title: Interobserver Reproducibility Among Gynecologic Pathologists in Diagnosing Heterologous Osteosarcomatous Component in Gynecologic Tract Carcinosarcomas.
abstract: Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci. Digital H&E images from 20 gynecologic tract carcinosarcomas were reviewed by 22 gynecologic pathologists with a request to determine the presence or absence of an osteosarcomatous component. The 20 preselected cases included areas of classic heterologous osteosarcoma (malignant cells producing osteoid; n=10) and osteosarcoma mimics (malignant cells with admixed nonosteoid matrix; n=10). Interobserver agreement was evaluated and SATB2 scored on all 20 cases and compared with the original diagnoses. Moderate agreement (Fleiss' κ=0.483) was identified for the 22 raters scoring the 20 cases with a median sensitivity of 7/10 and a median specificity of 9/10 for the diagnosis of osteosarcoma. SATB2 showed 100% sensitivity (10/10) and 60% (6/10) specificity in discriminating classic osteosarcoma from osteosarcoma mimics. Utilizing negative SATB2 as a surrogate marker to exclude osteosarcoma, 73% (16/22) of the reviewers would have downgraded at least 1 case to not contain an osteosarcomatous component (range, 1-6 cases, median 1 case). Gynecologic pathologists demonstrate only a moderate level of agreement in the diagnosis of heterologous osteosarcoma based on morphologic grounds. In such instances, a negative SATB2 staining may assist in increasing accuracy in the diagnosis of an osteosarcomatous component.
authors.affiliation: El Camino Hospital (A.R.S., M.K.), Mountain View UCSF (A.E.H., K.G., J.T.R., C.Z.), San Francisco Mills-Peninsula Hospital (M.C.), Burlingame UCSD (O.F.), San Diego Stanford University School of Medicine (A.K.F., T.L.), Stanford Cedars-Sinai Medical Center (J.R.), Los Angeles, CA Cleveland Clinic (A.A.R., J.K.M.), Cleveland, OH New York Presbyterian Hospital (L.H.E.) Memorial-Sloan Kettering Cancer Center (K.P., R.S.), New York, NY Emory University Hospital (K.H.), Atlanta, GA Clinical Pathology Associates (J.H.), Austin UT MD Anderson Cancer Center (A.Y.), Houston, TX Belfast Health and Social Care Trust (W.G.M.), Belfast, Northern Ireland, UK Brigham and Women's Hospital (M.R.N.) Massachusetts General Hospital (E.O.) Harvard Medical School/Beth Israel Deaconess Medical Center (A.H.B.), Boston, MA Yale School of Medicine (V.P.), New Haven, CT UAMS (C.M.Q.), Little Rock, AK Johns Hopkins Hospital (R.V.), Baltimore, MD.
authors.forename: Ankur R
authors.initials: AR
authors.lastname: Sangoi
authors.forename: Malti
authors.initials: M
authors.lastname: Kshirsagar
authors.forename: Andres A
authors.initials: AA
authors.lastname: Roma
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Horvai
authors.forename: Mamatha
authors.initials: M
authors.lastname: Chivukula
authors.forename: Lora H
authors.initials: LH
authors.lastname: Ellenson
authors.forename: Oluwole
authors.initials: O
authors.lastname: Fadare
authors.forename: Ann K
authors.initials: AK
authors.lastname: Folkins
authors.forename: Karuna
authors.initials: K
authors.lastname: Garg
authors.forename: Krisztina
authors.initials: K
authors.lastname: Hanley
authors.forename: Teri A
authors.initials: TA
authors.lastname: Longacre
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Haas
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Jesse K
authors.initials: JK
authors.lastname: McKenney
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Kay J
authors.initials: KJ
authors.lastname: Park
authors.forename: Vinita
authors.initials: V
authors.lastname: Parkash
authors.forename: Charles M
authors.initials: CM
authors.lastname: Quick
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Rabban
authors.forename: Joanne K L
authors.initials: JKL
authors.lastname: Rutgers
authors.forename: Robert
authors.initials: R
authors.lastname: Soslow
authors.forename: Russell
authors.initials: R
authors.lastname: Vang
authors.forename: Anna
authors.initials: A
authors.lastname: Yemelyanova
authors.forename: Charles
authors.initials: C
authors.lastname: Zaloudek
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Beck
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D002296:Carcinosarcoma / Q000473:pathology*; D005260:Female; D005833:Genital Neoplasms, Female / Q000473:pathology* / Q000628:therapy; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000032:analysis; D018200:Mixed Tumor, Mullerian / Q000473:pathology; D015588:Observer Variation; D012516:Osteosarcoma / Q000737:chemistry / Q000473:pathology*; D000072142:Pathologists; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D036961:Matrix Attachment Region Binding Proteins; C521297:SATB2 protein, human; D014157:Transcription Factors