Undifferentiated Pleomorphic Sarcoma after Pirfenidone Use: A Case Report.

INTRODUCTION: Pirfenidone was approved in 2014 for the treatment of idiopathic pulmonary fibrosis. Pirfenidone inhibits several factors such as tissue growth factor-ß and platelet-derived growth factor, leading to decreased epithelial and fibroblast proliferation and collagen synthesis. The drug improves progression-free survival and is well tolerated, with minimal side effects. However, data on its long-term effects are lacking. CASE PRESENTATION: We present a rare case in which an undifferentiated pleomorphic sarcoma developed in a 59-year-old man with idiopathic pulmonary fibrosis who was treated with pirfenidone for more than a year. DISCUSSION: Undifferentiated pleomorphic sarcoma, also known as malignant fibrous histiocytoma, is a soft-tissue sarcoma arising from fibroblasts. The disease presents in the extremities and the trunk of elderly patients, and rarely in the retroperitoneum. Surgical excision is the mainstay of treatment; however, recurrence is common in the form of lung and lymph node metastases. In this report we review this rare malignancy and highlight the need for postmarketing longitudinal studies to determine additional adverse effects in patients with idiopathic pulmonary fibrosis who are on pirfenidone therapy.

Injection-site malignant fibrous histiocytomas in a pegvisomant carcinogenicity study in SD rats.

In a 2-year rat carcinogenicity study, pegvisomant injected subcutaneously on a daily basis at doses of 0, 2, 8, or 20 mg/kg/day produced malignant fibrous histiocytomas (MFHs) at the injection sites of 3 male rats (5%) given 8 mg/kg/day and 5 males (8%) given 20 mg/kg/day. MFH was characterized by unencapsulated dermal and subcutaneous sheets of fusiform and spindle-shaped cells sometimes with areas of round and/or irregular, pleomorphic cells and variable numbers of large multinucleated giant cells. Some regions of MFH had a fibroblastic appearance with streaming cells forming storiform patterns, while other areas consisted primarily of round to plump irregular cells with more giant cells. Pegvisomant did not increase the incidence of MFH in female rats and did not produce any other neoplastic responses in rats. In the dermis and subcutis at the injection sites of many males and females, pegvisomant produced dose-related increased incidences and severity of histiocytic infiltrates consisting of vacuolated macrophages with variable mature or immature fibrous tissue. Neoplasms at injection sites did not result in marketing restrictions or a label warning for human cancer risk, highlighting that injection-site neoplasms in rats have low relevance for human risk assessment.