title: SMARCB1-deficient Vulvar Neoplasms: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 14 Cases.
abstract: Loss of expression of the SMARCB1 (INI1/BAF47/SNF5) tumor-suppressor protein, originally identified in pediatric malignant rhabdoid tumors, has been noted in significant percentages of epithelioid sarcomas of classical and proximal-type and in myoepithelial carcinomas. Epithelioid sarcoma and myoepithelial carcinoma are very rare in the vulvar region, and few of these cases have been evaluated for SMARCB1 protein loss by immunohistochemistry (IHC) or for SMARCB1 gene alterations by molecular genetic techniques. We studied the clinicopathologic, IHC, and molecular genetic features of 14 SMARCB1-deficient vulvar neoplasms. All available routinely stained sections were reexamined, and IHC analysis for wide-spectrum cytokeratins, high-molecular weight cytokeratins, epithelial membrane antigen, S100 protein, CD34, smooth muscle actin, desmin, and SMARCB1 was performed. Multiplex ligation-dependent probe amplification and DNA sequencing of the SMARCB1 gene was performed on 12 cases with sufficient available tissue. The 14 vulvar tumors occurred in adult women (mean age 46 y, range 22 to 62 y) and measured 1.1 to 8.8 cm in size (mean 4.7 cm). Tumors were classified as classical-type epithelioid sarcoma (N=1), proximal-type epithelioid sarcoma (N=6), myoepithelial carcinoma (N=4), and "SMARCB1-deficient vulvar sarcoma, not otherwise specified" (N=3) on the basis of combined histopathologic and IHC findings. One myoepithelial carcinoma showed divergent rhabdomyoblastic differentiation. All tested cases showed partial or complete SMARCB1 deletions (homozygous: 9 cases; heterozygous: 3 cases). One case with a heterozygous deletion also showed a c.528delC mutation in exon 5. Fluorescence in situ hybridization for EWSR1 rearrangement was performed for 3 cases classified as myoepithelial carcinoma and was negative. Follow-up (13 patients, range 5 to 72 mo, mean 31 mo) data showed 3 patients dead of disease, 1 alive with unresectable metastatic disease, 1 alive with radiographic evidence of extensive lymph nodal disease, and 8 alive without disease. We conclude that SMARCB1-deficient vulvar neoplasms chiefly comprise epithelioid sarcoma and myoepithelial carcinoma, although some defy easy classification. No association was seen between clinical behavior and the type of SMARCB1 alteration.
authors: *Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN ‡Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia ¶Department of Pediatrics at The Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA §Department of Pathology, Carolinas Medical Center, Charlotte, NC ∥Department of Pathology, Massachusetts General Hospital, Boston, MA †Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, UK.
authors: Andrew L
authors: AL
authors: Folpe
authors: J Kenneth
authors: JK
authors: Schoolmeester
authors: W Glenn
authors: WG
authors: McCluggage
authors: Lisa M
authors: LM
authors: Sullivan
authors: Katharine
authors: K
authors: Castagna
authors: William A
authors: WA
authors: Ahrens
authors: Esther
authors: E
authors: Oliva
authors: Jaclyn A
authors: JA
authors: Biegel
authors: G Petur
authors: GP
authors: Nielsen
mesh_terms: D000328:Adult; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D008967:Molecular Biology; D060885:Multiplex Polymerase Chain Reaction; D000071796:SMARCB1 Protein; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D000071796:SMARCB1 Protein; C513266:SMARCB1 protein, human; D014157:Transcription Factors