Thibault Kervarrec, Danna Westphal, Daniel Pissaloux, Mélanie Legrand, Franck Tirode, Anne Neuhart, Francoise Drouot, Jürgen C Becker, Nicolas Macagno, Alice Seris, Thomas Jouary, Fanny Beltzung, Marie-Laure Jullie, Paul W Harms, Bernard Cribier, Samia Mourah, Fanélie Jouenne, Gaelle Fromont, Baptiste Louveau, Maxence Mancini, Dmitry V Kazakov, Arnaud de la Fouchardière, Maxime Battistella
{"title":"伴有 PAK1/2/3 融合的肝癌：12 例系列病例。","authors":"Thibault Kervarrec, Danna Westphal, Daniel Pissaloux, Mélanie Legrand, Franck Tirode, Anne Neuhart, Francoise Drouot, Jürgen C Becker, Nicolas Macagno, Alice Seris, Thomas Jouary, Fanny Beltzung, Marie-Laure Jullie, Paul W Harms, Bernard Cribier, Samia Mourah, Fanélie Jouenne, Gaelle Fromont, Baptiste Louveau, Maxence Mancini, Dmitry V Kazakov, Arnaud de la Fouchardière, Maxime Battistella","doi":"10.1111/his.15214","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Aims</h3>\n \n <p>Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine <i>et al.</i> demonstrated the presence of <i>YAP1::MAML2</i> and <i>YAP1::NUTM1</i> fusions in most poromas and porocarcinomas. Recently, our group identified <i>PAK2-</i>fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring <i>PAK1/2/3</i> fusions.</p>\n </section>\n \n <section>\n \n <h3> Methods and Results</h3>\n \n <p>Five patients were male and the median age was 79 years (ranges: 59–95). Tumours were located on the trunk (<i>n</i> = 7), on the thigh (<i>n</i> = 3), neck (<i>n</i> = 1), or groin area (<i>n</i> = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced <i>LAMTOR1::PAK1</i> (<i>n</i> = 2), <i>ZDHHC5::PAK1</i> (<i>n =</i> 2), <i>DLG1::PAK2</i>, <i>CTDSP1::PAK1</i>, <i>CTNND1::PAK1</i>, <i>SSR1::PAK3</i>, <i>CTNNA1::PAK2</i>, <i>RNF13::PAK2</i>, <i>ROBO1::PAK2,</i> and <i>CD47::PAK2</i>. Activating mutation of <i>HRAS</i> (G13V, <i>n</i> = 3, G13R, <i>n</i> = 1, Q61L, <i>n</i> = 2) was present in six cases.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Our study suggests that <i>PAK1/2/3</i> fusions is the oncogenic driver of a subset of porocarcinomas lacking <i>YAP1</i> rearrangement.</p>\n </section>\n </div>","PeriodicalId":13219,"journal":{"name":"Histopathology","volume":null,"pages":null},"PeriodicalIF":3.9000,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15214","citationCount":"0","resultStr":"{\"title\":\"Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases\",\"authors\":\"Thibault Kervarrec, Danna Westphal, Daniel Pissaloux, Mélanie Legrand, Franck Tirode, Anne Neuhart, Francoise Drouot, Jürgen C Becker, Nicolas Macagno, Alice Seris, Thomas Jouary, Fanny Beltzung, Marie-Laure Jullie, Paul W Harms, Bernard Cribier, Samia Mourah, Fanélie Jouenne, Gaelle Fromont, Baptiste Louveau, Maxence Mancini, Dmitry V Kazakov, Arnaud de la Fouchardière, Maxime Battistella\",\"doi\":\"10.1111/his.15214\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <section>\\n \\n <h3> Aims</h3>\\n \\n <p>Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine <i>et al.</i> demonstrated the presence of <i>YAP1::MAML2</i> and <i>YAP1::NUTM1</i> fusions in most poromas and porocarcinomas. Recently, our group identified <i>PAK2-</i>fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring <i>PAK1/2/3</i> fusions.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods and Results</h3>\\n \\n <p>Five patients were male and the median age was 79 years (ranges: 59–95). Tumours were located on the trunk (<i>n</i> = 7), on the thigh (<i>n</i> = 3), neck (<i>n</i> = 1), or groin area (<i>n</i> = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced <i>LAMTOR1::PAK1</i> (<i>n</i> = 2), <i>ZDHHC5::PAK1</i> (<i>n =</i> 2), <i>DLG1::PAK2</i>, <i>CTDSP1::PAK1</i>, <i>CTNND1::PAK1</i>, <i>SSR1::PAK3</i>, <i>CTNNA1::PAK2</i>, <i>RNF13::PAK2</i>, <i>ROBO1::PAK2,</i> and <i>CD47::PAK2</i>. Activating mutation of <i>HRAS</i> (G13V, <i>n</i> = 3, G13R, <i>n</i> = 1, Q61L, <i>n</i> = 2) was present in six cases.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusion</h3>\\n \\n <p>Our study suggests that <i>PAK1/2/3</i> fusions is the oncogenic driver of a subset of porocarcinomas lacking <i>YAP1</i> rearrangement.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13219,\"journal\":{\"name\":\"Histopathology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2024-05-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1111/his.15214\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Histopathology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/his.15214\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Histopathology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/his.15214","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Porocarcinomas with PAK1/2/3 fusions: a series of 12 cases
Aims
Porocarcinoma is a malignant sweat gland tumour differentiated toward the upper part of the sweat duct and may arise from the transformation of a preexisting benign poroma. In 2019, Sekine et al. demonstrated the presence of YAP1::MAML2 and YAP1::NUTM1 fusions in most poromas and porocarcinomas. Recently, our group identified PAK2-fusions in a subset of benign poromas. Herein we report a series of 12 porocarcinoma cases harbouring PAK1/2/3 fusions.
Methods and Results
Five patients were male and the median age was 79 years (ranges: 59–95). Tumours were located on the trunk (n = 7), on the thigh (n = 3), neck (n = 1), or groin area (n = 1). Four patients developed distant metastases. Microscopically, seven cases harboured a benign poroma component and a malignant invasive part. Ductal formations were observed in all, while infundibular/horn cysts and cells with vacuolated cytoplasm were detected in seven and six tumours, respectively. In three cases, the invasive component consisted of a proliferation of elongated cells, some of which formed pseudovascular spaces, whereas the others harboured a predominant solid or trabecular growth pattern. Immunohistochemical staining for CEA and EMA confirmed the presence of ducts. Focal androgen receptor expression was detected in three specimens. Whole RNA sequencing evidenced LAMTOR1::PAK1 (n = 2), ZDHHC5::PAK1 (n = 2), DLG1::PAK2, CTDSP1::PAK1, CTNND1::PAK1, SSR1::PAK3, CTNNA1::PAK2, RNF13::PAK2, ROBO1::PAK2, and CD47::PAK2. Activating mutation of HRAS (G13V, n = 3, G13R, n = 1, Q61L, n = 2) was present in six cases.
Conclusion
Our study suggests that PAK1/2/3 fusions is the oncogenic driver of a subset of porocarcinomas lacking YAP1 rearrangement.
期刊介绍：
Histopathology is an international journal intended to be of practical value to surgical and diagnostic histopathologists, and to investigators of human disease who employ histopathological methods. Our primary purpose is to publish advances in pathology, in particular those applicable to clinical practice and contributing to the better understanding of human disease.
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