Cutaneous pleomorphic fibromas arising in patients with germline TP53 mutations

Abstract

Pleomorphic fibromas are rare benign cutaneous neoplasms associated with deletion/loss of chromosomes 13q and 17p, where RB1 and TP53 are located, respectively. Herein, we report five cases of pleomorphic fibroma arising in patients with germline TP53 mutations, suggesting a potential link with Li‐Fraumeni syndrome. All three patients were female and young (mean age 27) with a strong personal and/or family oncologic history and confirmed pathogenic germline TP53 mutations. In two patients, multiple pleomorphic fibromas were diagnosed. Clinically, the lesions arose at various cutaneous sites and were small (≤2 cm) and raised (4/5). Histopathologically, the tumors were paucicellular, composed of atypical spindled to stellate cells with hyperchromatic and variably pleomorphic nuclei. Mitotic activity was exceedingly low, although rare atypical mitotic figures were seen in one case. Immunohistochemically, the tumor cells were diffusely positive for p16 (3/3) and showed loss of Rb expression (5/5). All cases showed aberrant p53 expression (overexpression in 4, complete loss in 1). The tumors have followed a benign clinical course with no evidence of progression or recurrence. In conclusion, the development of multiple pleomorphic fibromas in a young patient may be a clue to an underlying genetic cancer syndrome involving TP53.

Pleomorphic acquired digital fibrokeratoma: A novel clinicopathologic entity

“…In contrast to pleomorphic fibromas, which stain for CD34 and variably for FXIIIa, 8–11 this case was negative for CD34 and positive for FXIIIa, further distinguishing this as a novel and separate tumor. Rb and p53 staining were also negative in lesional cells, consistent with findings previously observed in pleomorphic fibromas 6,7 . These suggest a mechanism whereby aberrations in chromosomes 13q and 17p may be involved in the formation of these tumors.…”

“…Rb and p53 staining were also negative in lesional cells, consistent with findings previously observed in pleomorphic fibromas. 6,7 These suggest a mechanism whereby aberrations in chromosomes 13q and 17p may be involved in the formation of these tumors. Alternatively, the patient's history of acute lymphocytic leukemia and chemotherapy raises the consideration that the pleomorphic changes were induced by mutations in tumor suppressor genes, such as TP53 and Rb.…”

“…In pleomorphic fibromas, the atypical giant cells stain positive for CD34 and variably for FXIIIa 5 . Pleomorphic fibromas have also been described in patients with TP53 and Rb mutations 6,7 . Despite such mutations, these lesions exhibit benign clinical courses.…”

“…5 Pleomorphic fibromas have also been described in patients with TP53 and Rb mutations. 6,7 Despite such mutations, these lesions exhibit benign clinical courses. Similar pleomorphic changes have been reported in other lesions including giant cell fibroblastomas, subungual pleomorphic fibromas, dermatofibromas, sclerotic fibromas, lipomas, and angiofibromas.…”

Slow-Growing Nodule in a Patient With Li-Fraumeni Syndrome: Answer

“…6 Pleomorphic fibromas with both RB1 and TP53 mutations have not been shown to be more clinically aggressive than those with RB1 loss alone, and all reported cases have had a benign clinical course. 6 Patients with Li-Fraumeni syndrome are at greatly elevated risk for the development of multiple malignancies including breast carcinomas, sarcomas, central nervous system tumors, adrenocortical carcinomas, and leukemias, with lifetime cancer risk approaching 100%. 7,8 There is a well-established link between TP53 mutations and nonmelanoma skin cancers 9 ; yet surprisingly, there are little published data on cutaneous malignancies in Li-Fraumeni syndrome.…”