EC may have a variety of unusual appearances which can cause difficulty in making correct diagnosis[2]. CHEC is a rare morphological variant of EC developing in the endometrium[4]. Lack of awareness of this entity may lead to misdiagnosis and unnecessary treatment.
Reports of CHEC are limited; updating to now, only 37 cases are described by two articles (written in English) retrieved from PubMed[4, 6]. From these studies, patient age ranged from 25 to 83 years, with a mean of 51 years. Among 27 patients with clinical staging data, 20 patients (74%) were at FIGO stage Ⅰ. Among 18 patients with follow-up information, 15 patients were alive with no evidence of disease, 1 patient was alive with disease, 1 patient died as a result of tumor, and 1 patient died of other causes. In the present case, the patient was only 26-year-old, at FIGO stage Ⅰand was alive with no evidence of disease for 8 months. We can conclude that CHEC tends to arise in younger patients compared with conventional endometrial EC, and usually develops at a lower stage with more favorable prognosis than conventional endometrial EC[7, 8]. However, CHEC is not uncommonly mistaken for a wide variety of diseases. In the present case, the patient was misdiagnosed as a mullerian mixed tumor in the curettage specimen. Accordingly, it’s of great significance to raise the awareness of CHEC to avoid over-treatment caused by over-diagnosis, especially in young patients and in curettage.
Histologically, all cases that have been reported consist of a component of conventional grade Ⅰ or Ⅱ conventional EC that accounts for 10–90%. Endometrial hyperplasia can be identified in most cases. The definition of CHEC is the presence of cords of epithelioid cells, spindled cells, or fusiform cells with or without hyalinized stroma. This component is generally restricted to the superficial aspects and often embedded within a striking hyalinized collagenous matrix which in some cases formed osteid. Increased squamous differentiation is often found.
As for immunohistochemical staining, tumor cells in the sex cord-like region show a different expression pattern from conventional adenocarcinoma. CK and vimentin are positive in both components in most cases, and vimentin shows more diffuse positivity while CK is more restricted and focally expressed in tumor cells in the sex cord-like region. Complete loss of expression of E-cadherin and EMA was seen in tumor cells in the sex cord-like region whereas it was well preserved in the area of conventional adenocarcinoma. Nuclear expression of β-catenin was noted in tumor cells in the sex cord-like region. Both components show a positive immunoreactive for ER in about half of the cases and p53 overexpression was rarely observed. Desmin, inhibin and CD10 are negative in both components. Molecularly, sequence analysis showed mutations in the exon 3 of β-catenin gene in tumor cells in the corded and hylinized region.
The main pathological differential diagnoses of the present case include carcinosarcoma, dedifferentiated EC, sertoliform EC, low-grade endometrial stromal sarcomas (LGESS), i.e.
CHEC tends to be easily misdiagnosed as carcinosarcoma, because of its striking biphasic appearance exhibiting both epithelioid and mesenchymal elements, especially in the setting of biopsy or curretage. Unlike CHEC, carcinosarcoma often occurs in elderly women and has a high-stage clinical presentation and more aggressive clinical behavior[9]. Moreover, pathologically carcinosarcoma is mostly composed of high-grade adenocarcinomatous and sarcomatous components with increased nuclear atypia and mitosis[10]. Also, p53 is diffusely and strongly expressed in adenocarcinoma while it is scattered positive in CHEC[11].
Dedifferentiated EC contains a component of either FIGO grade 1 or 2 EC and a second component of undifferentiated carcinoma. The undifferentiated carcinoma is composed of dyshesive cells of uniform size arranged in sheets without any corded or trabecular architecture which is seen in CHEC. The nuclear chromatin is usually condensed and most cases have > 25 mitotic figure per 10 HPF while the nuclei of the epithelioid and spindle cells showed less atypia and only rare mitotic figures in CHEC[12, 13]. The undifferentiated component grows beneath the differentiated endometrioid component while the epithelioid and spindle cells are restricted to the superficial aspects in CHEC. The undifferentiated components display evidence of epithelial differentiation in only occasional tumor cells, with intense EMA and CK18 expression in the absence of staining with pan-cytokeratins[14]. Also, a proportion of dedifferentiated EC appear to be associated with microsatellite instability[15].
In sertoliform EC, tumor cells are arranged as small hollow tubules in the areas resembling Sertoli and Sertoli-Leydig cell tumors, but sometimes they can arranged as cord and trabeculaes, which can be confused with CHEC. However, prominent stromal hyalinization and spindle cells are not a feature of the sertoliform EC of the endometrium and the sertoliform elements are always positive for EMA and CK, which helps us distinguish sertoliform EC with CHEC[16, 17].
LGESS can also show sex cord-like features and the tumor cells in this element are small and uniform without prominent nuclear atypia and mitotic activity[18]. However, typical EC is absent in LGESS. Immunohistochemically, the sex cord elements in LGESS show positive staining of endometrial stromal, smooth muscle markers. Sex cord markers including inhibin, CD99, calretinin and CD56 could also be positive[19, 20]. PHF1 rearrangement has been found to be predominant in the sex cord variant of LGESS[21].
Corded and hyalinized mesonephric-like adenocarcinoma can also mimick CHEC. Differentiating the tumor from CHEC is its heterogeneous architecture resembling mesonephric growth patterns, segments of attenuated epithelium, lack of squamous differentiation, essentially negative hormone receptor expression, considerable positivity for TTF1 and GATA3[22].
In summary, CHEC is not uncommonly mistaken for a wide variety of diseases. We report one case of CHEC in a 26-year-old woman. The
clinicopathologic, light microscopic, immunohistochemical fetaures of this tumor are described and the differential diagnosis is discussed. We hope that this report help to raise the awareness of CHEC and avoid misdiagnosis and mistreatment.