Gardner-associated fibromas (GAF) in young patients - A distinct fibrous lesion that identifies unsuspected Gardner syndrome and risk for fibromatosis

Gardner syndrome (GS), caused by mutations in the adenomatous polyposis coi l (APC) gene, is characterized by polyposis coli, osteomas, and various sof t-tissue tumors. If undetected or untreated, virtually all patients develop colonic carcinoma at a young age. Early detection, while essential, can be difficult because of attenuated phenotypes or spontaneous mutations. We pr esent the clinicopathologic features of 11 identical fibromatous lesions th at we have termed Gardner-associated fibroma (GAF), which not only appear t o be a part of the spec trum of lesions associated with GS but, in some cas es, represent the sentinel event leading to its detection. The GAFs occurre d in 11 patients (5 boys and 6 girls; age range, 3 months-14 years), were s olitary (n = 7) or multiple (n = 4), and occurred in the superficial and de ep soft tissues of the paraspinal region (n = 7), back(n = 3), face (n = 2) , scalp(n = 3), chest wall (n = 2), thigh (n = 1), neck (n = if, and flank (n = 1). Histologically, GAFs resemble nuchal-type fibromas (NFs), consisti ng of thick, haphazardly arranged collagen bundles between which are found occasional bland fibroblasts, and having margins that frequently engulf sur rounding structures including adjacent fat, muscle and nerves. After surgic al excision, four patients developed recurrences that were classic desmoid fibromatoses (DFs). In one patient with multiple GAFs, one lesion had the f eatures of GAF and DF in the absence of surgical trauma. A family history o f GS or polyposis (n = 6) or DF (n = 1) was known at the time of surgery in seven patients. In three patients, the diagnosis of GAF resulted in the di agnosis of unsuspected APC in older family members, with the detection of a n occult colonic adenocarcinoma in one parent. In the family of the remaini ng patient, no stigmata of GS were present. Genetic analysis of this child was performed to investigate the presence of a spontaneous (new) mutation: however, no abnormalities were detected. The significance of GAF is that it serves as a sentinel event for identifying GS kindreds, including those wi th a high risk for the development of DF, and it may potentially identify c hildren with spontaneous mutations of the APC gene. Because NFs and GAFs re semble one another, we suggest that a subset of NF occurring in multiple si tes, unusual locations. or children may be GAF.