Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches | Congenital Defects | JAMA Dermatology | JAMA Network
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Original Investigation
July 2017

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

Author Affiliations
  • 1Department of Dermatology, Uniformed Services University of the Health Sciences, Bethesda, Maryland
  • 2Naval Health Clinic, Pearl Harbor, Hawaii
  • 3Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland
  • 4Department of Medicine, Case Western Reserve University at MetroHealth Medical Center, Cleveland, Ohio
  • 5Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 6Lister Hill National Center for Biomedical Communications, US National Library of Medicine, Bethesda, Maryland
JAMA Dermatol. 2017;153(7):660-665. doi:10.1001/jamadermatol.2017.0298
Key Points

Question  What are the clinical characteristics of connective tissue nevi in patients with tuberous sclerosis complex (TSC)?

Findings  In this retrospective analysis of patient medical records and clinical photography of 104 adult patients with TSC, more than half of patients with TSC had at least 1 connective tissue nevus, and 51% of all nevi appeared on the lower back, while the other 49% were distributed throughout the upper and middle back, buttocks, and thighs.

Meaning  Tuberous sclerosis complex–related connective tissue nevi have various presentations, and their recognition is important for timely diagnosis.


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 Participants  A 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 (≥8 cm).

Main Outcome and Measures  Frequency, 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.