RESEARCH ARTICLE
Extraskeletal Myxoid Chondrosarcoma of the Vulva With PLAG1 Gene Activation: Molecular Genetic Characterization of 2 Cases Snjezana Dotlic, MD, PhD,* Zoran Gatalica, MD, DSc,w Wenhsiang Wen, MD, PhD,w Anatole Ghazalpour, PhD,w Chas Mangham, MD,z Damir Babic, MD, PhD,*y Josko Zekan, MD,8 and Semir Vranic, MD, PhDz
Abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm, rarely reported in the genitourinary tract with only 5 cases reported in the vulva. We investigated 2 cases of vulvar sarcomas whose morphologic appearance and immunohistochemical profiles were consistent with EMC using fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction, and a whole genome expression array. FISH and reverse-transcription polymerase chain reaction assays showed no EWSR1 and NR4A3 loci rearrangements. Microarray-based analysis also revealed no changes in NR4A3 and EWSR1 gene transcription levels. Microarray data showed a significant downregulation of the muscle-related genes (eg, myosin heavy chain family, actins, myoglobin, desmin, creatine kinase, troponins) and cytokeratins (KRT6A, 6B, 13, 14, and 78), upregulation of several neuronspecific genes [neural cell adhesion molecule 1 (NCAM-1/CD56), neurofilament (NEFH)], along with some well-characterized tumor biomarkers [carbonic anhydrase IX (CA-9), topoisomerase IIa (TOP2A), matrix metalloproteinases (MMP-7, MMP-9), CDKN2 gene (p16-INK4a), checkpoint homolog 2 (CHEK2)]. Notably, both tumors showed upregulation of the pleomorphic adenoma gene 1 (PLAG1), and in 1 case PLAG1 gene rearrangement was detected by break-apart FISH. Some vulvar tumors with morphologic and immunohistochemical characteristics of EMC may represent a molecular genetic entity separate from EMCs arising in other locations. PLAG1 gene Received for publication March 28, 2013; accepted April 22, 2013. From the *Department of Pathology and Cytology; 8Department of Obstetrics and Gynecology, University Hospital Center Zagreb; yDepartment of Pathology, University of Zagreb Medical School, Zagreb, Croatia; wCaris Life Sciences, Phoenix, AZ; zRobert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry and Royal Orthopaedic Hospital, Birmingham, UK; and zDepartment of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina. The authors declare no conflict of interest. Reprints: Semir Vranic, MD, PhD, Department of Pathology, Clinical Center of the University of Sarajevo, Bolnicˇka 25, BA-71000 Sarajevo, Bosnia and Herzegovina (e-mail: [email protected]). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Website, www. appliedimmunohist.com. Copyright r 2013 by Lippincott Williams & Wilkins
Appl Immunohistochem Mol Morphol
activation appears to be involved in the development of these neoplasms. Key Words: vulva, mesenchymal tumors, extraskeletal myxoid chondrosarcoma, translocations, fusion transcripts, PLAG1 gene (Appl Immunohistochem Mol Morphol 2014;22:537–542)
E
xtraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm of uncertain differentiation comprising
Extraskeletal Myxoid Chondrosarcoma of the Vulva With PLAG1 Gene Activation: Molecular Genetic Characterization of 2 Cases Snjezana Dotlic, MD, PhD,* Zoran Gatalica, MD, DSc,w Wenhsiang Wen, MD, PhD,w Anatole Ghazalpour, PhD,w Chas Mangham, MD,z Damir Babic, MD, PhD,*y Josko Zekan, MD,8 and Semir Vranic, MD, PhDz
Abstract: Extraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm, rarely reported in the genitourinary tract with only 5 cases reported in the vulva. We investigated 2 cases of vulvar sarcomas whose morphologic appearance and immunohistochemical profiles were consistent with EMC using fluorescence in situ hybridization (FISH), reverse-transcription polymerase chain reaction, and a whole genome expression array. FISH and reverse-transcription polymerase chain reaction assays showed no EWSR1 and NR4A3 loci rearrangements. Microarray-based analysis also revealed no changes in NR4A3 and EWSR1 gene transcription levels. Microarray data showed a significant downregulation of the muscle-related genes (eg, myosin heavy chain family, actins, myoglobin, desmin, creatine kinase, troponins) and cytokeratins (KRT6A, 6B, 13, 14, and 78), upregulation of several neuronspecific genes [neural cell adhesion molecule 1 (NCAM-1/CD56), neurofilament (NEFH)], along with some well-characterized tumor biomarkers [carbonic anhydrase IX (CA-9), topoisomerase IIa (TOP2A), matrix metalloproteinases (MMP-7, MMP-9), CDKN2 gene (p16-INK4a), checkpoint homolog 2 (CHEK2)]. Notably, both tumors showed upregulation of the pleomorphic adenoma gene 1 (PLAG1), and in 1 case PLAG1 gene rearrangement was detected by break-apart FISH. Some vulvar tumors with morphologic and immunohistochemical characteristics of EMC may represent a molecular genetic entity separate from EMCs arising in other locations. PLAG1 gene Received for publication March 28, 2013; accepted April 22, 2013. From the *Department of Pathology and Cytology; 8Department of Obstetrics and Gynecology, University Hospital Center Zagreb; yDepartment of Pathology, University of Zagreb Medical School, Zagreb, Croatia; wCaris Life Sciences, Phoenix, AZ; zRobert Jones and Agnes Hunt Orthopaedic and District Hospital, Oswestry and Royal Orthopaedic Hospital, Birmingham, UK; and zDepartment of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina. The authors declare no conflict of interest. Reprints: Semir Vranic, MD, PhD, Department of Pathology, Clinical Center of the University of Sarajevo, Bolnicˇka 25, BA-71000 Sarajevo, Bosnia and Herzegovina (e-mail: [email protected]). Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Website, www. appliedimmunohist.com. Copyright r 2013 by Lippincott Williams & Wilkins
Appl Immunohistochem Mol Morphol
activation appears to be involved in the development of these neoplasms. Key Words: vulva, mesenchymal tumors, extraskeletal myxoid chondrosarcoma, translocations, fusion transcripts, PLAG1 gene (Appl Immunohistochem Mol Morphol 2014;22:537–542)
E
xtraskeletal myxoid chondrosarcoma (EMC) is a rare mesenchymal neoplasm of uncertain differentiation comprising
