We describe the clinical history of two patients with late recurrence of endometrial cancer, treated, and followed at our center. We also performed a systematic PubMed search for case reports of case series of late (beyond year ten from treatment) systemic relapse from endometrial cancer. We focused only on recurrences from endometrial cancer occurring after radical surgery and excluded new primary endometrial cancers developing in extrauterine endometriosis many years after a hysterectomy performed for endometriosis.
Case report 1
A 56-year-old woman underwent ultrasonography of the abdomen in 1998 because of the appearance of abdominal swelling and pain. The exam revealed a pelvic mass, which was then confirmed to be uterine by an exploratory laparoscopy. Laparoscopy was therefore converted in laparotomy, and a hysterectomy with bilateral salpingo-oophorectomy without lymphadenectomy was performed. Histological examination of the surgical sample revealed a well-differentiated, estrogen receptor [ER] positive, endometrioid cancer with negative surgical margins. Preoperative staging performed with a total-body CT scan showed no distance metastasis, and FIGO stage was IB according to the 1996 edition [6]. Surgery was radical and, according to the guidelines at the time, the patient was considered low risk of relapse, then no adjuvant treatment was prescribed. Oncological follow-up was carried out with semestral clinical examination and CT scan, and it was negative during the following 5 years. In October 2014, the patient developed a chronic cough and underwent a CT scan of the chest, which revealed a 90 mm in diameter mass in the upper lobe of the right lung (Fig. 1). Full staging with total-body CT scan, gastroscopy, and colonoscopy did not show a primary tumor or other metastases. Bronchoscopy with biopsy revealed endometrial carcinoma cells staining positively for the ER. Immunostaining for Ki-67 was positive in 30% of malignant cells. Following multidisciplinary evaluation, the patient underwent neoadjuvant chemotherapy with carboplatin area under the curve (AUC) 5 plus paclitaxel 175 mg/m2 every 3 weeks. The first tumor imaging performed after three cycles of chemotherapy showed a partial response. Upon completion of 6 cycles of neoadjuvant chemotherapy, in February 2015, the patient underwent right lung lobectomy. Histopathology confirmed metastasis from endometrial carcinoma, which was ER positive, paired box 8 [PAX8] positive, thyroid transcription factor 1 [TTF-1] negative, and CDX2 negative (Fig. 2). Surgical margins were negative. After surgery, the patient was prescribed endocrine therapy with tamoxifen 20 mg/day. At the time of this writing, the patient is continuing hormonal treatment and oncological follow-up and remains disease free.
Case report 2
A 75-year-old woman underwent hysterectomy with bilateral salpingo-oophorectomy and lymphadenectomy because of the accidental discovery of a pelvic mass in 1997. Histological examination of the surgical sample showed a grade 1 differentiated, ER positive, PAX8 positive, TTF-1 negative, and CA125 negative endometrioid carcinoma. Preoperative staging performed with total-body CT scan showed no distance metastasis, and FIGO stage was II according to the 1996 edition [6]. According to Italian guidelines at the time, the patient underwent adjuvant radiotherapy with 40 Gray delivered by external beams. The following 5 years of oncological follow-up, with semestral clinical examination and CT scan, were uneventful. In January 2019, the patient was admitted to the emergency department of our hospital because of worsening dyspnea. While excluding pulmonary embolism, a computed angiography of the chest showed a 28 mm in diameter mass in the upper lobe of the right lung (Fig. 3). A positron-emission tomography (PET) with fludeoxyglucose showed intense uptake of the tracer in the lung lesion (standardized uptake value [SUV] 12.2). Histopathology of a biopsy of the lesion revealed endometrial carcinoma cells, which were ER and PAX8 positive, and TTF1 and CA125 negative. Because of no other systemic metastases, in March 2019, the patient underwent surgical resection of the lesion. Histopathology confirmed the endometrial origin (ER and PAX8 positive, and TTF1, CDX2, and CA125 negative) and showed clear surgical margins (Fig. 4). After 4 months of follow-up, the patient developed a painful cutaneous node in the abdominal wall of the right hypochondrium. A total-body CT scan showed a 45 mm in diameter lung mass near the site of metastasectomy, a 33 mm in diameter node of the abdominal wall, and other two smaller lesions in the muscles of the abdominal wall. The cutaneous node was surgically removed, and the histological examination revealed metastasis from endometrial carcinoma, ER and PAX8 positive, and TTF1, CDX2, and CA125 negative. Vascular carcinoma microemboli were observed in the surrounding adipose tissue. Because of systemic disease, our multidisciplinary team decided for first-line chemotherapy, which consisted of carboplatin AUC5 and paclitaxel 175 mg/m2 every 21 days. At the time of this writing, therapy is still ongoing, 22 years after the first diagnosis of endometrial carcinoma.