Dedifferentiated endometrioid carcinoma of the uterus : report of four cases and review of literature

A 77-year-old woman (body mass index [BMI], 19.6 kg/m²) presented with 1 week postmenopausal bleeding, which was preceded by vaginal spotting for 1 year and concomitant genital itching that had continued for 2 weeks. Transvaginal ultrasound revealed abnormally thickened endometrium (1.47 cm) and biopsy was recommended, but she refused. After 2 weeks, follow-up ultrasonography showed remarkably increased endometrium thickness (2.36 cm) with a 7 cm mixed-echoic lesion within the endometrial cavity. Endometrial curettage revealed poorly differentiated carcinoma. Magnetic resonance imaging (MRI) showed 8.6 × 3.7 cm heterogeneously enhanced mass on contrast-enhanced T1-weighted images (CET1WI) (Fig. 1a). In addition, tumor involvement of the cervical stroma was observed on CET1WI. The patient subsequently underwent total hysterectomy (TH) with bilateral salpingo-oophorectomy (BSO) and pelvic lymphadenectomy. The surgical specimen of the uterus showed white gray polypoid mass filling the endometrial cavity (Fig. 1b). Upon microscopic examination, the tumor with high cellularity and patternless growth without glandular differentiation invaded the full thickness of the lower uterine segment (Fig. 1c) extending to the cervical stroma. The tumor consisted of medium–sized monotonous cells with brisk mitosis (5 per high-power field (HPF)) and atypical mitotic figures (Fig. 1d). Moderately differentiated endometrioid adenocarcinoma component with squamous differentiation comprised the major proportion of the tumor mass of the uterine body and fundus, which invaded more than one half of the myometrial thickness. No lymph node (LN) metastasis was found. Cytokeratin 8/18 (CK8/18) and pancytokeratin (CK AE1/AE3) expressed both components but in different patterns. In the UC component, they were expressed as dot-like patterns, whereas they showed cytoplasmic expression in differentiated component (Figs. 1e, f). Epithelial membrane antigen (EMA), estrogen receptor (ER), progesterone receptor (PR), E-cadherin, and PAX-8 were expressed in the differentiated component alone (Table 2). Based on the FIGO system, the patient had stage II. She was recommended adjuvant external beam pelvic RT (EBRT), but she refused. A month after the surgery, she presented with difficulty in urination. Abdominal pelvic computed tomography (CT) revealed multiple, large, peritoneal seeding masses, and multiple lymph node metastases in the external and internal iliac chains with large amount of ascites which was positive for malignant cells on cytologic examination. She died 7 weeks later after surgery due to tumor lysis syndrome.

A 54-year-old postmenopausal woman (BMI: 22.5 kg/m²) was referred to our hospital after being diagnosed with endometrioid carcinoma FIGO grade 3 on biopsy at a local hospital. She experienced vaginal bleeding for 3 months. She had menopause at 51 year old hypertension history. MRI showed a 5.0 × 3.6 cm lobulated mass filling the endometrial cavity, which showed slightly high signal intensity (SI) on T2-weighted imaging (T2WI) and showed poor enhancement compared with the adjacent myometrium (Fig. 2a). Mildly enlarged pelvic LNs were noted in both external iliac areas. TH with BSO, pelvic lymphadenectomy, and para-aortic lymphadenectomy were performed. The mass was bulky and filled the entire endometrial cavity on gross examination (Fig. 2b). Microscopically, well-differentiated endometrioid adenocarcinoma and UC with abrupt transition were found between them (Fig. 2c). The UC component showed a solid monomorphic discohesive cell growth, showing no differentiation except for the presence of some rhabdoid cells (Fig. 2d). The invasion depth was less than one half of the myometrium, and LN metastasis was not observed. CK8/18, CK AE1/AE3, and EMA showed diffuse cytoplasmic expression in both components, and perinuclear cytokeratin dots were also observed in the UC component. The ER, PR, E-cadherin, and PAX-8 expressions were recognized in the differentiated component alone (Table 2). The final FIGO stage was IA, and adjuvant treatment was not performed. The patient has been disease-free for 19 months after the initial diagnosis.

A 60-year-old postmenopausal woman (BMI: 25.3 kg/m²) with a chief complaint of vaginal spotting for 1 year visited a local gynecologic clinic. She had menopause at 52 years old. Colposcopy showed necrotic tissue with bleeding at the right vaginal wall, and she was referred to our hospital for further evaluation. Ultrasonography showed an echogenic mass in the endometrial cavity. The MRI revealed a 7.2 × 3.5 cm lobulated mass extending to the right above the endocervix (Fig 3a). The mass showed high SI on T2WI and low SI on T1WI with heterogeneous enhancement. Another 5 cm, elongated mass involving the lower vagina was also found. Vaginal biopsy revealed poorly differentiated carcinoma, and cytologic test of the endocervix revealed adenocarcinoma. The patient underwent wide cuff TH with BSO, and the separated additional vaginal mass was not removed. The surgical specimen showed a polypoid mass with necrosis and hemorrhage, which invaded more than one half of the myometrium of the uterus (Fig. 3b), extending to the cervix. Most of the tumor comprised discohesive cell growth with a solid sheet pattern on microscopic examination, suggesting a UC component. They were occasionally segregated by delicate fibrovascular septa forming a vague alveolar pattern (Fig. 3c). The UC component showed small amount of myxochondroid stroma, reminiscent of cartilage (Fig. 3d). A small proportion (10%) of tumor consisted of low-grade endometrioid adenocarcinoma juxtaposed with UC component. The histological finding of the UC component was similar to that of the lesion in the vaginal wall, suggesting vaginal metastasis (drop metastasis). ER and PR were not expressed in both UC and differentiated component on immunohistochemical staining (Table 2). One month after the surgery, postoperative positron emission tomography-CT revealed multiple metastatic lymphadenopathies in para-aortic, retrocaval, paracaval, both common and external iliac chains, and superficial inguinal areas with bone metastasis. The patients was treated with sequential chemoradiation therapy, which comprised of chemotherapy (cisplatin + Adriamycin + cyclophosphamide) followed by EBRT, with a total dose of 50 Gy was administered for 5 weeks to the whole pelvis, vagina, and both inguinal lymph nodes, and high-dose intracavitary radiotherapy (ICR) (20 Gy in fractions). She presented with dyspnea 2 months after radiation therapy, and clinical examination revealed lung metastasis. She died 3 weeks later (10 months after surgery).

A 52-year-old nulligravid, perimenopausal woman (BMI 22.4 kg/m²) was admitted to our hospital for treatment of leiomyoma, manifested as 10 cm low-density mass in the endometrial cavity and cervical canal on pelvic CT at a local clinic (Fig. 4a). She experienced intermittent vaginal bleeding 3 years prior. During surgery, the surgeon observed a 10 cm necrotic mass protruding through the cervical canal, which seemed to fill the entire endometrial cavity. Frozen section revealed malignancy. Surgical stage was FIGO stage II, due to cervical stromal invasion. Any enlarged lymph node was not recognized. Hence, the patient was treated with bilateral salpingectomy with pelvic and para-aortic lymph node dissection. The fungating mass filling the entire endometrial cavity was recognized on gross examination (Fig. 4b). The tumor comprised of conventional endometrioid adenocarcinoma (FIGO grade 2) and UC with sharp border between them (Fig. 4c). CK8/18, CK AE1/AE3, and EMA were expressed focally as dot-like and cytoplasmic pattern in UC component (Fig. 4d). PAX-8 was diffusely expressed in both components (Table 2). The patient was treated with adjuvant EBRT in the whole pelvis with a total dose of 50 Gy in 28 fractions followed by vaginal cylinder ICR (20 Gy/4 fractions). No evidence of recurrence or progression of disease was found after 39 months after surgery.