title: Panniculitis With Necrotizing Granulomata in a Patient on BRAF Inhibitor (Dabrafenib) Therapy for Metastatic Melanoma.
abstract: There have been major developments in targeted therapeutics with the clinical development of selective BRAF inhibitors (BRAFi) for patients with metastatic BRAF V600E mutant melanoma. Objective response rate of almost 50% has been witnessed in BRAFi clinical trials. Frequent side effects range from squamoproliferative lesions, including hyperplasia, keratoacanthomas, and squamous cell carcinomas to second primary melanomas. We describe a 50-year-old Hispanic woman with BRAF V600E mutant metastatic melanoma who was treated with surgery, radiation therapy, interleukin-2, and was enrolled on a BRAFi (dabrafenib) trial. Two months after initiation, she developed multiple erythematous, indurated, tender subcutaneous nodules bilaterally on the anterior thighs, posterior arms, and left dorsal forearm without overlying epidermal change. Punch biopsy revealed panniculitis with necrotizing granulomata. Infectious and other causes for panniculitis were excluded. We believe the histology likely represents a reaction to BRAFi therapy based on the temporal relationship of its onset to initiation of BRAFi therapy and previously reported cases of neutrophilic panniculitis associated with BRAFi therapy. Panniculitis has been emerging as an important unusual side effect of BRAFi therapy. Our case illustrates a unique presentation of BRAFi-associated panniculitis demonstrating necrotizing granulomata.
authors.affiliation: Departments of *Pathology, and †Dermatology, The University of Texas MD Anderson Cancer Center, Houston, TX.
authors.forename: Nisha S
authors.initials: NS
authors.lastname: Ramani
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Curry
authors.forename: Jyoti
authors.initials: J
authors.lastname: Kapil
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Rapini
authors.forename: Michael T
authors.initials: MT
authors.lastname: Tetzlaff
authors.forename: Victor G
authors.initials: VG
authors.lastname: Prieto
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Torres-Cabala
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D005260:Female; D006099:Granuloma / Q000139:chemically induced*; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009336:Necrosis / Q000139:chemically induced; D010091:Oximes / Q000009:adverse effects*; D015434:Panniculitis / Q000139:chemically induced*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012867:Skin / Q000473:pathology*; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010091:Oximes; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib