Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.

Limited Incision Facelifts: A Contemporary Review of Approaches and Complications.

Limited incision facelifts (LIFs) have gained popularity as an alternative to traditional facelift procedures. While surgical techniques vary, these approaches share a common goal: to rejuvenate the face while minimizing scar visibility. Previous studies also suggest that the reduced tissue dissection in LIFs can lead to decreased postoperative swelling, shorter recovery periods, and fewer complications. In this systematic review we delved into the literature on LIFs, shedding light on the various surgical approaches and their respective safety profiles. A systematic review was conducted by independent evaluators who followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A random-effects model was utilized to summarize complications data, and meta-regressions were conducted to analyze associations with operative variables. The analysis encompassed a total of 20 articles, comprising data from 4451 patients. The vast majority (84%) of these patients underwent either local wide-awake surgery or conscious sedation, while the remaining 16% underwent general anesthesia. Our analysis revealed an overall complication frequency of 3.2%, with hematoma being the most common complication (2%), followed by temporary nerve injury (0.2%), and skin necrosis or wounds (0.06%). Notably, hematomas rarely required operating room interventions. Use of drains or tissue sealants was associated with an 86% decrease in complications. Limited incision facelifts can be performed with a low complication rate, utilizing a variety of techniques. Utilization of tissue sealants and drains may limit hematoma formation, which is the most common complication.

Toker Cell Hyperplasia in the Nipple-Areolar Complex of Transmasculine Individuals.

We previously reported breast histopathologic features associated with testosterone therapy in transmasculine chest-contouring surgical specimens. During that study, we observed a high frequency of intraepidermal glands in the nipple-areolar complex (NAC) formed by Toker cells. This study reports Toker cell hyperplasia (TCH)-the presence of clusters of Toker cells consisting of at least 3 contiguous cells and/or glands with lumen formation-in the transmasculine population. Increased numbers of singly dispersed Toker cells were not considered TCH. Among the 444 transmasculine individuals, 82 (18.5%) had a portion of their NAC excised and available for evaluation. We also reviewed the NACs from 55 cisgender women who were aged <50 years old and had full mastectomies. The proportion of transmasculine cases with TCH (20/82; 24.4%) was 1.7-fold higher than cisgender women (8/55; 14.5%) but did not achieve significance (P = .20). However, in cases with TCH, the rate of gland formation is 2.4-fold higher in transmasculine cases, achieving borderline significance (18/82 vs 5/55; P = .06). Among transmasculine individuals, TCH was significantly more likely to be present in those with higher body mass index (P = .03). A subset of 5 transmasculine and 5 cisgender cases were stained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), cytokeratin 7, and Ki67. All 10 cases were cytokeratin 7+ and Ki67-; 9 out of 10 cases were AR+. Toker cells in transmasculine cases demonstrated variable expression of ER, PR, and HER2. For cisgender cases, Toker cells were consistently ER+, PR-, and HER2-. In conclusion, there is a higher rate of TCH in the transmasculine than cisgender population, particularly among transmasculine individuals with high body mass index and taking testosterone. To our knowledge, this is the first study to demonstrate that Toker cells are AR+. Toker cell features display variable ER, PR, and HER2 immunoreactivity. The clinical significance of TCH in the transmasculine population remains to be elucidated.

Testosterone therapy and breast histopathological features in transgender individuals.

Testosterone therapy (TT) is administered to enhance masculinization in transgender individuals. The long-term effect of exogenous testosterone on breast tissues remains unclear. Our study evaluated the modulation of breast morphology by TT in transgender individuals with special attention to duration of TT. We reviewed 447 breast surgical specimens from gender affirming chest-contouring surgery, and compared histopathological findings including degree of lobular atrophy, and atypical and non-atypical proliferations between subjects who did (n = 367) and did not (n = 79) receive TT. TT for one patient was unknown. TT for >12 months was associated with seven histopathological features. Longer duration of TT was significantly associated with higher degrees of lobular atrophy (p < 0.001). This relationship remained significant after accounting for age at surgery, ethnicity, body mass index, and presurgical oophorectomy (adjusted p < 0.001). Four types of lesions were more likely to be absent in breast tissues exposed to longer durations of TT: cysts (median = 16.2 months; p < 0.01; adjusted p = 0.01), fibroadenoma (median = 14.8 months; p = 0.02; adjusted p = 0.07), pseudoangiomatous stromal hyperplasia (median = 17.0 months; p < 0.001; adjusted p < 0.001), and papillomas (median = 14.7 months; p = 0.04; adjusted p = 0.20). Columnar cell change and mild inflammation were also less likely to occur in subjects receiving TT (p < 0.05), but were not linked to the duration of TT. Atypia and ductal carcinoma in situ were detected in 11 subjects (2.5%) all of whom received TT ranging from 10.1 to 64.1 months. The incidental findings of high-risk lesions and carcinoma as well as the risk of cancer in residual breast tissue after chest-contouring surgery warrant the consideration of culturally sensitive routine breast cancer screening protocols for transgender men and masculine-centered gender nonconforming individuals. Long-term follow-up studies and molecular investigations are needed to understand the breast cancer risk of transgender individuals who receive TT.

Effect of testosterone therapy on breast tissue composition and mammographic breast density in trans masculine individuals.

Objective: Determine the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). Design: This is a cross-sectional study. Setting: TMIs (n=444) underwent chest-contouring surgeries to treat their gender dysphoria between 2013 and 2019 at an urban medical center. Participants: Of the 444 TMIs, 425 had pathology images analyzed by our deep-learning algorithm to extract breast tissue composition. A subset of 42/444 TMIs had mammography prior to surgery; mammography files were available for 25/42 TMIs and analyzed using a breast density software, LIBRA. Main Outcomes and Measures: The first outcome was the association of duration of TT and breast tissue composition assessed by pathologists (categories of lobular atrophy and stromal composition) or by our algorithm (% epithelium, % fibrous stroma, and % fat). The second outcome is the association of TT and breast density as assessed by a radiologist (categorical variable) or by LIBRA (percent density, absolute dense area, and absolute non-dense area). Results: Length of TT was associated with increasing degrees of lobular atrophy ( p <0.001) but not fibrous content ( p =0.821) when assessed by the pathologists. Every six months of TT was associated with decreased amounts of both epithelium (exp(ß)=0.97, 95% CI 0.95-0.98, adj p =0.005) and stroma (exp(ß)=0.99, 95% CI 0.98-1.00, adj p =0.051), but not fat (exp(ß)=1.01, 95%CI 0.98-1.05, p =0.394) in fully adjusted models. There was no association between TT and radiologist's breast density assessment ( p =0.575) or LIBRA measurements ( p >0.05). Conclusions: TT decreases breast epithelium and fibrous stroma, thus potentially reducing the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk. Summary Box: Very little is known about the effect of gender-affirming testosterone therapy on cancer risks, such as breast cancer.Epidemiological studies had different conclusions about the association between testosterone and breast cancer in cisgender women (positive association) and trans masculine individuals (inverse association).More laboratory-based research are needed to understand the effect of testosterone on breast cancer risk in the understudied trans masculine population.Our study provides quantitative histological evidence to support prior epidemiological reports that testosterone may reduce breast cancer risk in trans masculine individuals.

Nasal Tip Delamination: A Technique for Nasal Tip Projection and Control in Rhinoplasty.

BACKGROUND: Control of tip projection and rotation is critical to a successful rhinoplasty. Suture techniques that change the relationship of the medial crura to the caudal septum can effectively manage tip position, but may be technically challenging or require specialized sutures. The authors present a technique ("tip delamination") that allows symmetrical exposure of the medial crura and caudal septum for accurate placement of projection control sutures using commonly available suture materials. METHODS: We describe a novel technique to completely expose (or delaminate) the medial crura of the lower lateral cartilages to allow for 360-degree access to and manipulation of these critical structures. We present a case series of 3 patients. RESULTS: Exemplary cases with 1 intraoperative video will be reviewed to demonstrate how tip delamination allows for more precise control of the medial crura and nasal tip. CONCLUSIONS: Nasal tip delamination is a simple technique for manipulating the medial crura and nasal tip in rhinoplasty procedures. Nasal tip delamination adds minimal time and morbidity to the procedure and offers significant control for the surgeon, with beneficial outcomes for the patient.

Establishing a Cohort of Transgender Men and Gender Nonconforming Individuals to Understand the Molecular Impact of Testosterone on Breast Physiology.

Purpose: To characterize a cohort of transgender men and masculine-centered gender nonconforming individuals who underwent gender-affirming chest-contouring surgeries at our institution between 2013 and 2018. Methods: Demographics, medical history, and breast histopathological assessment for 340 patients were retrieved from medical records. Results: Most of our patients were white, non-Hispanic (75.0%), were taking testosterone (83.2%), and opted for chest-contouring surgery after 12-14 months of testosterone therapy. Ten patients were parous (2.9%). Seventy-nine (23.2%) and 27 (7.9%) patients had a family history of breast cancer or ovarian cancer, respectively. One transgender man was incidentally diagnosed with ductal carcinoma in situ at chest-contouring surgery. Conclusion: Future studies on this cohort will provide valuable insights about the impact of testosterone on breast physiology.

Anthropometric study of synostotic frontal plagiocephaly: before and after fronto-orbital advancement with correction of nasal angulation.

Surgical correction of synostotic frontal plagiocephaly (unilateral coronal synostosis) focuses on the asymmetry of the forehead and orbits. However, there is controversy regarding whether nasal angulation should be addressed during primary fronto-orbital advancement in infancy. This prospective study was undertaken to answer that question. Preoperative and postoperative anthropometric measurements were obtained for 19 infants with nonsyndromic synostotic frontal plagiocephaly. The measurements included nasal angulation, nasion-to-endocanthion distance, nasion-to-exocanthion distance, and exocanthion-to-tragion distance. All patients underwent bilateral parallelogrammatic fronto-orbital correction. Closing wedge nasal ostectomy was performed for group I (n = 14) and was not performed for group II (n = 5). The average age at the time of follow-up assessments was 3 years 8 months (range, 1 to 14 years) in group I and 5 years 5 months (range, 2 to 15 years) in group II. A statistically significant change was observed for patients who underwent primary correction of nasal angulation; the change correlated with improved naso-orbital symmetry, as judged with nasion-to-endocanthion and nasion-to-exocanthion measurements (p < 0.01 and p < 0.05, respectively). Group I patients exhibited an average preoperative nasal angulation of 9.15 +/- 0.8 degrees that decreased to 3.1 +/- 0.6 degrees postoperatively (p < 0.01). Group II patients exhibited an average preoperative nasal angulation of 6.4 +/- 0.7 degrees that was unchanged postoperatively at 7.2 +/- 1 degrees. The improvement in nasal angulation in group I was particularly striking because the patients in group II exhibited, on average, a lesser degree of preoperative nasal deviation (p < 0.01). This prospective comparison of fronto-orbital correction of synostotic frontal plagiocephaly with and without nasal correction confirmed an earlier study and demonstrated that angulation of the nasal pyramid does not self-correct within 5 years after traditional bilateral fronto-orbital repair. Closing wedge nasal ostectomy results in improved nasal angulation and naso-orbital symmetry, without evidence of distortion or inhibition of nasal growth.