Computerised morphometrical analysis in endometrial hyperplasia for the prediction of cancer development. A long term retrospective study from northern Norway

Ørbo, Anne; Baak, Jan P. A.; Kleivan, Inger; Lysne, S; Prytz, Per S; Broeckaert, Marc A M; Slappendel, André; Tichelaar, Hans J

doi:10.1136/jcp.53.9.697

Cited by 58 publications

(52 citation statements)

References 20 publications

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“…After diagnostic microscopy was completed and consensus was reached on the WHO94 classification, tissue morphometry and D-score analyses were conducted to improve risk stratification. The D-score method has been shown to be superior to WHO94 classification in predicting cancer outcomes (10,17,(27)(28)(29)(30). Patients with a D-score <0 are considered to have a high risk of co-existent or future carcinoma, and hysterectomy is recommended in such cases.…”

Section: Biopsy Materialsmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study

Sletten¹,

Arnes²,

Lyså³

et al. 2017

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Section: Biopsy Materialsmentioning

confidence: 99%

“…The measurements were performed using a Q-PRODIT image analysis system (version 6.1, Leica, Cambridge, UK). The D-score method has been described in detail in previous studies (10,17,(27)(28)(29)(30).…”

Section: Biopsy Materialsmentioning

confidence: 99%

Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study

Sletten¹,

Arnes²,

Lyså³

et al. 2017

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“…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][9][10][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.…”

mentioning

confidence: 99%

“…This morphometric group of patients has a 45-fold elevated risk of future endometrial carcinoma compared to those with a Dscore41. [7][8][9][10]12 Key elements of the D-score that correspond to heightened risk of cancer outcome include a lesion size exceeding 1 mm in maximum dimension and a surface area of glands that exceeds that of stroma.…”

mentioning

confidence: 99%

Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis

Hecht

Ince

Baak³

et al. 2005

Modern Pathology

129

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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 '...

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“…Prior studies testing the reproducibility of this terminology have involved teams consisting only of gynecological pathologists, moreover some of these were carried out using the morphometric D-score rather than plain light microscopy. 9,18,19 In this study we test the reproducibility of the EIN diagnosis using only light microscopy. We further tried to emphasize its simplicity, with respect to the ease of learning and application of the diagnostic criteria, even to the inexperienced routine pathologist.…”

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confidence: 99%

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists

et al. 2012

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Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists' diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted j values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

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Computerised morphometrical analysis in endometrial hyperplasia for the prediction of cancer development. A long term retrospective study from northern Norway

Cited by 58 publications

References 20 publications

Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study

Prediction of Relapse After Therapy Withdrawal in Women with Endometrial Hyperplasia: A Long-term Follow-up Study

Prediction of endometrial carcinoma by subjective endometrial intraepithelial neoplasia diagnosis

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists

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