Endometrial epithelial cytoplasmic change (EECC) is an adaptive cytoplasmic change commonly seen in the endometrium. Previously considered "metaplasia," EECC is now the preferred term because it offers a descriptive designation without implying a specific mechanism of development. There are 5 types of EECC: squamous, ciliated cell, eosinophilic, mucinous, and secretory (clear cell and hobmail cell) changes. Eosinophilic syncytial change (ESC) is a similar but unrelated degenerative change seen in endometrial breakdown. Some cases of ESC show atypical cytologic features that may resemble endometrial adenocarcinoma. Thirteen endometrial biopsy and curettage specimens with atypical ESCs (AESCs) were compared against 10 hysterectomy specimens with endometrial serous carcinoma. Clinical information and immunohistochemical staining profiles for markers phosphatase and tensin homologue deleted on chromosome 10 (PTEN), p53, and Ki-67 were evaluated in each case. All 13 cases of AESC (100%) showed moderate-to-strong staining for PTEN, whereas PTEN expression was absent in all endometrial serous carcinomas (P < .001). Seven cases of AESC (54%) showed focal, weak positivity for p53, whereas all cases of serous carcinoma (100%) showed strong staining (P < .001). The Ki-67 index was low (3%-15%) and found in only 3 cases in AESC (32%) but was high (60%-90%) in all cases of endometrial serous carcinoma (100%) (P < .001). Atypical ESC and serous carcinoma share several morphological features on hematoxylin and eosin-stained sections that may complicate accurate diagnosis. The PTEN, p53, and Ki-67 staining profile can effectively distinguish between AESC and malignancy in difficult cases, providing an invaluable tool for a challenging diagnostic dilemma.

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