Introduction

Gastrointestinal stromal tumors (GISTs) represent 0.1-1% of gastrointestinal malignancies. They are the most common mesenchymal tumors of the gastrointestinal tract. Generally, they are asymptomatic and found incidentally during surgical procedures or radiological studies. When symptomatic, these tumors tend to present as gastrointestinal bleeding, abdominal mass or abdominal pain. (1)

GIST may arise anywhere in the tubular gastrointestinal tract from the oesophagus to the rectum.

GISTs can be subserosal and extend into the abdominopelvic cavity or alternatively can arise from organs outside the luminal gastrointestinal tract and is termed extra gastrointestinal stromal tumour (EGIST). (2) Identical lesions may occur in extra-intestinal locations such as the mesentery, omentum and retroperitoneum, while rare sites include the gallbladder or bladder. In terms of distribution, 50-60% of lesions arise in the stomach, 20-30% in the small bowel, 10% in the large bowel, 5% in the oesophagus and 5% elsewhere in the abdominal cavity. (3)

Diagnosis is based on histopathology and immunohistochemistry. (1)

Case report

A 70 years old female, with 3 living issue, attained menopause 18 years back presented in our institute with white discharge vaginally for last 7-8 months with intravaginal mass and pain abdomen increasing in nature for 3-4 months. There was no hematemesis, malena or vomiting. She was a known case of hypertension and hypothyroidism for last 10 years and was on regular medication. There was no history of any addiction. No significant family history.

Her general and systemic examination were within normal limits. Per abdomen examination revealed a hard, fixed mass in suprapubic region.

On inspection, vulva appears to be normal. Per speculum examination was non-negotiable due to the mass filling up the introitus. Per vaginal examination revealed a hard, fixed mass arising from the posterior and left lateral vaginal wall obliterating the vaginal cavity. (Fig 1) Posterior fornix obliterated by the mass. Uterus size could not be appreciable very well due to the obliterating mass. Cervix felt and appears to be normal. On per rectal examination anterior rectal wall was indented by the vaginal mass and rectal mucosa was free.

Fig 1: Per vaginal examination revealed a hard, fixed mass arising from the posterior and left lateral vaginal wall obliterating the vaginal cavity

Her complete hemogram and biochemistry investigations, chest X-ray, Electrocardiogram, Thyroid profile were within normal limit.

Ultrasound of whole abdomen revealed anteverted uterus, 6cm in size with cervix appears flattened from behind. A well defined hypoechoic SOL 12x7cm noted behind the cervix may be along the vaginal wall. There was no ascites. MRI whole abdomen showed large, lobulated, hetrogeneous SOL (11x9x9.2cm) in lower abdomen and pelvis extending into bilateral adnexal region compressing the urinary bladder, rectum and adjacent bowel.

Biopsy from the vaginal mass done outside CNCI on which was suggestive of low grade malignant spindle cell tumour.

Slide review was done in CNCI showed haphazardly arranged spindle cell with elongated clumped nuclei and opened up nuclear chromatin suggestive of leiomyosarcoma (Fig 2). Pathologist in CNCI advised Immunohistochemistry (IHC) for confirmation of the diagnosis.

Fig 2: Haphazardly arranged spindle cell with elongated clumped nuclei and opened up nuclear chromatin

IHC expressed c-kit, CD 34, DOG 1 and are immunonegative for desmin, SMA, S 100 protein and cytokeratin. IHC confirmed as c-kit expressing Gastro intestinal stromal tumour (GIST).

Multidisciplinary board decision was taken and was advised chemotherapy as the mass was not ressectable followed by reassessment for surgery. Patient was started on neo adjuvant Tb Imatinib therapy, and currently undergoing the therapy. There is no evidence of any recurrence or disease on 3 months follow up.

Discussion

Gastrointestinal stromal tumors (GISTs), which are classified as soft tissue sarcomas due to mesenchymal origin, comprise around 1% of all primary gastrointestinal cancers. They are most common in the stomach (40 to 60%), jejunum/ileum (25 to 30%), duodenum (5%) and colorectum (5to15%). (1)

GISTs can be subserosal and extend into the abdomino pelvic cavity or alternatively can arise from organs outside the luminal gastrointestinal tract and is termed extragastrointestinal stromal tumor (EGIST). Most commonly, EGISTs occur in the mesentery, omentum and retroperitoneum. They have also been found to occur less commonly as free masses in the pelvic cavity, bladder, vagina and rectovaginal septum. (4)

Primary EGISTs originating from pelvic organs appear to be a diagnostic challenge and are frequently not on the clinician's differential diagnosis. Comprehensive literature review using PubMed, MEDLINE, and Google Scholar using the keywords: GIST, EGIST, vagina, and pelvis identified total of 37 cases of EGIST. (1)

They are postulated to arise from a precursor cell of the interstitial cells of Cajal (ICC), also known as intestinal “pacemaker” cells, due to the expression of CD117 (c-kit) on both the tumor cells and the ICC. (3)

Most GISTs harbor c-kit gene mutation (most frequently in exon 9 and 11) or platelet derived growth factor receptor alpha (PDGFRA) gene that results in activation of a c-kit receptor tyrosine kinase, and subsequent cell proliferation induction and apoptosis inhibition. (1)

Imatinib, a tyrosine kinase inhibitor, has shown dramatic and sustained clinical benefit in GIST. Imatinib works by blocking the ATP-binding pocket required for phosphorylation and activation of the KIT and/or PDGFRA signaling pathways. (5)

Misdiagnoses may have significant therapeutic and prognostic implications because of the targeted imatinib-based therapy now available.

Vaginal EGISTs : Our literature review identified 6 cases of vaginal EGISTs. Most of the patients with vaginal EGISTs were postmenopausal and the tumor presented as a mass protruding from the vaginal introitus with average tumor size in largest diameter was 4.5 cm (range 2–8 cm). Most of the vaginal EGISTs presented in the posterior vaginal wall. Case reports of EGISTs arising from the rectovaginal septum (Nasu et al., 2004; Lam et al., 2006; Melendez et al., 2014; Zhang et al., 2009; Vázquez et al., 2012; Muñoz et al., 2013) revealed that these tumors arise from the rectovaginal septum or extended from the rectum, as opposed to arising from the vaginal wall stroma. Pathologically, tumors seen as well-circumscribed masses that may resemble leiomyomas. Spindle cell morphology (which is the most common morphology in GIST) was seen in 100% of the cases as well. CD117 was expressed on 100% of the cases. Desmin, smooth muscle actin (SMA), S100 were not expressed on any of the tumors further excluding the diagnosis of smooth muscle tumors and melanomas. Molecular profiling was performed on only 2 out of 6 cases. It revealed exon 11 KIT mutation similar to the case presented here. Vaginal EGISTs had a mitotic rate ranging between 1 and 25/ 50HPF and none were metastatic on presentation. This suggests that these tumors are indolent and have a low rate of metastatic potential. Four out of six patients were treated surgically. The unresectable tumor was treated with imatinib for an unspecified amount of time and no follow up was documented. Furthermore, out of the four cases where follow up was documented (Nagase et al., 2007; Ceballos et al., 2004; Liu et al., 2016), only one had a local recurrence which was subsequently treated with repeat surgical excision and adjuvant imatinib (Nagase et al., 2007; Ceballos et al., 2004; Liu et al., 2016). All four cases eventually went into complete remission without local or distant recurrence.

Conclusion

EGISTs affecting the female reproductive tract and the pelvic cavity are rare entities. Primary EGISTs originating from pelvic organs appear to be a diagnostic challenge. Their presentation and imaging findings are nonspecific and this contributes to delay in diagnosis and treatment. Immunohistochemistry remains the most definitive method to diagnose EGISTs and differentiate them from other mesenchymal tumors. The current standard of care for EGIST is surgical resection as depicted in most of the cases. Neoadjuvant imatinib may be beneficial for locally advanced EGISTs because of the potential for shrinkage of the tumor size prior to any definitive surgery.