Lakhwinder Singh

Serous endometrial cancer with an elusive preoperative diagnosis

Uterine serous carcinoma (USC) is an aggressive histological subtype of endometrial cancer that frequently presents with early extrauterine spread, often without uterine symptoms. We report a diagnostically challenging case of a postmenopausal woman presenting with malignant ascites, peritoneal metastases and deep vein thrombosis, but no abnormal uterine bleeding. Preoperative imaging and biopsies were inconclusive, suggesting a possible leiomyoma or ovarian malignancy. Exploratory laparotomy revealed widespread peritoneal disease, and histopathology demonstrated serous carcinoma confined to an endometrial polyp with lymphovascular space invasion but no myometrial invasion. Immunohistochemistry showed p53 and p16 positivity, focal WT1 (Wilms tumor 1 protein) positivity, weak ER (estrogen receptor) expression and MMR (mismatch repair) proficiency, confirming primary USC (International Federation of Gynaecology and Obstetrics (FIGO) stage IVB). The patient was initiated on paclitaxel–carboplatin chemotherapy. This case highlights the diagnostic difficulties of USC, its potential to mimic ovarian carcinoma and the importance of integrating surgical, pathological and molecular evaluation for accurate diagnosis and management.

Liquid biopsy for diagnosing epithelial ovarian cancer: quantification of cell-free DNA and p53 mutational analysis

To isolate and quantify cell-free DNA, analysis for p53 mutations, and correlation with tumor burden in women with epithelial ovarian cancer compared with benign and borderline epithelial ovarian tumors. In this case-control study, plasma samples of eligible women collected 1 hour before surgery and based on final histopathology, women with epithelial ovarian cancer recruited as cases and borderline, and benign ovarian tumors as controls. Cell-free DNA extracted from plasma serum and quantified using Nanodrop Spectrophotometer. Amplification refractory mutation system-based polymerase chain reaction was used to detect point mutation in exon 8, codon 239 of p53 using primer pairs. p53 immunostaining was performed on tissue samples. A total of 40 women (20 cases of epithelial ovarian cancer and 10 each of benign and borderline ovarian tumors [controls]) were included in a 2:1:1 ratio. The mean cell-free DNA amount was 1330 ± 1705.4 ng/mL in women with epithelial ovarian cancer compared with 748.5 ± 444.8 and 448.5 ± 203.9 ng/mL in benign and borderline ovarian tumors, respectively (p = .023). In those with high-grade serous ovarian cancer, it was 2640 ± 2450.6 ng/mL compared with 600 ± 316.7 and 652.5 ± 158.9 ng/mL in low-grade serous and mucinous ovarian cancer, respectively (p = .006). In stage I and II ovarian cancer, these were 502.5 ± 134.4 and 330 ± 296.9 ng/mL, respectively, compared with 1655 ± 1924.8 ng/mL in stage III disease (p = .004). A total of 11 (55%) women with epithelial ovarian cancer harbored mutation in exon 8, codon 239 of p53 compared with 2 (20%) each in benign and borderline ovarian tumors (p = 0.07). Fair agreement was noted between cell-free DNA p53 mutation and abnormal tissue p53 staining on immunohistochemistry (κ = 0.41). Cell-free DNA amount was higher in women with epithelial ovarian cancer than women with benign and borderline ovarian tumors, with higher levels in advanced stage and high-grade serous carcinoma sub-type. Cell-free DNA p53 mutational analysis yielded fair concordance with tumor tissue p53 immunohistochemical results.