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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.<\/jats:p>","DOI":"10.1177\/0192623313517772","type":"journal-article","created":{"date-parts":[[2014,1,31]],"date-time":"2014-01-31T23:30:29Z","timestamp":1391211029000},"page":"1082-1091","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Injection-site Malignant Fibrous Histiocytomas in a Pegvisomant Carcinogenicity Study in SD Rats"],"prefix":"10.1177","volume":"42","author":[{"given":"Phillip M.","family":"Bartholomew","sequence":"first","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M.","family":"Kreeger","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Groton, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Morton","sequence":"additional","affiliation":[{"name":"Drug Safety Research and Development, Pfizer Inc., Cambridge, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2014,1,31]]},"reference":[{"key":"bibr1-0192623313517772","doi-asserted-by":"publisher","DOI":"10.1177\/019262339902700505"},{"key":"bibr2-0192623313517772","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1961.70"},{"key":"bibr3-0192623313517772","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/hed.21449","volume":"33","author":"Clark D. 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