Solitary Increase of 11 C-Choline Uptake in an Enchondroma Patient with Biochemical Recurrence of Prostate Cancer A

We report the case of a 72-yr-old prostate cancer patient with biochemical failure (PSA = 2.8 ng/mL) after radical prostatectomy in whom both bone scintigraphy and 11 C-choline PET/CT detected an isolated focal pathological activity in the proximal diaphysis of the left tibia. Surgery was performed and histological analysis revealed enchondroma. The finding is discussed on the basis of the specificity of radiolabeled choline for prostate cancer vs. other tumors or inflammation processes. Particularly, proliferation or concomitant inflammatory processes associated with bone remodeling in enchondroma are discussed and related to 11 C-choline uptake.


INTRODUCTION
72-yr-old prostate cancer patient with biochemical failure was referred to bone scintigraphy because of a biochemical recurrence (prostate specific antigen, PSA = 2.8 ng/mL). The patient had been treated with radical prostatectomy five years earlier owing to prostate cancer (pT2 pN0 cM0, Gleason 3 + 3 = 6). Bone scan revealed an isolated hot spot in the proximal diaphysis of the left tibia ( Figure 1).
No lesions were visible in the pelvis or in the spine, which made the isolated finding in the tibia unlikely to be related to prostate cancer. The traditional whole body 11 C-choline PET/CT, conducted from the cranial basis to the midthigh, did not reveal any pathological uptake site of 11 C-choline ( Figure 2). However, since the sensitivity of 11 C-choline positron emission tomography/computed tomography (PET/CT) is higher in comparison to bone scintigraphy and also because of the capability of PET/CT to investigate local recurrence and lymph node metastases, the patient underwent subsequent 11 C-choline PET/CT to further exclude macroscopic disease. Physiological uptake was seen in the right axillary vein, in the liver, in the spleen, in both kidneys, in the small bowel and in the bladder. In the additional static acquisition centered on the knees, a pathological increase of 11 C-choline uptake was seen in the proximal diaphysis of the left tibia which corresponded to the scintigraphic finding ( Figure 3A). The CT component of the PET/CT revealed an area of sclerosis ( Figure 3B). Fusion imaging demonstrates that the increased metabolic activity localizes to the sclerotic area ( Figure 3C).

Giovacchini and Ciarmiello
The patient decided to undergo surgery. Histological analysis revealed enchondroma ( Figure 4A and Figure 4B).

DISCUSSION
Enchondroma is a benign bone tumor, which results from the continued growth of residual benign cartilaginous rests that are displaced from the growth plate. The tumor growth occurs in the medullary cavity of bone [1]. Overall, they are particularly frequent in the phalanges and commonly in the pediatric and young adult age groups, but may also occur in the diaphysis of femur and tibia. This is being recognized in 1.7% of femura at autopsy [2,3]. Enchondromas usually present as a painless bony mass, and radiographically often ovoid in shape with endosteal scalloping; displaying occasionally chondroid type matrix mineralization and do not induce periosteal reactions [4,5]. Bone scintigraphy shows a variable increase of tracer uptake in the skeletal phase whilst the perfusion phase and the blood pool phase are normal [1,2,4]. Malignant transformation into chondrosarcoma is rare but may occur, especially in the diffuse form of multiple enchondromatosis [5,6]. PET/CT with 11 C-choline is frequently used for restaging prostate cancer in patients with biochemical failure. Several studies have shown that recurrent disease can be imaged for low PSA values [7][8][9], that PET/CT with radiolabeled choline might be more accurate than conventional imaging for the detection of lymph node and skeletal metastases [8,10-12], and that several clinical and pathological factors can be used to identify patients who have a higher risk of positive PET/CT [13 -15].
Studies indicated that radiolabeled choline accumulates in several malignancies other than prostate cancer or physiological variants, including lung cancer, brain tumors, bladder cancer, meningiomas, as well as inflammatory arthritis disease, Paget's disease, thymus hyperplasia, benign prostate hyperplasia [16][17][18][19][20][21][22]. Increased 11 C-choline uptake has also been observed in the pelvic and retroperitoneal lymph nodes of prostate cancer patients with biochemical failure and no histological evidence of disease. This was attributed to lymph node hyperplasia [23]. A simple diffusion mechanism, in addition to an energy-dependent specific transport, regulates the uptake of choline in mammalian cells [24]. Therefore, it is possible that, at least in some of these cases, nonspecific uptake might represent the cause of the false positive.
An alternative hypothesis is that uptake of 11 C-choline reflects increased proliferation of cell membranes or of some of their components [25]. It is unknown whether 11 C-choline uptake in enchondroma reflects cell proliferation or a concomitant inflammatory process associated with bone remodeling and/or inflammation [26]. The relation between tracer uptake and cellular proliferation is however complex. In humans, the extent of uptake of [ 11 C]choline in the prostate tumor is not related to the cell proliferation rate, as estimated by Ki67 [27].
Nevertheless, in various tumor cells, there was a significant correlation between choline uptake and cell proliferation, as reflected by the incorporation of [ 3 H]methyl-thymidine into DNA [28].
Al-Saeedi et al. found that the concentration of concentration of the water-soluble product phosphocholine was higher in breast cancer MCF-7 cells than in control cells [29]. In the same cells, methyl-[ 3 H]choline incorporation was found to be related to the fraction of cells in the S-phase as well as to the incorporation of [methyl-3 H]thymidine into DNA [30].

CONCLUSION
In summary, this case report highlights the necessity of keeping in mind enchondroma in the differential diagnosis of 11 C-choline uptake in the skeleton of patients undergoing [ 11 C]choline PET/CT.