Identification of Alzheimer's disease and vascular dementia based on a Deep Forest and near-infrared spectroscopy analysis method.

Alzheimer's disease (AD) and vascular dementia (VaD) typically do not exhibit distinct differences in clinical manifestations and auxiliary examination results, which leads to a high misdiagnosis rate. However, significant differences in treatment approaches and prognosis between these two diseases underscore the critical need for an accurate diagnosis of AD and VaD. In this study, serum samples from 33 patients with AD patients, 37 patients with VaD, and 130 healthy individuals were collected, employing near-infrared aquaphotomics technology in combination with deep learning for differential diagnoses. Through an analysis of water absorption patterns among different diseases via aquaphotomics, the efficacies of traditional machine learning methods (Support Vector Machine and Decision Trees) and deep learning approaches (Deep Forest) in modeling were compared. Ultimately, by leveraging feature extraction techniques in conjunction with deep learning, a differential diagnostic model for AD and VaD was successfully developed. The results revealed that aquaphotomics could identify a certain correlation between the number of hydrogen bonds in water molecules and the development of AD and VaD; the deep learning model was found to be superior to traditional machine learning models, achieving an accuracy of 98.67 %, sensitivity of 97.33 %, and specificity of 100.00 %. The bands identified using the Competitive Adaptive Reweighting Algorithm method, primarily located at approximately 1300-1500 nm, showed a significant correlation with water molecules containing four hydrogen bonds. These results highlighted the potential role of the water molecule hydrogen-bond network in disease development and were consistent with the aquaphotomics analysis results. Therefore, the differential diagnostic model developed by integrating near-infrared spectroscopy and deep learning was proven to be effective and feasible, providing accurate and rapid diagnostic methods for AD and VaD diagnoses.

A Study of MgZnO Thin Film for Hydrogen Sensing Application.

This research introduces a hydrogen sensor made from a thin film of magnesium zinc oxide (MgZnO) deposited using a technique called radiofrequency co-sputtering (RF co-sputtering). Separate magnesium oxide (MgO) and zinc oxide (ZnO) targets were used to deposit the MgZnO film, experimenting with different deposition times and power levels. The sensor performed best (reaching a sensing response of 2.46) when exposed to hydrogen at a concentration of 1000 parts per million (ppm). This peak performance occurred with a MgZnO film thickness of 432 nanometers (nm) at a temperature of 300 °C. Initially, the sensor's responsiveness increased as the film thickness grew. This is because thicker films tend to have more oxygen vacancies, which are imperfections that play a role in the sensor's function. However, further increases in film thickness beyond the optimal point harmed performance. This is attributed to the growth of grains within the film, which hindered its effectiveness. X-ray diffraction (XRD) and field-emission scanning electron microscopy (FE-SEM) were employed to thoroughly characterize the quality of the MgZnO thin film. These techniques provided valuable insights into the film's crystal structure and morphology, crucial factors influencing its performance as a hydrogen sensor.

Stabilization of polyacrylonitrile-based fiber with a quasi-traveling microwave applicator.

This study introduces a novel microwave applicator and optimized processing conditions to enhance the stability of Polyacrylonitrile (PAN)-based precursor fiber (PF). The innovative microwave applicator facilitates the propagation of the electromagnetic (EM) field akin to a quasi-traveling wave, thus circumventing standing wave nodes. This ensures a uniform thermal distribution and broadens the heating zone. Utilizing this applicator, the PF undergoes thermal stabilization in a streamlined two-step process, completing in just 13 min, a significant improvement over the conventional 90-min process. This not only saves manufacturing time, promoting energy efficient manufacturing but also aligns with the global trend towards green energy and lightweight carbon fiber-reinforced polymer matrix composites, potentially catalyzing rapid economic growth. Fiber characterization through Raman spectroscopy (RS), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and complex permittivity measurements reveals that the microwave-processed fiber meets the standard of commercial stabilization fiber (SF).

Dual-Frequency Impedance Matching Network Design Using Genetic Algorithm for Power Ultrasound Transducer.

Dual-frequency ultrasounds have demonstrated significant potential in augmenting thermal ablation efficiency for tumor treatment. Ensuring proper impedance matching between the dual-frequency transducer and the power amplifier system is imperative for equipment safety. This paper introduces a novel dual-frequency impedance matching network utilizing L-shaped topology and employing a genetic algorithm to compute component values. Implementation involved an adjustable capacitor and inductor network to achieve dual-frequency matching. Subsequently, the acoustic parameters of the dual-frequency HIFU transducer were evaluated before and after matching, and the effects of ultrasound thermal ablation with and without matching were compared. The proposed dual-frequency impedance matching system effectively reduced the standing wave ratio at the two resonance points while enhancing transmission efficiency. Thermal ablation experiments with matching circuits showed improved temperature rise efficiencies at both frequencies, resulting in an expanded ablation zone. The dual-frequency impedance matching method significantly enhances the transmission efficiency of the dual-frequency ultrasound system at two operational frequencies, thereby ensuring equipment safety. It holds promising prospects for application in dual-frequency ultrasound treatment.

Evaluation of Dual-Frequency Switching HIFU for Optimizing Superficial Ablation.

OBJECTIVE: Dual-frequency high-intensity focused ultrasound (HIFU) thermal ablation is an exceptionally promising technique for treating tumors due to its precision and effectiveness. However, there are still a few studies on improving the accuracy and efficiency of HIFU in superficial ablation applications. This study proposes a method utilizing dual frequency switching ultrasound (DFSU) to enhance the efficiency and precision of superficial treatments. METHODS: A dual-frequency HIFU transducer operating at 4.5 MHz and 13.7 MHz was designed, and a dual-frequency impedance matching network was designed to optimize electro-acoustic conversion efficiency. Phantom and ex vivo tests were conducted to measure and compare thermal lesion areas and temperature rises caused by single-frequency ultrasound (SFU) and DFSU. RESULTS: In both phantom and ex vivo tests, the utilization of DFSU resulted in larger lesion areas compared to SFU. Moreover, DFSU provided improved control and versatility, enabling precise and efficient ablation. CONCLUSION: DFSU exhibits the ability to generate larger ablation areas in superficial tissue compared to SFU, and DFSU allows flexible control over the ablation area and temperature rise rate. The acoustic power deposition of HIFU can be optimized to achieve precise ablation.

Multi-Frequency Ultrasound Imaging Fusion Method Based on Wavelet Transform for Guided Screw Insertion.

Intraosseous ultrasound imaging can serve as a guiding tool for the placement of pedicle screws during spinal fusion surgery; thus far, there has been limited scholarly exploration of methods for intraosseous multifrequency ultrasound imaging, which can achieve simultaneous high resolution and deep penetration. The proposed method introduced a dynamic fusion strategy grounded in wavelet transformation for multifrequency image decomposition. This strategy accomplished the effective amalgamation of high-frequency ultrasound images and low-frequency ultrasound images, enabling the obtaining of fused images with enhanced details and better overall image quality. A novel near-field effect elimination method was also proposed to improve the quality of ultrasound imaging in the near-field region. Experimental evaluations were conducted on isolated bovine circle bone and sheep spine with pedicle screw tracks. The fusion images are capable of effectively detecting areas within the pedicle screw track that have either ruptured or are in close proximity to rupture, even measuring the size of breaches. Evaluation criteria, including information entropy (IE), spatial frequency (SF), average gradient (AG), mutual information (MI), structural similarity index (SSIM), and edge information-based image fusion quality metric (QAB/F), were employed to assess the fusion performance; moreover, the influence of mother wavelet function selection and decomposition levels on computational complexity and fusion image quality was thoroughly discussed. The proposed method exhibited promising potential for intraosseous imaging navigation, which can aid in accurate diagnosis, treatment planning, and monitoring in fields such as orthopedics, surgery, and interventional procedures.

Echocardiographic measurements of left ventricular dimensions and function in newborns with omphalocele and pulmonary.

PURPOSE: The purpose of this study was to explore echocardiographic parameters of the left ventricle (LV) in relation to the outcomes of omphalocele neonates with pulmonary hypertension (PH). METHODS: This retrospective study was conducted among omphalocele patients with PH born from 2019 to 2020. Patients in this study did not have additional severe malformations or chromosomal aberrations. Patients who died under palliative care were excluded. The echocardiographic parameters of LV were obtained within 24 h after birth. Clinical and outcomes data were recorded, echocardiograms evaluated for left ventricular internal dimension in end-diastole (LVIDd), end-diastolic volume (EDV), stroke volume (SV) and cardiac output index (CI), among others. RESULTS: There were 18 omphalocele newborns with PH, of whom 14 survived and 4 died. Both groups were comparable in the baseline characteristics. Non-survival was associated with a smaller LV [LVIDd (12.2 mm versus15.7 mm, p < 0.05), EDV (3.5 ml versus 6.8 ml, p < 0.05)] and with worse systolic function [SV (2.3 ml versus 4.2 ml, p < 0.05), and CI (1.7 L/min/m2 versus 2.9 L/min/m2, p < 0.01)]. CONCLUSION: In the cohort of omphalocele patients with PH, lower LVIDd, EDV, SV and CI were associated with mortality. LEVEL OF EVIDENCE: Level III.

NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells.

Recent studies revealed that NOP2/Sun RNA methyltransferase 5 (NSUN5) - ferritin heavy chain (FTH1) pathway is associated with ferroptosis in stem cells, whereas its roles in gastric cancer are still unclear. Our study aims to investigate the roles of the NSUN5-FTH1 axis in gastric cancer (GC) and its molecular mechanisms. Stable cell lines were constructed on SGC7901 cells by using shRNAs and pcDNA3.1 expression vectors, respectively. CCK-8 kits were used to determine cell viability. Biochemicals assays were used to detect lipid reactive oxygen species (ROS) and intracellular Fe2+ levels. RNA immunoprecipitation assay, qPCR, and Western blotting were used to determine the changes in biomarkers. GC xenograft mouse model was established to confirm the observation in vivo. An elevation of NSUN5 was observed in GC tumor tissues. NSUN5 inhibited ferroptosis including decreasing cell viability and increasing levels of lipid ROS and Fe2+ in GC cells. Besides, a positive correlation was also observed between NSUN5 and FTH1. Interestingly, NSUN5 regulated the levels of FTH1, instead of FTH1 regulating NSUN5 in GC cells. NSUN5-FTH1 axis regulated erastin-induced ferroptosis in SGC7901 cells. Consistently, silencing NSUN5 or FTH1 inhibited the growth of the SGC7901 tumor in vivo. NSUN5-FTH1 axis promoted the growth of GC cells in part by the regulation of ferroptosis.

A Nomogram for Predicting Surgical Timing in Neonates with Necrotizing Enterocolitis.

OBJECTIVE: To explore the surgical risk variables in patients with necrotizing enterocolitis (NEC) and develop a nomogram model for predicting the surgical intervention timing of NEC. METHODS: Infants diagnosed with NEC were enrolled in our study. We gathered information from clinical data, laboratory examinations, and radiological manifestations. Using LASSO (least absolute shrinkage and selection operator) regression analysis and multivariate logistic regression analysis, a clinical prediction model based on the logistic nomogram was developed. The performance of the nomogram model was evaluated using the receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). RESULTS: A surgical intervention risk nomogram based on hypothermia, absent bowel sounds, WBC > 20 × 109/L or < 5 × 109/L, CRP > 50 mg/L, pneumatosis intestinalis, and ascites was practical, had a moderate predictive value (AUC > 0.8), improved calibration, and enhanced clinical benefit. CONCLUSIONS: This simple and reliable clinical prediction nomogram model can help physicians evaluate children with NEC in a fast and effective manner, enabling the early identification and diagnosis of children at risk for surgery. It offers clinical revolutionary value for the development of medical or surgical treatment plans for children with NEC.

Constant p.L424H Mutation in GTF2I in Micronodular Thymomas With Lymphoid Stroma: Evidence Supporting Close Relationship With Type A and AB Thymomas.

Micronodular thymoma with lymphoid stroma is a rare thymic neoplasm characterized by discrete nodules of epithelial tumor cells separated by abundant lymphoid stroma. The genetic features of micronodular thymoma with lymphoid stroma remain largely unexplored. Owing to the interference of abundant intratumoral, nonneoplastic lymphoid cells, a highly sensitive approach is necessary to study genetic changes in these tumors. In this study, we used a highly sensitive next-generation sequencing assay using the molecular barcoding Ion AmpliSeq HD technology to study the most commonly mutated genes in thymomas, including GTF2I, HRAS, NRAS, KRAS, and TP53. A total of 12 cases of micronodular thymomas with lymphoid stroma were tested, and 2 cases also had areas of type A thymoma in their tumor bed. Two micronodular thymic carcinomas with lymphoid stroma, a histological mimic of micronodular thymoma, were also included for comparison. Recurrent p.L424H mutations in GTF2I were found in all the cases of micronodular thymoma with lymphoid stroma but not in the cases of micronodular thymic carcinomas. In addition, 3 cases of micronodular thymoma with lymphoid stroma also had concomitant HRAS and/or KRAS mutations. Our study showed that p.L424H mutations in GTF2I is a constant genetic feature of micronodular thymoma with lymphoid stroma. This finding strongly suggests that micronodular thymoma with lymphoid stroma is closely related to type A and AB thymomas because they all share p.L424H mutations in GTF2I.

Evaluation of the dual-frequency transducer for controlling thermal ablation morphology using frequency shift keying signal.

PURPOSE: The catheter-based ultrasound (CBUS) can reach the target tissue directly and achieve rapid treatment. The frequency shift keying (FSK) signal is proposed to regulate and evaluate tumor ablation by a miniaturized dual-frequency transducer. METHODS: A dual-frequency transducer prototype (3 × 7 × 0.4 mm) was designed and fabricated for the CBUS applicator (OD: 3.8 mm) based on the fundamental frequency of 5.21 MHz and the third harmonic frequency of 16.88 MHz. Then, the acoustic fields and temperature field distributions using the FSK signals (with 0, 25, 50, 75, and 100% third harmonic frequency duty ratios) were simulated by finite element analysis. Finally, tissue ablation and temperature monitoring were performed in phantom and ex vivo tissue, respectively. RESULTS: At the same input electrical power (20 W), the output acoustic power of the fundamental frequency of the transducer was 10.03 W (electroacoustic efficiencies: 50.1%), and that of the third harmonic frequency was 6.19 W (30.6%). As the third harmonic frequency duty ratios increased, the shape of thermal lesions varied from strip to droplet in simulated and phantom experimental results. The same trend was observed in ex vivo tests. CONCLUSION: Dual-frequency transducers excited by the FSK signal can control the morphology of lesions. SIGNIFICANCE: The acoustic power deposition of CBUS was optimized to achieve precise ablation.

Homoharringtonine Attenuates Dextran Sulfate Sodium-Induced Colitis by Inhibiting NF-κB Signaling.

Homoharringtonine (HHT) exhibits an anti-inflammatory activity. The potential protective effects and mechanisms of HHT on dextran sulfate sodium- (DSS-) induced colitis were investigated. DSS-induced colitis mice were intraperitoneally injected with HHT. Body weight, colon length, disease activity index (DAI), and histopathological change were examined. The relative contents of interleukin- (IL-) 1ß, tumor necrosis factor- (TNF-) α, IL-6, and the chemokine (C-C motif) ligand 2 (CCL2) in the colon tissues and HHT-treated RAW264.7 cells were detected with the enzyme-linked immunosorbent assay. In the meantime, the levels of p-p65 and p-IκBα were detected by Western blot. The proportion of macrophages (CD11b+F4/80+) in the colon tissues was detected by flow cytometry. HHT alleviated DSS-induced colitis with downregulated TNF-α, IL-1ß, IL-6, and CCL2 expression; reduced activation of nuclear factor-kappa B (NF-κB) signaling; and diminished proportion of recruited macrophages in colon tissues. It was further testified that HHT inhibited lipopolysaccharide-induced macrophage activation with reduced activation of NF-κB signaling. In addition, HHT inhibited the M1 polarization of both human and mouse macrophages, while HHT did not affect the differentiation of human CD4 T cells into Th17, Th1, or Treg cells and did not affect the proliferation and migration of human colon epithelial cells. In summary, HHT attenuates DSS-induced colitis by inhibiting macrophage-associated NF-κB activation and M1 polarization, which could be an option for the treatment of ulcerative colitis.

Thermal Annealing Effects of V2O5 Thin Film as an Ionic Storage Layer for Electrochromic Application.

A vanadium pentoxide (V2O5) thin film with thermal annealing as an ionic storage layer for electrochromic devices is presented in our study. The V2O5 thin film was deposited on an ITO glass substrate by an RF magnetron sputtering. The electrochromic properties of the film were evaluated after various thermal annealing temperatures. The structural analysis of the film was observed by X-ray diffraction (XRD), field emission electron microscopy (FE-SEM), and atomic force microscopy (AFM). The structure of the V2O5 thin film transformed from an amorphous to polycrystalline structure with directions of (110) and (020) after 400 °C thermal annealing. The electrochromic properties of the film improved compared with the unannealed V2O5 thin film. We obtained a charge capacity of 97.9 mC/cm2 with a transparent difference ΔT value of 31% and coloration efficiency of 6.3 cm2/C after 400 °C thermal annealing. The improvement was due to the polycrystalline orthorhombic structure formation of V2O5 film by the rearrangement of atoms from thermal energy. Its laminate structure facilitates Li+ ion intercalation and increases charge capacity and transparent difference.

Atypical Teratoid/Rhabdoid Tumor in Taiwan: A Nationwide, Population-Based Study.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, highly aggressive embryonal brain tumor most commonly presenting in young children. METHODS: We performed a nationwide, population-based study of AT/RT (ICD-O-3 code: 9508/3) in Taiwan using the Taiwan Cancer Registry Database and the National Death Certificate Database. RESULTS: A total of 47 cases (male/female = 29:18; median age at diagnosis, 23.3 months (IQR: 12.5-87.9)) were diagnosed with AT/RT between 1999 and 2014. AT/RT had higher prevalence in males (61.70%), in children < 36 months (55.32%), and at infratentorial or spinal locations (46.81%). Survival analyses demonstrated that patients ≥ 3 years of age (n = 21 (45%)) had a 5y-OS of 41% (p < 0.0001), treatment with radiotherapy only (n = 5 (11%)) led to a 5y-OS of 60%, treatment with chemotherapy with or without radiotherapy (n = 27 (62%)) was associated with a 5y-OS of 45% (p < 0.0001), and patients with a supratentorial tumor (n = 11 (23%)) had a 5y-OS of 51.95%. Predictors of better survival on univariate Cox proportional hazard modeling and confirmed with multivariate analysis included older age (≥1 year), supratentorial sites, and the administration of radiotherapy, chemotherapy, or both. Gender had no effect on survival. CONCLUSION: Older age, supratentorial site, and treatment with radiotherapy, chemotherapy, or both significantly improves the survival of patients with AT/RT.

Efficacy Estimation of Microbubble-Assisted Local Sonothrombolysis Using a Catheter with a Series of Miniature Transducers.

Intravascular ultrasound has good prospects for clinical applications in sonothrombolysis. The catheter-based side-looking intravascular ultrasound thrombolysis (e.g., Ekosonic catheters) used in clinical studies has a high frequency (2 MHz). The lower-frequency ultrasound requires a larger-diameter transducer. In our study, we designed and manufactured a small ultrasound-based prototype catheter that can emit a lower frequency ultrasound (1.1 MHz). In order to evaluate the safety and efficacy of local low-frequency ultrasound-enhanced thrombolysis, a microbubble (MB) was introduced to augment thrombolysis effect of locally delivered low-intensity ultrasound. The results demonstrated that combination of ultrasound and MB realized higher clot lysis than urokinase-only treatment (17.0% ± 1.2% vs. 14.9% ± 2.7%) under optimal ultrasound settings of 1.1 MHz, 0.414 MPa, 4.89 W/cm2, 5% duty cycle and MB concentration of 60 µg/mL. When urokinase was added, the fibrinolysis accelerated by MB and ultrasound resulted in a further increased thrombolysis rate that was more than two times than that of urokinase alone (36.7% ± 5.5% vs. 14.9% ± 2.7%). However, a great quantity of ultrasound energy was required to achieve substantial clot lysis without MB, leading to the situation that temperature accumulated inside the clot became harmful. We suggest that MB-assisted local sonothrombolysis be considered as adjuvant therapy of thrombolytic agents.

An Improved Chirp Coded Excitation Based on Compression Pulse Weighting Method in Endoscopic Ultrasound Imaging.

Chirp coded excitation is an effective method to improve the signal-to-noise ratio (SNR) and penetration depth of high-frequency endoscopic ultrasound (EUS) imaging. In coded excitation, pulse compression is applied to compress the elongated coded signals into a short pulse, which determines the final imaging performance, including spatial resolution and SNR. However, with the current pulse compression methods, it is hard to get high performance in the peak sidelobe level (PSL), image contrast, and axial resolution at the same time. To solve this problem, in this article, a new method named compressed pulse weighting method (CPWM) was proposed based on the combination of two kinds of pulse compression signals. A brief theoretical derivation proved the feasibility of method. The proposed method was evaluated by the simulation and phantom experiments. Compared with traditional method, the results showed that the proposed adaptive weighting method can provide increases of 32.42% in the penetration depth, 9.48 dB in the SNR, 5.60 dB in the contrast ratio (CR), 5.46 in the contrast-to-noise ratio (CNR), and 0.13 mm in the axial imaging resolution for 12-MHz EUS. Therefore, this method can effectively improve the ultrasound penetration depth and imaging quality, which made it have good potential for high-frequency ultrasound imaging.

Upregulation of Protein Synthesis and Proteasome Degradation Confers Sensitivity to Proteasome Inhibitor Bortezomib in Myc-Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid rhabdoid tumors (ATRTs) are among the most malignant brain tumors in early childhood and remain incurable. Myc-ATRT is driven by the Myc oncogene, which directly controls the intracellular protein synthesis rate. Proteasome inhibitor bortezomib (BTZ) was approved by the Food and Drug Administration as a primary treatment for multiple myeloma. This study aimed to determine whether the upregulation of protein synthesis and proteasome degradation in Myc-ATRTs increases tumor cell sensitivity to BTZ. We performed differential gene expression and gene set enrichment analysis on matched primary and recurrent patient-derived xenograft (PDX) samples from an infant with ATRT. Concomitant upregulation of the Myc pathway, protein synthesis and proteasome degradation were identified in recurrent ATRTs. Additionally, we found the proteasome-encoding genes were highly expressed in ATRTs compared with in normal brain tissues, correlated with the malignancy of tumor cells and were essential for tumor cell survival. BTZ inhibited proliferation and induced apoptosis through the accumulation of p53 in three human Myc-ATRT cell lines (PDX-derived tumor cell line Re1-P6, BT-12 and CHLA-266). Furthermore, BTZ inhibited tumor growth and prolonged survival in Myc-ATRT orthotopic xenograft mice. Our findings suggest that BTZ may be a promising targeted therapy for Myc-ATRTs.

Molecular-Clinical Correlation in Pediatric Medulloblastoma: A Cohort Series Study of 52 Cases in Taiwan.

In 2016, a project was initiated in Taiwan to adopt molecular diagnosis of childhood medulloblastoma (MB). In this study, we aimed to identify a molecular-clinical correlation and somatic mutation for exploring risk-adapted treatment, drug targets, and potential genetic predisposition. In total, 52 frozen tumor tissues of childhood MBs were collected. RNA sequencing (RNA-Seq) and DNA methylation array data were generated. Molecular subgrouping and clinical correlation analysis were performed. An adjusted Heidelberg risk stratification scheme was defined for updated clinical risk stratification. We selected 51 genes for somatic variant calling using RNA-Seq data. Relevant clinical findings were defined. Potential drug targets and genetic predispositions were explored. Four core molecular subgroups (WNT, SHH, Group 3, and Group 4) were identified. Genetic backgrounds of metastasis at diagnosis and extent of tumor resection were observed. The adjusted Heidelberg scheme showed its applicability. Potential drug targets were detected in the pathways of DNA damage response. Among the 10 patients with SHH MBs analyzed using whole exome sequencing studies, five patients exhibited potential genetic predispositions and four patients had relevant germline mutations. The findings of this study provide valuable information for updated risk adapted treatment and personalized care of childhood MBs in our cohort series and in Taiwan.

BRAF and KRAS mutations in tubular apocrine adenoma and papillary eccrine adenoma of the skin.

Tubular apocrine adenoma (TAA) and papillary eccrine adenoma (PEA) are benign sweat gland tumors. Their names imply that they exhibit apocrine and eccrine differentiation, respectively. However, morphologically they are very similar and are often indistinguishable. The molecular pathogenesis of either tumor is poorly understood at present. On the basis of an index case of nipple adenoma that was morphologically reminiscent of cutaneous TAA/PEA and harbored a BRAFV600E mutation, we investigated whether a similar genetic change is also present in TAA/PEA. BRAF, RAS, and PIK3CA mutation analyses, and BRAFV600E-specific immunohistochemistry were performed for 24 TAAs/PEAs, 10 eccrine poromas, 7 apocrine cystadenomas, 2 TAA-like adenomas associated with nevus sebaceus, and one apocrine adenoma probably arising in anogenital mammary-like glands (AGMLGs). The results demonstrated that BRAFV600E mutations were present in TAAs (9/15, 60%) and PEAs (7/9, 78%), but not in other neoplasms. Two additional TAAs harbored KRASG12D mutations. In addition, a KRASG12C mutation was identified in one nevus sebaceus-associated TAA-like adenoma. The speculated AGMLG-related apocrine adenoma had a PIK3CAH1047R mutation. We concluded that activating BRAF and KRAS mutations were commonly present in TAAs/PEAs, indicating that in addition to a morphological resemblance, they are closely related genetically. Therefore, they could be considered to be united as a single entity. By contrast, the apocrine adenoma probably arising in AGMLG harbored a PIK3CA mutation, which is also commonly present in hidradenoma papilliferum. Further studies are necessary to determine whether the pathogenesis of AGMLG-related tumors is similar to breast tumors.

Frequent PIK3CA-activating mutations in hidradenoma papilliferums.

Hidradenoma papilliferum (HP) is a benign epithelial tumor most commonly seen in the vulva. It is proposed to be derived from the anogenital mammary-like glands and is histologically very similar to the mammary intraductal papilloma (IP). Approximately 60% of mammary IPs have activating mutations in either PIK3CA or AKT1, with each gene accounting for 30% of cases. In this study, we screened the mutation statuses of PIK3CA, AKT1, RAS, and BRAF in 30 HPs. The results showed that activating mutations in either PIK3CA or AKT1 were identified in 20 tumors (67%); 19 tumors had PIK3CA mutations (63%; 13 in exon 20 and 6 in exon 9), and 1 had an AKT1 E17K mutation (3%). BRAF V600E mutation was found in an HP that also had a PIK3CA H1047R mutation. No RAS mutation was found. The mutation status was not correlated with the degree of epithelial cell hyperplasia. We conclude that although there might be site-related variations in the mutation frequencies of PIK3CA and AKT1 genes, HP is histologically and also genetically very similar to the mammary IP, suggesting that HP can be viewed as the extramammary counterpart of mammary IP.