Diffuse Medullary Hyperdensities of the Femora and Humeri on Whole-Body Low-Dose Computed Tomography Identify Diffuse MRI Pattern of Involvement and Correlate with Advanced Disease Stage in Patients with Multiple Myeloma

Whole-Body Low-Dose Computed Tomography (WBLDCT) is considered one of the most accurate methods for the detection of osteolytic lesions in multiple myeloma (MM). On WBLDCT, hyperdense tumor deposits in the medullary cavities of the femora and humeri are often observed; these may represent the only evidence of myeloma in patients without osteolyses. These abnormal hyperdensities may be nodular or diffuse and their density is quantitated by Hounsfield Units (HU). The importance of these deposits has not been fully evaluated in MM. Furthermore, there are anecdotal observations that hyperdense myeloma deposits are more common in patients with a diffuse MRI pattern. The aim of this study was to evaluate the incidence and type of hyperdensities in newly-diagnosed MM (NDMM) patients with a diffuse MRI pattern who also underwent a WBLDCT at the time of diagnosis, compare the results with NDMM patients who had a normal or focal MRI pattern and correlate them with disease characteristics.

Seventy-four newly-diagnosed MM patients were evaluated. WBLDCT and MRI of the spine and pelvis were performed at diagnosis, before the administration of any kind of therapy. The median age of patients was 70.5 years; per ISS, 37% had ISS-1 disease, 35% ISS-2 and 28% ISS-3; per R-ISS, 23% had stage 1 disease, 62% stage 2 and 15% stage 3; per MRI, 29 patients had a diffuse pattern, 15 patients a focal and 30 patients a normal pattern. Patients with a diffuse MRI pattern had more often ISS-3 (n=16, 55%) and R-ISS-3 (n=10, 34%) disease. All MRIs and WBLDCTs were evaluated in consensus by two experienced radiologists (VK and LAM) who were blinded to the clinical data.

Five types of hyperdensities were identified: 1) Fatty (F) - only negative HUs were recorded throughout the medullary cavity, consistent with the presence of normal fatty (yellow) marrow, 2) Fatty marrow intermingled with indistinct hyperdensities (FIH) - a pattern more commonly seen in patients with a normal MRI pattern, consistent with the presence of various amounts of hematopoietic (red) and fatty marrow, 3) Nodular hyperdensities (N) - one or more circumscribed hyperdense nodules presumably representing tumor deposits. A variant of this pattern consisted of the presence of multiple confluent nodules, 4) Diffuse hyperdensities (D) - characterized by the presence of a very dense, homogeneous appearance of part or the whole of the medullary cavity, presumably representing diffuse tumoral involvement.

Out of the 29 patients with a diffuse MRI pattern 11 (38%) had no osteolyses on WBLDCT. 28/29 patients (97%) had medullary hyperdensities in the femora and/or humeri: 22 patients (76%) had diffuse hyperdensities (D) in at least one of the four bones (average density 68.7 HU) and 6 patients (21%) had only nodular hyperdensities (average density 76.5 HU). Interestingly, all patients with ISS-3 or R-ISS-3 and a diffuse MRI pattern had diffuse hyperdensities (D) on WBLDCT. Out of the 15 patients with a focal MRI pattern, only one patient (6.7%) displayed a diffuse hyperdensity (D) in at least one long bone; 7/15 patients (46.7%) had nodular hyperdensity lesions (N) in at least one long bone. Finally, out of the 30 patients with normal MRI pattern, there was only one patient (3.3%) with diffuse hyperdensities (D). In most of these patients either a fatty (F) or a mixed fatty with indistinct hyperdensities (FIH) pattern was identified on WBLDCT.

The presence of diffuse hyperdensities (D) in the medullary cavity of at least one bone had 96.5% sensitivity and 95.5% specificity for the diagnosis of a diffuse MRI pattern. In 10/29 patients (34.4%) medullary hyperdensities were the only sign of bone involvement, since no osteolyses were detected (1/29 patient had neither osteolyses nor hyperdensities).

In conclusion, in about one third of patients with multiple myeloma and a diffuse MRI pattern of involvement, the presence of hyperdensities in the medullary cavities of the femora and humeri may be the only abnormality detected on WBLDCT. Diffuse hyperdensities are the most commonly encountered type in this subset of patients and they seem to be associated with advanced myeloma at initial diagnosis (ISS-3 or R-ISS-3). Studies with larger number of patients and long follow-up will reveal if the type and extent of hyperdensities, as well as the levels of HU, can also provide prognostic information in myeloma patients.