopenia. The sensitivity of radiography versus bone scanning for detecting multiple myeloma has been reported from 75-91% for radiography and 46-60% for scintigraphy (Ludwig, Woolfenden). A Mayo Clinic study (Whaner) concluded that, for multiple myeloma, scintigraphy

is of limited value for initial evaluation,
adds little additional information to follow-up studies,
and, may show limited usefulness in evaluating bone pain with negative radiographs.

With respect to the latter, there have been reported cases where a painful region is radiographically negative, scintigraphically positive, and subsequently develops classic lytic changes for myeloma. However, the clinically utility of this has been questioned with regard to radiation therapy because the decision to radiate is clinical, and no difference in effect of treatment has been shown in scintigraphically positive versus negative painful sites (Whaner).

A recent case report of the successful palliation of painful multiple myeloma lesions with Sr-89 raises a new issue regarding the role of bone scanning in multiple myeloma (Edwards). The mechanisms responsible for positive scintigraphy in multiple myeloma may be an increase in bone surface area (Whaner), or osteoblastic activity present at the edge of a lytic lesion. The presence of such lesions in patients with myeloma might select a subgroup that will respond to Sr-89 therapy. However, fractures and infractions (local breakdown of trabecular structure) are the more common etiology for osteoblastic activity (Whaner) and pain from fractures will not respond to Sr-89 therapy (Edwards, Silberstein).

Conclusions:

The role of bone scanning in metastatic disease from the most common primaries remains clear. Bone scanning in multiple myeloma, while not classically done, should be considered in patients who have negative plain films with a clinically painful site. A potential new role for bone scanning in myeloma may also be in predicting response to Sr-89 therapy; however, this role needs further evaluation.

References:

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu