HPV51-associated Leiomyosarcoma: A Novel Class of TP53/RB1-Wildtype Tumor With Predilection for the Female Lower Reproductive Tract.

Inactivating mutations in tumor suppressor genes TP53 and RB1 are considered central drivers in leiomyosarcomas (LMSs). In high-risk human papillomavirus (HPV)-related tumors, a similar functional outcome is achieved through oncoproteins E6 and E7, which inactivate the p53 and RB1 proteins, respectively. Here, we hypothesized that HPV infection could provide an alternative mechanism for tumorigenesis in a subset of TP53/RB1-wildtype LMS. We evaluated tumor samples from 2585 consecutive unique patients carrying a diagnosis of gynecologic or soft tissue LMS. Tumor DNA and available RNA were analyzed by hybrid-capture-based next-generation sequencing/comprehensive genomic profiling of 406 genes and transcripts (FoundationOneHeme). Of the initial 2585 cases, we excluded 16 based on the presence of molecular alterations that are considered defining for sarcomas other than LMS. In the remaining 2569 cases, we searched for LMS that were TP53/RB1-wildtype (n=486 of 2569; 18.9%). We also searched LMS tumors for HPV sequences that we then classified into genotypes by de novo assembly of nonhuman sequencing reads followed by alignment to the RefSeq database. Among TP53/RB1-wildtype LMS, we identified 18 unique cases harboring HPV sequences. Surprisingly, most (n=11) were HPV51-positive, and these 11 represented all HPV51-positive tumors in our entire LMS database (n=11 of 2569; 0.4%). The absence of genomic alterations in TP53 or RB1 in HPV51-positive LMS represented a marked difference from HPV51-negative LMS (n=2558; 0% vs. 72% [P<0.00001], 0% vs. 53% [P=0.0002]). In addition, compared with HPV51-negative LMS, HPV51-positive LMS were significantly enriched for genomic alterations in ATRX (55% vs. 24%, P=0.027) and TSC1 (18% vs. 0.6%, P=0.0047). All HPV51-positive LMS were in women; median age was 54 years at surgery (range: 23 to 74 y). All known primary sites were from the gynecologic tract or adjacent anogenital area, including 5 cases of vaginal primary site. Histology was heterogeneous, with evaluable cases showing predominant epithelioid (n=5) and spindle (n=5) morphology. In situ hybridization confirmed the presence of high-risk HPV E6/E7 mRNA in tumor cells in three of three evaluable cases harboring HPV51 genomic sequences. Overall, in our pan-LMS analysis, HPV reads were identified in a subset of TP53/RB1-wildtype LMS. For all HPV51-associated LMS, the striking absence of any detectable TP53 or RB1 mutations and predilection for the female lower reproductive tract supports our hypothesis that high-risk HPV can be an alternative tumorigenic mechanism in this distinct class of LMS.

Split-face comparison of grid fractional radiofrequency vs 1064-nm Nd-YAG laser treatment of periorbital rhytides among Filipino patients.

Despite multiple individual studies proving efficacy of grid fractional monopolar radiofrequency (Grid RF) and near-infrared irradiation 1064-nm long-pulsed neodymium:YAG laser (Laser Genesis), there is a lack of controlled comparative trials between these devices. This study aims to compare the efficacy and safety of Grid RF versus Laser Genesis in the treatment of periorbital rhytides. This is a randomized, single-blind, split-face, prospective study. Eight patients with moderate to severe periorbital rhytides were treated with either Grid RF or Laser Genesis on each side of the face. Photographic and live assessment with the Lemperle Wrinkle Assessment grading scale was compared after 2 months. Difference in scores between Grid RF vs Laser genesis groups after 2 months was not statistically significant (P = 0.244). Each group showed statistically significant improvement months post-procedure (P < .05). Immediate adverse effects and satisfaction scale were similar for both groups (P > .05). At 2 months follow-up, no adverse effects were seen. Grid monopolar radiofrequency (Grid RF) vs near-infrared radiation 1064 nm long-pulsed Nd-YAG laser (Laser Genesis) were equally efficacious, safe, and well-tolerated among patients in the treatment of periorbital wrinkles (P > .05).

Efficacy and safety of single versus multiple intralesional immunotherapy with purified protein derivative (PPD) in the treatment of multiple verruca vulgaris.

BACKGROUND: Despite the numerous studies on the use of purified protein derivative (PPD), a protein extracted from Mycobacterium tuberculosis, in verruca vulgaris, there is no standardized regimen, and efficacy of single versus multiple injections has not been compared. METHODS: This is a randomized, open-label, superiority trial. Sixty-six patients with at least three warts in two different anatomic sites were randomized into two groups: a single injection (n = 29) and multiple injection (n = 29) groups. Patients were treated every 2 weeks until a maximum of six sessions. RESULTS: Multiple injections (79.3%) showed superior clearance rates compared to a single injection of PPD (58.6%) (P-value = 0.0236). Multiple injections also exhibited faster clearance at each time point (P = 0.048). Pain was statistically more significant in the multiple injection group (P = 0.0005). There was no statistically significant difference in incidence of adverse events (P = 0.1795). Amongst all cleared patients in both groups, there were no recurrences after 6 months. CONCLUSION: Multiple injections of warts with PPD cleared more patients with multiple common warts than the use of single injections at the end of 12 weeks and were faster in clearing patients at every time point. Single injection was better tolerated than multiple injections. Both treatments exhibited similar safety profiles and recurrence rates.