Tuberous sclerosis complex (TSC) is a rare autosomal dominant neurocutaneous syndrome characterized by various abnormalities, including benign hamartomatous tumors in multiple organs. It is the second most common phakomatosis behind neurofibromatosis type 1 and affects approximately 1.5 million people worldwide with a birth incidence of 1 in 6000. [1]

Around one third of cases of TSC are familial and caused by mutations in two tumor suppressor genes, TSC1 and TSC2. The other two thirds are sporadic and due to spontaneous mutations. 

TSC1 and TSC2 encode the proteins hamartin and tuberin respectively, which inhibit the mTOR cascade, regulating cell growth and differentiation. The absence of any of these proteins leads to uncontrolled growth of multisystemic hamartomatous tumors.

Mutations of TSC2 are more frequent than mutations of TSC1 and also associated with more severe disease. [1-2]

The updated diagnostic criteria for tuberous sclerosis from the second 2012 International Tuberous Sclerosis Complex Consensus Conference added genetic testing as a diagnostic criteria along with clinical and radiological manifestations.(3)

However, clinical manifestations of TSC are highly variable depending on age and organ manifestation. As a result, diagnosis can be difficult or even completely missed. 

A reliable diagnosis of TSC is extremely important, particularly for oligosymptomatic patients. Timely treatment with mTOR inhibitors can treat organ manifestations and dramatically improve prognostic outcome. (4)

Bone cysts had been previously considered minor diagnostic criteria for tuberous sclerosis, however the new guidelines have excluded them. [3,5] They are usually found in small bones of hands and feet [5].

Although they are not included in the updated diagnostic criteria, a relationship between other bone lesions (such as fibrous dysplasia and sclerotic bone lesions) and tuberous sclerosis has already been established in previous studies [2,5,6,7,8].

Sclerotic bone lesions of the axial skeleton are frequent manifestations related to tuberous sclerosis complex. They are easy to detect on CT scans and are morphologically comparable to focal bone islands [2]. 

Focal sclerotic lesions are usually found in vertebrae, ribs, spine (with predilection for vertebral bodies and posterior elements), sacrum and the iliac aspect of the sacroiliac joints [1,5,7,9]. They have been classically considered hamartomatous lesions of no clinical importance, since they usually don’t produce symptoms. Consequently, these patients do not undergo biopsy and there are no molecular studies of this lesions.

In relation to mutations, a study [5] showed a lower number of sclerotic bone lesions in patients with no mutations versus patients with TSC1 or TSC2 mutations, correlating with a study showing a lower number of some TSC manifestations in patients with no mutation identified versus patients with TSC1 or TSC2 mutations [10].  

It is important to note that  focal sclerotic bone lesions can also be associated with different diseases, most importantly osteoblastic metastases. [2]

Currently, since the pathological significance is not fully understood, screening or follow up of sclerotic bone lesions is not included in the recommendations of the new consensus guidelines for TSC. [3, 6]

The purpose of our study was to identify and characterize sclerotic bone lesions detected on CT studies of main body regions in tuberous sclerosis patients. 

Sclerotic-bone-lesions (SBL) could represent a potential imaging biomarker for the diagnosis of TSC. (6) 

Additionally, it is important to note that an adequate differential diagnosis should be performed with blastic bone metastases.