Uterine carcinosarcoma is rare and aggressive tumor with high rates of recurrence and distant metastases. However, brain involvement is exceedingly uncommon and only several cases have been reported so far. Surgery, chemotherapy, and radiotherapy have shown a survival benefit in patients with uterine carcinosarcoma, unfortunately complete remission is extremely rare, and the occurrence of brain metastases represents a very poor prognostic factor. In the case of the single brain metastasis, the removal of the brain lesion is the first oncological goal. 
We present a case of a 74-years old female patient who underwent surgery for brain metastasis 6 years after radical hysterectomy performed due to uterine carcinosarcoma.

Uterine carcinosarcoma (UCS) is also known as malignant mixed Mullerian tumor [1]. It is rare and aggressive tumor with high rates of recurrence and distant metastases. Common sites of metastases are lymph nodes, omentum, ovaries, and fallopian tubes [2]. Similar to other gynecologic malignancies, brain metastases areexceedingly uncommon and only several cases have been reported so far [3]. UCS is considered primarily a disease of women in post-menopausal period with the median age at diagnosis around 70 years. Recurrence-free and overall survival for UCS patients is poor, with five-year survival rates between 30 and 40%. The median interval from presentation to brain involvement and median survival, thereafter, have been reported to be 4.5 months and 3 months, respectively [3, 4]. We present a case of a 74-years old female patient who developed brain metastasis from UCS 6 years after a radical hysterectomy performed due to UCS.

We present a 74-years old female patient who was admitted to our emergency department after she had lost consciousness for several minutes, accompanied by malaise, loss of appetite, and fatigue. 

The patient's history was significant for UCS. This had presented with postmenopausal bleeding 6 years before admission to our neurosurgery department. She was operated in another institution and radical hysterectomy with partial omentectomy, and lymph nodes dissection was performed. Histological examination demonstrated UCS. She proceeded to neoadjuvant chemotherapy and radiotherapy, after which regular check-ups showed complete remission of the disease. The last check-up was about 3 months before she was admitted to our institution, when it was determined that there was no signs of UCS recurrence, and the patient was symptom free at that time. 

Patient’s physical examination at admission was unremarkable. Brain CT demonstrated a cerebral lesion in the right temporal lobe, 42x33mm in diameter, consistent with a partly solitary and partly cystic brain metastasis with a thin wall, showing contrast enhancement and small perifocal edema of the right temporal lobe. Ventricular system was enlarged, but without transependymal periventricular lucency, however this finding was known earlier since patient performed brain CT as part of oncological investigation when a uterine tumor was firstly discovered [Figure 1]. Also, the patient did not have a clinical sign of hydrocephalus, nor fundoscopy revealed signs of papilledema. Due to claustrophobia, the patient refused an MRI. Admission chest x-ray demonstrated two rounded nodules, one in the right lung with a diameter of 32 mm and second in the left lung with 24 mm in diameter corresponding to pulmonary metastases [Figure 2].

Figure 1: Preoperative contrast-enhanced brain CT showing single metastatic lesion in the right temporal lobe.

Figure 2:Chest X-rayshowing two rounded nodules, one in the right lung with a diameter of 32 mm and second in the left lung with 24 mm in diameter corresponding to pulmonary metastases.

CT TAP (Thorax-Abdomen-Pelvis) showed presence of the irregular mass in the central hilar zone on the left with approximately diameter of 44x37mm with atelectasis and similar mass in the right lung with a diameter of 33mm with several enlarged lymph nodes bilaterally in the pulmonary parenchyma. Also, a nodular mass lesion in the upper part of the left kidney sized approximately 30 x 20 mm, and similar lesion in the right adrenal gland with a diameter of 42x 26 mm were found, corresponding to metastatic lesions. 
    After an oncological consultation and examination by a cardiologist, pulmonologist and anesthesiologist, it was decided that the patient should be operated on since it was a solitary brain metastasis. The tumor was completely removed [Figure 3]. Control brain CT showed no signs of tumor remnant [Figure 4], and early postoperative period was uneventful. The patient was discharged from neurosurgery department on the 7th postoperative day. Histopathological examination demonstrated metastatic carcinosarcoma [Figure 5 and 6]. The patient was advised to undergo further oncological treatment. However, the patient did not report to the scheduled check-up. It was later found out that the patient refused further treatment and that she passed away 2 months after the operation.

Figure 3: Intraoperative view after tumor removal. FL-frontal lobe, TL-temporal lobe, OC-operative cavum.

Figure 4: Postoperative control brain CT with no signs of tumor remnant.

Figure 5: (A, B) Hematoxylin and eosin (H&E) stained slides of brain metastasis composed of an admixture of malignant epithelial and mesenchymal components with poorly/undifferentiated carcinoma tissue adjacent to sarcomatous component. (C) H&E specimens showing brain infiltration with tumor tissue. (D) H&E specimens at a higher magnification.

Figure 6: Immunohistochemical preparations of brain metastases showing (A) diffuse expression of Pan-Cytokeratin antibody in epithelial tumor component, and (B) diffuse expression of CD10 antibody in mesenchymal tumor part.

UCS is a rare and aggressive tumor with high rates of recurrence and distant metastases despite treatment. Most commonly metastases of UCS are found in regional lymph nodes, fallopian tubes, ovaries, and omentum. However, brain metastases have rarely been described [3]. We presented a 74-years old female patient with a single brain metastasis. To our knowledge only few cases of UCS brain metastasis have been described in literature so far. Ikeda et al. presented the largest case series of brain metastases from UCS with 8 patients. In their study, half of patients had only one brain metastasis, and the age ranged from 36 to 73 years [5]. Our patient had similar characteristics as the described patients. However, our patient was the oldest to develop brain metastasis from UCS at age 74. The median interval from clinical presentation to brain involvement has been reported to be 4.5 months, with median survival of 3 months after brain metastasis have occurred. Predictors of poor prognosis and short survival are large tumor size, lymph node metastasis and lymphovascular space involvement, adnexal spread, and invasion of myometrial wall [3,6]. Interestingly, our patient developed brain metastasis 6 years after she was operated because of UCS. To our knowledge this is the longest interval from initial presentation to CNS involvement, although patient had several predictors of poor outcome. 

Therapy of UCS is multimodal and requires coordination between oncologists, surgeons, and radiation therapists. Since it represents less than 5% of all uterine malignant tumors, therapy is largely extrapolated from trials done on patients with other carcinomas and sarcomas. However, survival benefits have been demonstrated, with complete gross resection of the tumor even in advanced disease, and also when brain or spine metastases are found, patients should be considered for resection, especially if single brain metastasis is found. According to limited available studies, resection followed by WBRT is indicated in patients with solitary brain metastases as it improves overall survival, performance status, and local control when compared to whole brain radiation therapy alone [3,7]. However, in patients with multiple lesions or unresectable lesion, palliative corticosteroids and radiation therapy are preferred. In our case, resection of brain metastasis was performed. Patient refused further treatment that was advised by an oncologist, and died 2 months after the operation. We cannot say that the resection of the single brain metastasis showed a survival benefit in our case, but we assume that the refusal of additional oncological therapy contributed to a poor treatment outcome.

UCS is a rare high malignant tumor most often seen in post-menopausal female patients. It is associated with high mortality and poor therapy response. It frequently metastasizes but brain involvement is exceedingly uncommon. While surgery, chemotherapy, and radiotherapy have shown a survival benefit, complete remission is extremely rare. In the case of the single brain metastasis, the removal of the lesion in the brain is the first oncological goal. Targeted treatment strategies for UCS are being studied, but so far have not been successful. Further understanding the genetic and molecular nature of the disease will probably help in the evolution of therapy.

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3.    Katiyar V, Araujo T, Farooq MZ, et al. Brain Metastasis in A Young Patient With Uterine Carcinosarcoma. Cureus. 2019;11:6:5010. 
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7.    Patil CG, Pricola K, Sarmiento JM, et al. Whole Brain Radiation Therapy (WBRT) Alone Versus WBRT and Radiosurgery for the Treatment of Brain Metastases. Cochrane Database Syst Rev. 2017;9:006121. 

Corresponding author: Filip Milanovic, University Children’s Hospital, Tirsova Street 10, 11030 Belgrade,Serbia. 

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