Undifferentiated endometrial carcinoma arising in the background of high‐grade endometrial carcinoma – Expanding the definition of dedifferentiated endometrial carcinoma

Abstract

Undifferentiated endometrial carcinoma arising in the background of high-grade endometrial carcinoma-Expanding the definition of dedifferentiated endometrial carcinoma Dedifferentiated endometrial adenocarcinoma (DEC) is defined by the coexistence of undifferentiated carcinoma with low-grade (FIGO grade 1 or 2) endometrioid carcinoma. Few cases of DEC arising in the background of high-grade carcinoma (DEC-HG) have been reported, however, this phenomenon is poorly characterized. In this study we describe the morphologic, immunohistochemical and clinico-pathologic characteristics of DEC-HG. 18 DECs were diagnosed at our institution between 2008-2019, and in 11 (61%), the undifferentiated component was associated with high-grade carcinoma (8 endometrioid FIGO grade 3, 2 with ambiguous features, 1 serous). The remaining 7 (39%) represented DEC-LG (3 FIGO grade 1 and 4 FIGO grade 2). 7/11 (64%) patients with DEC-HG presented with advanced stage (FIGO stage III/IV), whereas most with DEC-LG (6/7, 86%) were stage I. On follow up, 2 patients in the DEC-HG group died of disease and 2 had progressive disease within 2 months of surgery. There was only one recurrence in the DEC-LG, 6 months post-surgery. The DEC component in both groups showed similar morphology and immunophenotype, with predominantly focal or complete loss of expression of pan-keratin, EMA, E-cadherin, CK8/18, PAX8 and ER. The DEC component in the DEC-HG group had wild-type p53 expression in 8/11 (73%) cases, loss of MLH1 and PMS2 in 6/11 (55%) and loss of SMARCA4 in 3/ 9 (33%). Although numbers are small, we show that DEC-HG is a previously under-recognized phenomenon, with morphologic and immunophenotypic similarities to DEC-LG, which supports expanding the definition of DEC to include DEC-HG. DEC-HG may be more aggressive than DEC-LG.

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

“…In fact, UEC may show epithelioid, spindled, rhabdoid, or bizarre giant cells, with sometimes myxoid stroma [ 49 ]. The differentiated component of DEC may be high-grade EEC or even SEC [ 50 ]. UEC/DEC might be confused with high-grade EEC, SEC with solid growth pattern, NEEC, carcinosarcoma, or sarcomas, and is probably underrecognized in the common practice [ 51 ].…”

SWI/SNF‐deficiency defines highly aggressive undifferentiated endometrial carcinoma

“…Dedifferentiated/undifferentiated endometrial carcinoma (DDEC/UEC) is defined in the 2020 World Health Organization (WHO) classification as a malignant epithelial neoplasm with no overt cell lineage differentiation [1]. In the case of dedifferentiated carcinoma, the undifferentiated carcinoma occurs in combination with a clonally related typically International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2 endometrioid‐type carcinoma [2,3], though the association with high‐grade endometrioid‐type carcinoma also occurs, albeit less commonly [4]. Studies that employed centralized pathology review using strict histologic criteria have demonstrated an aggressive clinical behavior for DDEC/UEC, with significantly worse outcome than International Federation of Gynecology and Obstetrics (FIGO) grade 3 endometrioid carcinoma [2,5–7].…”

Rare Subtype of Endometrial Cancer: Undifferentiated/Dedifferentiated Endometrial Carcinoma, from Genetic Aspects to Clinical Practice

“…Recent immunochemistry stain findings of the above markers are listed in Table 1 . SWI/SNF complex deficiency ranged from 20.0 to 69.4%, and MMR deficiency (MMRd) ranged from 46.2 to 73.3% across different studies [ 8 , 11 , 18 , 19 , 20 , 21 ].…”

“…Due to the rarity of UDEC, there was little experience with novel treatment in case series. Real-world experience was limited to conventional chemotherapy and/or radiotherapy [ 49 , 50 ], as listed in Table 2 [ 11 , 21 , 45 , 49 , 50 , 51 ]. According to most clinical guidelines [ 52 , 53 ], comprehensive staging surgery should be performed in operable cases, including total hysterectomy with bilateral salpingo-oophorectomy, systematic lymphadenectomy, and infracolic omentectomy [ 53 ].…”

“…A case series (n = 18) compared DEC-HG with DEC-LG, in which DEC-HG presented with advanced disease (stage III–IV) (7/11, 64%), whereas most cases of DEC-LG were stage 1 (6/7, 86%). A total of four DEC-HG patients recurred or died, while only one DEC-LG patient recurred, with a mean follow-up of 23.2 months [ 21 ]. Goh et al reported seven DEC cases in Singapore, four of which had recurrent/progressive disease.…”