YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases
YAP1-TFE3- fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3- fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3- fused hemangioendothelioma showed a female predominance (17 female, 7 m...
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Veröffentlicht in: | Modern pathology 2021-12, Vol.34 (12), p.2211-2221 |
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creator | Dermawan, Josephine K. Azzato, Elizabeth M. Billings, Steven D. Fritchie, Karen J. Aubert, Sebastien Bahrami, Armita Barisella, Marta Baumhoer, Daniel Blum, Veronika Bode, Beata Aesif, Scott W. Bovée, Judith V. M. G. Dickson, Brendan C. van den Hout, Mari Lucas, David R. Moch, Holger Oaxaca, Gabriel Righi, Alberto Sciot, Raf Sumathi, Vaiyapuri Yoshida, Akihiko Rubin, Brian P. |
description | YAP1-TFE3-
fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of
YAP1-TFE3-
fused hemangioendothelioma to date. The 24 cases of
YAP1-TFE3-
fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20–78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor
YAP1-TFE3
gene fusions: majority with
YAP1
exon 1 fused to
TFE3
exon 4 (88%), or less commonly,
TFE3
exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4–360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing
YAP1-TFE3-
fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma. |
doi_str_mv | 10.1038/s41379-021-00879-7 |
format | Article |
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fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of
YAP1-TFE3-
fused hemangioendothelioma to date. The 24 cases of
YAP1-TFE3-
fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20–78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor
YAP1-TFE3
gene fusions: majority with
YAP1
exon 1 fused to
TFE3
exon 4 (88%), or less commonly,
TFE3
exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4–360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing
YAP1-TFE3-
fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/s41379-021-00879-7</identifier><identifier>PMID: 34381186</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>45/91 ; 631/67/1798 ; 692/699/67/1798 ; Adult ; Aged ; Asia ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - analysis ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics ; Biomarkers, Tumor - analysis ; Biomarkers, Tumor - genetics ; Bone tumors ; CD34 antigen ; Cytokeratin ; Cytoplasm ; Europe ; Exons ; Female ; Gene Fusion ; Genetic Predisposition to Disease ; Hemangioendothelioma - chemistry ; Hemangioendothelioma - genetics ; Hemangioendothelioma - pathology ; Hemangioendothelioma - surgery ; Hemangioendothelioma, Epithelioid - chemistry ; Hemangioendothelioma, Epithelioid - genetics ; Hemangioendothelioma, Epithelioid - pathology ; Hemangioendothelioma, Epithelioid - surgery ; Humans ; Laboratory Medicine ; Leukocytes (eosinophilic) ; Male ; Medicine ; Medicine & Public Health ; Metastases ; Middle Aged ; North America ; Nucleoli ; Pathology ; Patients ; Phenotype ; Progression-Free Survival ; Stroma ; Time Factors ; Tumors ; YAP-Signaling Proteins - genetics ; Yes-associated protein ; Young Adult</subject><ispartof>Modern pathology, 2021-12, Vol.34 (12), p.2211-2221</ispartof><rights>The Author(s), under exclusive licence to United States & Canadian Academy of Pathology 2021</rights><rights>2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.</rights><rights>The Author(s), under exclusive licence to United States & Canadian Academy of Pathology 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-dd1d1da350208fbc7cdda3257486e1c085134562a37fde0902e16807fb7af1733</citedby><cites>FETCH-LOGICAL-c419t-dd1d1da350208fbc7cdda3257486e1c085134562a37fde0902e16807fb7af1733</cites><orcidid>0000-0002-2137-7507 ; 0000-0003-2336-3691 ; 0000-0002-3373-0099 ; 0000-0002-3329-4186 ; 0000-0002-1139-2914 ; 0000-0002-7986-2839 ; 0000-0002-2278-5908 ; 0000-0003-1155-0481 ; 0000-0002-0657-3024 ; 0000-0003-2269-6216 ; 0000-0002-1074-0155 ; 0000-0003-2244-5839</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2597613163?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34381186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dermawan, Josephine K.</creatorcontrib><creatorcontrib>Azzato, Elizabeth M.</creatorcontrib><creatorcontrib>Billings, Steven D.</creatorcontrib><creatorcontrib>Fritchie, Karen J.</creatorcontrib><creatorcontrib>Aubert, Sebastien</creatorcontrib><creatorcontrib>Bahrami, Armita</creatorcontrib><creatorcontrib>Barisella, Marta</creatorcontrib><creatorcontrib>Baumhoer, Daniel</creatorcontrib><creatorcontrib>Blum, Veronika</creatorcontrib><creatorcontrib>Bode, Beata</creatorcontrib><creatorcontrib>Aesif, Scott W.</creatorcontrib><creatorcontrib>Bovée, Judith V. M. G.</creatorcontrib><creatorcontrib>Dickson, Brendan C.</creatorcontrib><creatorcontrib>van den Hout, Mari</creatorcontrib><creatorcontrib>Lucas, David R.</creatorcontrib><creatorcontrib>Moch, Holger</creatorcontrib><creatorcontrib>Oaxaca, Gabriel</creatorcontrib><creatorcontrib>Righi, Alberto</creatorcontrib><creatorcontrib>Sciot, Raf</creatorcontrib><creatorcontrib>Sumathi, Vaiyapuri</creatorcontrib><creatorcontrib>Yoshida, Akihiko</creatorcontrib><creatorcontrib>Rubin, Brian P.</creatorcontrib><title>YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>YAP1-TFE3-
fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of
YAP1-TFE3-
fused hemangioendothelioma to date. The 24 cases of
YAP1-TFE3-
fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20–78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor
YAP1-TFE3
gene fusions: majority with
YAP1
exon 1 fused to
TFE3
exon 4 (88%), or less commonly,
TFE3
exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4–360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing
YAP1-TFE3-
fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.</description><subject>45/91</subject><subject>631/67/1798</subject><subject>692/699/67/1798</subject><subject>Adult</subject><subject>Aged</subject><subject>Asia</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - analysis</subject><subject>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Biomarkers, Tumor - genetics</subject><subject>Bone tumors</subject><subject>CD34 antigen</subject><subject>Cytokeratin</subject><subject>Cytoplasm</subject><subject>Europe</subject><subject>Exons</subject><subject>Female</subject><subject>Gene Fusion</subject><subject>Genetic Predisposition to Disease</subject><subject>Hemangioendothelioma - chemistry</subject><subject>Hemangioendothelioma - genetics</subject><subject>Hemangioendothelioma - pathology</subject><subject>Hemangioendothelioma - surgery</subject><subject>Hemangioendothelioma, Epithelioid - chemistry</subject><subject>Hemangioendothelioma, Epithelioid - genetics</subject><subject>Hemangioendothelioma, Epithelioid - pathology</subject><subject>Hemangioendothelioma, Epithelioid - surgery</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Leukocytes (eosinophilic)</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metastases</subject><subject>Middle Aged</subject><subject>North America</subject><subject>Nucleoli</subject><subject>Pathology</subject><subject>Patients</subject><subject>Phenotype</subject><subject>Progression-Free Survival</subject><subject>Stroma</subject><subject>Time Factors</subject><subject>Tumors</subject><subject>YAP-Signaling Proteins - genetics</subject><subject>Yes-associated protein</subject><subject>Young Adult</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kUFvFCEYhomxsWv1D3gwk3jxguWDYWC8NU1rmzRpD_XgibAM7NIwsA5w2H9f1q2aeDAc4IPnewi8CH0A8gUIk-e5ByZGTChgQmRbiVdoBZyRtiX5a7QicmSYjZyeorc5PxECPZf0DTplPZMAclih-uPiAfDj9RXDrmY7dVs767jxycYpla0NPs36a6e7uYbisY-5-FKLT1GHzgQfvUk7XbYppI03XS512nfJdbTvNjba4o0OYY9Nis4vc_MbnW1-h06cDtm-f5nP0Pfrq8fLG3x3_-328uIOmx7GgqcJ2tCME0qkWxthplZRLno5WDBEcmA9H6hmwk2WjIRaGCQRbi20A8HYGfp89O6W9LPaXNTss7Eh6GhTzYrygUhGewEN_fQP-pTq0l55oEYxAIPhIKRHyiwp58U6tVv8rJe9AqIOoahjKKqFon6FokRr-viiruv2BX9afqfQAHYEcjuKG7v8vfs_2meOmpfQ</recordid><startdate>20211201</startdate><enddate>20211201</enddate><creator>Dermawan, Josephine K.</creator><creator>Azzato, Elizabeth M.</creator><creator>Billings, Steven D.</creator><creator>Fritchie, Karen J.</creator><creator>Aubert, Sebastien</creator><creator>Bahrami, Armita</creator><creator>Barisella, Marta</creator><creator>Baumhoer, Daniel</creator><creator>Blum, Veronika</creator><creator>Bode, Beata</creator><creator>Aesif, Scott W.</creator><creator>Bovée, Judith V. 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M. G. ; Dickson, Brendan C. ; van den Hout, Mari ; Lucas, David R. ; Moch, Holger ; Oaxaca, Gabriel ; Righi, Alberto ; Sciot, Raf ; Sumathi, Vaiyapuri ; Yoshida, Akihiko ; Rubin, Brian P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c419t-dd1d1da350208fbc7cdda3257486e1c085134562a37fde0902e16807fb7af1733</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>45/91</topic><topic>631/67/1798</topic><topic>692/699/67/1798</topic><topic>Adult</topic><topic>Aged</topic><topic>Asia</topic><topic>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - analysis</topic><topic>Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Biomarkers, Tumor - genetics</topic><topic>Bone tumors</topic><topic>CD34 antigen</topic><topic>Cytokeratin</topic><topic>Cytoplasm</topic><topic>Europe</topic><topic>Exons</topic><topic>Female</topic><topic>Gene Fusion</topic><topic>Genetic Predisposition to Disease</topic><topic>Hemangioendothelioma - chemistry</topic><topic>Hemangioendothelioma - genetics</topic><topic>Hemangioendothelioma - pathology</topic><topic>Hemangioendothelioma - surgery</topic><topic>Hemangioendothelioma, Epithelioid - chemistry</topic><topic>Hemangioendothelioma, Epithelioid - genetics</topic><topic>Hemangioendothelioma, Epithelioid - pathology</topic><topic>Hemangioendothelioma, Epithelioid - surgery</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Leukocytes (eosinophilic)</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metastases</topic><topic>Middle Aged</topic><topic>North America</topic><topic>Nucleoli</topic><topic>Pathology</topic><topic>Patients</topic><topic>Phenotype</topic><topic>Progression-Free Survival</topic><topic>Stroma</topic><topic>Time Factors</topic><topic>Tumors</topic><topic>YAP-Signaling Proteins - genetics</topic><topic>Yes-associated protein</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dermawan, Josephine K.</creatorcontrib><creatorcontrib>Azzato, Elizabeth M.</creatorcontrib><creatorcontrib>Billings, Steven D.</creatorcontrib><creatorcontrib>Fritchie, Karen J.</creatorcontrib><creatorcontrib>Aubert, Sebastien</creatorcontrib><creatorcontrib>Bahrami, Armita</creatorcontrib><creatorcontrib>Barisella, Marta</creatorcontrib><creatorcontrib>Baumhoer, Daniel</creatorcontrib><creatorcontrib>Blum, Veronika</creatorcontrib><creatorcontrib>Bode, Beata</creatorcontrib><creatorcontrib>Aesif, Scott W.</creatorcontrib><creatorcontrib>Bovée, Judith V. M. G.</creatorcontrib><creatorcontrib>Dickson, Brendan C.</creatorcontrib><creatorcontrib>van den Hout, Mari</creatorcontrib><creatorcontrib>Lucas, David R.</creatorcontrib><creatorcontrib>Moch, Holger</creatorcontrib><creatorcontrib>Oaxaca, Gabriel</creatorcontrib><creatorcontrib>Righi, Alberto</creatorcontrib><creatorcontrib>Sciot, Raf</creatorcontrib><creatorcontrib>Sumathi, Vaiyapuri</creatorcontrib><creatorcontrib>Yoshida, Akihiko</creatorcontrib><creatorcontrib>Rubin, Brian P.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dermawan, Josephine K.</au><au>Azzato, Elizabeth M.</au><au>Billings, Steven D.</au><au>Fritchie, Karen J.</au><au>Aubert, Sebastien</au><au>Bahrami, Armita</au><au>Barisella, Marta</au><au>Baumhoer, Daniel</au><au>Blum, Veronika</au><au>Bode, Beata</au><au>Aesif, Scott W.</au><au>Bovée, Judith V. M. G.</au><au>Dickson, Brendan C.</au><au>van den Hout, Mari</au><au>Lucas, David R.</au><au>Moch, Holger</au><au>Oaxaca, Gabriel</au><au>Righi, Alberto</au><au>Sciot, Raf</au><au>Sumathi, Vaiyapuri</au><au>Yoshida, Akihiko</au><au>Rubin, Brian P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2021-12-01</date><risdate>2021</risdate><volume>34</volume><issue>12</issue><spage>2211</spage><epage>2221</epage><pages>2211-2221</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><abstract>YAP1-TFE3-
fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of
YAP1-TFE3-
fused hemangioendothelioma to date. The 24 cases of
YAP1-TFE3-
fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20–78 years old, median 44). Tumors were most commonly located in soft tissue (50%), followed by bone (29%), lung (13%), and liver (8%), ranging from 3 to 115 mm in size (median 40 mm). About two-thirds presented with multifocal disease, including 7 cases with distant organ metastasis. Histopathologically, we describe three dominant architectural patterns: solid sheets of coalescing nests, pseudoalveolar and (pseudo)vasoformative pattern, and discohesive strands and clusters of cells set in a myxoid to myxohyaline stroma. These patterns were present in variable proportions across different tumors and often coexisted within the same tumor. The dominant cytomorphology (88%) was large epithelioid cells with abundant, glassy eosinophilic to vacuolated cytoplasm, prominent nucleoli and well-demarcated cell borders. Multinucleated or binucleated cells, prominent admixed erythrocytic and lymphocytic infiltrates, and intratumoral fat were frequently present. Immunohistochemically, ERG, CD31, and TFE3 were consistently expressed, while expression of CD34 (83%) and cytokeratin AE1/AE3 (20%) was variable. CAMTA1 was negative in all but one case. All cases were confirmed by molecular testing to harbor
YAP1-TFE3
gene fusions: majority with
YAP1
exon 1 fused to
TFE3
exon 4 (88%), or less commonly,
TFE3
exon 6 (12%). Most patients (88%) were treated with primary surgical resection. Over a follow-up period of 4–360 months (median 36 months) in 17 cases, 35% of patients remained alive without disease, and 47% survived many years with stable, albeit multifocal and/or metastatic disease. Five-year progression-free survival probability was 88%. We propose categorizing
YAP1-TFE3-
fused hemangioendothelioma as a distinct disease entity given its unique clinical and histopathologic characteristics in comparison to conventional epithelioid hemangioendothelioma.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>34381186</pmid><doi>10.1038/s41379-021-00879-7</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-2137-7507</orcidid><orcidid>https://orcid.org/0000-0003-2336-3691</orcidid><orcidid>https://orcid.org/0000-0002-3373-0099</orcidid><orcidid>https://orcid.org/0000-0002-3329-4186</orcidid><orcidid>https://orcid.org/0000-0002-1139-2914</orcidid><orcidid>https://orcid.org/0000-0002-7986-2839</orcidid><orcidid>https://orcid.org/0000-0002-2278-5908</orcidid><orcidid>https://orcid.org/0000-0003-1155-0481</orcidid><orcidid>https://orcid.org/0000-0002-0657-3024</orcidid><orcidid>https://orcid.org/0000-0003-2269-6216</orcidid><orcidid>https://orcid.org/0000-0002-1074-0155</orcidid><orcidid>https://orcid.org/0000-0003-2244-5839</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0893-3952 |
ispartof | Modern pathology, 2021-12, Vol.34 (12), p.2211-2221 |
issn | 0893-3952 1530-0285 |
language | eng |
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source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
subjects | 45/91 631/67/1798 692/699/67/1798 Adult Aged Asia Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - analysis Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics Biomarkers, Tumor - analysis Biomarkers, Tumor - genetics Bone tumors CD34 antigen Cytokeratin Cytoplasm Europe Exons Female Gene Fusion Genetic Predisposition to Disease Hemangioendothelioma - chemistry Hemangioendothelioma - genetics Hemangioendothelioma - pathology Hemangioendothelioma - surgery Hemangioendothelioma, Epithelioid - chemistry Hemangioendothelioma, Epithelioid - genetics Hemangioendothelioma, Epithelioid - pathology Hemangioendothelioma, Epithelioid - surgery Humans Laboratory Medicine Leukocytes (eosinophilic) Male Medicine Medicine & Public Health Metastases Middle Aged North America Nucleoli Pathology Patients Phenotype Progression-Free Survival Stroma Time Factors Tumors YAP-Signaling Proteins - genetics Yes-associated protein Young Adult |
title | YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases |
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