Superiority of Magnetic Resonance Imaging Over Conventional Radiographs in Multiple Myeloma

Case Report

We report on a 68-year-old gentleman who was admitted to our Medical Center in 3/2007 due to skeletal pain and fatigue. Blood sample testing showed the results as displayed in Table I. The RSS and externally performed body-CT revealed osteolytic lesions within his pelvis and vertebrae, correlating with 60% bone marrow (BM)-infiltrating plasma cells (PCs). Cytogenetic and Fluorescent in situ hybridization (FISH) analysis was performed on purified BM PCs, but was not informative due to few PCs being obtained. The patient was diagnosed with an IgG kappa (κ) MM, stage IIIA according to Salmon and Durie (ISS stage II; Table I). The patient's comorbidities included essential arterial hypertension and being considerably overweight (BMI 30 kg/m²). After informed consent, the patient was immediately treated with high-dose dexamethasone, localized vertebral irradiation and since he refrained from intensive therapy, such as autologous peripheral blood stem cell transplantation (auto-PBSCT), he was included in an institutionally guided study which randomized melphalan/prednisone (MP)-lenalidomide (MPR) to MP alone (internal study #554).

Within the MPR study, the patient was randomized to MP and initially responded, showing substantial relief of his initial symptoms (bone pain, night-sweat, fatigue), increase in his hemoglobin and decrease in his total protein (TP) and IgG-levels (6/2007; Table I). Nevertheless, after three MP cycles, he showed recurring bone pain. He was readmitted to our hospital and a diagnostic work-up was repeated. Since at that time, the TP and IgG had slightly increased (Table I), the RSS was repeated. This showed no changes, whereby the magnified view of his right hip suggested minor, if any, progression of his osteolytic lesions at the right femur and its large tubercle (Figure 1A, B). Since the reoccurrence of bone pain was contradicted only by subtle changes in the RSS, an MRI was added, which overtly demonstrated osteolysis of the right hip by extensive signal alterations in non-contrast-enhanced T1-weighted (T1w) and T2w sequences (Figure 2), massive BM infiltration, and soft tissue extramedullary disease. The extensive osteolytic lesion of the pelvis was assessed three days later by repetition of the plain x-ray, which was still not able to reproduce the patient's substantial osteolyses (Figure 1C).

Of note was that, consistent with his initially decreasing TP and IgG, the BM PC infiltration had decreased from 60% (3/2007) to 25% (8/2007; Table I). BM sections revealed still densely infiltrating, bi- and multinucleated PCs (Figure 3A), which proved to be κ positive (Figure 3B). Via histology, notable osteolytic features, with predominant osteoclasts (Figure 3C) and bone-infiltrating and bone-destructive PCs (Figure 3D) were detected (1). BM FISH analysis was repeated and revealed trisomy 11 and tetrasomy 9, but no deletion of chromosome 13, deletion of 17p13 (p53) or detection of t(4;14), t(11;14) or t(14;16) (Table I).

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Figure 1.

Radiological skeletal survey at initial presentation in 3/2007 (A), on recurrence of bone pain in 8/2007 (B) and after MRI (C). Osteolytic changes did not appear to be substantial at these times.

Due to these findings, more intensive anti-myeloma treatment with auto-SCT was again offered to the patient, now consented to by him and his family. He received intravenous etoposide (360 mg/m²), cyclophosphamide (1500 mg/m²) and epirubicine (75 mg/m²) (EVC). Peripheral blood stem cells were harvested after the 2nd EVC cycle and an auto-PBSCT (melphalan 200 mg/m² conditioning) was performed, thereby achieving a very good partial remission (vgPR). Pelvic (right hip) irradiation was performed for consolidation and due to the patient's aggressive bone destruction and only one PBSCT being performed (instead of two), low-dose thalidomide (100 mg/day) and prednisone (50 mg every 2nd day) maintenance was begun to further stabilize the obtained response (5). This was performed according to recent recommendations suggesting that thalidomide will elongate time to treatment failure, avoid early reinduction of anti-MM agents and may be equally effective as tandem-PBSCT upfront (5).

The patient course was complicated due to progression 10 months after auto-PBSCT: extramedullary sites recurred, peripheral blood PCs were 15%, whereas BM PCs remained at 20%. Despite anti-MM therapy with cyclophosphamide, dexamethasone and bortezomib (6), the response remained short-lived and progression persisted. Despite also use of lenalidomide and dexamethasone, κ-serum free light chains increased, whereas his IgG levels remained low. This disease evolution, induced with longer disease duration and/or extensive treatment, showing changes in the biological behaviour of MM and unusual relapse emergence, with a shift in secretion from intact immunoglobulins to free light chains only has recently been described by our group in the largest to date series of 10 patients (7). Our patient eventually died due to extramedullary progression 18 months after initial diagnosis (Table I).