{"title":"Utilizing PRAME Expression and a Meta-Analytic Framework for iSALT to Explore Atypical Late-Onset Nevi of the Elderly and Their Relationship With Lentiginous and Nested Nevoid Melanomas.","authors":"Steven Kossard, Shahin Sharifi, Linda Calvey","doi":"10.1097/DAD.0000000000002847","DOIUrl":"10.1097/DAD.0000000000002847","url":null,"abstract":"<p><strong>Background: </strong>In contrast to early-onset dysplastic nevi, late-onset atypical nevi of the elderly are more often precursors to distinctive nevoid melanomas. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry was applied to delineate the nevoid aspect of late-onset oncogenic nevoid pathway. Inducible Skin-Associated Lymphoid Tissue, regulatory T-cell mesenchymal hubs, has emerged as a translational tool and was used to define nevoid oncogenesis within a dynamic meta-analytic pathway.</p><p><strong>Methods: </strong>PRAME immunohistochemistry was applied after designating a histopathologic diagnosis. Late-onset atypical nested lentiginous nevus, lentiginous nested melanoma, and hypercellular nested nevoid melanoma were the diagnostic categories. A positive PRAME for melanoma was set at 75% percentage labeling.A wide-ranging published evidence-based database was incorporated to develop a meta-analytic framework for oncogenic nevogenesis. This combined inducible Skin-Associated Lymphoid Tissue incorporating the pleiotropic functions of regulatory T cells regulating immunity and gene regulatory epigenetics as principal modulators.</p><p><strong>Results: </strong>Concordant-negative PRAME expression was present in 64 of 81 (79%) atypical nested lentiginous nevi, concordant-positive PRAME expression occurred in 54 of 75 (72%) nevoid lentiginous and nested melanomas, and 18 of 23 (78%) nevoid hypercellular nested melanomas.</p><p><strong>Conclusions: </strong>PRAME expression confirmed the existence of a late-onset oncogenic nevoid pathway that can be defined by histopathology. Subsequent meta-analysis data linked to the meta-analytic framework revealed that PRAME is an epigenetic surrogate antigen expressed because of repression of retinoic acid receptor signaling, preventing ligand-induced retinoic acid cellular differentiation, growth arrest, and apoptosis, and promoting melanoma growth and survival for melanomas. PRAME is only a single antigen within a highly complex dynamic framework that governs nevoid oncogenesis. Significantly, the retinoic acid/retinoic acid receptor complex has been shown to modulate the immunosuppressive arm of regulatory T cells underpinning immune tolerance and is pertinent to the broad framework but is not linked to PRAME expression in this arm.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"825-832"},"PeriodicalIF":1.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11573072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"T-cell Clonality in Pleomorphic Dermal Sarcoma in Male Veterans: A Report of 2 Cases and a Review of the Literature.","authors":"Kei Shing Oh, Meera Mahalingam","doi":"10.1097/DAD.0000000000002832","DOIUrl":"10.1097/DAD.0000000000002832","url":null,"abstract":"<p><strong>Abstract: </strong>The standard treatment of choice for pleomorphic dermal sarcoma (PDS), a relatively uncommon soft tissue sarcoma and 1 morphologically similar to atypical fibroxanthoma, is wide local excision with close clinical follow-up. Studies regarding management of advanced/metastatic PDS with immune checkpoint inhibitors are limited as most STSs have historically been viewed as being immunologically inert. Contradicting this belief, in this report, we describe 2 cases of PDS with a robust host response. Histopathology of both cases revealed a dermal neoplasm comprising mitotically active, pleomorphic, spindled-to-ovoid cells, which were immunohistochemically negative for keratinocytic, melanocytic, and smooth muscle markers. An unusual feature in both cases was the presence of a brisk host response. Additional workup of the infiltrating lymphocyte population revealed an abnormal CD4:CD8 ratio in both cases, with the proportion of CD8 + lymphocytes surpassing (case 1) and equaling (case 2) that of the CD4 + T-lymphocyte population. The increased proportion of CD8 + lymphocytes prompted the additional workup of TCR gene rearrangement, which revealed a clonal population of T lymphocytes in both cases. The robust and clonal T-lymphocyte host response in both of our cases suggests that PDS appears to fit the classic model of an inflammatory-type tumor and may be a candidate for checkpoint inhibition. Future work includes additional reports of cases of PDS with an infiltrating clonal T-lymphocyte population and detailing the function and specificity of the infiltrating T lymphocytes to ascertain whether they have the potential to recognize and lyse the tumors they colonize.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"855-859"},"PeriodicalIF":1.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480048","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}
Mahzad Azimpouran, Chau M Bui, Bonnie Balzer, Sumire Kitahara
{"title":"Rapidly Progressive Primary Cutaneous Gamma Delta T-Cell Lymphoma With FYN Gene Alteration.","authors":"Mahzad Azimpouran, Chau M Bui, Bonnie Balzer, Sumire Kitahara","doi":"10.1097/DAD.0000000000002856","DOIUrl":"10.1097/DAD.0000000000002856","url":null,"abstract":"<p><strong>Abstract: </strong>Primary cutaneous gamma delta T-cell lymphoma (PCGDTCL) is a rare type of non-Hodgkin lymphoma accounting for <1% of primary cutaneous T-cell lymphomas. The exact cause of PCGDTCL is not known, however, it is thought that chronic antigen exposure in the skin may lead to immune dysregulation at the site, resulting in abnormal proliferation of mature, post-thymic cytotoxic gamma delta T cells. Mutations are the most common genetic alteration seen in PCGDTCL, while structural abnormalities such as gene fusions are not common. We report a case of PCGDTCL with atypical immunophenotypic features, including expression of CD5 with lack of cytotoxic marker expression, and a structural alteration leading to FYN deletion at exon 8. Recently, it was described that a deletion of the area between FYN exon 8 and TRAF3IP2 intron 2 results in a novel FYN::TRAF3IP2 fusion in peripheral T-cell lymphoma, not otherwise specified. We describe our patient's clinical course, differential diagnosis, and potential implications of FYN deletion on disease pathogenesis. To our knowledge, this is the first report of an FYN structural alteration to be described in PCGDTCL.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"e120-e123"},"PeriodicalIF":1.1,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480043","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}
Alyssa Breneman, Megan H Trager, Emily R Gordon, Apoorva Mehta, Sameera Husain, Alejandro A Gru, Faramarz H Samie
{"title":"Utilization of ChatGPT to Simplify Complex Dermatopathology Reports Into Patient-Friendly Language.","authors":"Alyssa Breneman, Megan H Trager, Emily R Gordon, Apoorva Mehta, Sameera Husain, Alejandro A Gru, Faramarz H Samie","doi":"10.1097/DAD.0000000000002868","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002868","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840196","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}
Pelin Sagut, Elliott Lyles, Jenna Vroman, Catherine S Barker, Hazem A Juratli, Evelyn Bruner, Sally Self, Dirk M Elston
{"title":"A Comparative Study of Direct Immunofluorescence Patterns in Linear IgA Bullous Dermatosis Versus Dermatitis Herpetiformis.","authors":"Pelin Sagut, Elliott Lyles, Jenna Vroman, Catherine S Barker, Hazem A Juratli, Evelyn Bruner, Sally Self, Dirk M Elston","doi":"10.1097/DAD.0000000000002864","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002864","url":null,"abstract":"<p><strong>Background: </strong>Dermatitis herpetiformis (DH) is typically characterized by granular IgA deposition in the papillary dermis on direct immunofluorescence (DIF), and linear IgA bullous dermatosis (LABD) is characterized by linear deposition of IgA along the basement membrane. Other DIF findings in both conditions may include IgG, IgM, and C3 deposition in various patterns. In cases where immunofluorescence findings are unclear, such as continuous but somewhat granular IgA deposition along the dermal-epidermal junction, additional DIF patterns may be helpful in the diagnostic process.</p><p><strong>Methods: </strong>Forty-five cases of digitized images of LABD and 48 digitized images of DH cases were analyzed. The data regarding the positivity and patterns of immunoglobulins were documented and analyzed.</p><p><strong>Results: </strong>None of the LABD cases had a picket fence pattern, while 47.9% (n = 23) of the DH cases had the pattern. Elevated levels of IgG and IgM were found in LABD compared with DH. In DH, higher IgM and kappa light chain levels were observed in the deposited particles compared with those in LABD.</p><p><strong>Conclusions: </strong>The \"picket fence pattern\" is highly specific for DH (Specificity 100%) but less sensitive (Sensitivity 47.9%). It may be helpful to differentiate between DH and LABD for a more accurate diagnosis.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689540","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}
Mariana Vargas-Clavijo, Nora Cardona-Castro, Juan Pablo Ospina-Gómez, Héctor Serrano-Coll
{"title":"Evaluating Advanced Machine Learning Models for Histopathological Diagnosis of Hansen Disease.","authors":"Mariana Vargas-Clavijo, Nora Cardona-Castro, Juan Pablo Ospina-Gómez, Héctor Serrano-Coll","doi":"10.1097/DAD.0000000000002875","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002875","url":null,"abstract":"<p><strong>Introduction: </strong>Leprosy is a neglected infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis and remains a public health challenge in tropical regions. Therefore, the development of technological tools such as machine learning (ML) offers an opportunity to innovate strategies for improving the diagnosis of this complex disease.</p><p><strong>Objective: </strong>To validate the utility of different ML models for the histopathological diagnosis of Hansen disease.</p><p><strong>Methodology: </strong>An observational study was conducted where 55 H&E-stained tissue slides from leprosy patients and 51 healthy skin controls were analyzed using microphotographs captured at various magnifications. These images were categorized based on histopathological findings and processed using the Cross-Industry Standard Process for Data Mining methodology for designing and training ML models. Five types of ML models were evaluated using standard metrics such as accuracy, sensitivity, and specificity, emphasizing data normalization as a fundamental step in optimizing model performance.</p><p><strong>Results: </strong>The artificial neural network (ANN) model demonstrated an accuracy of 70%, sensitivity of 74%, and specificity of 65%, demonstrating its ability to identify leprosy cases with moderate precision. The receiver operating characteristic curve of the ANN model showed an area under the curve of 0.71. Conversely, models such as decision trees, logistic regression, and random forests showed similar accuracy results but with slightly lower sensitivity, potentially indicating a higher risk of false negatives in detecting leprosy-positive cases.</p><p><strong>Conclusion: </strong>The ANN model emerges as a promising alternative for leprosy detection. However, further refinement of these models is necessary to enhance their adaptability across different clinical settings and participation in patient care.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":1.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584965","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}
Parnia Forouzan, Jodie Raffi, Linda T Doan, Michelle S Min
{"title":"Reactive Lobular Panniculitis in the Setting of Mpox (Monkeypox) Infection.","authors":"Parnia Forouzan, Jodie Raffi, Linda T Doan, Michelle S Min","doi":"10.1097/DAD.0000000000002795","DOIUrl":"10.1097/DAD.0000000000002795","url":null,"abstract":"<p><strong>Abstract: </strong>Mpox, previously referred to as monkeypox, was recently deemed a public health emergency in 2022. Our understanding of potential secondary cutaneous manifestations in the setting of this infection is still evolving. We report a rare case of a man who presented with erythematous, painful subcutaneous nodules on his extremities in the setting of recent mpox infection. Biopsy of a lesion from the lower legs revealed a lobular panniculitis with lupus panniculitis-like features on pathology. He was ultimately diagnosed with a unique case of reactive panniculitis secondary to mpox.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"781-783"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621754","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}
{"title":"Inflammatory Vitiligo: A Rare Cause of Pseudolymphoma.","authors":"Maged Daruish, Cecilia Grossmith, Saleem Taibjee","doi":"10.1097/DAD.0000000000002806","DOIUrl":"10.1097/DAD.0000000000002806","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"799-801"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141621750","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}
Savannah M Alvarado, Olivia G Cohen, Katherine Lattanzio, Paul Haun, Joel M Gelfand, Alison W Loren, Jina Chung, Emily Baumrin
{"title":"Histopathologic Analysis of Chronic Cutaneous Graft-Versus-Host Disease.","authors":"Savannah M Alvarado, Olivia G Cohen, Katherine Lattanzio, Paul Haun, Joel M Gelfand, Alison W Loren, Jina Chung, Emily Baumrin","doi":"10.1097/DAD.0000000000002841","DOIUrl":"10.1097/DAD.0000000000002841","url":null,"abstract":"<p><strong>Abstract: </strong>Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"755-760"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142300196","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}
Nada Shaker, George Niedt, Nuha Shaker, Nasir Saleem, Rafat Abu Shakra, Omar P Sangueza, Robert Phelps
{"title":"A Subcutaneous Spindle Cell Neoplasm Originating From the Undifferentiated Mesoderm: An Uncommon Tumor in an Unusual Site: Challenge.","authors":"Nada Shaker, George Niedt, Nuha Shaker, Nasir Saleem, Rafat Abu Shakra, Omar P Sangueza, Robert Phelps","doi":"10.1097/DAD.0000000000002781","DOIUrl":"10.1097/DAD.0000000000002781","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":"46 11","pages":"e100-e101"},"PeriodicalIF":1.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480051","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}