We report a rare case of primary nodal, poorly differentiated endometrioid carcinoma associated with Lynch syndrome. A 29-year-old female patient was referred by her general gynecologist for further imaging with suspected right-sided ovarian endometrioid cyst. Ultrasound examination by an expert gynecological sonographer at tertiary center revealed unremarkable findings in the abdomen and pelvis apart from three iliac lymph nodes showing signs of malignant infiltration in the right obturator fossa and two lesions in the 4b segment of the liver. During the same appointment ultrasound guided tru-cut biopsy was performed to differentiate hematological malignancy from carcinomatous lymph node infiltration. Based on the histological findings of endometrioid carcinoma from lymph node biopsy, primary debulking surgery including hysterectomy and salpingo-oophorectomy was performed. Endometrioid carcinoma was confirmed only in the three lymph nodes suspected on the expert scan and primary nodal origin of endometroid carcinoma developed from ectopic Müllerian tissue was considered. As a part of the pathological examination immunohistochemistry analysis for mismatch repair protein (MMR) expression was done. The findings of deficient mismatch repair proteins (dMMR) led to additional genetic testing, which revealed deletion of the entire EPCAM gene up to exon 1-8 of the MSH2 gene. This was unexpected considering her insignificant family history of cancer. We discuss the diagnostic work-up for patients presenting with metastatic lymph node infiltration by cancer of unknown primary and possible reasons for malignant lymph node transformation associated with Lynch syndrome.

• Keywords
• Lynch syndrome, adenocarcinoma, biopsy, genetic testing, hereditary nonpolyposis, immunohistochemistry, lymph nodes, ultrasonography,
• Publication type
• Journal Article MeSH
• Case Reports MeSH

OBJECTIVE: Previous work has suggested that the ultrasound-based benign simple descriptors (BDs) can reliably exclude malignancy in a large proportion of women presenting with an adnexal mass. This study aimed to validate a modified version of the BDs and to validate a two-step strategy to estimate the risk of malignancy, in which the modified BDs are followed by the Assessment of Different NEoplasias in the adneXa (ADNEX) model if modified BDs do not apply. METHODS: This was a retrospective analysis using data from the 2-year interim analysis of the International Ovarian Tumor Analysis (IOTA) Phase-5 study, in which consecutive patients with at least one adnexal mass were recruited irrespective of subsequent management (conservative or surgery). The main outcome was classification of tumors as benign or malignant, based on histology or on clinical and ultrasound information during 1 year of follow-up. Multiple imputation was used when outcome based on follow-up was uncertain according to predefined criteria. RESULTS: A total of 8519 patients were recruited at 36 centers between 2012 and 2015. We excluded patients who were already in follow-up at recruitment and all patients from 19 centers that did not fulfil our criteria for good-quality surgical and follow-up data, leaving 4905 patients across 17 centers for statistical analysis. Overall, 3441 (70%) tumors were benign, 978 (20%) malignant and 486 (10%) uncertain. The modified BDs were applicable in 1798/4905 (37%) tumors, of which 1786 (99.3%) were benign. The two-step strategy based on ADNEX without CA125 had an area under the receiver-operating-characteristics curve (AUC) of 0.94 (95% CI, 0.92-0.96). The risk of malignancy was slightly underestimated, but calibration varied between centers. A sensitivity analysis in which we expanded the definition of uncertain outcome resulted in 1419 (29%) tumors with uncertain outcome and an AUC of the two-step strategy without CA125 of 0.93 (95% CI, 0.91-0.95). CONCLUSION: A large proportion of adnexal masses can be classified as benign by the modified BDs. For the remaining masses, the ADNEX model can be used to estimate the risk of malignancy. This two-step strategy is convenient for clinical use. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Descriptores benignos y ADNEX en una estrategia de dos pasos para estimar el riesgo de malignidad de tumores ováricos: validación retrospectiva en la cohorte multicéntrica IOTA5 Objetivo Estudios previos han sugerido que los descriptores simples benignos (DB) basados en ecografías pueden excluir de forma fiable la malignidad en una gran proporción de mujeres que presentan una masa anexial. El objetivo de este estudio fue validar una versión modificada de los DB y validar una estrategia de dos pasos para estimar el riesgo de malignidad, en la que a los DB modificados les sigue el modelo de Evaluación de las Distintas Neoplasias en el modelo ADNEX si no se aplican los DB modificados. Métodos El estudio fue un análisis retrospectivo con datos del análisis provisional al cabo de 2 años del estudio Fase 5 del Análisis Internacional de Tumores de Ovario (IOTA, por sus siglas en inglés), en el que se reclutaron pacientes consecutivas con al menos una masa anexial, independientemente del tratamiento posterior (farmacológico o quirúrgico). El resultado principal fue la clasificación de los tumores como benignos o malignos, en función de la histología o de la información clínica y ecográfica durante 1 año de seguimiento. Se utilizó una imputación múltiple cuando el resultado basado en el seguimiento fue incierto según criterios predefinidos. Resultados Se reclutaron 8519 pacientes en 36 centros entre 2012 y 2015. Se excluyeron a las pacientes que ya estaban en seguimiento en el momento del reclutamiento y a todas las pacientes de 19 centros que no cumplían los criterios del estudio de datos quirúrgicos y de seguimiento de buena calidad, con lo que quedaron 4905 pacientes de 17 centros para el análisis estadístico. En total, 3441 (70%) tumores eran benignos, 978 (20%) malignos y 486 (10%) inciertos. Los DB modificados fueron aplicables a 1798/4905 (37%) tumores, de los cuales 1786 (99,3%) eran benignos. La estrategia de dos pasos basada en ADNEX sin CA125 tuvo un área bajo la curva de características operativas del receptor (ABC) de 0,94 (IC 95%, 0,92–0,96). El riesgo de malignidad se subestimó ligeramente, pero la calibración varió entre centros. Un análisis de sensibilidad en el que se amplió la definición de resultado incierto dio como resultado 1419 (29%) tumores con resultado incierto y un ABC de la estrategia de dos pasos sin CA125 de 0,93 (IC 95%, 0,91–0,95). Conclusión Una gran proporción de masas anexiales puede clasificarse como benignas mediante los DB modificados. Para estimar el riesgo de malignidad para las masas restantes puede utilizarse el modelo ADNEX. Esta estrategia de dos pasos es útil para el uso clínico.

• Keywords
• ADNEX model, IOTA, benign simple descriptor, ovarian neoplasm, ultrasonography, validation study,
• MeSH
• CA-125 Antigen MeSH
• Diagnosis, Differential MeSH
• Humans MeSH
• Ovarian Neoplasms * pathology   MeSH
• Adnexal Diseases * pathology   MeSH
• Retrospective Studies MeSH
• Sensitivity and Specificity MeSH
• Ultrasonography methods   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• CA-125 Antigen MeSH

This prospective multicentric study aiming to determine the incidence of complications (malignant transformation, torsion or rupture) during conservative management of adnexal masses was performed in two Portuguese tertiary referral hospitals. It included ≥18-year-old, non-pregnant patients with asymptomatic adnexal masses (associated IOTA ADNEX risk of malignancy < 10%) sonographically diagnosed between January 2016 and December 2020. Conservative patient management consisted of serial clinical and ultrasound assessment up to 60 months of follow-up, spontaneous resolution of the formation or surgical excision (median follow-up: 17.8; range 9-48 months). From the 573 masses monitored (328 premenopausal and 245 postmenopausal adnexal masses), no complications were observed in 99.5%. The annual lesion growth rates and increases in morphological complexity were similar in the premenopausal and postmenopausal patients. Spontaneous resolution, evidenced in 16.4% of the patients, was more common in the premenopausal group (p < 0.05). Surgical intervention was performed in 18.4% of the cases; one borderline and one invasive FIGO IA stage cancer were diagnosed. There was an isolated case of ovary torsion (0.17%). These data support conservative management as a safe option for sonographically benign, stable and asymptomatic adnexal masses before and after menopause and highlight the need for expedite treatment of symptomatic or increased-morphological-complexity lesions.

• Keywords
• IOTA ADNEX model, adnexal mass, benign lesions, conservative management, ultrasound,
• Publication type
• Journal Article MeSH