About a case of GIST occurring during pregnancy with immunohistochemical expression of epidermal growth factor receptor and progesterone receptor

doi:10.1016/j.prp.2005.08.013

Pathology - Research and Practice

Volume 202, Issue 2, 15 February 2006, Pages 119-123

https://doi.org/10.1016/j.prp.2005.08.013 Get rights and content

Abstract

The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is very rare. We are the first to add to the literature a case report of GIST occurring during pregnancy with immunohistochemical staining for epidermal growth factor receptor (EGFR) and progesterone receptor (PgR). A role of PgR and EGFR in tumor growth should not be excluded, and these findings indicate that the expression of these receptors could provide pertinent biological information required to determine adequate therapeutic regimens. In conclusion, considering that GIST occurring during pregnancy is a rare event, with frequent delay in diagnosis, it is important to consider this diagnosis for early recognition, correct diagnosis, and a better outcome.

Introduction

Gastric cancer developing during pregnancy is very rare, with only 92 cases reported over the last 30 years [7]. The coexistence of gastrointestinal stromal tumors (GISTs) and pregnancy is also very rare, with only one case reported in the literature [19].

We present a case of GIST occurring during pregnancy with immunohistochemical staining for epidermal growth factor receptor (EGFR) and progesterone receptor (PgR).

Section snippets

Case report

A 29-year-old female, in the 22nd week of gestation, presented with complaints of abdominal pain. Her past medical history was negative for any disease. She denied sickness, emesis, constipation, or vaginal bleeding. Physical and obstetrical examinations were normal except for the presence of abdominal fluid. Laboratory evaluation demonstrated hemoglobin of 9.2 g/dl. An echographic examination demonstrated intrauterine fetus without anomalies and a large amount of abdominal fluid (Fig. 1). Fluid

Discussion

The literature contains only few reports of gastric tumors occurring during pregnancy, the majority of them being adenocarcinomas [9], [13]. It is very rare that GISTs develop during pregnancy.

Usually, GISTs are detected in adults over 30 years of age, affecting men and women equally. GISTs may appear singly or in clusters, and their size may vary from small intramural lesions to bulky tumor masses. In general, small tumors of the stomach are asymptomatic, benign intramural lesions; large

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Cited by (23)

Diagnosis and management of high risk gastrointestinal stromal tumor in first trimester pregnancy: A case report and review of the literature
2023, Heliyon
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.
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.
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.
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.
Niclosamide nanocrystal for enhanced in-vivo efficacy against gastrointestinal stromal tumor via regulating EGFR/STAT-3/DR-4 axis
2023, Journal of Drug Delivery Science and Technology
Currently, available gastrointestinal stromal tumor therapy is marred with limited efficacy and resistance. Considering the involvement of epidermal growth factor receptor- Signal transducer and activator of transcription 3 mediated signaling in gastrointestinal stromal tumors progression, we hypothesized that the signal transducer and activator of transcription 3 inhibitor, niclosamide could be repurposed to treat gastrointestinal stromal tumors. Niclosamide nanocrystal was developed to enhance solubility and bioavailability. Cytotoxicity and the nature of cell death were accessed by various in vitro assays. Niclosamide showed dose-dependent cytotoxicity, mitochondrial damage, and apoptotic-like cell death in the gastrointestinal stromal tumor cell line. Niclosamide nanocrystal displayed a 2-fold enhancement in in-vitro anticancer activity. Immunoblotting and immuno-flow-cytometry confirmed that epidermal growth factor stimulation had increased phosphorylation Signal transducer and activator of transcription 3 via epidermal growth factor receptor and downregulated Death receptor 4 mediated apoptosis which was reversed by niclosamide treatment. Moreover, niclosamide nanocrystal (50 mg/kg) showed better tumor suppression than pure niclosamide (50 mg/kg), indicating that niclosamide nanocrystal has more bioavailability than niclosamide. This study demonstrated that nanocrystals might become a promising delivery strategy for delivering niclosamide to treat the gastrointestinal stromal tumor.
A rare maternal gastrointestinal stromal tumor found in the second trimester of pregnancy: A case report
2020, Case Reports in Women's Health
Citation Excerpt :
The tumors very rarely present during pregnancy. We found ten reported cases of GIST in pregnancy (Table 1) [3–12]. Their average time at diagnosis was 18 weeks of gestation (13–28 weeks).
Gastrointestinal stromal tumors are rare, and in pregnancy they are extremely rare. We present a case of a maternal gastrointestinal stromal tumor found in the second trimester of pregnancy. A 29-year-old woman, gravida 1 para 0, complained of bloody vomiting at 14 weeks of gestation. She had no significant medical history. We performed plain computed tomography and upper gastrointestinal endoscopy. Precise examination revealed a large mass in the stomach and an exposed blood vessel on the surface. An exposed blood vessel can be harmful for mother and fetus as it might rupture during the pregnancy. We performed a distal gastrectomy at 16 weeks of gestation. Histology confirmed a localized gastrointestinal stromal tumor with a high risk of recurrence, and adjuvant imatinib was recommended. The patient elected to delay adjuvant imatinib until after delivery. The postoperative and antenatal course was favorable, and the patient was followed up by ultrasound every 2 months after the operation. After she gave birth at 40 weeks of gestation, she started adjuvant imatinib 400 mg/day. There was no evidence of recurrence 1 year after surgery. There are no guidelines for the management of gastrointestinal stromal tumors in pregnancy. Given the treatment challenges, we believe that pregnant patients should be managed by a multidisciplinary team with expertise in gastrointestinal tumors and fetal-maternal medicine.
Bone and soft tissue sarcomas during pregnancy: A narrative review of the literature
2016, Journal of Advanced Research
Citation Excerpt :
Imatinib treatment during pregnancy or breast feeding is contra-indicated since spontaneous miscarriages and birth defects have been reported. Prognosis of women with gestational GIST remains favorable [57–65]. Gestational synovial sarcomas are rare sarcomas.
Bone or soft tissue sarcomas are rarely diagnosed during pregnancy. Until today 137 well documented cases have been reported in the English literature between 1963 and 2014. Thirty-eight pregnant mothers were diagnosed with osteosarcoma, Ewing’s sarcoma or chondrosarcoma, whereas 95 other cases of soft tissue sarcomas of various types have been documented. We present the clinical picture and therapeutic management of this coexistence.
An elective combined caesarean section and small bowel GIST resection during the third trimester of pregnancy: Report of a case
2013, International Journal of Surgery Case Reports
Citation Excerpt :
Rarely, patients may present acutely due to either an obstruction or a perforation of a viscus.14 Constitutional symptoms are not uncommon in pregnancy and thus the presentation of GISTs in pregnancy can pose a diagnostic challenge.8 Attaining a diagnosis in pregnancy is difficult, as it is normally recommended that computed tomography is undertaken to accurately stage the tumour.11,15
Gastro-Intestinal Stromal Tumours (GISTs) are rare with an estimated incidence of only 11–15 per million. In pregnancy, GISTs are an extremely rare occurrence and are thus complex to manage from an ethical, surgical and oncological perspective.
We present the first reported case in the literature of a successful combined lower segment caesarean section (LSCS) and a tumour resection in a 31-year-old pregnant patient presenting with a small bowel GIST.
We compare and contrast our case with other reported cases of GIST resection in pregnancy and discuss the challenges faced by both patients and clinicians.
Our case demonstrates that a combined LSCS and GIST resection is feasible. In addition, our case highlights the importance of both the multidisciplinary setting and the consideration of patients’ wishes in the successful management of this complex group of patients.
HER-2 status in gastrointestinal stromal tumor
2008, Annals of Diagnostic Pathology
Citation Excerpt :
The KIT and PDGFRA genes encode for similarly named receptor tyrosine kinase proteins that are involved in intracellular signaling pathways that control cell survival [9,10], and the KIT/PDGFRA tyrosine kinase inhibitor imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland) has been used for the treatment of GIST by reducing receptor tyrosine kinase activity [11]. The role of other growth factor receptors has been investigated in GIST, including the EGFR [12-16]. However, only 2 studies [12,13] were published so far regarding HER-2 and GIST.
Human epidermal growth factor receptor–2 (HER-2) encodes for the transmembrane glycoprotein HER-2 that is involved in activation of intracellular signal transduction pathways that control cell growth and differentiation. HER-2 is overexpressed in approximately 20% of patients with breast cancer and has been associated with poorer prognosis. Since 1998, the anti–HER-2 antibody trastuzumab has been used for the treatment of patients with HER-2–positive breast cancers. However, little information is available about the relationship between HER-2 and gastrointestinal stromal tumors. This study's purpose was to determine the HER-2 status in gastrointestinal stromal tumors. We found that all 477 cases included in this study were negative (score 0) by immunohistochemistry using HercepTest, and no HER-2 gene amplification was detected in 71 cases submitted to fluorescence in situ hybridization. These results show that HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may not be suitable for treatment with trastuzumab.

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TEACHING CASEAbout a case of GIST occurring during pregnancy with immunohistochemical expression of epidermal growth factor receptor and progesterone receptor

Abstract

Introduction

Section snippets

Case report

Discussion

Am. J. Pathol.

Mod. Pathol.

Hum. Pathol.

Eur. J. Obstet. Gynecol. Reprod. Biol.

Gastroenterology

Int. J. Gynaecol. Obstet.

Am. J. Pathol.

Expression of transforming growth factor-α and epidermal growth factor receptor in gastrointestinal stromal tumours

Virchows Arch.

The reappraisal of gastrointestinal stromal tumors: from Stout to the KIT-revolution

Virchows Arch.

Diagnosis of gastrointestinal stromal tumors: a consensus approach

Hum. Pathol.

Advanced gastric cancer and a concomitant pregnancy associated with disseminated intravascular coagulation

Am. J. Perinatol.

TEACHING CASE
About a case of GIST occurring during pregnancy with immunohistochemical expression of epidermal growth factor receptor and progesterone receptor