{"title":"A Rare Case of Bullous Melanoma With Subepidermal Separation","authors":"Gamze Taş-Aygar, Müzeyyen Gönül, Bengü Çevirgen-Cemil, Aysun Gökçe, Selda Pelin Kartal","doi":"10.1111/cup.14789","DOIUrl":"10.1111/cup.14789","url":null,"abstract":"<div>\u0000 \u0000 <p>Several rare subtypes of melanoma, beyond the classic variants, have been described in the literature. The rarity of these variants can hinder recognition and lead to delays in clinical diagnosis. Bullous melanoma is one such rare subtype. Blister formation in bullous melanoma can occur either intraepidermally or subepidermally. While most reported cases exhibit intraepidermal separation, only three cases with subepidermal separation have been documented to date. Here, we present a rare case of bullous melanoma with subepidermal separation characterized by exceptional recurrent bullous episodes.</p>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 4","pages":"294-298"},"PeriodicalIF":1.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374151","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}
Diana Frimpong, Sahar Naz, Murtaza Kadhum, Magdalena Rogut, Taiba Farooque, Jennifer O'Neill, Ann Fleming
{"title":"A Rare Case of Cutaneous Intraneural Glomus Tumor","authors":"Diana Frimpong, Sahar Naz, Murtaza Kadhum, Magdalena Rogut, Taiba Farooque, Jennifer O'Neill, Ann Fleming","doi":"10.1111/cup.14793","DOIUrl":"10.1111/cup.14793","url":null,"abstract":"<div>\u0000 \u0000 <p>The cutaneous intraneural glomus tumor has been described twice in the literature and remains a rare phenomenon. We present the case of a painful cutaneous lesion on the back of a 77-year-old man. Histopathologic examination of the resected lesion revealed a solid dermal nodule set within an expanded peripheral nerve. Immunohistochemistry confirmed the morphological findings with an Smooth Muscle Actin (SMA) positive nodule encased by nerve fascicles demonstrating S100 positivity with a peripheral layer of Epithelial Membrane Antigen (EMA) positive perineural cells. These findings are in keeping with the previous reported cases of cutaneous intraneural glomus tumors and this entity should be considered in the differential diagnosis of painful cutaneous lesions.</p>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 5","pages":"346-349"},"PeriodicalIF":1.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374153","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}
Jeffrey M. Cloutier, Rami N. Al-Rohil, Rajiv M. Patel, Jennifer S. Ko, Konstantinos Linos
{"title":"Ancillary Tools for the Diagnosis of CIC-Rearranged Sarcoma: A Comprehensive Review","authors":"Jeffrey M. Cloutier, Rami N. Al-Rohil, Rajiv M. Patel, Jennifer S. Ko, Konstantinos Linos","doi":"10.1111/cup.14792","DOIUrl":"10.1111/cup.14792","url":null,"abstract":"<p>\u0000 <i>CIC</i>-rearranged sarcoma is a rare and aggressive undifferentiated round cell sarcoma that presents significant diagnostic challenges due to its histologic overlap with other round cell sarcomas. This review, conducted on behalf of the American Society of Dermatopathology Appropriate Use Criteria Committee (soft tissue subgroup), provides an overview of current immunohistochemical, cytogenetic, and molecular tests used to support the diagnosis of <i>CIC</i>-rearranged sarcoma. This comprehensive analysis included 36 studies, encompassing 436 <i>CIC</i>-rearranged sarcomas. The immunohistochemical markers, CD99 (typically non-diffuse), nuclear WT1, ETV4, and DUX4, were found to be relatively highly sensitive for <i>CIC</i>-rearranged sarcoma (CD99: 87%, WT1: 83%, ETV4: 85%, DUX4: 97%). However, the specificity of these markers is variable, with CD99 being highly non-specific, while WT1 (81%–90%), ETV4 (95%), and DUX4 (100%) offering greater specificity. <i>CIC</i> break-apart FISH can be a helpful and cost-effective assay for detection of <i>CIC</i>-rearrangements, but has a false-negative rate that ranges from 26% to 43%. Next-generation sequence RNA fusion analysis also carries a risk of false negatives, which may be partly mitigated through manual data review. Ultimately, an accurate diagnosis of <i>CIC</i>-rearranged sarcoma requires careful morphologic assessment in combination with immunohistochemical studies and cytogenetics/molecular assays.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 4","pages":"324-331"},"PeriodicalIF":1.6,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14792","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374156","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}
Julian Stashower, Ugochukwu Kingsley Odega, Nakisa Sadeghi, Briana Heinly, Karlyn Pollack, Vimal K. Derebail, Matthew Helm, Sarah Gradecki, Galen Foulke, R. Hal Flowers
{"title":"Presence and Propensities of Cutaneous Immunofluorescence in ANCA-Associated Vasculitis","authors":"Julian Stashower, Ugochukwu Kingsley Odega, Nakisa Sadeghi, Briana Heinly, Karlyn Pollack, Vimal K. Derebail, Matthew Helm, Sarah Gradecki, Galen Foulke, R. Hal Flowers","doi":"10.1111/cup.14787","DOIUrl":"10.1111/cup.14787","url":null,"abstract":"","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 5","pages":"342-345"},"PeriodicalIF":1.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006046","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}
Christopher R. Cunningham, Yiannis P. Dimopoulos, Ian M. García-Quiñones, Denái R. Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G. Prieto, José A. Lasalde-Dominicci, Leomar Y. Ballester, Phyu P. Aung
{"title":"Nicotinic Acetylcholine Receptor Expression in Merkel Cell Carcinoma Is Associated With Clinical and Histopathologic Parameters","authors":"Christopher R. Cunningham, Yiannis P. Dimopoulos, Ian M. García-Quiñones, Denái R. Milton, Manuel Delgado-Vélez, Woo Cheal Cho, Victor G. Prieto, José A. Lasalde-Dominicci, Leomar Y. Ballester, Phyu P. Aung","doi":"10.1111/cup.14773","DOIUrl":"10.1111/cup.14773","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored. In this study, we investigated if MCC expresses nAChRs and if nAChR expression correlates with patient characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The study included 71 MCC cases diagnosed with sufficient tissue available to perform immunohistochemical analysis. The median follow-up was 29.8 months (range, 2.7–234.1). We performed immunohistochemistry using antibodies against the α3, α5, and α7nAChR subunits.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our results show that the majority of MCC cases expressed α3, α5, and α7-nAChR subunits. Of the 71 cases, 59 (83%) expressed α3-nAChR, 71 (100%) expressed α5-nAChR, and 63 (88%) expressed α7-nAChR. Location of immunoreactivity differed between cases and included cytoplasmic only and nuclear/peri-nuclear, with variation in the intensity of staining. There were significant correlations between the intensity or location of immunoreactivity and clinical and histopathologic parameters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These findings seem to support that MCC displays the features of neural crest cells, and suggest the potential for nAChR-targeted therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 4","pages":"317-323"},"PeriodicalIF":1.6,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006045","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":"Blue Nevus-Like Metastatic Melanoma in a Patient With Primary Lentigo Maligna Melanoma","authors":"Kristen Fernandez, Mitul B. Modi, Jodi J. Speiser","doi":"10.1111/cup.14765","DOIUrl":"10.1111/cup.14765","url":null,"abstract":"<div>\u0000 \u0000 <p>Metastatic melanoma with unusual histopathology can be diagnostically challenging. One exceptionally rare cutaneous manifestation of metastases is blue-nevus-like metastatic melanoma (BNLMM). A 74-year-old male presented with a blue-gray lesion on his left helix in the same anatomical region of a previously resected lentigo maligna. Histopathological sections demonstrated an atypical biphasic proliferation of dendritic melanocytes with pigment incontinence and epidermal sparing, measuring > 0.05 mm in diameter. Although the majority of the cell population exhibited cytologic features consistent with a blue nevus, there was a subset of dendritic cells with irregular epithelioid contours and rare, typical dermal mitotic figures. Sections showed an increased Mart-1/Ki67 rate. Perineural and angiotropic involvement by the atypical melanocytes was identified. Immunohistochemical (IHC) stains for SOX-10, HMB45, and PRAME highlighted melanocytic proliferation. BAP-1 IHC was retained, and p16 IHC showed complete loss. No previous procedure site changes were present, indicating that the dendritic cell proliferation was separated from the primary invasive melanoma by normal dermis. The histopathological and immunohistochemical findings led to a diagnosis of microsatellite BNLMM. We report this case to highlight the importance of this rare entity and to avoid misdiagnosis of BNLMM, which would significantly impact patient prognosis, treatment, follow-up, and outcomes.</p>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 4","pages":"287-293"},"PeriodicalIF":1.6,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949619","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":"White Depressed Areas and Tumor Infiltrating Lymphocytes: The Cancer Cure That Lies Within?","authors":"George F Murphy","doi":"10.1111/cup.14768","DOIUrl":"https://doi.org/10.1111/cup.14768","url":null,"abstract":"<p><p>This brief overview is inspired by seminal contributions by the late Dr. Martin C. Mihm, Jr. who provided a basis for recognition and better understanding of interactions between lymphocytes (tumor-infiltrating lymphocytes [TILs]) that home to and permeate cancers. In primary melanomas, this phenomenon may produce what Dr. Mihm called white depressed areas, prescient clues to what would fuel future attempts at harnessing anticancer immunity. The critical and sequential TIL attributes of antigenic stimulation, homing, and effector-target cell apoptotic injury herein are briefly reviewed in light of more recent advances in the field of immuno-oncology. The intent is to emphasize how fundamental clinical and histopathological observations, as forged by Dr. Mihm and his associates, have led to critically important prognostic paradigms as well as to translational insights that now have become transformative in the field of cancer immunotherapy.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949621","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}
Lyn M Duncan, Steven R Tahan, Mai P Hoang, George F Murphy
{"title":"Martin C. Mihm, Jr. and Dermatopathology Education at Harvard Medical School.","authors":"Lyn M Duncan, Steven R Tahan, Mai P Hoang, George F Murphy","doi":"10.1111/cup.14747","DOIUrl":"https://doi.org/10.1111/cup.14747","url":null,"abstract":"","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949620","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":"Aging Skin: A Dermatitis To Which All Flesh Is Heir?","authors":"George F Murphy","doi":"10.1111/cup.14756","DOIUrl":"https://doi.org/10.1111/cup.14756","url":null,"abstract":"<p><p>The human body is composed mostly of water fortified by a variety of proteins, fats, carbohydrates, vitamins, minerals, and other nutrients, all organized into an elegant structurally complex and functionally efficient machine in which our consciousness resides. This heterogeneous assemblage of essential ingredients is enclosed in a container known as the integument, or simply, the skin. The container is as important as its contents; when itself devoid of structural and functional integrity, it will both leak as well as become infused with potentially harmful external agents. As we age, skin loses its integrity, and over time it is not unreasonable to conceive of the skin as becoming progressively \"leaky.\" With this deterioration, skin becomes dry, scaly, accessible to microbes, pruritic, and inflamed, the latter setting up the potentially vicious cycle known as \"inflammaging.\" One major example of the effects of chronological aging on the barrier function of skin involves depletion of filaggrin, a 37-kD histidine-rich protein which originates within keratohyaline granules of the epidermis. Some of the consequences of age-related filaggrin depletion may be inferred by experiments of nature known as ichthyosis vulgaris and atopic dermatitis (AD), the latter with atopy being the most common inflammatory disease worldwide. In AD, loss of function mutations in the FLG gene encoding for the filaggrin precursor, profilaggrin, are associated with skin that, as with aging, is also dry, scaly, accessible to microbes, pruritic and inflamed. In this mini-review, AD will be compared and contrasted with aging in terms of the consequences of deficient filaggrin barrier function. The goal is to enhance recognition that one of the most clinically symptomatic and visible signs of aging is a subtle yet ubiquitous form of \"dermatitis\" due to \"leaky\" skin, one that may be addressed therapeutically with smart combinatorial strategies that restore the molecular basis for skin barrier dysfunction.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949618","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}
Erol Can Bayraktar, Phyu P. Aung, Pavandeep Gill, Guomiao Shen, Varshini Vasudevaraja, Zongshan Lai, Luis Chiriboga, Doina Ivan, Priyadharsini Nagarajan, Jonathan L. Curry, Carlos A. Torres-Cabala, Victor G. Prieto, George Jour
{"title":"Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes","authors":"Erol Can Bayraktar, Phyu P. Aung, Pavandeep Gill, Guomiao Shen, Varshini Vasudevaraja, Zongshan Lai, Luis Chiriboga, Doina Ivan, Priyadharsini Nagarajan, Jonathan L. Curry, Carlos A. Torres-Cabala, Victor G. Prieto, George Jour","doi":"10.1111/cup.14782","DOIUrl":"10.1111/cup.14782","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a comprehensive genomic and transcriptomic analysis of DPAC (<i>n</i> = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel. Gene expression in DPAC was compared to that in hidradenoma (<i>n</i> = 10). Immunohistochemistry was employed to validate gene expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Two out of eight DPACs showed fusion gene rearrangements (<i>CRTC3</i>::<i>MAML2</i> and <i>TRPS1</i>::<i>PLAG1</i>). No uniform mutational signature was detected in DPAC. Comparative gene expression analysis revealed an enrichment of genes related to matrix remodeling, metabolism, and DNA damage repair. Hallmark pathway analysis demonstrated significant upregulation of E2F target genes in DPAC compared to hidradenoma (<i>p =</i> 0.00710). Human papillomavirus-42 was found to be positive in all of our tested DPAC cases. Immunohistochemistry confirmed increased protein expression of CD56, CDC20, and SOX10 in DPAC. Notably, most DPAC tumors also exhibited B-cell infiltration, as indicated by CD20 staining.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings reveal novel fusions and validate altered replication pathways related to HPV42 in DPAC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 4","pages":"309-316"},"PeriodicalIF":1.6,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932023","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}