Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia

Travaglino, Antonio; Raffone, Antonio; Saccone, Gabriele; Mollo, Antonio; Placido, Giuseppe De; Mascolo, Massimo; Insabato, Luigi; Zullo, Fulvio

doi:10.1111/apm.12945

Cited by 35 publications

(12 citation statements)

References 25 publications

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“…Two alternative classification systems have been proposed for this purpose , . The WHO system differentiates ‘atypical EH’ (premalignant) from ‘non‐atypical EH’ (benign), based on the presence of cytologic atypia , , , . The endometrial intraepithelial neoplasia (EIN) system differentiate ‘EIN’ (premalignant) from ‘benign EH’ based on glandular crowing, lesion diameter > 1 mm and cytology different from adjacent endometrium, careful exclusion of benign mimics and cancer , , , .…”

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confidence: 99%

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Raffone

Travaglino

Saccone

et al. 2019

APMIS

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Raffone A, Travaglino A, Saccone G, Cieri M, Mascolo M, Mollo A, Insabato L, Zullo F. Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer. APMIS 2019; 127: 597-606.AT-rich interaction domain 1A (ARID1A) is a tumor suppressor protein involved in endometrioid carcinogenesis. The expression of ARID1A may be lost in the premalignant phase. Our aim was to assess ARID1A as: (i) diagnostic marker to differentiate premalignant endometrial hyperplasia (EH) form benign EH; (ii) prognostic marker for the risk of occult cancer in premalignant EH. A systematic review and meta-analysis were performed by searching electronic databases from their inception to October 2018 for all studies assessing ARID1A in EH by immunohistochemistry. Sensitivity, specificity, positive and negative likelihood ratios (LR+ and LRÀ), and diagnostic odds ratio (DOR) were calculated for both diagnostic and prognostic accuracy. LR+ > 5, LRÀ < 0.2, DOR > 25 defined good accuracy; LR+ > 10, LRÀ < 0.1, DOR > 100 defined excellent accuracy. Seven studies with 467 EH were included. As diagnostic marker, ARID1A showed sensitivity = 0.12, specificity = 0.99, LR+ = 4.34, LRÀ = 0.85, DOR = 5.12. As prognostic marker for occult cancer, ARID1A showed sensitivity = 0.33, specificity = 0.99, LR+ = 20.70, LRÀ = 0.49, DOR = 49.59. In conclusion, ARID1A loss is highly specific, but little accurate as diagnostic marker of premalignant EH. Instead, ARID1A loss in premalignant EH is an accurate and almost perfectly specific prognostic marker for coexistent cancer.

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Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Raffone

Travaglino

Saccone

et al. 2019

APMIS

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“…Las dos exclusiones finales (Travaglino y col. (14) y Doherty y col. (17) ) se hicieron porque estos me-taanálisis no compararon las clasificaciones de hiperplasia endometrial.…”

Section: Resultsunclassified

Section: Introductionunclassified

“…La clasificación de la OMS de 1994 fue revisada en 2003, eliminando la categoría de hiperplasia endometrial simple atípica, dejando las de hiperplasia simple, compleja y atípica (13,14) . Sin embargo, dado el impacto científico del sistema EIN, en 2014 la OMS propuso una clasificación dual de 'sin atipia' y atípica, estableciendo la diferencia entre benigna y premaligna (hiperplasia endometrial atípica / neoplasia intraepitelial endometrioide), con base en la atipia citológica (14) . Esta clasificación reporta 'EIN', lo que puede crear confusión, porque no está claro si hace referencia al sistema EIN mencionado anteriormente (aunque la clasificación de la OMS de 2014 no está bien integrada con los criterios de EIN) (14) .…”

Section: Introductionunclassified

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Comparación entre las clasificaciones de hiperplasia endometrial. Revisión sistemática y evaluación de calidad

Mariño

2021

Rev peru ginecol obstet.

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Antecedentes. La hiperplasia endometrial se clasifica actualmente en hiperplasia sin atipia o benigna y en lesión precancerosa, hiperplasia atípica / neoplasia intraepitelial endometrioide o EIN, según dos sistemas, el de la Organización Mundial de la Salud (OMS) que modificó sus anteriores clasificaciones en 2014 -aunque la de 1994 sigue siendo muy usada- y el sistema de neoplasia intraepitelial endometrial (EIN). Aún no está claro qué sistema de clasificación de la hiperplasia endometrial debe utilizarse para el control y tratamiento de las pacientes. Objetivo. Revisar y evaluar metaanálisis que comparen los sistemas de clasificación para la hiperplasia endometrial de la Organización Mundial de la Salud y el sistema EIN. Métodos. Revisión sistemática de estudios de metaanálisis utilizando los términos de búsqueda ‘hiperplasia endometrial’ en las bases de datos PubMed, Embase y Lilacs. Los metaanálisis finalmente seleccionados se calificaron con la herramienta de evaluación AMSTAR 2. Resultados. Se encontraron 154 artículos de los cuales, después de selección y lectura completa, finalmente se extrajeron tres para análisis cualitativo. La calificación de los metaanálisis revisados con la herramienta de evaluación AMSTAR 2 encontró que la confianza general de sus resultados fue críticamente baja. Conclusiones. Los datos muestran que la morfometría objetiva en el sistema EIN es más confiable que los criterios de la OMS para evaluar el riesgo de progresión de la hiperplasia endometrial a cáncer. La comparación entre el sistema de la OMS y el sistema subjetivo de EIN dio como resultado valores pronósticos similares. Otro metaanálisis mostró una clara discrepancia entre el sistema de la OMS de 1994 y el sistema EIN. La evaluación mediante la herramienta de evaluación AMSTAR-2 mostró que la confianza general en los resultados de los estudios evaluados fue críticamente baja.

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“…Four domains were assessed in each study: (1) patient selection (i.e., if patient selection criteria and period of recruitment were reported); (2) index test (i.e., if the Stanford parameters were clearly reported); (3) reference standard (i.e., if recurrence data were clearly reported); and (4) flow and timing (i.e., if all patients were assessed with the same criteria). The risk of bias was categorized as "low," "unclear," or "high" as previously described [28][29][30][31].…”

Section: Risk Of Bias Within Studies Assessmentmentioning

confidence: 99%

Stanford parameters stratify the risk of recurrence in gynecologic smooth muscle tumors of uncertain malignant potential

Travaglino

Raffone

Gencarelli

et al. 2021

APMIS

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Smooth muscle tumor of uncertain malignant potential (STUMP) is an ill‐defined category of neoplasms, which represent a diagnostic challenge. We aimed to assess whether the Stanford parameters, that is, high mitotic index (≥10/10HPF), significant atypia (moderate‐to‐severe), and coagulative tumor cell necrosis (CTCN), even when focal or ambiguous, may be used to stratify the risk of recurrence in gynecological smooth muscle tumor of uncertain malignant potential (STUMP). Electronic databases were searched from their inception to October 2019. All studies assessing the Stanford parameters in gynecological STUMP series were included. STUMPs were subdivided according to the presence of the three Stanford parameters: high mitotic index, significant atypia, and CTCN. A Kaplan–Meier survival analysis was performed for recurrence‐free survival; hazard ratio (HR) was calculated in each category. Fourteen studies with 219 STUMPs were included. In 15.5% of cases, none of the three Stanford parameters were present, with a recurrence risk of 5.9%; 2.7% of cases showed high mitotic index alone, with a recurrence risk of 0% (HR = not calculable); 43.8% of cases showed significant atypia alone, with a recurrence risk of 18.7% (HR = 3.3; p = 0.012); 26.5% of cases showed CTCN alone, with a recurrence risk of 17.2% (HR = 3.1; p = 0.029); and 11.4% of cases showed at least two Stanford parameters, with a recurrence risk of 32% (HR = 7.5; p = 0.003). Stanford parameters may stratify the risk of recurrence of STUMP. Significant atypia and CTCN, but not high mitotic index, may be stand‐alone risk factors for recurrence in STUMP. The presence of at least two Stanford parameters, even if equivocal (e.g., uncertain or focal CTCN, focal significant atypia, mitotic index around 10/10HPF), might still be enough to support a diagnosis of leiomyosarcoma. Further studies are necessary in this field.

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Complexity of glandular architecture should be reconsidered in the classification and management of endometrial hyperplasia

Cited by 35 publications

References 25 publications

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Diagnostic and prognostic value of ARID1A in endometrial hyperplasia: a novel marker of occult cancer

Comparación entre las clasificaciones de hiperplasia endometrial. Revisión sistemática y evaluación de calidad

Stanford parameters stratify the risk of recurrence in gynecologic smooth muscle tumors of uncertain malignant potential

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