Journal of Cutaneous Pathology最新文献

{"title":"Cytokeratin and Neuroendocrine Positivity in Cutaneous Small Blue Round Cell Tumor—Is It Always Merkel Cell Carcinoma?","authors":"Simon Moubarak,&nbsp;John McAfee,&nbsp;Karen Fritchie,&nbsp;Jennifer S. Ko,&nbsp;Steven D. Billings,&nbsp;Shira Ronen","doi":"10.1111/cup.14844","DOIUrl":"10.1111/cup.14844","url":null,"abstract":"<p>We present a case of a 39-year-old woman initially diagnosed with Merkel cell carcinoma (MCC), a highly aggressive neuroendocrine carcinoma, due to the presence of cytokeratin and neuroendocrine marker expression. The tumor was dermal based, showing small round blue cells with fine chromatin, scant cytoplasm, and scattered mitotic figures arranged in sheets, small cohesive nests, and cords within sclerotic to edematous stroma. Provided immunohistochemical stains showed strong pancytokeratin expression coupled with perinuclear dot-like staining for cytokeratin 20 in a distinct regional distribution, predominantly in areas where the tumor cells formed cohesive nests and cords within sclerotic stroma. Stains for neuroendocrine markers, including synaptophysin, INSM1, and CD56, were positive, albeit focal or regional in the more cohesive areas. Given the patient's age and unusual regional staining patterns, additional testing was performed, which revealed diffuse membranous CD99 staining and <i>EWSR1::ERG</i> fusion. These findings led us to revise the diagnosis to cutaneous Ewing sarcoma (ES). The distinction between MCC and cutaneous ES is crucial due to their different survival rates and treatment approaches. This case underscored the importance of considering alternative diagnoses when encountering cutaneous small round blue cell tumors in the presence of unusual histologic and immunohistochemical findings, particularly in younger patients.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 10","pages":"605-610"},"PeriodicalIF":1.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14844","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608476","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":"Early Skin Biopsy in Conradi-Hünermann-Happle Syndrome (X-Linked Dominant Chondrodysplasia Punctata)","authors":"Cathal O'Connor,&nbsp;Neidín Bussmann,&nbsp;Sarah Ni Mhaolcatha,&nbsp;Cynthia Heffron,&nbsp;Sally O'Shea","doi":"10.1111/cup.14837","DOIUrl":"https://doi.org/10.1111/cup.14837","url":null,"abstract":"&lt;p&gt;Conradi-Hünermann-Happle syndrome (CHHS) or X-linked dominant chondrodysplasia punctata (CDPX2, OMIM 302960) is a rare type of chondrodysplasia punctata associated with X-linked dominant variants in the emopamil binding protein (&lt;i&gt;EBP&lt;/i&gt;) gene, which impairs cholesterol biosynthesis [&lt;span&gt;1&lt;/span&gt;]. The syndrome is characterized by the triad of ichthyosis (usually presenting as congenital ichthyosiform erythroderma) in 95%, skeletal dysplasia in 80%, and congenital cataracts in 60% [&lt;span&gt;1&lt;/span&gt;]. Scarring alopecia can also be present [&lt;span&gt;2&lt;/span&gt;]. Dystrophic calcifications in keratotic follicular plugs represent a unique histopathologic feature of CHHS in newborns that has not been noted in other forms of ichthyoses [&lt;span&gt;3&lt;/span&gt;]. The characteristic congenital ichthyosiform eruption clears spontaneously within a few weeks, so early biopsy is essential to capture the corresponding diagnostic histopathologic features [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;We report the case of a first-born female infant who was delivered at term with widespread redness and scale. There was no family history of genodermatoses or inflammatory dermatoses. There was no parental consanguinity and no history of miscarriages. On examination, there was erythroderma, generalized thick adherent scale in a feathery pattern following lines of Blaschko, and shiny red whorls on the dorsolateral feet (Figure 1A–1F). There was no skin peeling or skin fragility. Several fingernails were hypoplastic. The nasal bridge was flat, and the neck was short. Red reflexes were present bilaterally, but both eyes were noted to be small. The head and trunk were large relative to the limbs, and the proximal limb segments were proportionately short.&lt;/p&gt;&lt;p&gt;Given the constellation of signs, CHHS was suspected clinically. Skin biopsies in the first 12 h of life from linear scaly streaks showed orthohyperkeratosis and numerous dilated follicular ostia with keratin plugs (Figure 2A–2B). Foci of calcification were seen in the corneocytes of the stratum corneum and hair follicles, highlighted with a von Kossa stain (Figure 2C–2D). Skeletal survey showed symmetric punctate calcification/stippling of the proximal femoral epiphysis and ankle bilaterally and of the right humeral epiphysis and right carpus, in keeping with chondrodysplasia punctata, although no gross rhizomelia was appreciated radiologically. Ophthalmology review did not identify congenital cataracts. Renal and cranial ultrasounds were normal, and audiology was normal. Blood tests showed normal hematologic, renal, and bone parameters, and a hyperbilirubinemia meeting the phototherapy threshold. The erythema was noted to improve following 12 h of phototherapy. Urea 10% cream was helpful in reducing the scale. Single gene testing for a variant in the &lt;i&gt;EBP&lt;/i&gt; gene was requested from blood, and a pathogenic variant was detected (c.184C&gt;T; p.Arg62Trp), confirming the diagnosis of CHHS. Parental genetic testing for the variant was negative.","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 10","pages":"597-600"},"PeriodicalIF":1.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14837","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927251","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":"Re: “Rethinking the Semantics of Cutaneous Squamous Cell Carcinoma In Situ”","authors":"Ankan Gupta","doi":"10.1111/cup.14838","DOIUrl":"https://doi.org/10.1111/cup.14838","url":null,"abstract":"","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 10","pages":"636-637"},"PeriodicalIF":1.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144927250","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":"Unusual Morphologic Presentation of Perineural Spread From Cutaneous Squamous Cell Carcinoma: Diagnosis Aided by Comprehensive Molecular Analysis and Machine Learning","authors":"Madhurya Ramineni,&nbsp;Hassan Ghani,&nbsp;Bruce R. Smoller,&nbsp;Rajnish Bharadwaj","doi":"10.1111/cup.14832","DOIUrl":"10.1111/cup.14832","url":null,"abstract":"<p>Neoplasms of unknown primary frequently pose a diagnostic challenge due to their nonspecific morphological and immunohistochemical features. Definitive classification of these neoplasms has a profound impact on treatment decisions. Mutational and gene expression profiling can provide diagnostic and prognostic information in these challenging cases. We present a case of pontine and cranial nerve lesions in an elderly male with no clinically identifiable index lesion at the time of presentation. The lesion's morphology and immunoprofile did not provide a definitive diagnosis. The whole-exome and transcriptome sequencing identified a UV signature confirming the tumor's cutaneous origin. In addition, pathogenic mutations in multiple genes, including those frequently associated with squamous cell carcinoma (e.g., <i>NOTCH1</i>), were identified. The molecular data was also analyzed by “Caris MI GPSai,” a machine-learning algorithm that compares the neoplasm's gene expression and mutational profile against an extensive reference database of genomic and transcriptomic alterations observed in various neoplasms. This predicted the cancer to be cutaneous squamous cell carcinoma with a 66% probability, enabling appropriate treatment for the patient. This case highlights the deceptive morphology of cutaneous squamous cell carcinoma with perineural spread and demonstrates how molecular profiling with machine learning can aid in achieving a definitive diagnosis.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"568-573"},"PeriodicalIF":1.1,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14832","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528203","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":"Clinical, Serologic, and Histopathologic Features of Patients With Pemphigus With Either Positive or Negative IgG4 Intercellular Deposition by Direct Immunofluorescence (DIF): A Retrospective Case–Control Study of 55 DIF Biopsy Specimens","authors":"Clint Christian T. Garbanzos,&nbsp;Austin Todd,&nbsp;Heather D. Hardway,&nbsp;Julia S. Lehman","doi":"10.1111/cup.14835","DOIUrl":"10.1111/cup.14835","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Intercellular IgG4 deposition is variably present on DIF in patients with pemphigus. Whether this feature has clinical, serologic, or histopathologic correlates was unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We identified 34 patients with pemphigus who had 55 DIF specimens reported to show intercellular IgG, IgG4, and/or C3 deposition (8/22/2017–11/30/2023). Patients and biopsies were stratified by intercellular IgG4 status. Clinical and serologic data were extracted from electronic records, and corresponding biopsy slides were reviewed for histopathologic findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Among the 34 patients with pemphigus, patients with positive IgG4 were significantly more likely to have detectable serum anti-desmoglein 1/3 antibodies by ELISA (<i>p</i> = 0.014 and <i>p</i> = 0.030, respectively). Paraneoplastic pemphigus (PNP) was more frequent in the IgG4-negative group (<i>p</i> = 0.037), particularly among patients with ocular involvement. Of 55 DIF biopsy specimens meeting inclusion criteria, 52 (94.5%) had intercellular IgG deposition and 42 (76.4%) had intercellular IgG4 on DIF. Compared to IgG4-negative specimens, IgG4-positive specimens were significantly more likely to represent a vesiculobullous lesion (<i>p</i> = 0.024), to be derived from the trunk (<i>p</i> = 0.047), to show histologic acantholysis (<i>p</i> = 0.019) and to lack lichenoid inflammation (<i>p</i> = 0.0004).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>For pemphigus, DIF IgG4 status correlated with ocular involvement, the clinical morphology selected for biopsy, the likelihood of detecting circulating desmoglein antibodies, the presence of specific histopathologic features such as acantholysis and lichenoid inflammation, and the likelihood of having a final diagnosis of PNP. Further studies are needed to determine whether the presence of tissue-bound intercellular IgG4 antibodies correlates with particular disease variants or lesion-specific characteristics.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"580-589"},"PeriodicalIF":1.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484570","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":"An Unusual Case of Cutaneous Langerhans Cell Sarcoma Lacking S100 Expression: A Case Report and Review of the Literature","authors":"Randa Obid,&nbsp;Austin R. Green,&nbsp;Sion W. Jasmine,&nbsp;Rachel P. Kowal,&nbsp;Brooj Abro,&nbsp;Laura M. Warmke,&nbsp;Magdalena B. Czader,&nbsp;Ahmed K. Alomari,&nbsp;Carina A. Dehner","doi":"10.1111/cup.14833","DOIUrl":"10.1111/cup.14833","url":null,"abstract":"<p>Langerhans cell sarcoma (LCS) is a rare neoplastic proliferation of Langerhans cell with aggressive clinical behavior and involves multiple organ systems, including the skin. LCS is characterized by marked cytologic atypia, frequent mitoses including atypical ones, and expression of CD1a, S100, and langerin (CD207). CD1a and Langerin-positive but S100− negative LCS is extremely rare in clinical practice. We present a case of a 71-year-old female with a history of melanoma and atypical fibroxanthoma who presented with an erythematous plaque on her left knee. Histopathologic examination revealed a dermal infiltrate comprised of large pleomorphic cells with irregular nuclear contours, prominent longitudinal grooves, and vesicular chromatin, and a high mitotic rate. Notably, there were epidermotropism and a distinctive immunohistochemical profile: S100−, CD1a+, Langerin+, and focal CD68+. Next-generation sequencing identified copy number loss of <i>CDKN2A</i>, <i>CDKN2B</i>, and <i>FOXA1</i>, mutations in <i>TP53</i>, <i>POT1</i>, <i>SH2B3</i>, and <i>SMARCA4</i>, and a high tumor mutational burden. Herein, we discuss the clinical and pathologic features of 38 cases of LCS with cutaneous involvement reported in the literature, including recent advances in understanding molecular characteristics of this disease. This exceptional case may contribute to our understanding of the etiology of this rare neoplasm.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"554-567"},"PeriodicalIF":1.1,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14833","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144484569","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":"Metastatic Gastrointestinal Stromal Tumor to the Scalp: A Case Report Highlighting Diagnostic Challenges and Molecular Correlation","authors":"Andrew C. Sanchez,&nbsp;Oyewale O. Shiyanbola,&nbsp;Xiaohua Qian,&nbsp;Di Yan,&nbsp;Kathleen M. Sheahon,&nbsp;Jennifer Y. Wang,&nbsp;Roberto A. Novoa,&nbsp;Kerri E. Rieger,&nbsp;Ryanne A. Brown","doi":"10.1111/cup.14829","DOIUrl":"10.1111/cup.14829","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastrointestinal stromal tumors (GISTs) are rare gastrointestinal mesenchymal neoplasms. While the liver and peritoneum are the most common metastatic sites, skin involvement is rare. Nevertheless, recognizing skin metastases is crucial as it guides targeted treatment and indicates the possibility of widespread disease. Skin metastases pose diagnostic challenges due to histopathologic and clinical variability, often resembling other tumors. We present an 81-year-old female with metastatic GIST involving the scalp with corroborative molecular data. This case underscores the fundamental nature of clinicopathologic correlation and the role of molecular analysis in aiding diagnosis, guiding treatment decisions, and revealing the prognostic implications of rare metastatic patterns of GISTs.</p>\u0000 </div>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"549-553"},"PeriodicalIF":1.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340159","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":"Subungual Epidermoid Inclusions–A Series of 8 Cases and a Review of Literature","authors":"Sarah M. Alnaqshabandi,&nbsp;Anurag Sharma,&nbsp;Ahmed Bakhshwin,&nbsp;Shira Ronen,&nbsp;Jennifer S. Ko,&nbsp;Steven D. Billings","doi":"10.1111/cup.14830","DOIUrl":"10.1111/cup.14830","url":null,"abstract":"<p>Subungual epidermoid inclusions (SEI) are benign cystic lesions of the nail bed. To our knowledge, there has been only one case series describing SEI. We report eight cases of SEI. The patients had a median age of 72 years (range 3–84) with a female: male ratio of 1.6. Five occurred in toenails and three in fingernails. Histologically, SEI is characterized by bulbous proliferation of rete ridges and unilocular cysts lined by thin squamous epithelium with hypogranulosis, filled with orthokeratin. The connection to the nail bed epithelium may be disrupted and calcified. SEI are tumors that should be kept in the differential diagnosis of the subungual nail bed lesions.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"574-579"},"PeriodicalIF":1.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14830","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266360","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":"Review of Literature to Determine Recommended Application of HPV-42 Molecular Testing for Digital Papillary Adenocarcinoma","authors":"Michelle Y. Zhu,&nbsp;Leting Zhang,&nbsp;Mahyar Khazaeli","doi":"10.1111/cup.14823","DOIUrl":"10.1111/cup.14823","url":null,"abstract":"<p>Digital Papillary Adenocarcinoma (DPA) is a rare tumor that can cause metastasis and death. It can morphologically mimic benign sweat gland tumors. In 2022, the novel association of HPV-42 and DPA was discovered by means of DNA sequencing. In this scoping review, we aimed to systematically evaluate alternatives to HPV-42 molecular sequencing. Of 87 articles on DPA identified in a PUBMED meta-search, eight met the inclusion criteria. We found that DNA sequencing for HPV-42 is most sensitive (94%). Comparable tests included HPV-42 in situ hybridization (ISH), which had 82% sensitivity, and p16 immunohistochemistry, which had 70%–75% sensitivity. We further evaluated the performance of HPV-42 ISH and performed a stratified analysis of HPV-42 ISH-negative DPA cases. There was a statistically significant difference in HPV-42 positivity in patients younger than and older than 60 years old (<i>p</i> = 0.02). We recommend HPV-42 ISH for cases with equivocal morphology from patients aged over 60 years. Tumors with equivocal morphology from patients under the age of 60 years should be sequenced for HPV-42. For cases with classic morphology, p16 can be used to support the diagnosis, but molecular testing for HPV-42 is unnecessary.</p>","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 9","pages":"590-594"},"PeriodicalIF":1.1,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cup.14823","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144266359","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":"Skin Biopsy Revealing Langerhans Cell Histiocytosis During Therapy for T-Cell Acute Lymphoblastic Leukemia: A Fatal Outcome","authors":"Swetha Palla,&nbsp;Prateek Bhatia,&nbsp;Narender Kumar,&nbsp;Debajyoti Chatterjee,&nbsp;Rajender Kumar,&nbsp;Deepak Bansal","doi":"10.1111/cup.14831","DOIUrl":"10.1111/cup.14831","url":null,"abstract":"","PeriodicalId":15407,"journal":{"name":"Journal of Cutaneous Pathology","volume":"52 8","pages":"514-516"},"PeriodicalIF":1.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234293","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}