Clear cell endometrial carcinoma precursors: presentation of two cases and diagnostic issues

Abstract

Background The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature. Case presentation Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC. Conclusions In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.

Endometrial Metaplastic/Reactive Changes Coexistent with Endometrial Hyperplasia and Carcinoma: A Morphological and Immunohistochemical Study

“…However, to our knowledge, no study specifically assessed EMRCs that coexist with endometrial carcinoma. Such a topic may be of value, as not all endometrial carcinoma precursors are associated with architecture complexity [ 5 , 16 , 17 ]. This is especially true for non-endometrioid carcinoma and, possibly, for a subset of endometrioid carcinomas that arise in atrophic endometrium [ 5 , 16 , 17 , 18 ].…”

“…Reactive changes may also be found admixed with other types of metaplasia [ 3 , 4 ]. These endometrial metaplastic/reactive changes (EMRCs) rarely show cytological atypia, in the form of nuclear enlargement with dispersed chromatin or hyperchromasia, nuclear pleomorphism, and evident nucleoli [ 3 , 4 , 5 ]. Furthermore, EMRCs are often found in association with endometrial carcinomas [ 1 ].…”

“…However, to the best of our knowledge, no study assessed whether simple EMRCs associated with endometrial carcinoma may represent premalignant lesions. In the last decades, the emergence of new possible endometrial precancers devoid of architectural complexity makes it mandatory to assess the malignant potential of simple lesions [ 5 , 16 , 17 , 18 ]. The aim of this study was to assess the relationship between EMRCs and endometrial neoplastic lesions.…”

Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Endometrial Cancer: A Review on Immunohistochemistry Staining Patterns and Clinical Implications

“…The MSI/hypermutated group includes 30% of ECs and has a high mutational rate (18 × 10 −6 mutations per megabase). This TGCA subgroup includes both low-grade and high-grade endometroid ECs, but also other histotypes, and its overall prognosis is generally intermediate [15,16]. To date, immunohistochemistry for MMR proteins (MLH1, MSH2, MSH6 and PMS2) represents the gold-standard surrogate to identify the MSI hypermutated group.…”

Diagnosis subtype of endometrial carcinoma using a deep learning model based on histopathological images

“…ESC is typically characterized by the frequent presence of a complex papillary pattern and branching papillae with prominent budding of smaller papillae with large pleomorphic nuclei 20 . ECCC was hobnail, cuboidal, or polygonal cells with clear or eosinophilic cytoplasm combined by papillary, tubulocystic, and solid architectural patterns 21 . ECS is a biphasic endometrial carcinoma composed of malignant epithelial and mesenchymal differentiation 22 .…”