A retrospective analysis was performed from a pool of 66 patients, ranging in age from 4-76 years, with a definite diagnosis of TSC from our hospital databases. Only 40 patients had useful imaging studies (chest, body and cranial CTs) for the evaluation of sclerotic bone lesions, (80%) were females and (20%) males with a median age of 42.
Two radiologists compared between each other the number and distribution in the skeletal system of the sclerotic bone lesions in the CT scans.
The following information was collected: Age when the CT was performed, gender, mutational study, number and characteristics of these bone lesions. Multiple lesions were defined as three or more.
All lesions were small, hyperdense, with well defined margins and absent cortical disruption. Sclerotic bone lesions were found in 33 (83%) patients. Of those, 27 had multiple (3 or more) lesions.
Our study found a high frequency (83%) of these lesions in adults with TSC, supporting the results of another study in 107 adult TSC patients with chest CT that demonstrated a high prevalence of multiple SBLs (four or more) in 91% of cases, and 98% of patients showed at least one SBL [7], and 89% in another study [5].
As already shown in that study, we also found that the most common location of this lesions was the spine (Fig. 1 Fig. 2) (with a preference for vertebral bodies and posterior elements of the spine): 91%, followed by the pelvis (Fig. 3 Fig. 4) : 76% and chest: (ribs, sternum, clavicles): 55%. Less frequently sclerotic bone lesions were found in upper extremities: 15% and lower extremities: 18% The skull bone was affected in only one patient (Fig. 5 ).
Regarding gender, 79% of patients with sclerotic bone lesions were female and 21% were male.
In our study only 40% of patients had mutations in TSC1 or TSC2 genes, while the remaining 60% had no mutations. Although it has been described in the literature [5,10], we found no significant difference in presence and number of sclerotic bone lesions between patients with TSC1/TSC2 mutations and those without.
An important clinical aspect of TSC SBLs is differentiating them from osteoblastic metastases (Fig. 6 Fig. 7 Fig. 8 Fig. 9 ). Awareness of SBLs in TSC is important to avoid unnecessary clinical testing and misdiagnosis. Patients with TSC present frequently with tumors, and the finding of multiple sclerotic lesions in the spine may lead to the wrong diagnosis of osteoblastic metastases (Fig. 10) in some cases, particularly if the clinical manifestations of TSC are mild or TSC has not been diagnosed yet. Moreover, the posterior aspects of the vertebral bodies, which also account for typical sites of spine metastases in adults, are the main location of SBLs in TSC. CT and MR imaging characteristics may help in differentiating these entities Fig. 11 [7].
SBLs as a potential imaging biomarker could be especially important in the diagnostic workup of the following patient collectives: First, for oligosymptomatic or younger patients, who do not fully meet the diagnostic TSC guideline criteria. Second, as an index finding in all patients with undiagnosed TSC, in which a CT scan is performed due to other clinical indications. In these patients, the recognition of SBLs as a typical imaging sign of TSC could represent the crucial connection towards a timely diagnosis and, if indicated, a specific therapy.