ABSTRACT
Rapid eye movement (REM) sleep has been hypothesized to promote emotional resilience, but any neuronal circuits mediating this have not been identified. We find that in mice, somatostatin (Som) neurons in the entopeduncular nucleus (EPSom)/internal globus pallidus are predominantly active during REM sleep. This unique REM activity is both necessary and sufficient for maintaining normal REM sleep. Inhibiting or exciting EPSom neurons reduced or increased REM sleep duration, respectively. Activation of the sole downstream target of EPSom neurons, Vglut2 cells in the lateral habenula (LHb), increased sleep via the ventral tegmental area (VTA). A simple chemogenetic scheme to periodically inhibit the LHb over 4 days selectively removed a significant amount of cumulative REM sleep. Chronic, but not acute, REM reduction correlated with mice becoming anxious and more sensitive to aversive stimuli. Therefore, we suggest that cumulative REM sleep, in part generated by the EP â LHb â VTA circuit identified here, could contribute to stabilizing reactions to habitual aversive stimuli.
Subject(s)
Anxiety , Sleep, REM , Animals , Mice , Sleep, REM/physiology , Anxiety/physiopathology , Male , Ventral Tegmental Area/physiology , Mice, Inbred C57BL , Basal Ganglia/physiology , Basal Ganglia/physiopathology , Neurons/physiology , Entopeduncular Nucleus/physiology , Somatostatin/metabolism , Habenula/physiology , Vesicular Glutamate Transport Protein 2/metabolism , Vesicular Glutamate Transport Protein 2/geneticsABSTRACT
The therapeutic effect of gefitinib on colorectal cancer (CRC) is unclear, but it has been reported that stromal cells in the tumor microenvironment may have an impact on drug sensitivity. Herein, we established a microfluidic co-culture system and explored the sensitivity of CRC cells co-cultured with cancer-associated fibroblasts (CAFs) to gefitinib. The system consisted of a multichannel chip and a Petri dish. The chambers in the chip and dish were designed to continuously supply nutrients for long-term cell survival and create chemokine gradients for driving cell invasion without any external equipment. Using this system, the proliferation and invasiveness of cells were simultaneously evaluated by quantifying the area of cells and the migration distance of cells. In addition, the system combined with live cell workstation could evaluate the dynamic drug response of co-cultured cells and track individual cell trajectories in real-time. When CRC cells were co-cultured with CAFs, CAFs promoted CRC cell proliferation and invasion and reduced the sensitivity of cells to gefitinib through the exosomes secreted by CAFs. Furthermore, the cells that migrated out of the chip were collected, and EMT-related markers were determined by immunofluorescent and western blot assays. The results demonstrated that CAFs affected the response of CRC cells to gefitinib by inducing EMT, providing new ideas for further research on the resistance mechanism of gefitinib. This suggests that targeting CAFs or exosomes might be a new approach to enhance CRC sensitivity to gefitinib, and our system could be a novel platform for investigating the crosstalk between tumor cells and CAFs and understanding multiple biological changes of the tumor cells in the tumor microenvironment.
Subject(s)
Antineoplastic Agents , Cell Proliferation , Coculture Techniques , Colorectal Neoplasms , Gefitinib , Gefitinib/pharmacology , Humans , Coculture Techniques/instrumentation , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Cancer-Associated Fibroblasts/drug effects , Cancer-Associated Fibroblasts/metabolism , Cancer-Associated Fibroblasts/pathology , Cell Movement/drug effects , Epithelial-Mesenchymal Transition/drug effects , Cell Line, Tumor , Lab-On-A-Chip Devices , Microfluidic Analytical Techniques/instrumentation , Microfluidic Analytical Techniques/methods , Exosomes/metabolism , Exosomes/chemistry , Exosomes/drug effects , Tumor Microenvironment/drug effects , Drug Resistance, Neoplasm/drug effectsABSTRACT
Inflammatory pseudotumour (IP) is a rare proliferative disease characterized by a dense infiltrate of plasma cells, lymphocytes, eosinophils and neutrophils in the fibrous stroma. It primarily affects the lungs of pediatric patients or young adults. Cutaneous IP is an extremely rare condition, with limited documentation in the English literature. In this case report, we presented an unusual instance of a 62-year-old male endured recalcitrant cutaneous IP for 8 years and exhibited poor response to topical glucocorticoid therapy, as well as intralesional injections of pingyangmycin and/or corticosteroid. Notably, after undergoing four sessions of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), the patient experienced a significant reduction in erythema and nodules. This observation suggests that ALA-PDT may represent a promising and safe treatment option for cutaneous IP.
Subject(s)
Granuloma, Plasma Cell , Photochemotherapy , Male , Young Adult , Humans , Child , Middle Aged , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Granuloma, Plasma Cell/drug therapy , Aminolevulinic Acid/therapeutic use , SkinABSTRACT
The accurate pathological diagnosis of endometrial cancer (EC) improves the curative effect and reduces the mortality rate. Deep learning has demonstrated expert-level performance in pathological diagnosis of a variety of organ systems using whole-slide images (WSIs). It is urgent to build the deep learning system for endometrial cancer detection using WSIs. The deep learning model was trained and validated using a dataset of 601 WSIs from PUPH. The model performance was tested on three independent datasets containing a total of 1,190 WSIs. For the retrospective test, we evaluated the model performance on 581 WSIs from PUPH. In the prospective study, 317 consecutive WSIs from PUPH were collected from April 2022 to May 2022. To further evaluate the generalizability of the model, 292 WSIs were gathered from PLAHG as part of the external test set. The predictions were thoroughly analyzed by expert pathologists. The model achieved an area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of 0.928, 0.924, and 0.801, respectively, on 1,190 WSIs in classifying EC and non-EC. On the retrospective dataset from PUPH/PLAGH, the model achieved an AUC, sensitivity, and specificity of 0.948/0.971, 0.928/0.947, and 0.80/0.938, respectively. On the prospective dataset, the AUC, sensitivity, and specificity were, in order, 0.933, 0.934, and 0.837. Falsely predicted results were analyzed to further improve the pathologists' confidence in the model. The deep learning model achieved a high degree of accuracy in identifying EC using WSIs. By pre-screening the suspicious EC regions, it would serve as an assisted diagnostic tool to improve working efficiency for pathologists.
ABSTRACT
Metastasis is a leading cause of cancer-related deaths. Hence, the discovery of more reliable metastasis-related biomarkers is crucial to improve the survival rate of cancer patients. W3 is an aptamer previously produced by the subtractive cell-SELEX using metastatic colorectal cancer cells as target cells and non-metastatic cells as negative cells. In this study, we aimed to evaluate whether the target molecule of W3 can potentially act as a metastatic biomarker. First, we obtained two cell subpopulations with different expression levels of the target molecule by W3-based cell sorting. Subsequently, we demonstrated that W3high cells have a higher metastatic potential than W3low cells both in vitro and in vivo. Further, immunohistochemical analysis revealed that W3 target expression is positively associated with metastasis and poor prognosis of CRC patients. Using mass spectrometry (MS) combined with pull-down, we identified that Ephrin type-A receptor 2 (EphA2) is the target of W3. EphA2's potential as a metastatic predictor was demonstrated by capturing W3-positive circulating tumor cells from CRC patients using a W3 probe. Based on these results, we put forward a stratagem for cell-SELEX-based biomarker discovery: selecting an aptamer through subtractive cell-SELEX towards the phenotype of interest; evaluating the functional phenotype of the target molecule by aptamer-based target cell sorting and analysis of clinical samples; and identifying the aptamer's target molecule using MS and aptamer-based target enrichment. This stratagem not only shortens the time for the clinical application of aptamers but also enables a more targeted and efficient discovery of biomarkers.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Colorectal Neoplasms , Aptamers, Nucleotide/chemistry , Biomarkers, Tumor/genetics , Colorectal Neoplasms/diagnosis , Humans , SELEX Aptamer Technique/methodsABSTRACT
BACKGROUND: Convolutional neural networks (CNNs) have demonstrated expert-level performance in cutaneous tumour classification using clinical images, but most previous studies have focused on dermatologist-versus-CNN comparisons rather than their combination. The objective of our study was to evaluate the potential impact of CNN assistance on dermatologists for clinical image interpretation. METHODS: A multi-class CNN was trained and validated using a dataset of 25,773 clinical images comprising 10 categories of cutaneous tumours. The CNN's performance was tested on an independent dataset of 2107 images. A total of 400 images (40 per category) were randomly selected from the test dataset. A fully crossed, self-control, multi-reader multi-case (MRMC) study was conducted to compare the performance of 18 board-certified dermatologists (experience: 13/18 ≤ 10 years; 5/18ï¼10 years) in interpreting the 400 clinical images with or without CNN assistance. RESULTS: The CNN achieved an overall accuracy of 78.45% and kappa of 0.73 in the classification of 10 types of cutaneous tumours on 2107 images. CNN-assisted dermatologists achieved a higher accuracy (76.60% vs. 62.78%, P < 0.001) and kappa (0.74 vs. 0.59, P < 0.001) than unassisted dermatologists in interpreting the 400 clinical images. Dermatologists with less experience benefited more from CNN assistance. At the binary classification level (malignant or benign), the sensitivity (89.56% vs. 83.21%, P < 0.001) and specificity (87.90% vs. 80.92%, P < 0.001) of dermatologists with CNN assistance were also significantly improved than those without. CONCLUSIONS: CNN assistance improved dermatologist accuracy in interpreting cutaneous tumours and could further boost the acceptance of this new technique.
Subject(s)
Melanoma , Skin Neoplasms , Dermatologists , Dermoscopy/methods , Humans , Melanoma/pathology , Neural Networks, Computer , Skin Neoplasms/diagnostic imaging , Skin Neoplasms/pathologyABSTRACT
Previous studies on deep learning (DL) applications in pathology have focused on pathologist-versus-algorithm comparisons. However, DL will not replace the breadth and contextual knowledge of pathologists; rather, only through their combination may the benefits of DL be achieved. A fully crossed multireader multicase study was conducted to evaluate DL assistance with pathologists' diagnosis of gastric cancer. A total of 110 whole-slide images (WSI) (50 malignant and 60 benign) were interpreted by 16 board-certified pathologists with or without DL assistance, with a washout period between sessions. DL-assisted pathologists achieved a higher area under receiver operating characteristic curve (ROC-AUC) (0.911 vs. 0.863, P = 0.003) than unassisted in interpreting the 110 WSIs. Pathologists with DL assistance demonstrated higher sensitivity in detection of gastric cancer than without (90.63% vs. 82.75%, P = 0.010). No significant difference was observed in specificity with or without deep learning assistance (78.23% vs. 79.90%, P = 0.468). The average review time per WSI was shortened with DL assistance than without (22.68 vs. 26.37 second, P = 0.033). Our results demonstrated that DL assistance indeed improved pathologists' accuracy and efficiency in gastric cancer diagnosis and further boosted the acceptance of this new technique.
Subject(s)
Deep Learning , Stomach Neoplasms , Algorithms , Humans , Pathologists , ROC Curve , Stomach Neoplasms/diagnosisABSTRACT
Follicular dendritic cell sarcoma (FDCS) is a rare malignant neoplasm that was classified by the World Health Organization (WHO) under histiocytic and dendritic cell neoplasms in the 2016 revision. Considering the rarity of this tumor, there is no standardized treatment. It is usually treated by complete surgical resection. Adjuvant chemotherapy and radiotherapy are alternative methods. Immune checkpoint inhibitors (ICIs) represented by the programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) antibody have achieved significant clinical benefits in a variety of solid tumors. However, reports on the treatment of FDCS with ICIs are rare. FDCS often expresses high levels of PD-L1, which provides a rationale to use immunotherapy in cases of FDCS. Here, we present a 51-year-old Filipino-Chinese man with FDCS who was treated with multimodal treatment, including the PD-1 inhibitor pembrolizumab and achieved a relatively long disease-free survival of 24 months. This case emphasizes that the application of ICIs under the guidance of NGS technology seems to be a meaningful treatment option for patients with FDCS.
ABSTRACT
As a drug carrier, ethosome is found to be efficient in delivering drug to the deep skin layers through stratum corneum, and the purpose of this paper is to develop luridazole ethosomes acting as an optimal choice for transdermal antifungal drugs. The luliconazole ethosomes were prepared by thin-film hydration, and evaluated for morphology, size, entrapment efficiency (EE), stability and deformability. In vitro, the transdermal experiment was performed on excised rat skin by Franz diffusion cell, and minimum inhibitory concentration (MIC) was applied to determine antifungal activity. In vivo, the irritation of luliconazole ethosomes was also observed in rats. The luliconazole ethosomes were prepared with 5% (w/v) lecithin, 45% (v/v) ethanol and 8-min ultrasound, and characterised with small and uniform particle size, high EE of about 70%. These ethosomes possessed good deformability, were stable and affected by light and high temperature. The cumulative amount permeated of different dosage forms at 48 h from high to low was: ethosome > ointment > liposome > hydroalcoholic solution (p < 0.05), and the sum of the luliconazole retention of skin from high to low at 48 h was: ethosome/ointment > liposome > hydroalcoholic solution (p < 0.05). In the antifungal experiment, the MICs from high to low were: hydroalcoholic solution > liposome > ethosome (p < 0.05), and Trichoderma was more sensitive to luliconazole than Candida. There was no skin irritation observed after treatment of luliconazole ethosomes. The luliconazole ethosomes are firstly prepared in our study, which have little stimulation, better permeation effect and antifungal activity, offering a new perspective for choosing clinical antifungal drugs in the Department of Dermatology.
Subject(s)
Skin Absorption , Skin , Administration, Cutaneous , Animals , Imidazoles , Liposomes/metabolism , Liposomes/pharmacology , RatsABSTRACT
Mycosis fungoides (MF) is characterized by epidermotropic atypical lymphocytes infiltrate with α/ß T-helper memory immunophenotype (ßF1+, CD3+, CD4+, CD45Ro+, and CD8-). Angiocentricity is always associated with aggressive behavior or poor outcome in primary or secondary cutaneous lymphomas. Rare cases of angiocentric MF with a T-cytotoxic immunophenotype (CD3+, CD4-, CD8+, TIA-1+) have been described. Here, we report a 27-year-old man diagnosed with MF, clinically presenting with ichthyosiform lesions on his trunk and limbs. Biopsy demonstrated a CD3+ and CD8+ atypical lymphocytic infiltrate with marked epidermotropism and angiocentricity. Awareness of this rare MF variant with unusual clinicopathological characteristics is important to avoid misdiagnosis.
Subject(s)
Mycosis Fungoides , Skin Neoplasms , Adult , Biopsy , CD8-Positive T-Lymphocytes/pathology , Humans , Immunophenotyping , Male , Mycosis Fungoides/pathology , Skin Neoplasms/pathologyABSTRACT
When mice are exposed to external warmth, nitric oxide synthase (NOS1) neurons in the median and medial preoptic (MnPO/MPO) hypothalamus induce sleep and concomitant body cooling. However, how these neurons regulate baseline sleep and body temperature is unknown. Using calcium photometry, we show that NOS1 neurons in MnPO/MPO are predominantly NREM and REM active, especially at the boundary of wake to NREM transitions, and in the later parts of REM bouts, with lower activity during wakefulness. In addition to releasing nitric oxide, NOS1 neurons in MnPO/MPO can release GABA, glutamate and peptides. We expressed tetanus-toxin light-chain in MnPO/MPO NOS1 cells to reduce vesicular release of transmitters. This induced changes in sleep structure: over 24 h, mice had less NREM sleep in their dark (active) phase, and more NREM sleep in their light (sleep) phase. REM sleep episodes in the dark phase were longer, and there were fewer REM transitions between other vigilance states. REM sleep had less theta power. Mice with synaptically blocked MnPO/MPO NOS1 neurons were also warmer than control mice at the dark-light transition (ZT0), as well as during the dark phase siesta (ZT16-20), where there is usually a body temperature dip. Also, at this siesta point of cooled body temperature, mice usually have more NREM, but mice with synaptically blocked MnPO/MPO NOS1 cells showed reduced NREM sleep at this time. Overall, MnPO/MPO NOS1 neurons promote both NREM and REM sleep and contribute to chronically lowering body temperature, particularly at transitions where the mice normally enter NREM sleep.
ABSTRACT
Objective To develope a deep learning algorithm for pathological classification of chronic gastritis and assess its performance using whole-slide images (WSIs). Methods We retrospectively collected 1,250 gastric biopsy specimens (1,128 gastritis, 122 normal mucosa) from PLA General Hospital. The deep learning algorithm based on DeepLab v3 (ResNet-50) architecture was trained and validated using 1,008 WSIs and 100 WSIs, respectively. The diagnostic performance of the algorithm was tested on an independent test set of 142 WSIs, with the pathologists' consensus diagnosis as the gold standard. Results The receiver operating characteristic (ROC) curves were generated for chronic superficial gastritis (CSuG), chronic active gastritis (CAcG), and chronic atrophic gastritis (CAtG) in the test set, respectively.The areas under the ROC curves (AUCs) of the algorithm for CSuG, CAcG, and CAtG were 0.882, 0.905 and 0.910, respectively. The sensitivity and specificity of the deep learning algorithm for the classification of CSuG, CAcG, and CAtG were 0.790 and 1.000 (accuracy 0.880), 0.985 and 0.829 (accuracy 0.901), 0.952 and 0.992 (accuracy 0.986), respectively. The overall predicted accuracy for three different types of gastritis was 0.867. By flagging the suspicious regions identified by the algorithm in WSI, a more transparent and interpretable diagnosis can be generated. Conclusion The deep learning algorithm achieved high accuracy for chronic gastritis classification using WSIs. By pre-highlighting the different gastritis regions, it might be used as an auxiliary diagnostic tool to improve the work efficiency of pathologists.
Subject(s)
Deep Learning , Gastritis , Algorithms , Gastritis/diagnosis , Humans , ROC Curve , Retrospective StudiesABSTRACT
BACKGROUND: Deep learning has the potential to improve diagnostic accuracy and efficiency in medical image recognition. In the current study, we developed a deep learning algorithm and assessed its performance in discriminating melanoma from nevus using whole-slide pathological images (WSIs). METHODS: The deep learning algorithm was trained and validated using a set of 781 WSIs (86 melanomas, 695 nevi) from PLA General Hospital. The diagnostic performance of the algorithm was tested on an independent test set of 104 WSIs (29 melanomas, 75 nevi) from Tianjin Chang Zheng Hospital. The same test set was also diagnostically classified by 7 expert dermatopathologists. RESULTS: The deep learning algorithm receiver operating characteristic (ROC) curve achieved a sensitivity 100% at the specificity of 94.7% in the classification of melanoma and nevus on the test set. The area under ROC curve was 0.99. Dermatopathologists achieved a mean sensitivity and specificity of 95.1% (95% confidence interval [CI]: 92.0%-98.2%) and 96.0% (95% CI: 94.2%-97.8%), respectively. At the operating point of sensitivity of 95.1%, the algorithm revealed a comparable specificity with 7 dermatopathologists (97.3% vs. 96.0%, P = 0.11). At the operating point of specificity of 96.0%, the algorithm also achieved a comparable sensitivity with 7 dermatopathologists (96.5% vs. 95.1%, P = 0.30). A more transparent and interpretable diagnosis could be generated by highlighting the regions of interest recognized by the algorithm in WSIs. CONCLUSION: The performance of the deep learning algorithm was on par with that of 7 expert dermatopathologists in interpreting WSIs with melanocytic lesions. By pre-screening the suspicious melanoma regions, it might serve as a supplemental diagnostic tool to improve working efficiency of pathologists.
ABSTRACT
Castleman disease (CD) is an unusual lymphoproliferative disorder characterized by multiple lymphadenopathy accompanied by marked systemic inflammatory symptoms. CD can be unicentric (UCD) or multicentric (MCD), and it can be classified into three types based on histopathology: hyaline vascular type, plasma cell type, and mixed hyaline vascular and plasma cell type. CD involving skin is an unusual clinical manifestation. Abnormalities including rash, hyperpigmentation, cherry hemangiomatosis, paraneoplastic pemphigus, and Kaposi sarcoma have been reported to occur in MCD. Here, we reported an unusual case of MCD which presented initially with disseminated dark brown papules, patches, and plaques, and pathologically demonstrated plasma cell type CD, a finding which is rarely reported. The peculiar clinicopathological features will be discussed.
Subject(s)
Bone Marrow/pathology , Castleman Disease/diagnosis , Lymph Nodes/pathology , Lymphoproliferative Disorders/pathology , Plasma Cells/pathology , Adult , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Asian People/ethnology , Biopsy , Castleman Disease/drug therapy , Castleman Disease/pathology , Drug Therapy, Combination , Female , Glucocorticoids/administration & dosage , Glucocorticoids/therapeutic use , Hemangioma/pathology , Humans , Hyalin , Hyperpigmentation/pathology , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Skin Abnormalities/pathology , Treatment OutcomeABSTRACT
The ventral tegmental area (VTA), an important source of dopamine, regulates goal- and reward-directed and social behaviors, wakefulness, and sleep. Hyperactivation of dopamine neurons generates behavioral pathologies. But any roles of non-dopamine VTA neurons in psychiatric illness have been little explored. Lesioning or chemogenetically inhibiting VTA GABAergic (VTAVgat) neurons generated persistent wakefulness with mania-like qualities: locomotor activity was increased; sensitivity to D-amphetamine was heightened; immobility times decreased on the tail suspension and forced swim tests; and sucrose preference increased. Furthermore, after sleep deprivation, mice with lesioned VTAVgat neurons did not catch up on lost sleep, even though they were starting from a sleep-deprived baseline, suggesting that sleep homeostasis was bypassed. The mania-like behaviors, including the sleep loss, were reversed by valproate, and re-emerged when treatment was stopped. Lithium salts and lamotrigine, however, had no effect. Low doses of diazepam partially reduced the hyperlocomotion and fully recovered the immobility time during tail suspension. The mania like-behaviors mostly depended on dopamine, because giving D1/D2/D3 receptor antagonists reduced these behaviors, but also partially on VTAVgat projections to the lateral hypothalamus (LH). Optically or chemogenetically inhibiting VTAVgat terminals in the LH elevated locomotion and decreased immobility time during the tail suspension and forced swimming tests. VTAVgat neurons help set an animal's (and perhaps human's) mental and physical activity levels. Inputs inhibiting VTAVgat neurons intensify wakefulness (increased activity, enhanced alertness and motivation), qualities useful for acute survival. In the extreme, however, decreased or failed inhibition from VTAVgat neurons produces mania-like qualities (hyperactivity, hedonia, decreased sleep).
Subject(s)
GABAergic Neurons , Ventral Tegmental Area , Animals , Dopaminergic Neurons , Hypothalamic Area, Lateral , Mania , MiceABSTRACT
Hypereosinophilic syndrome (HES) is a rare multisystem disease that predominantly includes skin with severe and persistent itching. A lack of understanding about the pathological condition and mechanism of dermatosis caused by HES hinders its treatment. In the present study, we applied a quantitative proteomics approach to characterize the cellular responses of skin tissue to idiopathic HES (IHES) at the proteome level. We identified hundreds of skin tissue proteins that were differentially expressed between IHES patients and healthy individuals. IHES patients display severely damaged microenvironment, including extracellular matrix (ECM) organization and disassembly, immune disorders, decreased metabolic capacity, and susceptibility to microbial infection. Moreover, there was abnormal proliferation of basal epidermal stem cells, which was closely related to high expression of the epigenetic regulator, histone deacetylase 2, providing mechanistic insight into the abnormal epidermal thickening of IHES skin tissues. Overall, our study provides a comprehensive framework for a system-level understanding of IHES-induced dermatosis (IHESiD) tissues at the protein and cell pathway levels. Our findings may facilitate a new approach to diagnosis and treatment to alleviate skin clinical symptoms, monitor the activity of IHES, and determine therapeutic effects.
Subject(s)
Hypereosinophilic Syndrome/pathology , Skin/pathology , Systems Biology , Cell Proliferation , Down-Regulation , Epidermis/pathology , Histone Deacetylase 2/metabolism , Humans , Mass Spectrometry , Proteomics , Stem Cells/pathologyABSTRACT
Lymphomatoid papulosis (LyP) type E is a recently described variant characterized by the occurrence of large necrotic eschar-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates of CD30+ lymphocytes, frequently coexpressing CD8. Rare cases of LyP type E with a CD56+ immunophenotype have been described. Herein, we describe a 36-year-old woman with LyP type E, characterized by purpura-like lesions on her left ankle. Initially, she presented with left ankle swelling, petechiae and ecchymosis, and rapidly developing necrotic papules, all of which resolved spontaneously over a period of a few months without intentional therapy. Biopsy revealed CD30 and CD56 positive atypical cell infiltrates with marked angiocentricity and angiodestruction. Awareness of this rare LyP variant and its correct recognition, even if the clinical presentation is unusual, is important to avoid aggressive treatment.
Subject(s)
CD56 Antigen , Lymphomatoid Papulosis , Neoplasm Proteins , Purpura , Skin Neoplasms , Adult , CD56 Antigen/immunology , CD56 Antigen/metabolism , Female , Humans , Immunophenotyping , Lymphomatoid Papulosis/immunology , Lymphomatoid Papulosis/metabolism , Lymphomatoid Papulosis/pathology , Neoplasm Proteins/immunology , Neoplasm Proteins/metabolism , Purpura/immunology , Purpura/metabolism , Purpura/pathology , Skin Neoplasms/immunology , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: 5-aminolevulinic acid photodynamic therapy (PDT) for genital warts is effective, safe, and can prevent recurrence. It is believed that PDT can induce immune responses, but the mechanism is not completely understood. OBJECTIVES: The objectives of this article are to confirm the effect of PDT for genital warts on local immunity and to investigate the recruitment and significance of immune cells in tissues. METHODS: Local immune changes in T lymphocytes (CD3+, CD4+, CD8+), plasmacytoid dendritic cells (pDCs) (CD123+), and myeloid dendritic cells (CD1a+) after PDT in patients were evaluated by immunohistochemistry staining. Changes in mRNA levels of IFN-γ, IFN-α, IFN-ß, interferon-stimulated gene 15 kDa (ISG-15), Mx2, Toll-like receptor 9 (TLR9), and interferon regulatory factor 7 (IRF7) were analyzed by real-time quantitative polymerase chain reaction. RESULTS: At 4 hours after PDT, CD4+ increased, accompanied by increased levels of mRNA expression of IFN-γ, but CD4+ and mRNA expression levels of IFN-γ were decreased at 24 hours after PDT. CD123+ pDCs showed an increasing trend. CD1a+ LCs in the epidermis gradually decreased, and DCs in the epidermis gradually increased. CD3+ infiltrated and migrated to the superficial dermis, but CD8+ did not change significantly after PDT. The mRNA expression levels of IFN-α, IFN-ß, ISG-15, Mx2, TLR9, and IRF7 showed an increasing trend after PDT. As compared with the patients without significantly increased IFN-α and IFN-ß after PDT sessions, patients with significant increases needed fewer sessions of PDT for remission. CONCLUSIONS: PDT for genital warts can activate T lymphocyte-mediated, DC-related, and pDC-related immunity. The clinical efficacy of PDT for genital warts may be related to the increased levels of IFN-α and IFN-ß after treatment.