title: Current morphologic criteria perform poorly in identifying hereditary leiomyomatosis and renal cell carcinoma syndrome-associated uterine leiomyomas.
abstract: The contemporary oncologic pathology report conveys diagnostic, prognostic, predictive, and hereditary predisposition information. Each component may be premised on a morphologic feature or a biomarker. Clinical validity and reproducibility are paramount as is standardization of reporting and clinical response to ensure individualization of patient care. Regarding hereditary predisposition, morphology-based genetic referral systems in some instances have eclipsed genealogy-based systems, for example, cell type in ovarian cancer and BRCA screening. In other instances such as Lynch syndrome, morphology-based schemas supplement clinical schemas and there is an emerging standard of care for reflex biomarker testing. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndrome predisposes patients to uterine and cutaneous leiomyomas (LMs) and renal cell carcinomas (RCCs). Several authors have emphasized the role pathologists may play in identifying this syndrome by recognizing the morphologic characteristics of syndromic uterine LMs and RCCs. Recently immunohistochemical overexpression of S-(2-succinyl) cysteine (2SC) has been demonstrated as a robust biomarker of mutation status in tumors from HLRCC patients. In this blinded control-cohort study we demonstrate that the proposed morphologic criteria used to identify uterine LMs in HLRCC syndrome are largely irreproducible among pathologists and lack sufficient robustness to serve as a trigger to triage cases for 2SC immunohistochemistry or patients for further family/personal history inquiry. Although refinement of morphologic criteria can be considered, in view of the availability of a clinically robust biomarker, consideration should be given to reflex testing of uterine LMs with an appropriate age cut off or in the setting of a suspicious family history.
authors.affiliation: Department of Laboratory Medicine and Pathobiology (S.A.), Sunnybrook Health Sciences Centre Department of Pediatric Laboratory Medicine (C.C.), The Hospital For Sick Children Department of Laboratory Medicine and Pathobiology (A.M.M., B.A.C.), University Health Network, University of Toronto, Toronto, ON Department of Pathology (S.K., C.B.G.), University of British Columbia, Vancouver, BC, Canada Dammam Regional Laboratory (S.A.), Ministry of Health, Dammam, Saudi Arabia Department of Histopathology (M.E.B.), Imperial College, Hammersmith Hospital, London Molecular and Population Genetics Laboratory (I.P.T.), Wellcome Trust Centre for Human Genetics Oxford Biomedical Research Centre (I.P.T.), Wellcome Trust Centre for Human Genetics Henry Wellcome Building for Molecular Physiology (P.J.P.), University of Oxford, Oxford Department of Pathology (W.G.M.), Royal Group of Hospitals Trust, Northern Ireland, UK Department of Pathology and Microbiology (N.A.), Jordan University of Science and Technology, Ar Ramtha, Jordan Department of Pathology (T.B.P.), B.P.Koirala Memorial Cancer Hospital, Chitwan, Nepal.
authors.forename: Sana
authors.initials: S
authors.lastname: Alsolami
authors.forename: Mona
authors.initials: M
authors.lastname: El-Bahrawy
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.forename: Nagla
authors.initials: N
authors.lastname: AlDaoud
authors.forename: Tilak B
authors.initials: TB
authors.lastname: Pathak
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Chung
authors.forename: Catherine T
authors.initials: CT
authors.lastname: Cheung
authors.forename: Anna Marie
authors.initials: AM
authors.lastname: Mulligan
authors.forename: Ian P
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pollard
authors.forename: C Blake
authors.initials: CB
authors.lastname: Gilks
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Blaise A
authors.initials: BA
authors.lastname: Clarke
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018231:Leiomyomatosis / Q000175:diagnosis*; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary; D010338:Pathology, Clinical / Q000592:standards*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012878:Skin Neoplasms / Q000175:diagnosis*; D014594:Uterine Neoplasms / Q000175:diagnosis*