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Clear Cell Lesions of the Mullerian System: Not Always That “Clear”!

A spectrum of lesions, benign and malignant, of the Mullerian system display clear cells. Interpretation of this finding can be confusing resulting in significant interobserver variability even among gynecologic pathologists. It is critical to distinguish bona fide clear cell carcinoma from other endometrial lesions as management is significantly different. We present some key morphologic aspects of endometrial clear cell carcinoma and compare it with 2 other endometrial lesions with clear cells: endometrial surface epithelial changes, clear cell type (SECs), and AriasStella reaction, posing a major diagnostic pitfall, especially when present in small biopsy material. The first case, endometrial tissue from a 41-year-old female with abnormal bleeding, showing endometrial glands with papillary and glandular architectural growth pattern. The papillae show vascular cores that lack hyalinization and are lined by a single layer of eosinophilic cuboidal cells with cytoplasmic clearing, hobnailing, and hyperchromasia with a degree of mild to moderate atypia (Figure 1A). Immunohistochemical stain was negative for Napsin A (Figure 1B). On enquiry, the patient was found to have spontaneous abortion recently. The second case is a 54-year-old woman with abnormal uterine bleeding who on hysterectomy had an endometrial tumor with solid and pseudopapillary architecture. The papillae were lined by a single layer of eosinophilic and clear cuboidal cells with hyperchromatic nuclei, focal hyalinization, and neutrophilic infiltration (Figure 2A). Napsin A was negative (Figure 2B). These features represent “endometrial surface epithelial changes, clear cell type” in an otherwise low-grade endometrioid adenocarcinoma. The distinction is important as clear cell carcinoma is regarded as high-grade carcinoma and treated more aggressively than a low-grade endometrioid carcinoma. The third case, an 86-year-old female with abnormal uterine bleeding who had a hysterectomy, shows a polypoid endometrial tumor invading the upper one third 835929 IJSXXX10.1177/1066896919835929International Journal of Surgical PathologyWawire et al research-article2019