Uterine carcinosarcoma in a resource-limited setting: clinical presentation, pathological diagnosis, and management challenges (case report)

¹Department of Pathology, Catholic University of Health and Allied Sciences, Histopathology and Morbid Anatomy Department, Bugando Medical Centre, Mwanza, Tanzania, ²Department of Obstetrics and Gynaecology, Catholic University of Health and Allied Sciences and Bugando Medical Centre, Mwanza, Tanzania

^&Corresponding author
Oscar Ottoman, Department of Pathology, Catholic University of Health and Allied Sciences, Histopathology and Morbid Anatomy Department, Bugando Medical Centre, Mwanza, Tanzania

Introduction    

Uterine carcinosarcoma, formerly known as malignant mixed Müllerian tumour, is a rare and highly aggressive uterine malignancy composed of both carcinomatous and sarcomatous elements [1,2]. It accounts for less than 5% of all uterine cancers and predominantly affects postmenopausal women [2-4]. Although it shares several risk factors with endometrial carcinoma, uterine carcinosarcoma is associated with a poorer prognosis [1,3,5] and requires histopathological confirmation, often supplemented by immunohistochemistry for definitive diagnosis [3,6]. The diagnosis and management of uterine carcinosarcoma remain challenging, particularly in resource-limited settings where access to advanced diagnostic modalities may be restricted [6-8]. We report a case of uterine carcinosarcoma in a 67-year-old postmenopausal woman presenting with recurrent vaginal bleeding, highlighting the diagnostic difficulties, pathological findings, and management considerations encountered in a low-resource setting [9,10]. This case underscores the importance of maintaining a high index of suspicion for uterine malignancy in postmenopausal women and the critical role of histopathological evaluation in establishing the diagnosis [7,9,10].

Patient and observation     

Patient information: a 67-year-old multiparous [para 12, living 12] postmenopausal woman presented to Bugando Medical Centre (BMC), Mwanza, Tanzania, with a two-month history of heavy irregular vaginal bleeding. The bleeding was associated with intermittent lower abdominal pain and passage of blood clots, requiring the use of up to four sanitary pads per day. She denied any previous history of postmenopausal bleeding or abnormal vaginal discharge. Her medical history was significant for poorly controlled hypertension due to poor adherence to antihypertensive medications. She also had a history of early-stage breast cancer for which she underwent a mastectomy at Muhimbili National Hospital in 2020. Histopathology and staging reports from the previous breast cancer were unavailable; however, she did not receive adjuvant therapy and had no evidence of disease recurrence during follow-up. There was no significant family history of malignancy or other relevant hereditary conditions.

Timeline of current episode: the patient was well until two months before presentation, when she developed heavy, irregular postmenopausal vaginal bleeding, associated with intermittent lower abdominal pain and the passage of blood clots. She initially presented to Bugando Medical Centre, where clinical evaluation and a transabdominal pelvic ultrasound were performed; however, the ultrasound findings were inconclusive. Owing to poorly controlled hypertension, she was referred for medical evaluation and optimisation of blood pressure control. During this period, the vaginal bleeding temporarily subsided. Three weeks later, she re-presented with recurrent heavy vaginal bleeding, prompting surgical intervention. She subsequently underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH-BSO), and a sample was sent for pathological evaluation and diagnosis (Figure 1). Histopathological examination of the surgical specimen revealed uterine carcinosarcoma (Figure 2). Immunohistochemical staining for Pancytokeratin and Vimentin was positive throughout the tumour, confirming the diagnosis (Figure 3). Postoperative staging with contrast-enhanced computed tomography (CT) of the chest, abdomen, and pelvis demonstrated no evidence of residual or metastatic disease, consistent with FIGO stage IB disease. Following multidisciplinary team review, the patient received six cycles of adjuvant carboplatin-paclitaxel chemotherapy administered according to institutional protocol, which she tolerated well. At follow-up after completion of chemotherapy, she remained clinically stable, with normal haemoglobin and CA-125 levels and no evidence of disease recurrence.

Clinical findings: on physical examination, the patient was obese, with a body mass index (BMI) of 36 kg/m². She was not pale and had an elevated blood pressure of 169/107 mmHg. Other vital signs were within normal limits. Abdominal and pelvic examinations revealed no significant abnormalities. Cervical cytology (Pap smear) demonstrated chronic cervicitis without evidence of malignancy.

Diagnostic assessment: a transabdominal pelvic ultrasound was initially performed, but the findings were inconclusive. Given recurrent heavy vaginal bleeding and the patient's postmenopausal status, a total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed. Intraoperatively, the uterus appeared slightly bulky with an intact serosal surface. Both ovaries and fallopian tubes appeared grossly normal (Figure 1). There was no evidence of ascites, peritoneal deposits, or macroscopic metastatic disease, and the remaining intra-abdominal organs were unremarkable. Histopathological examination revealed a biphasic malignant neoplasm comprising carcinomatous and sarcomatous elements. The epithelial component consisted of poorly formed malignant glands exhibiting a cribriform architecture in some areas. The neoplastic glandular cells were round to oval, with hyperchromatic vesicular nuclei, and lacked a discernible basement membrane. The mesenchymal component comprised malignant spindle cells arranged in interlacing fascicles and haphazard bundles, with numerous atypical and bizarre mitotic figures. Extensive tumour necrosis, involving approximately 30% of the examined tissue, was identified (Figure 2). The tumour invaded more than two-thirds of the myometrial thickness. However, the uterine serosa, bilateral ovaries, fallopian tubes, and parametrial resection margins were free of tumour involvement. Immunohistochemical analysis demonstrated positivity for both pan-cytokeratin and vimentin within the neoplastic cells, confirming the biphasic epithelial and mesenchymal differentiation characteristic of carcinosarcoma (Figure 3).

Diagnosis: the final pathological diagnosis was uterine carcinosarcoma (malignant mixed Müllerian tumour). Based on histopathological findings showing invasion of more than 50% of the myometrium without extension beyond the uterus, the tumour was classified as FIGO stage IB. Differential diagnoses considered included high-grade endometrial carcinoma with spindle cell differentiation and uterine leiomyosarcoma; however, the biphasic morphology and immunohistochemical profile supported the diagnosis of carcinosarcoma.

Therapeutic interventions: the patient underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy as the primary surgical intervention. Following histopathological diagnosis, contrast-enhanced CT of the chest, abdomen, and pelvis was performed for staging and showed no evidence of residual or metastatic disease. Following multidisciplinary team review, the patient received six cycles of adjuvant platinum-based chemotherapy with carboplatin and paclitaxel, in accordance with institutional oncology protocols. She tolerated the treatment well, with no significant adverse effects or treatment interruptions.

Follow-up and outcome of interventions: the patient completed all six planned cycles of chemotherapy successfully. During follow-up visits, she remained clinically stable with no evidence of disease recurrence. Laboratory investigations demonstrated normal haemoglobin and serum CA-125 levels following completion of treatment. She reported good treatment adherence and tolerated chemotherapy without major complications. She continues to attend scheduled oncology follow-up appointments for surveillance.

Patient perspective: the patient expressed satisfaction with the care she received and appreciated the timely diagnosis and treatment. She reported that receiving a clear explanation regarding her diagnosis, treatment options, prognosis, and follow-up plan helped her understand her condition and adhere to the recommended treatment. She was pleased with her recovery and remains committed to ongoing follow-up care.

Informed consent: written informed consent was obtained from the patient for publication of this case report and the accompanying clinical and histopathological images.

Discussion     

This report describes a rare case of uterine carcinosarcoma, confirmed by histopathology and immunohistochemistry, in a 67-year-old postmenopausal Tanzanian woman presenting with recurrent heavy vaginal bleeding. It highlights critical diagnostic and management lessons for resource-limited settings. Recurrent postmenopausal bleeding, as seen in this obese, multiparous woman, remains the cardinal symptom, reported in over 90% of uterine carcinosarcoma cases [7,9]. Intermittent abdominal pain, although less specific, is also a common feature [10]. The inconclusive transabdominal ultrasound reflects the diagnostic challenges in sub-Saharan Africa, where transvaginal ultrasound, hysteroscopy, and MRI are frequently unavailable [7,8]. The decision to proceed directly to total abdominal hysterectomy with bilateral salpingo-oophorectomy was clinically appropriate given persistent postmenopausal bleeding despite inconclusive imaging, particularly after blood pressure optimisation [7,8].

The biphasic morphology, with poorly formed malignant glands in a cribriform architecture, interlacing spindle cell fascicles, hyperchromatic vesicular nuclei, bizarre mitoses, and approximately 30% tumour necrosis, represents the classic histopathological features of uterine carcinosarcoma, now classified as a metaplastic biphasic carcinoma of monoclonal origin rather than a collision tumour [2,3,8]. Extensive necrosis and deep myometrial invasion (>50% of myometrial thickness) are recognized adverse prognostic indicators [2,7], thereby justifying a postoperative FIGO stage IB classification. Pan-cytokeratin and vimentin positivity confirmed epithelial-mesenchymal co-differentiation, distinguishing carcinosarcoma from high-grade endometrial carcinoma with spindle cell change and from pure leiomyosarcoma [2,8].

A significant limitation is the absence of systematic pelvic lymphadenectomy, due to constraints in anaesthetic and pathology capacity in low-resource settings. This omission compromises precise FIGO staging, as microscopic nodal metastases are common even in uterine-confined disease [1,7]. Furthermore, preoperative imaging was limited to transabdominal ultrasound; the IHC panel included only two markers; and no molecular profiling was performed, precluding subtyping into homologous versus heterologous subtypes or correlation with TP53 mutation patterns [1,2]. The patient's incomplete breast cancer records from 2020 also preclude inference about possible tamoxifen exposure, a recognized risk factor [3]. Follow-up remains short, leaving the long-term recurrence risk unresolved given the tumour's known late recurrence pattern [1,4].

The patient's favourable early outcome, with stable haemoglobin, normal CA-125, and no recurrence after six cycles of adjuvant carboplatin-paclitaxel, reflects three evidence-based principles: complete primary surgical cytoreduction with TAH-BSO, an accurate IHC-confirmed histopathological diagnosis, and platinum-taxane adjuvant chemotherapy, which remains the standard systemic approach given the high metastatic potential of uterine carcinosarcoma [1,7]. This case meaningfully contributes to the scarce African literature. It reinforces that, in low-resource settings where advanced imaging is limited, definitive diagnosis often depends on hysterectomy specimen pathology, and that clinical suspicion should remain high in any postmenopausal woman presenting with abnormal vaginal bleeding [2,7,8].

Conclusion     

Uterine carcinosarcoma is a rare, aggressive, biphasic malignancy. Timely diagnosis requires a high index of clinical suspicion in any postmenopausal woman presenting with abnormal vaginal bleeding, even when imaging is inconclusive. This case highlights that surgical intervention should not be unduly delayed in patients with persistent postmenopausal bleeding, as definitive diagnosis frequently depends on histopathological evaluation of the hysterectomy specimen, supplemented by immunohistochemistry with pan-cytokeratin and vimentin to confirm dual epithelial-mesenchymal differentiation and to distinguish the tumour from high-grade endometrial carcinoma with spindle cell change and from pure uterine sarcoma. Complete primary cytoreduction, followed by adjuvant carboplatin-paclitaxel chemotherapy delivered within a multidisciplinary framework, represents the most effective therapeutic strategy and, in this case, produced a favourable early outcome despite the resource-constrained setting. Prolonged oncological surveillance remains essential given the tumour's recognised propensity for late local and distant recurrence.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Patient management: Dismas Keneth Matovelo, Godfrey Philemon Kaizilege and Edgard Mweyunge Ndaboine. Data collection: Colman Calisty Mayomba, Ngutunyi Chacha Jackson and Oscar Ottoman Muhini. Pathological review and final diagnosis: Oscar Ottoman Muhini and Ngutunyi Chacha Jackson. Manuscript drafting: Colman Calist Mayomba, Ngutunyi Jackson Chacha, Edgar Mweyengu Ndaboine and Oscar Ottoman Muhini. Manuscript revision: Oscar Ottoman Muhini, Edgar Mweyengu Ndaboine and Dismas Keneth Matovelo. All authors have read and approved the final version of this manuscript.

Figures     

Figure 1: gross macroscopic view of total abdominal hysterectomy with a tumour lesion within the uterine cavity

Figure 2: histological section showing uterine carcinosarcoma under hematoxylin and eosin stain (x10 HPF)

Figure 3: pancytokeratin and vimentin immunohistochemical stain showing positive staining along tumour areas (x10 HPF)

References