Accurate characterization of ^99mTc-MDP uptake in extraosseous neoplasm mimicking bone metastasis on whole-body bone scan: contribution of SPECT/CT

Whole-body bone scans (WBSs) using ^99mTc-labelled methylene diphosphonate (^99mTc-MDP) is the most sensitive examination for the detection of bone metastasis in patients with known cancer [1, 2]. Normally, ^99mTc-MDP uptake is seen in the skeletal structure and urinary system. However, a few studies have suggested that ^99mTc-MDP uptake can occasionally be identified in some extraosseous neoplasms (including primary tumour [3‐5] and metastatic lesions [6‐8]) by WBS, which may be misinterpreted as bone metastases or skeletal involvement. To distinguish this finding from bone metastasis is important for patients with known cancer; however, this is particularly difficult if WBS is used alone because of limited anatomical resolution. SPECT/CT offers the opportunity to acquire both anatomical and functional images, hence enabling more precise anatomical localization and characterization of abnormal radiotracer uptake by SPECT using CT images, possibly reducing confusion and enhancing the diagnostic value of the study when interpreting WBS images question, thereby altering patient management. [1, 9‐11].

In the last few decades, various authors have reported the potential value of SPECT/CT in the localization and characterization of ^99mTc-MDP uptake in extraosseous neoplasms, including breast cancer, gastrointestinal stromal tumour, Ewing sarcoma, pyelonephritis, sclerosing pneumocytoma, and other diseases [3‐8, 12‐15]. Generally, these case reports and pictorial essays refer to a single case or to a limited number of patients. Nevertheless, the incidence and imaging features of SPECT/CT in such extraosseous uptake have not been systematically summarized, and the exact mechanisms remain unclear. Therefore, the aims of present study were first, to investigate the frequency of extraosseous uptake of ^99mTc-MDP in soft-tissue neoplasms and to discuss the possible mechanism, and second, to assess the additional value of SPECT/CT in the localization and characterization of this unusual uptake compared to WBS alone.

^99mTc-MDP uptake in extraosseous neoplasms is occasionally encountered by WBS in clinical practice. However, to the best of our knowledge, no previous study has measured the incidence of such unusual uptake by WBS and SPECT/CT. In our series, ^99mTc-MDP uptake in extraosseous neoplasm was observed in 0.6% by WBS and 1.1% by SPECT/CT, usually localized in the breast, liver, and lung.

Radiological familiarity with ^99mTc-MDP uptake in extraosseous neoplasms is crucial to differentiate form osseous metastasis and prevent unnecessary treatment. However, the diagnosis of such extraosseous uptake can be a challenge if WBS is used alone, since extraosseous uptake frequently overlaps with skeletal structures, often mimicking osseous metastasis. Of the cases examined in our study, WBS had an accuracy of only 35% (14/40) based on the standard criteria. In our study [9, 10] and those of others [2, 16], SPECT/CT effectively resolved diagnostic uncertainty. In the present study, SPECT/CT correctly located and diagnosed all 40 sites (100%) of lesions in 23 patients. Early detection or exclusion of osseous metastasis has a profound influence on the management of patients with known malignancy. Therefore, the use of SPECT/CT is likely to result in altering patient management.

Nevertheless, the exact mechanism of ^99mTc-MDP uptake in extraosseous neoplasms is difficult to identify with precision, and various factors have been proposed. In some studies, histological evidence of calcium deposition has been proposed to be the most important factor [4, 6, 7, 12, 14, 15]. In our series, intratumoural calcification was noted in 31 lesion sites (77.5%, 31/40). We performed SPECT/CT in two patients with osteosarcoma in which the fused functional and anatomic images allowed increased sensitivity for the detection of lymph nodes, pleura, lung, subcutaneous and peritoneal metastasis due to metastatic lesions with calcification. Similar findings were reported by Mebarki M and colleagues [12] for the investigation of osteosarcoma. Classically, primary osteosarcoma and its metastases show extraosseous uptake due to bone matrix formation. Adenocarcinoma (both primary and metastatic) may calcify and accumulate ^99mTc-MDP, including carcinomas of the breast and lung, as well as colorectal cancer and ovarian cancer [14, 15, 17]. Among the primary malignancies in our series, breast cancer (n = 24) most frequently showed extraosseous uptake of ^99mTc-MDP. In our series, increased ^99mTc-MDP uptake was also described in a wide variety of primary neoplasms, including ovarian thecoma, malignant teratoma, and hepatocellular carcinoma. Extraosseous uptake in metastatic lesions were most frequently found in the liver, accounting for 42.3% (11/26) of lesions. The exact mechanism of extraosseous uptake of ^99mTc-MDP in breast, lung, and colorectal cancer is that adenocarcinoma and its metastases possess a mucinous component that may calcify because of internal tumour glycoprotein that binds calcium [14, 15, 17]. In addition, studies reported that calcification in colorectal liver metastasis is generally considered a good indicator of the response to treatment [18]. Therefore, WBS and SPECT/CT may be a potentially useful imaging modality to evaluate responses to treatment for patients with colorectal liver metastasis. Six patients had an absence of intratumoural calcification. Three of these patients had breast cancer, and one patient each had medullary thyroid cancer, endometrial cancer and liver metastatic disease from lung cancer. The mechanism of ^99mTc-MDP uptake in these patients may be increased tumour vascularity or hair-like calcification that is invisible on CT [14, 15].

This study has some limitations. First, the study was limited by its retrospective design, and the sample size was not large. Second, the actual rates of extraosseous uptake may have been underestimated because some lesions may be missed by WBS due to extraosseous ^99mTc-MDP uptake equal to or lower than that of adjacent bone; therefore, further SPECT/CT was not performed. Third, some lesions were not confirmed by histology, and the exact mechanism of extraosseous uptake may remain unknown in these patients.

^99mTc-MDP uptake in extraosseous neoplasms can be observed as 0.6% on WBS and is usually localized to the breast, liver, and lung. Nuclear physicians should be familiar with such extraosseous uptake when interpreting WBSs. SPECT/CT offers better accuracy than WBS alone for locating the majority of lesions present with intratumoural calcification.