Recent literature shows an increased interest in cancer complicating pregnancy. This is a result of the realization that oncological treatment modalities, including surgery and chemotherapy, can be applied after the first gestational trimester without hampering the fetus [¹,²].

Evidence from western countries shows that mainly breast cancer and hematological malignancies are diagnosed during pregnancy [³]. Gynecological cancers also significantly contribute to the problem. Cancer of the cervix is the second most common cancer among women worldwide and the most common gynecological cancer in the developing world [⁴]. Incidence rates of cancer complicating pregnancy therefore vary around the world. Especially with this perspective in mind, guidelines for the treatment of gynaecological cancer were recently proposed [⁵]. In contrast, sarcomas are uncommon and increase with age. Apart from bone sarcomas, we are not aware of other sarcomas complicating pregnancy. Here, we describe a fatal case of a high-grade endometrial stromal sarcoma (ESS) diagnosed at a gestational age of 19 weeks.

To the best of our knowledge, this is the first case of a transperitoneal high-grade ESS complicating pregnancy. Despite our policy to explore all possibilities in order to maintain the pregnancy, we were unable to save the fetus.

After diagnostic work-up, we agreed that the tumor resembled a high-grade ESS. However, this designation should be used cautiously. Most previously so-called high-grade tumors lack the typical growth pattern and vascularity of low-grade ESS and show destructive myometrial invasion rather than the lymphatic permeation of a low-grade ESS. Moreover, they demonstrate marked cellular pleomorphism and brisk mitotic activity. Tumours that used to be termed high-grade ESS are currently called poorly differentiated or undifferentiated uterine sarcoma [⁷,⁸]. Occasional tumors as the one described here have been reported that are high-grade and of endometrial stromal derivation [⁷]. Although we were unable to examine the uterus and confirm this diagnosis, the combination of morphological, immunohistochemical, chromosomal and a mutational analysis suggests high-grade ESS. We emphasise that some would call this an undifferentiated sarcoma. Based on the absence of hormone receptors, we do not believe that hormonal stimulation during pregnancy has a role in the origin of the sarcoma. Cancers complicating pregnancy reflect the young age of the mother rather than an etiologic role of pregnancy.

In order to treat the patient and preserve the pregnancy, we considered major surgery and chemotherapy. Laparoscopy and explorative surgery were performed in this patient. Laparoscopy can be performed safely in experienced hands and has the same advantages as in non-pregnant women [^9-11]. The carbon dioxide pneumoperitoneum and carbon monoxide production during electro-coagulation seems not to be hazardous to the fetus as long as the maximal pressure (13-15 mmHg) and operation time (25-90 minutes) are respected. Open laparoscopy (opening of the peritoneum under direct visualisation instead of using the Verres-needle) is advised in order to avoid uterine perforation. Abdominal surgery can be performed safely during pregnancy if physiologic adaptations are considered and the patient is monitored adequately, preventing hypoxia, hypotension and hypoglycemia [¹²]. Outcome data described in literature suggest there is no increased risk of miscarriage and congenital anomalies. Only in cases of peritonitis is the fetal loss rate increased [¹³]. Apart from urgent surgery, including appendectomy and cholecystectomy, oncological surgery can also be performed. We based our decision to attempt to cytoreduce the patient on previous successful experience including debulking surgery with preservation of the pregnancy for advanced stage ovarian cancer [¹⁴,¹⁵].

Chemotherapy can be administered in the second and third trimester of pregnancy, after organogenesis [¹]. Anthracyclines have a particular efficacy against sarcomas. From previous experience in breast cancer and hematological malignancies occurring during pregnancy, there is considerable evidence on the safety of anthracyclines on the fetus [¹,²].

We opted for an exploratory laparotomy to remove the tumor. However, the operative findings proved untenable given the diffuse and deep infiltration of the abdominal wall and small bowel and colon. The decision to terminate the pregnancy was based on the extensive transperitoneal spread of a high-grade sarcoma, the limited sensitivity of sarcomas to cytotoxic drugs and the diffuse uterine involvement. This situation would not allow a pregnancy to develop. This option was discussed preoperatively with the parents and allowed us to surgically remove the pregnancy by hysterotomy rather than bring her to labor ward for a prostaglandin induction.

This case shows that loss of pregnancy may be inevitable, despite the theoretical potential to perform major surgery and to administer chemotherapy during pregnancy. The treatment of gynecological cancer during pregnancy is case dependent.

Alpha-SMA: alpha-smooth muscle actin; DHPLC: denaturing high-performance lquid chromatography; ESS: endometrial stromal sarcoma; PCR: polymerase chain reaction.

Written informed consent was obtained from the patient's next of kin for publication of this case report and accompanying images. A copy of the written consent is available for review by the journal's Editor-in-Chief.

The authors declare that they have no competing interests.

The manuscript was written by FA, KVC and LH. MDR performed the genetic analysis; KODB provided the MRI images; XS was responsible for the pathological examination. BB, FA and IV were involved in the diagnosis and treatment of the patient. All authors provided review and editing of the manuscript. All authors read and approved the final manuscript.

FA is Senior Clinical Investigator for the Research Fund-Flanders (Belgium) and KVC is Researcher for the Research Fund-Flanders (Belgium).

The authors are grateful to Marieke Taal for secretarial assistance.