High-grade carcinosarcoma of the endometrium identified via papanicolaou smear: Rare diagnostic findings

A 50-year-old postmenopausal woman presented with irregular vaginal bleeding beginning in March 2023. A Papanicolaou smear revealed malignant cells [Figure 1A] characterized by dyscohesive, pleomorphic, and hyperchromatic nuclei with prominent nucleoli, and differential diagnoses including high-grade carcinoma or sarcoma were considered. Above cytological findings prompted further diagnostic evaluation. Two months after initial symptoms (May 2023), abdominal CT was performed, and a 5.7-cm endometrial mass with local invasion into the urinary bladder was detected [Figure 1B]. The patient underwent a partial cystectomy and hysterectomy in June 2023. Surgical findings revealed a 9 cm × 8.7 cm polypoid tumor within the endometrial cavity, infiltrating over half of the myometrial wall and extending into the cervical stroma.Figure 1: The malignant cells in the Papanicolaou smear are composed of dyscohesive, pleomorphic, and hyperchromatic nuclei with prominent nucleoli intermixed with scattered RBCs and some inflammatory cells (A, Papanicolaou stain, 400×). Dyscohesive tumor cells indicate the possibility of high-grade sarcoma or poorly differentiated carcinoma. An ill-defined 5.7-cm endometrial mass (arrow) with focally invading into adjacent urinary bladder wall (B)Histopathological analysis confirmed high-grade homologous carcinosarcoma, exhibiting biphasic morphology with both undifferentiated endometrioid adenocarcinoma [Figure 2A and B] and high-grade endometrial stromal sarcoma [Figure 2C and D]. The final diagnosis confirmed carcinosarcoma, an aggressive malignancy combining malignant epithelial and mesenchymal elements.[1] After surgery, she received adjuvant chemotherapy with paclitaxel and carboplatin, as well as radiotherapy, to treat the metastasis detected in supraclavicular lymph nodes in August 2023.Figure 2: The epithelial cells in carcinosarcoma are often poorly differentiated, exhibiting high nuclear-to-cytoplasmic ratios, hyperchromatic nuclei, and prominent nucleoli (A, H&E stain, 200×) with positive immunohistochemical staining for cytokeratin (CK) (B, CK stain, 200×). In contrast, the sarcomatous component is composed of relatively dyscohesive pleomorphic round-to-spindle cells (C, H&E stain, 200×) with positive mesenchymal immunohistochemical staining for vimentin (D, vimentin stain, 200×). H&E = hematoxylin and eosinEndometrial carcinosarcoma is a relatively rare but highly aggressive malignancy, accounting for less than 5% of all endometrial cancers.[1] It is characterized by a biphasic histopathological nature that complicates treatment planning. Carcinosarcoma detected in Papanicolaou smears may exhibit pleomorphic, hyperchromatic cells with high mitotic activity, necrosis, and inflammation, which are nonspecific findings and overlap with those of other high-grade uterine malignancies. In fact, it is quite difficult to directly confirm carcinosarcoma in Papanicolaou smear as carcinosarcoma can mimic high-grade endometrial carcinoma or endometrial stromal sarcoma, especially in cytological samples, where the tissue architecture is not preserved. Furthermore, cytological specimens (e.g., Papanicolaou smear, endometrial brushings, and fluid cytology) may inadequately represent the tumor’s heterogeneity, missing essential diagnostic elements such as heterologous differentiation. Recognizing sarcomatous components (spindle cells, chondroid, and osteoid material) can be difficult without a histological context.[2] Despite the limitations in detecting carcinosarcoma in a Papanicolaou smear, this case emphasizes the role of such incidental findings in early intervention for aggressive endometrial malignancies. The management of nonmetastatic disease is based on a multimodal approach with optimal surgery, followed by concomitant or sequential chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent settings, with carboplatin/paclitaxel combination serving as the first-line regimen. Although introducing immunotherapy ± a tyrosine kinase inhibitor shifted the paradigm of treating patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination.[3] The 5-year overall survival rate for uterine carcinosarcoma was approximately 30%–39%, and approximately 50% of the disease incidences are confined to the uterus (stage I), indicating a generally poor prognosis. This case underscores the importance of evaluating postmenopausal bleeding as a possible indicator of severe underlying pathology and tailored treatment options for carcinosarcoma, aiming to enhance patient outcomes and survival rates. Ethics statement This study was performed in accordance with and conforming to the Declaration of Helsinki. The authors certify that they have obtained all appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed. Author contributions Conceptualization, K.-C. C. and H.-W. G.; methodology, H.-W. G.; software, H.-W. G.; validation, K.-C. C. and T.-Y. T.; writing—original draft preparation, K.-C. C.; writing—review & editing, H.-W. G.; visualization, H.-W. G.; supervision, H.-W. G. All authors have read and agreed to the final version of the manuscript. Data availability statement Raw data were generated at Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan. Derived data supporting the findings of this study are available from the corresponding author H.-W. G. upon request. Financial support and sponsorship Nil. Conflicts of interest Dr. H.-W. G., a section editor at Tungs’ Medical Journal, had no role in the peer review process of or the decision to publish this article. The other authors declared no conflicts of interest in writing this manuscript.