The radiologic and FDG uptake findings of osseous lesions incidentally detected on 18F-FDG-PET/CT imaging

Abstract

Background

In routine clinical practice, incidental solitary bone lesions are commonly seen on various imaging modalities. 18F-FDG-positron emission tomography (PET)/computed tomography (CT) imaging provides functional and morphological information in oncology patients, and incidental bone lesions are often detected during the scan.

Purpose

To evaluate the metabolic characteristics and CT morphological findings of incidental bone lesions detected in patients undergoing 18F-FDG-PET/CT imaging.

Material and Methods

SUVmax values and CT characteristics of incidental osseous lesions reported in 86 patients undergoing 18F-FDG-PET/CT imaging between 2019 and 2023 were evaluated. In addition, the SUVmax values of the lesions were compared with bone areas without adjacent/contralateral density/FDG changes. CT characteristics of incidental osseous lesions were evaluated.

Results

The study group included 52 women and 34 men (age range = 26–89 years). CT identified typical bone haemangioma lesions in 45/86 (52%) cases. Non-haemangioma lesions were mainly benign bone pathologies: fibrous dysplasia; Paget's disease; perineural cyst; osteonecrosis; and osteoma. The mean SUVmax value of 41 non-haemangioma bone lesions (4.27 ± 3.71) was significantly higher than that in adjacent/contralateral normal density areas (2.31 ± 1.27; P = 0.01).

Conclusion

18F-FDG-PET/CT imaging shows varying FDG uptake in incidental osseous lesions. Morphological features on CT play a critical role in diagnosis and avoiding unnecessary imaging or interventions.

Keywords

Bone lesions computed tomography 18F-FDG-PET/CT

Introduction

Incidental bone lesions are frequently observed in routine clinical practice using various imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. These lesions should be evaluated in detail for aggressive and non-aggressive features, such as bone destruction, lesion margins, tumor matrix, and periosteal reactions (1,2).

Incidental lesions include benign bone tumors and tumor-like lesions. Benign bone tumors are often asymptomatic and are typically discovered incidentally during examinations performed for other reasons. These lesions exhibit minimal potential for local invasion and have limited growth capacity. Although usually asymptomatic or associated with mild symptoms, they can pose diagnostic challenges by mimicking true pathological lesions. For instance, asymptomatic benign bone lesions may be misinterpreted as metastases when incidentally detected in a patient with known cancer (3).

Benign/incidental bone lesions exhibit morphological characteristics consistent with a non-aggressive appearance. Their margins are often observed with a sclerotic pattern. The periosteal reaction caused by benign lesions is typically seen as a thick, solid, and unilamellar type. In contrast, the lamellar or spiculated periosteal reaction frequently observed in malignant aggressive lesions is absent. Cortical expansion in non-aggressive lesions is not disrupted by cortical lysis, and the cortex may appear relatively thick (4).

18F-FDG-PET/CT is widely utilized in clinical oncology for tumor characterization, staging, treatment monitoring, and restaging. 18F-FDG-PET/CT, which combines functional and morphological information, assesses tumor glycolytic activity, an essential marker of tumor biology and differentiation. The 18F-FDG compound used in this examination enables the detection and characterization of numerous lesions due to its property of metabolic retention. However, 18F-FDG is not specific to malignant lesions (5 –7).

Studies on 18F-FDG-PET-CT have described many benign pathologies showing 18F-FDG uptake as high as malignant lesions. Bone metastases are common in the oncological patient group and are frequently encountered in clinical practice. There is a significant overlap in FDG uptake values between benign and malignant osseous lesions. Some benign bone lesions may show similar or higher uptake than malignant lesions. This may lead to diagnostic errors and unnecessary treatment protocols. Benign tumors and tumor-like conditions are frequently detected incidentally on 18F-FDG-PET/CT during serial follow-up studies of cancer patients and must be differentiated from metastases. Therefore, it is recommended that the CT morphology of bone lesions be evaluated in detail to ensure accurate diagnosis (8 –10).

The aim of the present study was to evaluate the CT morphological findings and FDG metabolic properties of incidental osseous lesions in patients undergoing 18F-FDG-PET/CT imaging for oncological disease.

Material and Methods

This study protocol was reviewed and approved by the Ege University Medical Research Ethics Committee (decision no. 24-4.1 T/13, dated 25 April 2024). Informed consent was obtained from all patients during the examination.

The images of 86 patients with incidental osseous lesions reported in bone areas on 18,200 18F-FDG-PET/CT scans in the PACS archive of Ege University Department of Nuclear Medicine between 2019 and 2023 were retrospectively analyzed. Patients who underwent PET/CT due to malignancy diagnoses and were incidentally found to have benign bone lesions in bone structures were included in the study. SUVmax values and morphological features of incidental osseous lesions on CT images were evaluated in 86 patients who were examined for oncological diseases. Malignant and metastatic bone lesions were excluded from the study. In addition, patients with incomplete imaging data or inadequate clinical follow-up, as well as cases where the benign nature of the lesions could not be confidently confirmed through imaging features or follow-up, are included in the exclusion criteria.

Image acquisition and reconstruction

Patient preparation, acquisition protocols, and reconstruction parameters were standardized for all patients. PET/CT studies were performed using a Siemens Biograph 16 TruePoint PET/CT device with a slice thickness of 5 mm. OSEM iterative reconstruction (3 iterations, 21 subsets) method was used (True X, FWHM: 4.0 mm, zoom: 1). Patients with a blood glucose level below 200 mg/dL after fasting for at least 6 h received an IV injection of 7–10 mCi FDG. Patients who rested in a quiet environment for 45 min 1 h after injection were placed on the PET/CT scanner bed after emptying the bladder. The same acquisition protocol was applied for each patient and the body area from the vertex to the proximal femur (head tip-thigh) of the patient lying in the supine position was included in the acquisition. The images were generally performed in 3 min/bed mode with 7–8 bed positions. PET/CT images with attenuation correction with CT were analyzed as standard for evaluation. When necessary, images without attenuation correction were also evaluated.

Image analysis

The images were evaluated by an experienced nuclear medicine specialist and a musculoskeletal radiologist. SUVmax values of incidental lesions were compared with neighboring or contralateral bone areas without density/FDG changes. For the control group, SUV max measurements of FDG uptake were obtained from the normal adjacent bone area for vertebral lesions and from the contralateral normal bone area for extremity lesions. Bone lesions were evaluated from the CT images of the examination by a radiologist experienced in musculoskeletal radiology. CT morphological features were categorized based on the patterns observed in elementary bone lesions. For lesion characterization, density features were categorized as lytic, sclerotic, or ground-glass opacity, along with trabecular or cortical thickening. In our study, the benign nature of the lesions was confirmed by their stability in previous or follow-up examinations of the cases, and in some patients, by diagnostic correlation with MRI.

Statistical analysis

The obtained data were entered into SPSS version 23.0 (IBM Corp., Armonk, NY, USA) and a P value of 0.05 was considered statistically significant. Quantitative variables were described using mean, standard deviation, and ranges. Statistical analyses were performed using the Mann–Whitney U-test. The Shapiro–Wilk test was performed to assess whether the data were normally distributed. Since the normality assumption was not satisfied, the Mann–Whitney U-test was conducted to compare the two groups.

Results

A total of 86 patients (52 women, 34 men; age range = 26–89 years) were included in the present study. The oncological diagnoses of the patients included breast cancer (18.6%), colon cancer (11.6%), and other malignancies.

CT dimensions of the lesions were in the range of 1–20 cm. Of the 86 incidental lesions, 45 (52%) were identified as osseous haemangioma with a vertically thickened trabecular appearance within a lytic area on CT. CT findings of non-hemangioma lesions were consistent with bone pathologies such as fibrous dysplasia, Paget's disease, perineural cyst, osteonecrosis, and osteoma. The location of the evaluated incidental lesions is presented in Table 1.

Table 1.

Distribution of incidental osseous lesions detected on PET/CT imaging.

Diagnosis	No. of patients	Range SUVmax	Location
Fibrous dysplasia	6	1–9.8	Iliac bone (n = 2), scapula (n = 1), humerus (n = 1), femur (n = 2)
Osteoma	4	1.9–3	Frontal (n = 2), zygomatic bone (n = 1), ethmoid bone (n = 1)
Osteomyelitis	2	3.1–4.7	Mandible (n = 2)
Osteonecrosis	9	1.1–19.5	Mandible (n = 4), tibia (n = 1), femur (n = 1), pelvis (n = 3)
Paget	6	1.9–8.5	Pelvis (n = 4), scapula (n = 1), cranium (n = 1)
Perineural cyst	6	1.2–2.7	Sacrum (n = 5), vertebra (n = 1)
Subchondral cyst	8	1–5.5	Femoral head (n = 4), tibial plato (n = 1), acetabulum (n = 3)
Hemangioma	45	1.5–3.5	Vertebra (n = 43), humerus (n = 1) pubic ramus (n = 1)

The diagnosis and SUVmax distribution of incidental osseous lesions after CT characterization are given in Table 1. Fibrous dysplasia, Paget, osteonecrosis, and subchondral cysts showed both high and low FDG uptake according to SUVmax values, whereas a homogeneous distribution was observed in other bone lesions in our study group.

The mean SUVmax value of all incidental detected osseous lesions was 3.24 ± 2.5 and the mean SUVmax value of the adjacent/contralateral normal density areas was 2.8 ± 1.1. There was no statistically significant difference between the SUVmax values of the lesion and normal bone densities (P = 0.38). The mean SUVmax value of 41 non-hemangioma osseous lesions was 4.02 ± 3.43 and the mean SUVmax value in the adjacent/contralateral normal density areas was 2.33 ± 1.04, with a statistically significant difference (P = 0.01) (Table 2). While bone haemangiomas showed low metabolic activity on PET imaging, the mean metabolic activity of other benign osseous lesions was found to be higher than that of the adjacent/contralateral normal area. In addition, SUVmax values of non-hemangioma lesions were found to be in a wide range. Imaging findings of two different lesions demonstrating low and high FDG uptake are presented in Figs. 1 and 2.

Fig. 1.

A 70-year-old male patient diagnosed with laryngeal cancer and ankylosing spondylitis. (a) 18F-FDG-PET/CT imaging revealed a large osteolytic lesion in the left acetabulum, consistent with a subchondral cyst. (b) The lesion's FDG uptake (SUVmax = 2.6) is low.

Fig. 2.

A 60-year-old male patient with lung carcinoma. (a, b) In 18F-FDG-PET/CT imaging, high FDG uptake (SUVmax = 13.1) was detected in sclerotic lesions within the body of the L3 vertebra. The lesion's periphery appears sclerotic, while the central portion exhibits a ground-glass density (arrow). (c, d) In addition, osteolytic lesions with ground-glass densities (arrow), and similarly high FDG uptake were observed in both femoral necks. The patient was diagnosed with polyostotic fibrous dysplasia.

Table 2.

Comparison of SUVmax values of the incidental osseous lesion and adjacent/contralateral region.

	n	Incidental osseouslesionSUVmax	Adjacent/contralateral regionSUVmax	P
Incidental osseous lesions	86	3.24 ± 2.5	2.87 ± 1.1	0,38
Non-hemangioma osseous lesions	41	4.02 ± 3.43	2.33 ± 1.04	0.01

Values are given as n or mean ± SD.

Discussion

In this study, the evaluation of bony lesions incidentally detected in patients undergoing 18F-FDG-PET/CT imaging for oncological diseases, along with their CT imaging morphological findings, is important in distinguishing metastases or other malignant bone lesions, which plays a crucial role in treatment planning. Therefore, assessing the CT morphological characteristics of bone lesions with high 18F-FDG uptake on PET/CT imaging by an experienced radiologist contributes significantly to achieving an accurate diagnosis.

In our study, bone hemangiomas exhibited low levels of metabolic activity on PET imaging, while the average metabolic activity of other benign osseous lesions was higher compared to areas with no adjacent/opposing density or FDG change. In addition, SUVmax values were found to exhibit a wide range.

In our case series, the most frequently detected lesion was intraosseous hemangioma (45 patients, 52%). Osseous hemangiomas are asymptomatic, incidental findings. Intraosseous hemangiomas are relatively common, with vertebral hemangiomas occurring in approximately 10% of the adult population. They are slightly less frequent in male individuals (M: F = 0.7:1) and are most commonly observed in the fifth decade of life, though they can occur at any age (11). The majority of hemangiomas are located in the vertebrae (>75%), calvarium, and long bones. Vertebral hemangiomas present a classic “corduroy” appearance on plain radiographs, which corresponds to the “polka dot” appearance on CT scans (12 –14). Rarely, osseous hemangiomas may exhibit locally aggressive features such as expansion and occasional soft tissue mass formation, potentially causing neurological symptoms. These cases are referred to as aggressive hemangiomas. In our cohort, all osseous hemangiomas were vertebral in location, with typical radiological features. FDG uptake in hemangiomas is generally low to absent, with only one-third of lesions demonstrating uptake higher than the blood pool (15). In our cases, SUVmax values were in the range of 1.5–3.5, consistent with the literature. Despite the generally low FDG uptake in osseous hemangiomas, cases with high FDG uptake have been reported (16). Cohen et al. described a vertebral hemangioma with mild FDG uptake that later exhibited increased SUVmax on follow-up imaging, which was attributed to metastatic foci within the hemangioma (17). Hu et al. reported a plasma cell myeloma mimicking hemangioma with similar FDG uptake and CT imaging characteristics (18).

In our study, six cases were diagnosed with fibrous dysplasia. All lesions exhibited characteristic findings, such as a sclerotic rim surrounding the lesion, and some demonstrated mild expansion with a ground-glass appearance, eliminating the need for further investigation (MRI or biopsy). Fibrous dysplasia (FD) arises due to a defect in osteoblast differentiation and maturation caused by GNAS1 gene mutations, leading to the replacement of normal bone with a fibrous stroma interspersed with immature bone. The classical radiological feature of FD is the “ground-glass” appearance, formed by immature osseous tissue and fibrous stroma. The lesions are centrally located within the medullary region of the metaphysis or metaphyseal-diaphyseal junction of long bones. FD most commonly involves the proximal femur, tibia, calvarium, facial bones, and ribs. On radiographs and CT, FD appears as a sclerotic, well-defined lesion with mild expansion, occasionally causing cortical thinning and endosteal scalloping (19).

Aoki et al. reported high FDG uptake in cases of giant cell tumors, chondroblastoma, fibrous dysplasia, sarcoidosis, Langerhans cell histiocytosis, and non-ossifying fibroma (20). The reason behind the hypermetabolic appearance of moderately biologically active lesions such as fibrous dysplasia or osteofibrous dysplasia remains unclear. Active-phase FD with biological activity can exhibit high FDG uptake (21,22). In our cohort, SUVmax values of FD lesions were in the range of 1–9.8, showing significant differences compared to normal bone. Some lesions demonstrated high FDG uptake due to their active phase, raising suspicion for metastasis.

Four cases in our series were consistent with osteomas. Only one of these patients exhibited FDG uptake reaching SUVmax values of 9.3, mimicking malignancy. The other lesions demonstrated minimal FDG uptake. In the literature, case reports have presented examples of osteomas exhibiting FDG uptake as high as that observed in malignancies, similar to our patient (23,24). Consistent with the literature, FDG uptake in osteomas is typically low, and characteristic CT features are more diagnostic than FDG avidity (15). On CT, three lesions were sharply demarcated and densely sclerotic, while one lesion exhibited a sclerotic periphery with a relatively lower-density center, typical of mature osteomas. Osteomas are hamartomatous lesions resulting from abnormal proliferation of compact bone without stromal cellular proliferation, frequently located in craniofacial bones and paranasal sinuses. The differential diagnosis of osteoma includes osteoblastic metastases. A key feature in distinguishing osteomas is their density, which is as high as that of cortical bone (25).

In our series, four patients demonstrated CT findings consistent with osteonecrosis in the mandible (n = 4), long bones (n = 3), and iliac wings (n = 2). Lesions in long bones and the iliac wings appeared as well-defined sclerotic regions with geographic-serpiginous patterns, while mandibular lesions displayed heterogeneous density, coarsened trabecular bone, and cortical thickening. FDG uptake was in the range of 1.1–19.5, with higher uptake reflecting active-phase osteonecrosis.

Six cases were diagnosed with Paget's disease. Paget's disease, characterized by excessive osteoclast activity followed by compensatory osteoblastic activity, is usually incidentally detected after the age of 50 years. It commonly affects the pelvis, proximal long bones, skull, and spine, presenting in three stages: early (osteolytic); mixed (intermediate); and late (sclerotic). The appearance of imaging, including PET/CT, depends on the stage of the disease (15). Long bones exhibit cortical thickening, expansion, and coarsened trabecular bone, while skull lesions in the lytic phase appear as “osteoporosis circumscripta.” In the spine, Paget's disease can result in “picture frame vertebra” due to cortical thickening or “ivory vertebra” in sclerotic lesions, necessitating differentiation from metastases, osteosarcoma, lymphoma, or carcinoma (26). The lesions in our series exhibited a mixed lytic and sclerotic appearance, with trabecular coarsening and cortical thickening. Active Paget’s disease is characterized by cortical and trabecular thickening and may demonstrate FDG uptake with SUVmax values exceeding 5, which is an important consideration in evaluating metastases in older patients. In a study conducted by Üstün et al., it was reported that the metabolic parameters (SUVmax and SUVmean) obtained through 18F-FDG-PET/CT in 45 patients with Paget's disease of bone were insufficient in distinguishing the stage of the disease. In other patient series with Paget's disease, the majority of lesions did not exhibit abnormal 18F-FDG uptake, although significant FDG uptake mimicking malignancy was reported in a few cases (27). In our series, SUVmax values were in the range of 1.9–8.5. CT imaging findings and the patient's prior investigations achieved the differentiation of lesions showing high FDG uptake from metastatic processes.

Six cases exhibited typical features of perineural cysts (Tarlov cysts) with SUVmax values of 1.2–2.7. Tarlov cysts, also known as perineural cysts, are cerebrospinal fluid-filled dilations of the nerve root sheath located at the dorsal root ganglion (posterior nerve root sheath). These cysts are common, occurring in approximately 4.6% of the population, with a higher prevalence in girls/women. They typically appear as simple cystic structures with cerebrospinal fluid density and very thin walls, closely associated with sacral and lower lumbar nerves. They can lead to enlargement of the sacral foramina (28,29). On CT imaging, they are observed as well-defined cystic lesions.

Eight cases demonstrated subchondral cysts, appearing as well-defined lytic lesions with sclerotic rims on CT. SUVmax values were in the range of 1–5.5, with increased uptake attributed to surrounding edema or inflammation. Subchondral cysts (or geodes) are intraosseous non-neoplastic cysts with a fibrovascular lining containing mucoid material. These cysts frequently involve the hip, knee, and carpal bones and are commonly associated with arthritic disorders, particularly osteoarthritis. On radiographs, they appear as radiolucent lesions with a sclerotic rim, typically located in the subchondral region. The subchondral location, non-aggressive imaging features, and associated degenerative joint changes support the diagnosis (3).

Two cases with lesions located in the iliac wings and mandible, with SUVmax values of 3.1 and 4.7, respectively, showed CT features consistent with osteomyelitis, including permeative lytic patterns, periosteal thickening, and density changes in adjacent soft tissues.

18F-FDG PET/CT is a valuable tool in the evaluation of primary bone tumors; however, the degree of FDG uptake does not always reflect the malignant potential. FDG accumulation can occur in both benign and malignant bone lesions due to increased glucose metabolism. As observed in our study, benign lesions such as osteoid osteoma, fibrous dysplasia, and Paget's disease of bone can exhibit high FDG uptake, whereas certain low-grade malignant tumors may demonstrate lower FDG activity. This finding underscores the limitations of assessments based solely on FDG uptake. Studies have demonstrated that FDG PET/CT exhibits high sensitivity in identifying the primary tumor site in patients with malignancy of unknown origin. Although this highlights the diagnostic utility of FDG PET/CT, the absence of morphological evaluation can lead to false-positive or false-negative results. Therefore, a careful analysis of the morphological characteristics observed in the CT component of PET/CT scans is crucial for accurate lesion characterization. It is essential to recognize that FDG uptake alone is insufficient, and morphological analysis must complement metabolic imaging. This integrative approach enables more reliable outcomes in the processes of accurate diagnosis, staging, and monitoring of treatment response.

Studies in the literature on dual-time point 18F-FDG PET and 18F-sodium fluoride PET have led to the development of specific indications and interpretation criteria over time to achieve better diagnostic accuracy in musculoskeletal lesions and clinical applications (5,30).

The present study has some limitations. This study evaluated data on incidental benign lesions in 86 patients who underwent PET-CT scans for oncological diagnoses. The findings could be further expanded by increasing the sample size. In addition, histopathological evaluation was not performed in these patients due to the high specificity of the radiological appearance and the stable nature of the lesions.

In conclusion, to successfully differentiate and manage incidentally detected bone lesions, their CT morphological features must be evaluated in conjunction with FDG characteristics. The variability of FDG uptake in intraosseous lesions limits the standalone use of 18F-FDG-PET/CT for predicting malignant potential. Incidental osseous FDG uptake can be diagnostically challenging due to numerous underlying physiological and pathological causes. However, the integration of tumor morphology from the CT component of 18F-FDG-PET/CT with the patient's clinical history and additional imaging studies facilitates focused differential diagnosis. For lesions where a definitive benign diagnosis cannot be established through CT imaging, MRI, or follow-up PET/CT imaging may be performed. If uncertainty remains regarding the nature of the lesion after imaging and clinical evaluation, biopsy for histopathological diagnosis should be recommended. The decision to proceed with further investigation should be made on a case-by-case basis, taking into account the patient's clinical condition, lesion characteristics, and the need for additional diagnostic confirmation. Musculoskeletal radiologists play a crucial role in accurately characterizing these lesions, guiding treatment management, and preventing unnecessary procedures.

Footnotes

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Ipek Tamsel

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