ABSTRACT
Objective: There are less than 20 reported cases of gastrointestinal stromal tumors in pregnancy. Of these reported cases, there are only two that detail GIST in the first trimester. We report our experience with the third known GIST diagnosis in the first trimester of pregnancy. Notably, our case report highlights the earliest known gestational age at time of GIST diagnosis. Methods: We conducted a literature review of GIST diagnosis in pregnancy via PUBMED, using a combination of the following terms: (pregnancy or gestation) and (GIST). We utilized Epic for chart review of our patient's case report. Results: A 24 year old G3P1011 presented to the Emergency Department at 4w6d by last menstrual period (LMP) with worsening abdominal cramping, bloating, and associated nausea. Physical exam revealed a large, mobile, nontender mass palpated in the right lower abdomen. Transvagianl ultrasound noted the presence of a large pelvic mass of unknown etiology. Pelvic magnetic resonance imaging (MRI) was obtained for further characterization, revealing a 7.3× 12.4 × 12.2 cm mass with multiple fluid levels, centered in the anterior mesentery. Exploratory laparotomy was performed with en bloc resection of small bowel and pelvic mass, with pathology demonstrating a 12.8 cm spindle cell neoplasm compatible with GIST and notable for a mitotic rate of 40 mitoses/50 high power field (HPF). Next generation sequencing (NGS) was pursued in order to predict tumor responsiveness to Imatinib, which revealed a mutation at KIT exon 11, suggesting a response to tyrosine kinase inhibitor therapy. The patient's multidisciplinary treatment team, consisting of medical oncologists, surgical oncologists, and maternal fetal medicine specialists, made the recommendation for adjuvant Imatinib therapy. The patient was offered termination of pregnancy with immediate initiation of Imatinib, as well as continuation of pregnancy with either immediate or delayed treatment. Interdisciplinary counseling focused on both the maternal and fetal implications of each proposed management plan. She ultimately elected termination of pregnancy, and underwent an uncomplicated dilation and evacuation. Conclusions: GIST diagnosis in pregnancy is exceedingly rare. Patients with high-grade disease encounter a multitude of decision-making dilemmas, often with competing maternal and fetal interests. As additional cases of GIST in pregnancy are added to the literature, clinicians will be able to implement evidence-based options counseling for their patients. Shared decision-making is contingent upon patient understanding of diagnosis, risk of recurrence, available treatment options, and the treatment-related implications on maternal and fetal outcomes. A multidisciplinary approach is crucial for optimization of patient-centered care.
ABSTRACT
The endometrium is a resilient and highly dynamic tissue, undergoing cyclic renewal in preparation for embryo implantation. Cyclic endometrial regeneration depends on the intact function of several cell types, including parenchymal, endothelial, and immune cells, as well as adult stem cells that can arise from endometrial or extrauterine sources. The ability of the endometrium to undergo rapid, repeated regeneration without scarring is unique to this tissue. However, if this tissue renewal process is disrupted or dysfunctional, women may present clinically with infertility due to endometrial scarring or persistent atrophic/thin endometrium. Such disorders are rate-limiting in the treatment of female infertility and in the success of in vitro fertilization because of a dearth of treatment options specifically targeting the endometrium. A growing number of studies have explored the potential of adult stem cells, including mesenchymal stem cells (MSCs), to treat women with disorders of endometrial regeneration. MSCs are multipotent adult stem cells with capacity to differentiate into cells such as adipocytes, chondrocytes, and osteoblasts. In addition to their differentiation capacity, MSCs migrate toward injured sites where they secrete bioactive factors (e.g. cytokines, chemokines, growth factors, proteins and extracellular vesicles) to aid in tissue repair. These factors modulate biological processes critical for tissue regeneration, such as angiogenesis, cell migration and immunomodulation. The MSC secretome has therefore attracted significant attention for its therapeutic potential. In the uterus, studies utilizing rodent models and limited human trials have shown a potential benefit of MSCs and the MSC secretome in treatment of endometrial infertility. This review will explore the potential of MSCs to treat women with impaired endometrial receptivity due to a thin endometrium or endometrial scarring. We will provide context supporting leveraging MSCs for this purpose by including a review of mechanisms by which the MSC secretome promotes regeneration and repair of nonreproductive tissues.
