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American Journal of Dermatopathology最新文献

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Progressive Immunotherapy-Related Mucocutaneous Eruption: A Mimicker of SJS-TEN. 进行性免疫治疗相关粘膜皮肤爆发：模拟SJS-TEN。
IF 1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-30 DOI: 10.1097/DAD.0000000000003083
Kishan A Sangani, Victoria Lee, Liesl Schroedl, Christopher R Shea, Oluwakemi Onajin, Angad A Chadha
{"title":"Progressive Immunotherapy-Related Mucocutaneous Eruption: A Mimicker of SJS-TEN.","authors":"Kishan A Sangani, Victoria Lee, Liesl Schroedl, Christopher R Shea, Oluwakemi Onajin, Angad A Chadha","doi":"10.1097/DAD.0000000000003083","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003083","url":null,"abstract":"<p><strong>Abstract: </strong>Immune checkpoint inhibitors are an integral component of oncology treatment. Adverse systemic effects of this immune modulation are often manifested in the skin and, therefore, must be carefully described and characterized to inform clinical decision making in medically complex patients. Here we report 2 cases of progressive immunotherapy-related mucocutaneous eruption that resemble Stevens-Johnson Syndrome but is unique in its clinical and histopathologic presentation, supporting a distinction from classic medication-induced Stevens-Johnson syndrome and toxic epidermal necrolysis.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144745893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Malignant Melanoma With Transdifferentiation Into a Ganglioneuroblastic Phenotype After Anti-PD-1 Therapy. 抗pd -1治疗后恶性黑色素瘤转分化为神经节神经母细胞表型。
IF 1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-28 DOI: 10.1097/DAD.0000000000003080
Madison S Harris, Claire Castaneda, Aaron Wieland, Daniel D Bennett, Alexander Birbrair, Eliza Kapinski, Mark R Albertini, Darya G Buehler, Vincent T Ma
{"title":"Malignant Melanoma With Transdifferentiation Into a Ganglioneuroblastic Phenotype After Anti-PD-1 Therapy.","authors":"Madison S Harris, Claire Castaneda, Aaron Wieland, Daniel D Bennett, Alexander Birbrair, Eliza Kapinski, Mark R Albertini, Darya G Buehler, Vincent T Ma","doi":"10.1097/DAD.0000000000003080","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003080","url":null,"abstract":"<p><strong>Abstract: </strong>The clinicopathologic spectrum of dedifferentiated, undifferentiated, and transdifferentiated melanoma occurring de novo or following systemic therapy is gaining recognition. Here, we present a patient with locally advanced cutaneous melanoma who received neoadjuvant anti-PD-1 therapy and whose post-treatment excisional pathology revealed transdifferentiation into a ganglioneuroblastic phenotype. This rare phenotype is hypothesized to be connected to melanoma's shared origin from pluripotent neural crest cells. This case report highlights the proposed pathogenic mechanisms underlying this transition after immune checkpoint therapy, including the pathways and factors that affect the tumor and its microenvironment.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bumps on My Head-A Case of Acute T-Cell Lymphoblastic Lymphoma. 我头上的肿块——一例急性t细胞淋巴母细胞淋巴瘤。
IF 1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-28 DOI: 10.1097/DAD.0000000000003081
Lisa Brambert, Aashni Bhukhan, Victoria Dukharan, Panagiotis Mitropoulos, Etan Marks
{"title":"Bumps on My Head-A Case of Acute T-Cell Lymphoblastic Lymphoma.","authors":"Lisa Brambert, Aashni Bhukhan, Victoria Dukharan, Panagiotis Mitropoulos, Etan Marks","doi":"10.1097/DAD.0000000000003081","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003081","url":null,"abstract":"<p><strong>Abstract: </strong>T-cell lymphoblastic lymphoma (T-LBL) is an aggressive, rare neoplasm of immature T-cell precursors, typically presenting with lymphadenopathy, a mediastinal mass, and bone marrow involvement. We report the case of a 25-year-old man who presented with plaques and subcutaneous nodules on the scalp, forehead, and left cheek, accompanied by posterior cervical lymphadenopathy. Immunohistochemical studies of intralesional punch, lymph node, and bone marrow biopsies confirmed a diagnosis of T-LBL. In addition, NOTCH1 oncogene mutations, a common feature of T-LBL, were detected. Although cutaneous involvement in T-LBL is rare and uncommonly the most prominent symptom, this case highlights a rare presentation with predominantly cutaneous manifestations. This emphasizes the importance of early recognition when malignancy is suspected to prevent the development of more severe complications.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144735121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simultaneous Presentation of Cutaneous Waldenström Macroglobulinemia and Acalabrutinib-Related Toxicity. 皮肤Waldenström巨球蛋白血症和阿卡拉替尼相关毒性同时出现。
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-24 DOI: 10.1097/DAD.0000000000003077
Tania Platero-Portillo, Vicki Mercado-Evans, Nisha Ramani, Bhuvaneswari Krishnan
{"title":"Simultaneous Presentation of Cutaneous Waldenström Macroglobulinemia and Acalabrutinib-Related Toxicity.","authors":"Tania Platero-Portillo, Vicki Mercado-Evans, Nisha Ramani, Bhuvaneswari Krishnan","doi":"10.1097/DAD.0000000000003077","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003077","url":null,"abstract":"<p><strong>Abstract: </strong>Waldenström macroglobulinemia (WM) is a rare B-cell lymphoplasmacytic lymphoma associated with clonal IgM gammopathy, comprising 1%-2% of hematological malignancies. The clinical presentation exhibits diverse cutaneous manifestations, including paraproteinemia-related effects, autoimmune phenomena, and neoplastic cell infiltration. Next-generation Bruton tyrosine kinase inhibitors, such as zanubrutinib and acalabrutinib, have revolutionized WM treatment by enhancing selectivity but are associated with various dermatologic lesions. We report a case of a 74-year-old man with simultaneous presentation of cutaneous WM and an acalabrutinib-induced eruption. The drug reaction presented as blanching macules and papules, histologically showing superficial perivascular dermatitis and lymphocytic panniculitis with predominantly T cells. The cutaneous WM showed diffuse, dense dermal lymphocytic infiltrates, which were predominantly B cells. Recognizing these distinct histopathological patterns is crucial for accurate diagnosis and timely intervention. The evolving landscape of Bruton tyrosine kinase inhibitors necessitates vigilant clinical awareness of the delicate balance between harnessing therapeutic benefits and managing associated cutaneous complexities in patients with WM. In addition, these patients are susceptible to opportunistic infections. Awareness of the various cutaneous reactions and vigilant monitoring are required.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144709769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Subcutaneous Panniculitis-Like T-Cell Lymphoma in a 2-Year-Old: Case Report and Literature Review. 2岁皮下泛膜炎样t细胞淋巴瘤病例报告及文献复习。
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-21 DOI: 10.1097/DAD.0000000000003070
Clara Ureña-Paniego, Francisco Vílchez-Márquez, María Narváez-Simón, Elena Masana-Flores, Salvador Arias-Santiago
{"title":"Subcutaneous Panniculitis-Like T-Cell Lymphoma in a 2-Year-Old: Case Report and Literature Review.","authors":"Clara Ureña-Paniego, Francisco Vílchez-Márquez, María Narváez-Simón, Elena Masana-Flores, Salvador Arias-Santiago","doi":"10.1097/DAD.0000000000003070","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003070","url":null,"abstract":"<p><strong>Abstract: </strong>Subcutaneous panniculitis-like T-cell lymphoma is a rare cutaneous T-cell lymphoma characterized by cytotoxic T-cell infiltration of subcutaneous fat that clinically mimics panniculitis. It predominantly affects adults and is rarely present in young children. We report a case of subcutaneous panniculitis-like T-cell lymphoma in a 2-year-old child and review the pediatric literature to highlight the unique clinical features and outcomes in this age group.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Utility of Immunohistochemistry in Diagnosis of Papillary Eccrine Adenoma/Tubular Apocrine Adenoma (PEA/TAA). 免疫组织化学在乳头状腺瘤/管状大汗腺瘤（PEA/TAA）诊断中的应用
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-17 DOI: 10.1097/DAD.0000000000003069
Amanda J Nguyen, Ruifeng Ray Guo, Margot S Peters
{"title":"Utility of Immunohistochemistry in Diagnosis of Papillary Eccrine Adenoma/Tubular Apocrine Adenoma (PEA/TAA).","authors":"Amanda J Nguyen, Ruifeng Ray Guo, Margot S Peters","doi":"10.1097/DAD.0000000000003069","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003069","url":null,"abstract":"<p><strong>Abstract: </strong>Papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA) is a rare sweat gland neoplasm. Because PEA/TAA shares morphologic features with other sweat gland tumors, including digital papillary adenocarcinoma, histologic diagnosis may be challenging. We report a case of PEA/TAA presenting as a nodule on the left foot of a 43-year-old man. Histopathologic examination revealed a well-circumscribed dermal proliferation of variably sized glands composed of ductal cells with an outer layer of myoepithelial cells. By immunohistochemistry, the ductal tumor cells showed strong, diffuse expression of BRAF V600E, and the myoepithelial cells were positive for p63. This case illustrates the utility of immunohistochemistry in the diagnosis of this rare neoplasm. Particularly when PEA/TAA is located on an acral site, distinction from digital papillary adenocarcinoma is critical, because these tumors show significant differences in clinical behavior.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Giant Vulvar Pseudoangiomatous Stromal Hyperplasia After Bilateral Breast and Axillary Lesions: A Delayed Multifocal Presentation. 双侧乳腺和腋窝病变后巨大外阴假性血管瘤间质增生：延迟多灶表现。
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-16 DOI: 10.1097/DAD.0000000000003066
Ceren Unal, Sebile Guler Cekic, Zuhal Gucin, Serdar Aydin
{"title":"Giant Vulvar Pseudoangiomatous Stromal Hyperplasia After Bilateral Breast and Axillary Lesions: A Delayed Multifocal Presentation.","authors":"Ceren Unal, Sebile Guler Cekic, Zuhal Gucin, Serdar Aydin","doi":"10.1097/DAD.0000000000003066","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003066","url":null,"abstract":"<p><strong>Abstract: </strong>Pseudoangiomatous stromal hyperplasia (PASH) is a benign myofibroblastic proliferation frequently encountered in the breast but rarely affects anogenital mammary-like glands, where it typically presents as small nodules. We report a rare case of a 38-year-old woman who developed a 95 × 60 × 60-mm vulvar mass 4 months after undergoing bilateral mastectomy and axillary excisions for histologically confirmed PASH. Pelvic MRI revealed a well-circumscribed, hypointense lesion in the posterolateral vaginal wall. Wide local excision was performed. Histopathology demonstrated a dense collagenous stroma with bland spindle cells forming interanastomosing slit-like, endothelial-free pseudovascular spaces, confirming the diagnosis of PASH. No fibroadenomatous component was observed. Immunohistochemical staining was positive for SMA and negative for CD31 and Factor VIII in the pseudovascular spaces, aiding in the exclusion of vascular neoplasms such as angiosarcoma. The patient remains recurrence-free at 1 year. This case highlights the potential for delayed multifocal PASH involving hormonally responsive anogenital sites, emphasizes its inclusion in the differential diagnosis of large vulvar masses, and underscores the need for surveillance of ectopic mammary-like tissues in patients with a history of PASH.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retrospective Analysis of the Utility of Polymerase Chain Reaction-Reverse Sequence-Specific Oligonucleotide (GENOSEARCH HPV31) and Human Papillomavirus Immunohistochemistry (BSB-66) in the Diagnosis of Digital Papillary Adenocarcinoma. 聚合酶链反应-反序列特异性寡核苷酸（GENOSEARCH HPV31）和人乳头瘤病毒免疫组化（BSB-66）在数字乳头状腺癌诊断中的应用回顾性分析
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-14 DOI: 10.1097/DAD.0000000000003065
Tsubasa Hiraki, Toshihiro Takai, Yoshifumi Iwahashi, Shin-Ichi Murata, Yuna Noda, Masatoshi Jinnin, Shusuke Yoshikawa, Keisuke Goto
{"title":"Retrospective Analysis of the Utility of Polymerase Chain Reaction-Reverse Sequence-Specific Oligonucleotide (GENOSEARCH HPV31) and Human Papillomavirus Immunohistochemistry (BSB-66) in the Diagnosis of Digital Papillary Adenocarcinoma.","authors":"Tsubasa Hiraki, Toshihiro Takai, Yoshifumi Iwahashi, Shin-Ichi Murata, Yuna Noda, Masatoshi Jinnin, Shusuke Yoshikawa, Keisuke Goto","doi":"10.1097/DAD.0000000000003065","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003065","url":null,"abstract":"<p><strong>Abstract: </strong>Digital papillary adenocarcinoma (DPA) is a rare malignant sweat gland tumor associated with human papillomavirus genotype 42 (HPV42). Currently, the only established test for detecting HPV42 in DPA is RNAscope in situ hybridization. However, this test incurs extremely high acquisition and running costs. To find an alternative method for the detection of human papillomavirus (HPV) in DPA, we evaluated the utility of polymerase chain reaction-reverse sequence-specific oligonucleotide (PCR-rSSO) (GENOSEARCH HPV31) and immunohistochemistry (IHC) using an anti-HPV antibody (BSB-66) for the detection of HPV in DPA. A total of 6 cases of DPA and 16 cases of other cutaneous tumors were reviewed, all of which had been practically performed by GENOSEARCH HPV31 using formalin-fixed paraffin-embedded (FFPE) tissues. The results revealed the presence of HPV42 in all 5 available cases of DPA (5/5, 100%) in GENOSEARCH HPV31. However, 1 case of DPA could not be processed because of poor DNA quality. HPV42 was not detected in the remaining 16 controls. IHC for HPV (BSB-66) showed no reactivity in any of the 6 DPA tumors. For the detection of HPV42 in the FFPE tissue of DPA, GENOSEARCH HPV31 can be used as an alternative to RNAscope in situ hybridization, unless the DNA quality in the FFPE tissue is poor. A notable advantage of GENOSEARCH HPV31 is its lower financial burden, both regarding purchase and operational costs, compared with RNAscope. Furthermore, GENOSEARCH HPV31 can identify additional 30 major genotypes of HPV, other than HPV42. By contrast, HPV (BSB-66) IHC cannot be used to detect HPV in DPA.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144627686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Histiocytoid Variant of Cutaneous Apocrine Carcinoma: A Rare Case With Literature Review. 皮肤大汗腺癌的组织细胞样变异：一例罕见病例并文献复习。
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-10 DOI: 10.1097/DAD.0000000000003061
J N Aparnna, Biswanath Behera, Naveen Purushothaman, Madhusmita Sethy, Deepak Kumar Sahu, Pavithra Ayyanar
{"title":"Histiocytoid Variant of Cutaneous Apocrine Carcinoma: A Rare Case With Literature Review.","authors":"J N Aparnna, Biswanath Behera, Naveen Purushothaman, Madhusmita Sethy, Deepak Kumar Sahu, Pavithra Ayyanar","doi":"10.1097/DAD.0000000000003061","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003061","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Architecturally Low-Grade Pure Cylindrocarcinoma With CYLD1 Mutation. 低级别纯柱状癌伴CYLD1突变。
IF 1.1 4区 医学
American Journal of Dermatopathology Pub Date : 2025-07-08 DOI: 10.1097/DAD.0000000000002984
Ronan Knittel, Shona Hendry, Benjamin A Wood
{"title":"Architecturally Low-Grade Pure Cylindrocarcinoma With CYLD1 Mutation.","authors":"Ronan Knittel, Shona Hendry, Benjamin A Wood","doi":"10.1097/DAD.0000000000002984","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002984","url":null,"abstract":"<p><strong>Abstract: </strong>Cylindrocarcinoma is a very rare malignant adnexal neoplasm. The diagnosis of cylindrocarcinoma typically requires identifying a precursor benign component; indeed the current World Health Organization classification classifies these lesions within the group of malignant neoplasms arising from cylindroma. We present a unique case of architecturally low-grade pure cylindrocarcinoma, supported by striking morphologic and immunohistochemical features and showing an inactivating CYLD1 mutation.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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