Giang Huong Tran, Ngoc Hong Nguyen, Huong Ngoc-Thien Duong, Duy Duc Nguyen, Lam Ngoc Nguyen, Khoa Anh Luong
{"title":"Ber-EP4 Expression and Staining Patterns in Cutaneous Basal Cell Carcinoma: A Clinicopathological Study From a Vietnamese Cohort.","authors":"Giang Huong Tran, Ngoc Hong Nguyen, Huong Ngoc-Thien Duong, Duy Duc Nguyen, Lam Ngoc Nguyen, Khoa Anh Luong","doi":"10.1097/DAD.0000000000003287","DOIUrl":"10.1097/DAD.0000000000003287","url":null,"abstract":"<p><strong>Background: </strong>Ber-EP4 is an immunohistochemical marker targeting epithelial cell adhesion molecule and is widely applied in the diagnosis of cutaneous basal cell carcinoma (BCC). Although highly sensitive, variability in expression level and staining distribution may complicate interpretation in routine practice.</p><p><strong>Objective: </strong>This study aimed to characterize Ber-EP4 expression and staining patterns in cutaneous BCC and to assess their associations with clinicopathological features.</p><p><strong>Materials and methods: </strong>Sixty surgically excised cases of cutaneous BCC were retrospectively analyzed. Ber-EP4 immunohistochemistry was performed using an automated staining platform. Expression was evaluated according to the proportion of positive tumor cells, and staining patterns were classified based on spatial distribution. Associations between Ber-EP4 expression and clinicopathological features were analyzed.</p><p><strong>Results: </strong>All cases demonstrated Ber-EP4 positivity, with a mean percentage of Ber-EP4-positive tumor cells per case of 78.1%. High-level expression was observed in 68.3% of cases. Diffuse staining was the predominant pattern, identified in 85.0% of tumors, while nondiffuse patterns accounted for the remaining 15.0%. Ber-EP4 expression showed no significant associations with most clinicopathological variables; however, ulceration was significantly associated with reduced Ber-EP4 expression (aOR = 12.05; 95% confidence interval, 2.41-60.15; P = 0.002).</p><p><strong>Conclusions: </strong>Ber-EP4 is a highly sensitive immunohistochemical marker for cutaneous BCC, showing predominantly diffuse expression across diverse clinicohistologic contexts. However, reduced expression in ulcerated tumors and the presence of nondiffuse staining patterns highlight potential diagnostic pitfalls, particularly in superficially sampled lesions. These findings underscore the need for cautious interpretation and integrated histomorphological and immunohistochemical assessment to ensure diagnostic accuracy.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"698-704"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147635021","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":"Collision Tumor of Basal Cell Carcinoma and Primary Extramammary Paget Disease: A Case Report and Literature Review.","authors":"Keiko Fukuda, Yasuhiro Mitsui, Kohei Ogawa, Kohei Morita, Anna Ochi, Takaya Fukumoto, Akihiko Yoshizawa, Satoru Shinkuma","doi":"10.1097/DAD.0000000000003368","DOIUrl":"10.1097/DAD.0000000000003368","url":null,"abstract":"<p><strong>Abstract: </strong>We present the case of a 75-year-old woman with a vulvar collision tumor consisting of basal cell carcinoma (BCC) and primary extramammary Paget disease (EMPD). The patient presented for evaluation of a pigmented nodule on the right labium majus identified 1 year ago. The nodule was excised, and histopathology revealed nests of basaloid cells with nuclear palisading surrounded by myxoid stroma, consistent with nodular BCC. In addition, scattered intraepidermal cells with clear amphophilic cytoplasm at the periphery of the specimen raised suspicion for EMPD coexistence. Further visual inspection revealed bilateral hypopigmented patches on the labia majora. Gynecological and urological examination showed no abnormal findings. The hypopigmented lesion was excised with a 1-cm margin. Histopathology showed an intraepidermal pagetoid spread of tumor cells with atypical nuclei and abundant amphophilic cytoplasm. A diagnosis of a collision tumor comprising BCC and primary EMPD was made. A BCC-EMPD collision is rarely reported. This case highlights that coexisting EMPD can be overlooked, particularly when evaluating vulvar BCC, underscoring the diagnostic challenge posed by basaloid proliferation and pagetoid spread. Furthermore, our review of the literature elucidated the unique clinicopathological features of BCC-EMPD collision and discussed its differentiation from secondary EMPD with Pinkus-like changes and BCC with pagetoid spread.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"678-681"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304034","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":"Malignant Melanoma With Rhabdomyosarcomatous Differentiation: Report of 2 New Cases.","authors":"Maged Daruish, Hazem Ibrahim","doi":"10.1097/DAD.0000000000003292","DOIUrl":"10.1097/DAD.0000000000003292","url":null,"abstract":"<p><strong>Abstract: </strong>Divergent differentiation in primary cutaneous malignant melanoma is a rare phenomenon that can pose a significant diagnostic challenge. We present two new cases of primary cutaneous malignant melanoma with rhabdomyosarcomatous differentiation, highlighting its aggressive nature. Thorough histological sampling and inclusion of skeletal muscle immunostains are essential for accurate diagnosis, particularly when rhabdoid morphology is identified.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"730-733"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147640415","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":"Verrucous Variant of Bowen Disease.","authors":"Zita Álvarez Bobillo, Angel Fernandez-Flores","doi":"10.1097/DAD.0000000000003300","DOIUrl":"10.1097/DAD.0000000000003300","url":null,"abstract":"<p><strong>Background: </strong>Bowen's disease (BD), or squamous cell carcinoma in situ, is a common cutaneous neoplasm with an incompletely understood etiopathogenesis often linked to human papillomavirus (HPV). While the classic presentation is an erythematous macule, rare variants such as verrucous BD exist and can pose significant diagnostic challenges.</p><p><strong>Case report: </strong>We present the case of a 91-year-old woman with a long-standing, 25 mm yellowish, verrucous lesion on her left leg. Clinically, the lesion was highly suggestive of verrucous carcinoma, leading to surgical excision. Histopathological examination revealed an exophytic verrucous tumor without dermal invasion. High magnification showed full-thickness architectural disarray, cytological atypia, and pagetoid spread. Immunohistochemical studies demonstrated strong, diffuse positivity for p16 and Ki67 across all epidermal layers, while p53 was negative. These findings confirmed a diagnosis of the verrucous variant of BD.</p><p><strong>Discussion: </strong>Verrucous BD is a rare subtype that is easily misdiagnosed as verrucous carcinoma, an infiltrative neoplasm generally considered unrelated to HPV. Differentiation is critical, as verrucous BD often shows a strong association with high-risk HPV types. Immunohistochemistry serves as a vital tool; intense p16 expression is a highly suggestive marker for HPV-related BD, whereas verrucous carcinoma typically shows low or absent p16 expression.</p><p><strong>Conclusion: </strong>This case highlights the importance of considering verrucous BD in the differential diagnosis of exophytic, hyperkeratotic lesions. Accurate identification through histopathology and immunohistochemical markers like p16 is essential to distinguish this in situ variant from more aggressive, invasive entities like verrucous carcinoma.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"725-729"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334317","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}
Maha Kazmi, Marin P Melloy, Sabine Abukhadra, Jessica R Terrell, Qian Li, Guannan Zhu, Danielle Tartar, Theresa Keegan, Emanual Maverakis, Maija Kiuru
{"title":"Observational Study Profiling the Immune Microenvironment of Pregnancy-associated Melanoma.","authors":"Maha Kazmi, Marin P Melloy, Sabine Abukhadra, Jessica R Terrell, Qian Li, Guannan Zhu, Danielle Tartar, Theresa Keegan, Emanual Maverakis, Maija Kiuru","doi":"10.1097/DAD.0000000000003335","DOIUrl":"10.1097/DAD.0000000000003335","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"745-748"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13645177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334314","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}
José González Fernández, Mar García García, Diego Larrosa Martínez, Mariano Ara Martín, Sonia de la Fuente Meira, Lucía Prieto Torres
{"title":"Galli-Galli Disease (Dowling-Degos Disease Type 3) Associated with a Novel POGLUT1 Nonsense Variant: Clinicopathologic and Immunohistochemical Correlation.","authors":"José González Fernández, Mar García García, Diego Larrosa Martínez, Mariano Ara Martín, Sonia de la Fuente Meira, Lucía Prieto Torres","doi":"10.1097/DAD.0000000000003328","DOIUrl":"10.1097/DAD.0000000000003328","url":null,"abstract":"<p><strong>Abstract: </strong>Mutations in KRT5, POFUT1, POGLUT1, and PSENEN define four genetic subtypes of Dowling-Degos disease (DDD), with varied clinical and histologic expression including those previously reported as Galli-Galli disease. We report a case of DDD3 associated with a novel early nonsense variant in POGLUT1 (c.12G>A; p.Trp4*), representing, to the best of our knowledge, the first documented case in Spain. A 55-year-old man presented with recurrent pruritic erythematous scaly papules on the trunk and hyperkeratotic brown papules on the cervical and thoracic regions. Direct microscopic examination of scales from erythematous lesions revealed yeast cells and short hyphae compatible with Malassezia sp. Initial histopathologic evaluation of a pigmented papule was interpreted as simple lentigo. Subsequent biopsy demonstrated elongated rete ridges and focal suprabasal acantholysis without dyskeratosis, raising suspicion for DDD. Whole-exome sequencing identified a heterozygous nonsense variant in POGLUT1, confirming the diagnosis of DDD3. Previous studies have shown that diffuse cytokeratin 5 (CK5) expression throughout all epidermal layers may support the diagnosis of DDD3. This case highlights diagnostic pitfalls related to subtle and focal acantholysis, emphasizes the importance of clinicopathologic correlation and serial sectioning.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"e91-e94"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334206","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}
Sarah John, Briana Heinly, Klaus Helm, Matthew Helm
{"title":"Persistent Diffuse Telangiectatic Eruption Associated With Loncastuximab Tesirine.","authors":"Sarah John, Briana Heinly, Klaus Helm, Matthew Helm","doi":"10.1097/DAD.0000000000003317","DOIUrl":"10.1097/DAD.0000000000003317","url":null,"abstract":"<p><strong>Abstract: </strong>Loncastuximab tesirine (LT) is a CD19-directed antibody-drug conjugate approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma. We report a case of a persistent, diffuse telangiectatic eruption that developed shortly after initiation of LT. Histopathologic examination revealed mild epidermal thinning with superficial ectatic vessels, large conspicuous fibroblasts, solar elastosis, and scattered dermal melanophages. This case highlights a distinctive, minimally inflammatory, vascular-predominant reaction pattern associated with LT. This morphology has been only recently recognized as a potential adverse effect of antibody-drug conjugate medications, with very few published literature on the subject. Because the use of antibody-drug conjugates continues to expand, recognition of this pattern is important, particularly given its persistence even after therapy cessation and limited response to corticosteroid treatment.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"675-677"},"PeriodicalIF":0.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334347","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}
Julian D S Willett, Taylor A Kalomeris, Christina Del Guzzo, Cynthia Magro
{"title":"Biopsied Cutaneous Adverse Effects of PD-1 and PD-L1 Checkpoint Inhibitors and Progression-free Survival: A Retrospective Case Series of 75 Patients.","authors":"Julian D S Willett, Taylor A Kalomeris, Christina Del Guzzo, Cynthia Magro","doi":"10.1097/DAD.0000000000003406","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003406","url":null,"abstract":"<p><strong>Abstract: </strong>Programmed cell death-1 checkpoint inhibitors have significantly improved cancer survival outcomes. More than half of patients on programmed cell death-1 checkpoint inhibitors develop cutaneous immune-related complications. The prognostic significance of eruptions biopsied in routine clinical practice remains underexplored. We aimed to characterize biopsy-confirmed cutaneous toxicities associated with checkpoint inhibitors and assess their association with survival. We conducted a retrospective study of biopsy-confirmed checkpoint inhibitor-associated dermatoses at our single institution between September 2014 and June 2025, analyzing clinical features, histopathology, treatment outcomes, and progression-free (PFS) and overall survival. Seventy-five patients were included (mean age 67.0 years [24, 95]; 52% female). Most developed reactions within 6 months of initiating therapy. Most took pembrolizumab and nivolumab. Histopathologic categories included type IV hypersensitivity (T4HS) lichenoid (N = 29; 39%), T4HS eczematoid (N = 10; 13%), other T4HS patterns (N = 6; 8%) including 1 fatal case of toxic epidermal necrolysis, vesiculobullous (N = 12; 16%), psoriasis (N = 4; 5%), reversible epitheliotropic T-cell dyscrasia (N = 4; 5%), sclerodermoid (N = 4; 5%), Sweet syndrome (N = 3; 4%), and miscellaneous (N = 3; 4%). Most eruptions improved or remained stable with treatment with 1 fatal case of toxic epidermal necrolysis. Patients with T4HS-mediated reaction, 60% of our cohort, had reduced tumor progression hazard with longer PFS (hazard ratio = 0.49 [0.23-1.05], P = 0.07; PFS-padj = 0.06, PFS-late-weighted padj = 0.04). Overall survival did not differ. Our study is limited by sample size. Checkpoint inhibitor-associated dermatoses resemble established standard cutaneous adaptive B- and T-cell-driven dermatoses. Regulatory T-cell inhibition, allowing emergence of autoreactive B and T cells or unmasking of subclinical hypersensitivity, is likely pathogenetically key.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842058","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}
Benjamin A Wood, Nathan T Harvey, Nima Mesbah Ardakani
{"title":"WNT/β-Catenin-Activated Rosette-Forming Carcinoma With Sarcomatoid Differentiation.","authors":"Benjamin A Wood, Nathan T Harvey, Nima Mesbah Ardakani","doi":"10.1097/DAD.0000000000003412","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003412","url":null,"abstract":"<p><strong>Abstract: </strong>WNT/β-catenin activated rosette forming carcinoma is a recently described high grade primary cutaneous carcinoma. These tumours, which commonly involve sun-exposed skin in elderly patients, are associated with inactivation of RB1 and mutations in APC or CTNNB1 genes, leading to activation of WNT/β-catenin signalling pathways. We report a case of WNT/β catenin activated rosette forming carcinoma with sarcomatoid differentiation, which has not previously been described.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842100","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}
Jose Fuentes-Ros, Ainhoa Ordóñez-Arrillaga, Julia Castro-Martín, Jesús Pinto, Luis Requena, Ángel Santos-Briz
{"title":"Perineal Nodular Induration of the Cyclist: A Dermatopathologic Study of Eight Cases with Practical Diagnostic Clues.","authors":"Jose Fuentes-Ros, Ainhoa Ordóñez-Arrillaga, Julia Castro-Martín, Jesús Pinto, Luis Requena, Ángel Santos-Briz","doi":"10.1097/DAD.0000000000003405","DOIUrl":"https://doi.org/10.1097/DAD.0000000000003405","url":null,"abstract":"<p><strong>Abstract: </strong>Perineal nodular induration (PNI), also known as cyclist's nodule, is an uncommon reactive pseudotumoral lesion related to repetitive mechanical trauma in saddle sports. Although clinically recognized, its histopathologic spectrum remains incompletely characterized. We performed a retrospective dermatopathologic study of 8 cases of PNI independently reviewed by 2 experienced dermatopathologists using conventional microscopy and digital slide imaging. The study included 7 men and 1 woman, with a median age of 48.5 years (range, 34-76 years). All cases showed a poorly circumscribed fibrohyaline proliferation centered within the deep dermis and subcutaneous tissue. Consistent findings included marked stromal hyalinization, rounded hyalinized collagen nodules, septal remodeling, adipose tissue entrapment, low cellularity, bland spindle cells, and vasculolymphatic dilatation. Significant cytologic atypia, mitotic activity, pseudocyst formation, and neural hyperplasia were absent in all cases. Rounded hyalinized collagen nodules were identified in all cases, and although previous reports describe stromal hyalinization and dense collagen deposition, this nodular collagenous pattern has not been specifically emphasized. Immunohistochemical studies, performed in 2 cases, were nonspecific and overlapped with previously reported profiles. Orcein staining, performed in 2 cases, demonstrated marked reduction or near-complete absence of elastic fibers in both specimens. Our findings suggest that PNI exhibits a reproducible fibrohyaline pattern that may facilitate recognition on routine hematoxylin-eosin sections in the appropriate clinicopathologic setting and may reduce the need for ancillary immunohistochemical studies in selected cases.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":""},"PeriodicalIF":0.8,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820198","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}