Anaplastic Pelvic Carcinoma Secondary to Low-grade Endometrial Carcinoma

Case Report

A 73-year-old Caucasian woman, gravida 3, para 3, body-mass index 26, non-smoker, having reached menopause at 56 years, with no history of hormonal replacement therapy, was brought to our attention. Her mother died of renal cell carcinoma. The patient had suffered for years from temporal lobe epilepsy, which was treated with valproic acid. In February 2008, she underwent diagnostic dilation and curettage because of post-menopausal bleeding and a thick (20 mm) endometrium on transvaginal ultrasound. Histology revealed an intermediate differentiated EC of the endometrioid type. The patient underwent midline laparotomy, peritoneal washing, total abdominal hysterectomy, and bilateral salpingo-oophorectomy. According to the histological grade and depth of the myometrial invasion, as determined intraoperatively, no lymphonodectomy was performed. The final histology (Figure 1A) confirmed an EC of the endometrioid type, moderately-differentiated (G2) tumor of 2 cm in diameter, with a polyp-like growth, and myometrial infiltration of 3 of 15 mm [stage 1 A with the new FIGO 2009 staging system, 1 B according to the FIGO 1988 staging (9)]. The lymphovascular space was not invaded and peritoneal washings were negative. The old FIGO stage II A was discussed [II A stage is no longer present in the 2009 FIGO classification (9)] because of the microscopic evidence of superficial spread to the cervical epithelium. Staining was positive for vimentin, estrogen receptor, and progesterone receptor. Staging investigations (chest X-ray and abdominal ultrasound) were negative. The patient received no postoperative radiation.

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Figure 1.

Hematoxylin and eosin staining, ×100. A: Endometrioid adenocarcinoma, grade 2, with visible glandular formations. B: Solid growing anaplastic carcinoma, with enlarged bizarre nuclei and numerous atypical mitoses.

In May 2008 (10 weeks after operation), following complaints of 5 kg weight loss and joint pain in the upper extremities and knees, a “seronegative rheumatoid arthritis” (RA) was diagnosed. Remarkably, a panel of 23 rheumatologic autoantibodies and serological markers for Borrelia, Salmonella and Yersinia infection were negative. The patient received oral prednisone (20 mg daily). During this time, no liver, spleen, or para-aortic metastases were visible on ultrasound. In July 2008, the patient was admitted to our hospital because of further weight loss (10 kg from March to June), increased abdominal circumference, and discomfort in the lower abdomen. The serum concentration of carbohydrate antigen-125 (CA-125) was slightly elevated (67 U/ml), while the concentration of carcinoembryonic antigen (CEA) was within the normal range (0.3 ng/ml). On ultrasound and computed tomographic (CT) scan, multiple intra-abdominal tumor masses up to 10 cm in diameter were confirmed in the pelvis, middle abdomen, omentum, and abdominal wall, accompanied by ascites, disseminated liver metastases, enlarged mesenteric lymph nodes, and obstructive compression of the left ureter. A CT-guided core biopsy of the closest tumor (left iliac crest level) revealed an anaplastic carcinoma, with weak focal epithelial differentiation and necroses. Because of the confusing diagnosis, the specimens of the primary malignancy (low-grade EC) were re-examined by two pathologists from another pathological institute, and conversely, the specimens of the secondary malignancy were cross-checked by two gynecological pathologists from the first institute. Two weeks later, a re-laparotomy, with removal of bulky tumors (omental cake: 400 g, pelvis: 200 g), and multiple biopsies were performed. Histology revealed a “large cell, undifferentiated, in solid formations and pseudo-rosettes growing malignancy, with in size and chromatin highly varying, leptochromatic and mitotic active nuclei, accompanied by extensive, partially hemorrhagic necrosis”. The tumor lacked any glandular differentiation (Figure 1B). Extensive immunhistochemistry was conducted with a panel of 27 markers (Table I), which supported the diagnosis of APC, being positive only for vimentin and Ki67, and focally positive for epithelial membrane antigen (EMA). On the third postoperative day, the patient reported pain in the right abdominal wall. A palpable tumor (6 cm) appeared on the CT scan as a postoperative hematoma or an abscess; in reality, it was a rapidly growing APC metastasis of the right rectus abdominis muscle. On the seventh postoperative day, the Karnofsky index of the patient fell to 50%. The intended chemotherapy with carboplatin was considered unsafe for the patient. The postoperative course became complicated with ileus, bilateral pleural effusions, hypokalemia, hypoalbuminemia with anasarca, thrombocytopenia, and impaired wound healing. In August 2008, the patient refused all but palliative treatments and requested to be discharged. She died two weeks later, five weeks after the diagnosis of APC and five months after the operation for low-grade EC.