Section 6 -

Gardner Fibroma and Desmoid Fibromatosis Cheryl M. Coffin, M.D. David M. Parham, M.D.

Clinical History: A 12-year old boy developed a painful enlarging nodular and plaque-like mass in the superior paraspinal region. He had a history of superficial soft tissue masses in the paraspinal region, head, chest wall, and posterior thigh since two years of age. Biopsies in the past had revealed benign fibrous lesions, including one from the same site. The family history was remarkable for rhabdomyosarcoma in a paternal uncle at 3 years of age, desmoid tumors and colonic adenomas in the father, and colonic adenocarcinomas in paternal relatives. Genetic testing of the child and his father revealed an APC mutation. Discussion and Differential Diagnosis: This case is an example of Gardner fibroma with development of a desmoid fibromatosis in the same site, in a patient with APC. The points for discussion are the clinicopathologic features and differential diagnosis of Gardner fibroma and desmoid tumor, the association with APC, and manifestations of APC in childhood and adolescence. The rubbery plaque-like areas of the mass showed typical features of Gardner-associated fibroma with hypocellular sheets of haphazardly arranged collagen fibers separated by clear cracks and bland spindle cells. The Gardner fibroma entrapped adipose tissue, blood vessels, and nerve fibers. Immunohistochemistry revealed reactivity for CD34 in the bland spindle cells. The round nodular area showed histologic features of desmoid fibromatosis with interlacing bundles of uniform spindle cells separated by variable collagen and delicate curing blood vessels. The spindle cells had oval to elongated nuclei, abundant cytoplasm, and indistinct cell borders. In some areas, the tumor cells had a more plump stellate configuration, and myxoid foci were present. There was variable immunohistochemical reactivity for smooth muscle actin. Occasional mitoses were seen, but no atypical mitoses were identified. Gardner fibroma is a distinctive, densely collagenized, sheet-like proliferation of bland spindle cells. It entraps normal tissues, such as fat nerve and blood vessels. Frequently it is an early manifestation of familial adenomatous polyposis and may be associated with classic desmoid fibromatosis, as in this case. It occurs in superficial and deep soft tissues of the trunk, head and neck, and extremities. Gardner fibroma in childhood can serve as a sentinel event for identifying an individual or a family with adenomatous polyposis coli. Desmoid tumor accounts for up to 60% of fibrous tumors of childhood, although it has traditionally been considered an adult-type fibromatosis. There is a well-established association with familial adenomatous polyposis (FAP, Gardner syndrome) and with antecedent trauma, surgery, and irradiation. A desmoid fibromatosis in early childhood may be the initial manifestation of an APC mutation or may occur in the same site as a pre-existing or concurrent Gardner fibroma. The firm, grey-white, oval or fusiform mass has irregular infiltrative margins and a white, whorled, or trabeculated cut surface. There is limited information to suggest that foci of mucoid degeneration, abundant plump stellate tumor cells, and a large number of small slit-like blood vessels in the central portions of the tumor may be associated with a higher tendency for recurrence. The local recurrence rate is 33 to 68%. The advancing border of the tumor infiltrates between and entraps adjacent tissue, and chronic inflammation may be seen at the periphery. It is usually very difficult to determine the surgical margins at the time of operation. Desmoid fibromatosis is a clonal neoplasm which may harbor trisomies 8 and 20 and 5q deletion in addition to APC mutation. The differential diagnosis includes fibromatoses, keloid or hypertrophic scar, nuchal fibroma, infantile myofibromatosis, nerve sheath tumors, inflammatory myofibroblastic tumor, and low-grade spindle cell sarcomas such as myofibrosarcoma and low-grade fibromyxoid sarcoma. In most instances the distinction can be made on the basis of histopathology and immunohistochemistry. This case highlights the association between FAP and Gardner fibroma and emphasizes that Gardner fibroma can be the sentinel event for the diagnosis of adenomatous polyposis coli in a child and family members. In FAP the average onset of intestinal adenomas is 25 years and the lifetime risk of intestinal adenocarcinoma is 100%. Extracolonic manifestations of adenomatous polyposis coli seen in children include gastrointestinal, soft tissue, and other types of lesions. 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