Contribution of Beta-HPV Infection and UV Damage to Rapid-Onset Cutaneous Squamous Cell Carcinoma during BRAF-Inhibition Therapy.

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.

Importance of vertical pathology of debulking specimens during Mohs micrographic surgery for lentigo maligna and melanoma in situ.

BACKGROUND: Recent Recovery Audit Contractor audits have targeted Mohs micrographic surgery (MMS) if permanent-section pathology codes have been used on the same day. In lentigo maligna (LM) or melanoma in situ (MIS) cases, this is done to further evaluate the tumor for staging. OBJECTIVE: To determine the percentage of LM, MIS, and thin invasive melanomas upstaged when a central debulking specimen from MMS is sent for permanent vertical sections. METHODS: A single-center retrospective study examining LM, MIS, and thin melanomas treated with MMS between January 1, 2004, and September 30, 2011, at Vanderbilt University was performed. The elements needed for staging, sex, age, tumor location, size, and previous skin cancer history were obtained. RESULTS: Fourteen of 173 cases (8.1%; 95% confidence interval = 4.9-13.1%) were identified in which the tumor was upstaged; 13 of the cases initially diagnosed as LM or MIS were invasive (average Breslow depth 0.69 mm). One melanoma at 0.6 mm depth on initial biopsy increased to 1.2 mm after the debulking specimen from Mohs surgery was examined histologically. Debulking in four cases revealed a depth of 1 mm or greater. No differences existed in characteristics between upstaged and nonupstaged cases. CONCLUSION: When performing MMS for LM or MIS, it is appropriate and necessary to send the central debulking specimen for permanent histology for accurate tumor staging.

Vesicular eruption on the arm of an infant.

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.