ABSTRACT
PURPOSE: BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. UV radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for ß-genus HPV is suspected in BRAFi-cSCC. Cutaneous ß-HPV may act in concert with host and environmental factors in BRAFi-cSCC. EXPERIMENTAL DESIGN: Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. RESULTS: Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During vemurafenib therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional cSCC when controlled for gender and UV exposure (P value = 0.03). Among all BRAFi-cSCC, ß-genus HPV-17, HPV-38, HPV-111 were most frequently isolated, and novel ß-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK, and EGFR mutations also detected. CONCLUSIONS: We examined clinical, histopathologic, viral, and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; ß-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered ß-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general.
Subject(s)
Carcinogenesis/genetics , Carcinoma, Squamous Cell/genetics , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/genetics , Adult , Aged , Carcinogenesis/radiation effects , Carcinoma, Squamous Cell/complications , Carcinoma, Squamous Cell/physiopathology , Carcinoma, Squamous Cell/virology , Female , Humans , Indoles/administration & dosage , Male , Middle Aged , Papillomaviridae/genetics , Papillomaviridae/pathogenicity , Papillomavirus Infections/complications , Papillomavirus Infections/genetics , Papillomavirus Infections/physiopathology , Papillomavirus Infections/virology , Skin Neoplasms/complications , Skin Neoplasms/physiopathology , Skin Neoplasms/virology , Sulfonamides/administration & dosage , Ultraviolet Rays , VemurafenibSubject(s)
Carcinoma, Squamous Cell/chemically induced , Melanoma/drug therapy , Neoplasms, Second Primary/chemically induced , Proto-Oncogene Proteins B-raf/adverse effects , Proto-Oncogene Proteins B-raf/antagonists & inhibitors , Skin Neoplasms/drug therapy , Biopsy, Needle , Carcinoma, Squamous Cell/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Immunohistochemistry , Melanoma/pathology , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Neoplasms, Second Primary/pathology , Proto-Oncogene Proteins B-raf/supply & distribution , Risk Assessment , Skin Neoplasms/pathology , Withholding TreatmentABSTRACT
Cutaneous mucormycosis is an uncommon disease and occurs mainly in immunocompromised patients. We report an immunocompetent infant who developed primary cutaneous mucormycosis at an intravenous line site secured with an arm board and elastic bandage. The isolate was identified as the zygomycete, Rhizopus sp. High mortality rates are reported with invasive mucormycosis; however, early identification of the causative agent and antifungal therapy led to complete cure of the lesions in the reported case.
