American Journal of Dermatopathology最新文献

{"title":"Matrical Tumors: A Comparative Molecular Analysis of Six Cases With Histological Correlations.","authors":"Shira Ronen, Daniel Stieber, Mary Ferrier, Adrián Nogales-Moro, Ignacio Pinilla-Pagnon, Steven D Billings, Francesco Feoli","doi":"10.1097/DAD.0000000000002949","DOIUrl":"10.1097/DAD.0000000000002949","url":null,"abstract":"<p><strong>Abstract: </strong>Pilomatrical tumors include pilomatricoma, melanocytic matricoma, and pilomatrical carcinoma. Similar to the normal anagen hair follicle bulb, they may be associated with benign and, rarely, with atypical pigmented dendritic melanocytes. It has been recently suggested that the term \"melanocytic matricoma\" be replaced with \"pilomatricoma with melanocytic hyperplasia\" (PMMH). Occasional cases of PMMH show intermediate grades of histological atypia. Their clinical behavior is uncertain. Interestingly, we found in one of these atypical tumors a molecular characterization compatible with a malignant profile. In this study, we compare this case with the molecular profiles of two PMMHs, one atypical PMMH, whose histology was previously published, and of two unpublished cases: a pilomatrical carcinoma and a large matrical tumor of difficult categorization. We also correlate histology with the molecular results. Although histologically the six cases form a morphological continuum with increasing grades of architectural and cytological atypia, our molecular analysis distinctly segregates the lesions into two molecular groups. The first group exhibits only isolated alterations in CTNNB1 , a low tumor mutational burden, and a relatively stable chromosomal profile. The second group, by contrast, demonstrates mutations of TP53, biallelic inactivation of CDKN2A or RB1 , and an elevated tumor mutational burden, in addition to mutations in CTNNB1 or loss of APC. The tumors in the second group are clearly different from the benign PMMHs. Atypical PMMHs could represent an early stage in the development of tumors that, since their beginning, have a malignant molecular profile different from that of PMMHs and can progressively drive their evolution toward overt malignancy.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"365-372"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558659","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":"A Case of Pancreatitis-Panniculitis-Polyarthritis Syndrome due to Primary Hepatic Neuroendocrine Tumor.","authors":"Wenjin Fan, Huan Wang, Lin Hou, Shanshan Li","doi":"10.1097/DAD.0000000000002947","DOIUrl":"10.1097/DAD.0000000000002947","url":null,"abstract":"<p><strong>Abstract: </strong>A 66-year-old male patient presented to our department with subcutaneous nodules in both lower extremities accompanied by pain. Skin pathology suggested pancreatic panniculitis. Subsequent imaging and histopathology identified a rare case of pancreatitis-panniculitis-polyarthritis syndrome secondary to a primary hepatic neuroendocrine tumor. This case highlights the rare association between nonpancreatic conditions and pancreatic panniculitis.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"e57-e60"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473236","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":"Late Recurrent Spitz Melanoma With a TMEM106B :: BRAF Fusion.","authors":"Shunsuke Koga, Giorgos C Karakousis, Guang Yang, David E Elder","doi":"10.1097/DAD.0000000000002946","DOIUrl":"10.1097/DAD.0000000000002946","url":null,"abstract":"<p><strong>Abstract: </strong>Melanoma is a clinically and genetically heterogeneous malignancy that can recur long after initial treatment. We report the case of a 70-year-old man who presented with metastatic cutaneous melanoma 36 years after the initial diagnosis. Initially diagnosed with nodular melanoma on the left heel at age 34 years, the patient experienced metastatic spread to the left groin lymph nodes by age 36 years, followed by various systemic therapies, including interferon and cytokine therapy, and subsequent observation, over 15 years. Two years before his current presentation, the patient noted a growing mass in his right thigh and an enlarged left inguinal lymph node. Fine-needle aspiration biopsy of the lymph node confirmed the recurrence of melanoma. He subsequently underwent inguinofemoral lymph node dissection and resection of the right thigh mass. Histopathological evaluation revealed melanoma characterized by tumorigenic proliferation of pleomorphic epithelioid and spindle cells with abundant eosinophilic cytoplasm, large nuclei with prominent nucleoli, sparse lymphocyte infiltration, and minimal necrosis, consistent with an initial diagnosis of Spitzoid melanoma. Genetic profiling using targeted next-generation sequencing identified a novel TMEM106B :: BRAF fusion, along with CHEK2 and MUTYH mutations. The BRAF fusion supports the diagnosis of Spitz melanoma, a genetically defined subset of Spitzoid melanoma. This case represents the first report of a TMEM106B :: BRAF fusion in melanoma, emphasizing the critical role of molecular profiling in diagnosing and managing this malignancy, and suggesting a potential avenue for future therapeutic exploration.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"387-390"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473294","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":"Monkeypox and Malignant Syphilis Coinfection in an HIV Patient.","authors":"Rafael Fayos-Gregori, Miguel Mansilla-Polo, Fernando Navarro-Blanco, Rodolfo David Palacios-Díaz, Javier López-Davia, Vicent Martínez-Cozar, Rafael Botella-Estrada","doi":"10.1097/DAD.0000000000002955","DOIUrl":"10.1097/DAD.0000000000002955","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"414-416"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659707","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":"NSD3::FGFR1 : A Novel Gene Fusion First to Be Described in Merkel Cell Carcinoma.","authors":"Volha Lenskaya, Richard K Yang, Phyu P Aung, Victor G Prieto, Priyadharsini Nagarajan, Woo Cheal Cho","doi":"10.1097/DAD.0000000000002953","DOIUrl":"10.1097/DAD.0000000000002953","url":null,"abstract":"<p><strong>Abstract: </strong>Merkel cell carcinomas (MCCs) exhibit diverse molecular profiles, often categorized by their association with Merkel cell polyoma virus (MCPyV). MCPyV-associated MCCs typically display a low tumor mutational burden (TMB), lacking both somatic mutations and ultraviolet signature. By contrast, MCPyV-negative MCCs commonly arise in sun-exposed skin and frequently exhibit a high TMB, along with TERT promoter mutation (TPM) and somatic mutations, particularly in TP53 and RB1 . Gene fusions are exceedingly rare in MCCs, and their specific frequency and fusion transcripts remain largely unexplored. Here, we present a unique case of MCPyV-associated MCC characterized by NSD3::FGFR1 fusion, representing a novel fusion transcript not previously reported in MCCs. A 72-year-old White man presented with a cyst-like nodule on the left elbow, which had progressively increased in size over a span of 6 months. Excisional biopsy specimen revealed a neuroendocrine carcinoma diffusely expressing CK20 (perinuclear dot-like), synaptophysin, CD56, NSE, and MCPyV, consistent with MCC. Next-generation sequencing identified a NSD3::FGFR1 fusion without any additional somatic mutations, including TP53 and RB1 mutations, or TPM. Although NSD3::FGFR1 fusion has been sporadically reported in other solid tumors, such as pulmonary squamous cell carcinoma, its identification in an MCC is unprecedented to our knowledge. This novel finding not only underscores the uniqueness of our case but also contributes to the evolving understanding of the molecular landscape of MCCs, particularly MCPyV-associated MCCs.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"400-403"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558044","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":"Comparison of the IHC Expression of p16, p53, and MIB-1 in Extragenital Skin Bowenoid Lesions With High- and Low- Chronic Sun Damage.","authors":"Pedro Gil-Pallares, Maria E Gil-Pallares, Alba Navarro-Bielsa, Olalla Figueroa-Silva, Laura Taboada-Paz, José M Suárez-Peñaranda","doi":"10.1097/DAD.0000000000002939","DOIUrl":"10.1097/DAD.0000000000002939","url":null,"abstract":"<p><strong>Background: </strong>Bowen disease and bowenoid actinic keratosis are difficult to distinguish due to overlapping histopathology. This study evaluates the role of p16, p53, and MIB-1 staining patterns in differentiating high-chronic sun damage (H-CSD) and low-chronic sun damage bowenoid lesions.</p><p><strong>Methods: </strong>Sixty extragenital in situ squamous cell carcinomas were included. Lesions with elastosis were considered H-CSD. P16, p53, and MIB-1 staining patterns were classified as block, gradient, or focal.</p><p><strong>Results: </strong>Seventy-two percent of lesions were H-CSD. Full-thickness dysplasia was observed in all lesions, and basal layer involvement in 97%. P16 staining was positive in 80%, matching areas of higher atypia, with block pattern more frequent in H-CSD (58% vs. 47%, P = 0.047). P53 was positive in 47%, with block pattern more common in H-CSD (40% vs. 18%, P = 0.02). MIB-1 was positive in all cases. P16 and MIB-1 patterns coincided in 75%, independently of sun exposure.</p><p><strong>Conclusions: </strong>P16 and p53 expression may be less frequent in bowenoid lesions than previously described. Histopathological features like basal layer and adnexal or follicular involvement may not differentiate H-CSD from low-chronic sun damage lesions or Bowen disease from bowenoid actinic keratosis. Variations in p16, p53, and MIB-1 staining could indicate different dysplasia pathways, although further studies are needed to clarify their prognostic significance.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"373-378"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257261","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":"A Changing Papule on the Thigh: Challenge.","authors":"Vikas Nishadham, Thomas N Helm, Matthew F Helm","doi":"10.1097/DAD.0000000000002967","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002967","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":"47 5","pages":"e52"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056059","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":"Acute Disseminated Blistering and Desquamation in a 63-Year-Old Woman: Answer.","authors":"Marisa R Diiorio, Payal C Shah, Dorothea T Barton, Robert E LeBlanc, Alicia T Dagrosa","doi":"10.1097/DAD.0000000000002966","DOIUrl":"https://doi.org/10.1097/DAD.0000000000002966","url":null,"abstract":"","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":"47 5","pages":"408-409"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014256","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":"Artificial Intelligence and Convolutional Neural Networks-Driven Detection of Micro and Macro Metastasis of Cutaneous Melanoma to the Lymph Nodes.","authors":"Nada Shaker, Sean Niu, Heath Blankenship, Nuha Shaker, Hossam Arafat, Raed Sbenaty, Ahmed Yones, Mohammad Shaker, Noor Shaker, Omar P Sangueza","doi":"10.1097/DAD.0000000000002954","DOIUrl":"10.1097/DAD.0000000000002954","url":null,"abstract":"<p><strong>Background: </strong>Lymph node (LN) assessment is a critical component in the staging and management of cutaneous melanoma. Traditional histopathological evaluation, supported by immunohistochemical staining, is the gold standard for detecting LN metastases. However, the process is labor-intensive, requiring the analysis of multiple tissue levels, which increases both time and cost. With the growing integration of artificial intelligence (AI) into clinical workflows, there is potential to streamline this process, enhancing efficiency and accuracy.</p><p><strong>Method: </strong>This study analyzed 53 WSIs (12 negative samples). Images are all derived from hematoxylin-eosin (H&E) stains and were uploaded to the Orca AI cloud-based platform (SpatialX Diagnostics, Inc.), a commercially available platform specifically designed for AI pathology. An AI-driven model was developed and trained to detect melanoma metastases directly from H&E histopathological images, bypassing additional immunohistochemical staining. The algorithm was designed to identify the presence of metastases and classify tumor deposits based on size, specifically distinguishing deposits greater than 0.1 mm and less than 1.0 mm in diameter, which are critical thresholds for prognostic evaluation. The model was validated on 9 WSIs (2 negative) that were not seen by the model. For every WSI in the validation set, one of the following 4 classes was assigned: normal, metastasis (<0.1 mm), metastasis (0.1-1 mm), and metastasis (>1 mm). The class corresponding to the highest metastasis size range was assigned to the whole sample. The results were then examined by a board-certified pathologist.</p><p><strong>Results: </strong>The AI algorithm demonstrated high accuracy in detecting LN metastases in patients with melanoma. It effectively identified and classified tumor deposits with a specificity of 0.91 and a sensitivity of 0.74. The model also distinguishes between smaller deposits (>0.1 mm) and larger deposits (>1.0 mm). This stratification is essential for accurate staging, prognosis determination, and treatment planning, highlighting the algorithm's potential clinical value. When evaluating the model performance in the WSI classification tasks, the model showed high agreement with the pathologist's classification, correctly identifying 7 WSIs as metastasis (>1 mm) and labeling 1 normal WSI as metastasis (0.7 mm).</p><p><strong>Conclusion: </strong>The study's findings underscore the potential of AI in revolutionizing the detection of melanoma metastasis in lymph nodes. By significantly reducing the reliance on time-consuming and costly immunohistochemical staining, AI-driven tools can streamline diagnostic workflows, improve accuracy, and potentially enhance patient outcomes. As AI technology continues to evolve, its application in melanoma management could become a cornerstone of modern pathology, offering a powerful adjunct to traditional diagnostic methods.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"361-364"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659703","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":"Clinicopathologic Features of PRAME-Positive Common Melanocytic Nevi: A Case-Control Study.","authors":"Ronan J Knittel, Nathan T Harvey, Nima Mesbah Ardakani, Blake O'Brien, Stephen Lee, Benjamin A Wood","doi":"10.1097/DAD.0000000000002932","DOIUrl":"10.1097/DAD.0000000000002932","url":null,"abstract":"<p><strong>Abstract: </strong>Preferentially Expressed Antigen in Melanoma (PRAME) immunohistochemistry has been found to be relatively sensitive and specific for the diagnosis of melanoma, although the detection of PRAME positivity in some melanocytic nevi is a significant limitation. This study was designed to investigate the features of common melanocytic nevi showing PRAME staining, encountered in routine community practice. We reviewed all pathology reports on common melanocytic nevi seen in routine practice for a 1-month period and found that 7.1% of nevi stained with PRAME were considered positive by the original reporting pathologist. A total of 41 PRAME-positive nevi (representing 4.7% of nevi) and a control group of 43 PRAME-negative nevi collected during the same period were identified. The histologic features were reviewed, and the diagnosis and PRAME staining were recorded in a masked fashion by 3 dermatopathologists. Our results suggest that caution is warranted in the interpretation of PRAME in the assessment of small lentiginous melanocytic nevi with a low level of suspicion for melanoma, because these are not infrequently PRAME positive. We found a statistically significant association between the presence of solar elastosis and lentiginous growth pattern, and PRAME status ( P < 0.01). When comparing the original diagnosis with the reviewer's diagnosis, the original diagnosis was severely atypical in 54% of PRAME-positive cases, while only 7% were considered to show severe atypia on review masked to PRAME status ( P < 0.001). There was no such discrepancy among PRAME-negative cases (9% vs. 19%, considered severely atypical). This finding provides evidence of a \"PRAME bias\" in the interpretation of melanocytic lesions with no or mild atypia, whereby such lesions are classified as severely atypical when PRAME is positive, likely with the intention of prompting re-excision.</p>","PeriodicalId":50967,"journal":{"name":"American Journal of Dermatopathology","volume":" ","pages":"379-386"},"PeriodicalIF":1.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257173","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}