High-grade endometrial stromal sarcoma presenting in a 28-year-old woman during pregnancy: a case report

A 28-year-old Caucasian woman consulted her gynecologist with pain in the right fossa at a gestational age of 15 weeks. Her medical history was straightforward. She smoked 10 cigarettes per day for more than 10 years. Sonographic examination suggested an appendicular plastron and was interpreted as an ovarian mass. Subsequently, a laparoscopy was performed in a district hospital. Due to the pregnancy and the adhesions the view was incomplete (the uterus and ovaries could not clearly be identified) but peritoneal spread of malignant plaques was evident. Microscopic examination of the peritoneal lesions showed a solid, fat-infiltrating mass, composed of cancerous cells with storiform growth pattern. Cancer cells have a spindle form containing a moderate quantity of eosinofilic cytoplasm and a polymorph vesicular nucleus, sometimes containing a prominent nucleolus. More than 10 mitotic figures per 10 high-power fields were present, including abnormal mitotic figures. This morphology corresponds to a high grade sarcoma. Immunohistochemistry was performed and the tumor cells revealed the following immunophenotype: desmin (-), alpha SMA (+++), CK7 (+), CK20 (-), CD117/C-Kit (-), S100 (-), CD34 (-), C125 (-), EMA (-), CD10 (diffuse +++), calretinine (-), CK 5.6 (-), MDM 2 (-), ER (-), PR (-). The positive staining for CD10 and alpha-smooth muscle actin (alpha-SMA) in the absence of desmin expression may be indicative for a sarcoma of endometrial stromal origin.

Chromosome preparations from the tumor specimen were obtained using standard primary culture procedures. For diagnostic purposes the karyotype was determined:

66-71<3N>,XXX,+X,-1,der(2)t(1;2)(p35;q37)),-7,+11,-13,-14,der(14;15)(q10;q10),-15,-16,+17,der(18)t(7;18)(q11;q23),+20,+21,+21 [cp17]. Hence, the tumor karyotype was not specific for any known translocation-related or other sarcomas.

In order to exclude the possibility of KIT-immunonegative gastrointestinal stromal tumor, mutational analyses were performed using a combination of polymerase chain reaction (PCR) amplification, denaturing high-performance liquid chromatography (D-HPLC) pre-screening, and bi-directional sequencing, as described previously [6]. Tumor specimen showed wild-type genotype for exons 9, 11, 13, 17 of the KIT or exons 12, 14 and 18 of PDGFRA genes. Thus, the mutational analysis was not indicative for any particular sarcoma. Therefore, the final diagnosis was most suggestive for high-grade ESS.

Subsequently, she was transferred to our hospital. Magnetic resonance imaging showed diffuse peritoneal and omental tumoral implants, spreading along the visceral surfaces of the small bowel and large bowel, without a definable primary mass (Figure 1). Also a moderate amount of ascites was present. There were no signs of hepatic and lymph node metastasis. Computer tomography of the lungs excluded metastasis.

We discussed the diagnosis of a high-grade ESS with transperitoneal spread, but without distant metastasis, with the patient and her husband. Psychological support was provided. We explained that the situation was life threatening for both the mother and fetus. Given the young age of the patient and expected limited response to chemotherapy, we opted for a maximal surgical effort during cytoreductive surgery. If this had been a case of a significant cytoreduction, we would have considered anthracyclin based chemotherapy, even in the presence of an ongoing pregnancy. We agreed that if the maternal situation seemed prospectless, termination of pregnancy should be performed. In which case, hysterotomy would appear to be a better solution when compared to induction and labor. At midline laparotomy, the tumor was diffusely spread throughout the pelvis and upper abdomen. The disease at the level of the peritoneum was infiltrating the sub-peritoneal fat and this infiltration was responsible for the pain at the right fossa. The uterine serosa was diffusely involved (Figure 2). The small and large bowel and the omentum contained diffuse and multiple tumoral plaques. Given the diffuse and sometimes deep infiltration of both the peritoneum and intestines, she was considered inoperable. A hysterotomy was performed, leaving the uterus in situ. The placenta was macroscopically and microscopically normal. Three days later, intestinal obstruction was diagnosed. We agreed that chemotherapy was not likely to be a clinical benefit for a high-grade sarcoma causing intestinal obstruction whereas the potential for sepsis was considerable. Symptomatic treatment was initiated. She died at home six weeks after diagnosis.