Low-grade chondrosarcomas: a difficult target for radionuclide imaging. Case report and review of the literature

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Abstract

Bone scan with Tc-99m (technetium) diphosphonate is sensitive, but non-specific for musculoskeletal tumors. Tl-201 (thallium), Tc-99m-sestamibi, Tc-99m-tetrofosmin, and F-18-fluorodeoxyglucose (F-18-FDG) can visualize tumors more specifically and are therefore useful in orthopedic oncology. However, cartilaginous tumors are characterized by histological and biological features, which potentially impair specific radionuclide imaging. A case of a patient with a low-grade primary chondrosarcoma of the femur and a false negative Tl-201 scan is presented. Tc-99m-based tumor-localizing compounds (sestamibi, tetrofosmin), as well as metabolic and receptor-imaging radiopharmaceuticals have also been reported to fail in low-grade chondrosarcomas imaging. Low cellularity, mitochondrial specialization and the presence of an efflux membrane pump may contribute to poor imaging. A negative Tl-201 or Tc-99m-sestamibi scan should be interpreted with caution, when the possibility of a chondrosarcoma is not negligible.

Introduction

Chondrosarcomas are chondrogenic tumors, classified as primary and secondary. Eighty-five percent of primary chondrosarcomas, typically found in adults, are low-grade tumors [1]. Both normal cartilage and chondrogenic tumors are characterized by the presence of chondrocytes dispersed within and surrounded by cartilaginous matrix. The three-grade (I–III) system proposed by Evans et al. [2] for the classification of bone chondrosarcomas is based on histological features, such as nuclear size, mitotic rate, frequency of lacunae containing multiple nuclei, character of intercellular background and cellularity. Plain radiography is the initiating imaging modality. Computed tomography (CT) and magnetic resonance imaging (MRI) provide a wealth of information about location, shape, size and composition, thus allowing an accurate locoregional staging of chondrogenic tumors [3].

Bone scan with Tc-99m (technetium) diphosphonate is the standard scintigraphic modality for the evaluation of both local tumor conditions and remote bone involvement. Tl-201 (thallium), Tc-99m-sestamibi, Tc-99m-tetrofosmin and metabolic positron emission tomography (PET) radiopharmaceuticals are characterized as ‘tumor seeking’ agents and have been found useful in initial diagnosis, grading and post-therapy evaluation of primary bone tumors [4]. Tl-201 in particular, has been widely applied in musculoskeletal tumor imaging. Persistently high Tl-201 uptake indicates the presence of viable neoplasmatic tissue. Tracer uptake depends mainly on blood flow and cellularity of the tumor. However, differentiation between benign and malignant tumors is unsatisfactory as considerable uptake has been reported by some benign lesions [5]. Nevertheless, a negative predictive value of 94% has been reported for bone sarcomas, thus limiting the use of invasive diagnostic procedures [6]. The aims of the present study are to report on a false negative Tl-201 scan in a patient with a histologically proven low-grade chondrosarcoma and review the literature on scintigraphic diagnosis of chondrosarcoma with tumor-localizing radiopharmaceuticals.

Section snippets

Case report

The patient was a 67-year-old lady with a short history of left hip swelling and pain. Hematological laboratory values and chest radiograph (CXR) were normal. A radiograph of the femurs showed an extensive osteolytic lesion occupying and deforming the proximal third of the left femur (Fig. 1(a)). CT revealed both intra and extra-osseus expansion of the lesion (Fig. 1(b)). Three-phase bone-scan with 740 MBq (20 mCi) Tc-99m-methylene diphosphonate (MDP) showed increased blood flow, hyperemia and

Review of the literature

Data on chondrosarcoma imaging with Tl-201, Tc-99m-sestamibi, Tc-99m-tetrofosmin or F-18-fluorodeoxyglucose (F-18-FDG) were collected from literature [7], [8], [9], [10], [11], [12]. Only base-line studies reporting individual L/N ratios were considered, allowing descriptive statistics (mean, standard deviation and ranges) to be calculated for each set of data (Table 1). Data on osteosarcomas, where available, are juxtaposed.

Discussion

Chondrosarcomas, in general, showed a lower L/N ratio than osteosarcomas in both early and late phases of Tl-201 scan (Table 1). L/N ratio in a chondrosarcoma has been found lower than the lowest L/N ratio of three osteosarcomas (1.72 vs 2.01) [7]. Caluser et al. [8] were the first to report the unusually high rate of false negative Tl-201 scans (three out of five in their series) in chondrosarcomas, without commenting on tumor grade. The authors attributed the reduced Tl-201 uptake to poor

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