Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis

Abstract

Endometrial intraepithelial neoplasia (also known as 'EIN') is a precursor to endometrioid endometrial adenocarcinoma characterized by monoclonal growth of mutated cells, a distinctive histopathologic appearance, and 45-fold elevated cancer risk. We have applied diagnostic criteria for EIN to 97 successive endometrial biopsies classified as hyperplastic according to World Health Organization criteria and correlated results with computer-assisted morphometry (D-score) and clinical cancer outcomes. Three pathologists separately reviewed all cases for presence or absence of EIN using published criteria (gland area4stromal area, cytologic change in focus of altered architecture, lesion size 41 mm, and exclusion of cancer and mimics). Discordant cases were resolved by a consensus review at a multiheaded scope. Clinical outcomes were obtained in 84 patients from patient visit and pathology records. Diagnoses of presence or absence of EIN were unanimous among all three pathologists in 75% of cases, and intraobserver-reproducibility was very good (kappa 0.73-0.90). Cases rediagnosed as EIN encompassed hyperplasias previously diagnosed as atypical (n ¼ 18) or nonatypical (eight complex, two simple). Eight follow-up cancers were scattered between hyperplasia types (5/21 atypical, 3/63 nonatypical), but all classified as EIN (8/25) and D-score r1 (8/38). Subjective application of criteria for diagnosis of EIN correlates well with objective morphometry and successfully segregates patients into high and low cancer risk subgroups with better reproducibility than atypical hyperplasia diagnosis. Keywords: EIN; endometrial hyperplasia; histomorphometry; precancer; pathology; prognosis Diagnosis and therapeutic ablation of premalignant lesions of the endometrium is central to endometrial cancer prevention. Accurate diagnosis of precursors to endometrioid endometrial cancer (Type I), 1,2 which may precede cancer by several years, presents a major challenge to pathologists. The World Health Organization (WHO) endometrial hyperplasia schema captures many precancers in the atypical hyperplasia subgroup, but is a poorly reproducible system. This report examines clinical performance of the alternative EIN diagnostic schema as practiced subjectively at our institution (BWH) since 2002.The endometrial intraepithelial neoplasia (EIN) diagnostic schema 3,4 is the end product of combined molecular, 5,6 objective histomorphometric, 7 and clinical outcome studies 8-11 specifically intended to redefine the histopathologic appearance of highrisk endometrial lesions. Premalignant lesions arise as clonal outgrowths of somatically mutated cells that present histologically as an expanding discrete focus of crowded glands with a distinctly different cytology than the background endometrium. The EIN schema more precisely defines 'atypia' and gland crowding than previous criteria for hyperplasia. The absolute cytology of EIN lesions varies greatly between patients, and in a number of cases lacks prominent nucleoli or nuclear rounding, definitions of '...

Inflammation, prostatitis, proliferative inflammatory atrophy: ‘Fertile ground’ for prostate cancer development?

“…For example, threshold functions applied to prostate histopathology may be conceived and elaborated. The 'D-score' histomorphometric qualitative threshold function, conceived to predict the progression of endometrial intraepithelial neoplasia to endometrial cancer, has shown enhanced predictive power as compared to alternate systems (73,74).…”

Problems with the current diagnostic approach to complex atypical endometrial hyperplasia

“…It is noteworthy that large studies correlating endometrial biopsies and/or curettages with findings on close follow-up hysterectomy are to our knowledge lacking, but these data are now beginning to be reported. 8 Longacre et al eschewed the empiric approach and based their distinction of CAH from WDA on morphologic features that correlated retrospectively with myometrial invasion specifically, a clinically relevant "gold standard." 9 Using their criteria, myoinvasive carcinomas should be extraordinarily rare in hysterectomies after a diagnosis of CAH.…”

“…It would be informative to redo the expert panel review segment of GOG Protocol 167 keeping in mind the importance of defining an adequate or representative sample using pathologists schooled in the approaches of Mutter, Baak, and Longacre. [5][6][7][8][9] If consensus was reached, I would propose devising training sessions to be followed by tests of interobserver agreement and feasibility. It would be a worthy challenge.…”

Hiperplasia Endometrial: Análisis De Serie De Casos Diagnosticados en Biopsia Endometrial

“…Dadas las dificultades existentes para la categorización de la hiperplasia endometrial atípica o el adenocarcinoma, algunos autores han creado el concepto de neoplasia endometrial intraepitelial, que clasifica aparentemente de manera más eficaz a las pacientes con riesgo alto y bajo de cáncer y con mejor reproducibilidad que la hiperplasia endometrial atípica (9,15,16,17). Sin embargo, la OMS (5,6) aún mantiene la clasificación con base en la histopatología de presencia o no de atipia celular, que se resume en la Tabla I. Dicha clasificación es la que actualmente la mayoría de patólogos aún consideran describiendo estas lesiones intraepiteliales dentro del grupo de las hiperplasias atípicas (5,6,8,9,10,11,18,19).…”