Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches

Abstract

IMPORTANCE Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC.OBJECTIVE To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex. DESIGN, SETTING, AND PARTICIPANTSA retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to <4 cm), medium (4 to <8 cm), and large (Ն8 cm). MAIN OUTCOME AND MEASURESFrequency, anatomic location, size, and histological appearance of connective tissue nevi in patients with TSC.RESULTS Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis, fibroblasts grown from shagreen patches expressed higher levels of phosphorylated ribosomal protein S6 than paired fibroblasts from normal-appearing skin.CONCLUSIONS AND RELEVANCE Tuberous sclerosis complex-related connective tissue nevi are not limited to the lower back, and occasionally present on the central or upper back, buttocks, or thighs. Elastic fibers are typically decreased. Recognition of these variable presentations can be important for TSC diagnosis.

Fibrous cephalic plaques in tuberous sclerosis complex

“…Interestingly, FCPs were more common on the left side in our cohort. It appears that large shagreen patches in TSC patients also predominate on the left [27]. This may be spurious but a potential biologil explanation can be postulated based on the role of the primary cilium in lateralization.…”

“…Patients with histopathologically confirmed, small FCP-like lesions should be questioned for a personal or family history suggestive for TSC, closely examined for additional mucocutaneous features of TSC, and considered for complete diagnostic evaluation. This presentation and work-up is analogous to small collagenomas <1cm diameter that do not meet criteria for shagreen patch [27].…”

Folliculocystic and collagen hamartoma of tuberous sclerosis: A new case in a female patient and review of literature

“…Shagreen patch may also mimic FCCH clinically, but histopathologically it is a connective tissue nevus, characterized by haphazardly arranged collagen with no follicular structures involved and absence of fibrosis . If ruptured cysts predominate in the lesion, it may be misdiagnosed as acne or acne keloidalis nuchae, but the clinical presentation usually helps to differentiate those entities.…”

Multiple hypomelanotic macules in an infant cannot be ignored

“…Shagreen patch, a type of collagenoma, is another characteristic feature of TSC that very rarely appears before 1 year of age. 4 Because seizures and cardiac rhabdomyomas occur in the majority of affected infants, systemic examinations for asymptomatic infants with skin lesions alone should be performed. Notably, our patient presented with hypopigmented macules and shagreen patch; it was highly unusual for a neonate of this age with TSC to exhibit a complete spectrum of cutaneous presentations.…”