Primary Extra-Gastrointestinal Stromal Tumor (GIST) arising from mesentery of small bowel and presenting as abdominal mass: A rare entity

doi:10.4236/ojgas.2013.35045

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Open Journal of Gastroenterology, 2013, 3, 267-271 OJGas

http://dx.doi.org/10.4236/ojgas.2013.35045 Published Online September 2013 (http://www.scirp.org/journal/ojgas/)

Primary Extra-Gastrointestinal Stromal Tumor (GIST)

arising from mesentery of small bowel and presenting as

abdominal mass: A rare entity

Alok Kumar Tiwari1*, Anil Kumar Choudhary2, Hemant Khowal1, Poras Chaudhary1,

Mohinder P. Arora1

1Department of Surgery, Lady Hardinge Medical College, New Delhi, India

2Department of Surgery, Dr R.M.L Hospital, New Delhi, India

Email: *[email protected], [email protected], [email protected], [email protected], [email protected]

Received 20 July 2013; revised 21 August 2013; accepted 29 August 2013

cense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Introduction: Majority of mesenchymal tumors of

gastrointestinal tract are Gastrointestinal Stromal

Tumor (GIST). It is, however, a rare tumor, account-

ing for less than 1% of primary gastrointestinal (GI)

neoplasms. Though, these tumors are refractory to

conventional chemotherapy or radiotherapy but show

a good response to targeted adjuvant chemotherapy

with tyrosine kinase inhibitors following surgical re-

section. Case Report: we report here a case of pri-

mary Extra-GIST tumor arising from mesentry of

small bowel near duodeno-jejunal junction in a 69

years old male patient. The patient presented with a

palpable mass in upper abdomen for past 15 days. On

examination, a non-tender mobile lump of size around

17 × 10 cm, with bosselated surface and firm in con-

sistency was palpable involving epigastric, left hypo-

chondrium and umbilical region. Contrast enhanced

computed tomography of abdomen revealed a het-

erogenous mesentric mass. On surgical intervention a

mass was found involving mesentery near dudeno-

jejunal junction without involvement of gastrointes-

tinal tract. Complete surgical resection of the tumor

was done and adjuvant chemotherapy with Imatinib

mesylate was started as HPE revealing GIST with

mitotic index of >10/50 HPF and 17 × 10 cm size

placed the patient in high risk category. Patient was

discharged on 12th of post-operative day with advice

of regular follow-up. Conclusion: GIST occurrence is

not restricted to bowel but can involve unusual sites

also. The mainstay of treatment remains surgical re-

section with adequate margin. In cases where tumour

has malignant potential (high mitotic figures on histo-

pathology) adjuvent treatment with tyrosine kinase

may prevent or delay relapse.

Keywords: Extra-Gastrointestinal Stromal Tumors;

GIST; Mesentric Tumors; Imatinib Mesylate; Abdominal

Mass

1. INTRODUCTION

Gastrointestinal Stromal Tumors coined by Mazur and

Clark are the most common mesenchymal tumors of gas-

trointestinal tract found to be immunohistochemically

and ultrastructurally different from other spindle cell

tumors [1]. GISTs can occur anywhere in the gastrointes-

tinal (GI) tract, commonest site being stomach (Ap-

proximately 60% - 70% of GISTs), followed by small

intestine (25% - 35%), colon, rectum, appendix (together

5%), and esophagus (2% - 3%). Rarely, they may arise

from the mesentery or omentum [2].

The clinical manifestations of GISTs depend on the

location and size of the tumors and are often nonspecific

although patients with advanced disease may present

with symptoms of a mass lesion, abdominal pain, or

bleeding [3,4].

The availability of the KIT tyrosine kinase inhibitor

(STI-571, imatinib/Gleevec/Novartis) has revolutionized

the treatment of gastrointestinal stromal tumors, thereby

making it important to know this disease entity.

We report here a case of extra-gastrointestinal stromal

tumor arising from mesentery of small intestine present-

ing as an abdominal mass.

2. CASE REPORT

A 69 years old male patient presented with history of

*Corresponding author.

OPEN ACCESS

A. K. Tiwari et al. / Open Journal of Gastroenterology 3 (2013) 267-271

268

progressively increasing mass in upper abdomen without

any other significant complaints for last 15 days. When

evaluated clinically patient was found haemodynamically

stable and his per-abdominal examination revealed a

mass of size 17 × 10 cm which was mobile , non-tender,

with bosselated surface and firm in consistency involving

epigastric , left hypochondrium and umbilical region.

His laboratory workups were unremarkable and Con-

trast Enhanced Computed Tomography (CECT) of ab-

domen depicted a heterogenous mesentric mass (Figure

1).

On laparotomy, 17 × 10 cm mass involving the mes-

entery (Figure 2) near the duodeno-jejunal junction was

found without any gross evidence of gastrointestinal tract

involvement, peritoneal deposits, ascitis and lymph node

enlargement. Resection of the tumor along with the

mesentery and ligation of the feeding vessels was carried

out and specimen was sent for histopathological exami-

nation.

Figure 1. CECT abdomen showing a heterogenous mass (ar-

row).

Figure 2. Large mesenteric mass near duodeno-jejunal junction

(thin arrow) away from transverse colon (thick short arrow) and

small intestine (thick long arrow).

Histopathological examination grossly revealed grey

white soft tissue mass of size 17 × 10 cm with encapsu-

lated and nodular external surface. Microscopical ex-

amination showed features of malignant spindle cell tu-

mors arranged in short fascicles and focally forming

whorls with myxoid areas and multiple foci of necrosis.

Individual tumor cells revealed moderate nuclear pleo-

morphism, brisk mitosis (>10/HPF). On the basis of im-

munohistochemistry, the tumor cells were found to be

positive for Vimentin/smooth muscle actin/(SMA) and

CD-117.

The patient was discharged on 12th of post operative

day on Imatinib mesylate adjuvent chemotherapy and is

on regular follow up.

3. DISCUSSION

Gastro-Intestinal Stromal Tumor (GIST) appears to arise

from the interstitial cell of Cajal [5,6] but the exact cell

of origin and precise steps in tumorogenesis are not well

established. However, mutation in the proto-oncogene

c-kit leading to increased expression of KIT (type III

tyrosine kinase receptor) and platelet-derived growth fac-

tor receptor-alpha (PDGFRA, found in 5% - 10%) and

loss of heterozygosity of the NF1 gene are thought to

play a major role.

Microscopically GISTs are classified into: spindle cell

type (70%), epitheloid type (20%), and mixed spindle

cell and epithelioid cell type. On immunohistochemical

staining, 95% are CD117 (c-kit) positive, 70% are CD34,

and 40% stain positive for smooth muscle actin.

Liver and peritoneum are the most common sites of

metastasis via hematogenous route while metastasis to

the lung, bones, and lymph nodes is rare.

GISTs may grow into large size by displacing adjacent

structures rather than invading them and so they are

symptomatic where as small tumors are asymptomatic.

The symptoms expressed are non-specific GI symptoms

such as nausea, vomiting, dyspepsia, abdominal pain,

distension, or change in bowel behavior. The symptoms

of obstruction, bleeding, or rupture into the peritoneal

cavity are less common.

GISTs initially presenting as an abdominal mass are

exceedingly rare, and only 21 such cases including 4

cases involving only mesentery as primary site have been

reported in the world literature since 2001 [7-10].

In accordance with all larger clinicopathologic series,

GISTs have a predilection to adults over 50 years of age

with the median ages varying between 55 - 65 years in

different sites with no clear sex predilection. Whereas the

proportion of patients under 40 years of age ranged be-

tween 5% and 20% but they are reported to be extremely

rare in children.

A number of GISTs have been reported outside the

A. K. Tiwari et al. / Open Journal of Gastroenterology 3 (2013) 267-271 269

Gastrointestinal (GI) tract in the abdomen as a result of

metastasis from GI-tract proper specifically in omentum,

mesenteries, retroperitoneum and urinary bladder serosa

[11,12]. However, GIST originating from these sites as a

primary tumor is rare. The primary site of disseminated

intra-abdominal GIST involving multiple intestines, peri-

toneal surfaces and other abdominal organ is often im-

possible to ascertain. More commonly, GISTs in these lo-

cations represents intra-abdominal metastases from gas-

tric or intestinal primaries. Search of origin of primary

tumor whether it is from stomach or intestines is always

necessary for apparent extra-GI GISTs.

Small GISTs are often firm and sometimes rubbery,

whereas larger and malignant GISTs tend to be soft with

fish-flesh or lymphoma-like consistency.

In order to carry out detection, staging, surgical plan-

ning and follow-up of patients with GIST, CT, MRI and

fluorine-18-fluorodeoxyglucose (FDG) positron emission

tomography (PET) are considered to be the imaging mo-

dality of choice. The majority of GISTs appear to be well-

defined, extraluminal or intramural masses with varying

attenuation on CT. Small lesions, which are usually be-

nign, tend to be well-defined and relatively homogene-

ous, While larger lesions normally show well-defined or

ill-defined margins, inhomogeneous density both on un-

enhanced and on contrast-enhanced scans and a tendency

to spread to surrounding structures. Large tumors (>6 cm)

frequently show central areas of necrosis or haemorrhage

[13].

Primary gastrointestinal stromal tumor in the omentum

and mesentery can be suggested as a diagnosis in a pa-

tient with a well-marginated, lobulated mass that con-

tains large areas of low attenuation and lacks central gas.

The imaging appearance of mesenteric and omental GISTs

is indistinguishable from that of other sarcomas that may

arise in these locations [11].

Unlike gastrointestinal adenocarcinomas, GISTs me-

tastasizing to the lymph nodes are extremely rare. The

CT characteristics of metastatic lesions of GISTs are si-

milar to those of primary tumors, enhancing masses that

can be heterogeneous because of necrosis, hemorrhage,

or cystic degeneration.

4. TREATMENT

The treatment goal for localized primary GIST is com-

plete resection followed by adjuvant chemotherapy with-

out the need for lymphadenectomy or wide resection

margins.

Neoadjuvant Imatinib is not recommended where a

change in tumor size will not affect surgery [14]. It can,

however, be considered where a tumor response could

permit function-sparing surgery, e.g., rectum or oesopha-

gus.

The tumor should be removed en bloc with a clear

margin. The pseudocapsule should be removed and not

be penetrated. Therefore, either a wedge resection in case

of stomach or segmental resection in case of intestine is

required.

Lymph node dissection or biopsy is not recommended

mainly due to the pattern of spread of GISTs because

lymph node metastases are rare.

GIST shows a very dramatic response to a Tyrosine

kinase inhibitor, Imatinib mesylate (STI-571/Gleevec/

Novartis/Basel). This drug is a molecular targeted ther-

apy, and acts on the c-kit growth factor receptor, which is

the most important diagnostic marker of GISTs. This

drug also inhibits several other tyrosine kinase receptors

with varying affinity as also the BCR-ABL fusion pro-

tein and the platelet derived growth factor receptor

(PDGFR). The cases resistant to Imatinib or showing pro-

gression can be controlled by sunitinib malate (SU11248/

Sutent).

In general practice, contrast-enhanced CT is routinely

used to monitor tumor response following treatment with

tyrosine kinase inhibitors. The degree and pattern of en-

hancement observed on CT scans are useful for identify-

ing post treatment changes. On Contrast-Enhanced Com-

puted Tomography (CECT), a response to Imatinib is

characterized by rapid transition from a heterogeneously

hyper-attenuating pattern to a homogeneously hypo-at-

tenuating pattern with resolution of the enhanced tumor

nodules and a decrease in tumor vessels.

The density of hepatic metastases decreases after treat-

ment to approximately 20 - 25 H, which is near to, but

greater than that for a true cyst (<15 H). Follow-up CT

scans showing that the mass has become homogeneous

with significant decreases in the attenuation and size of

the tumor indicate a good response to imatinib [13].

Tumor size, anatomic location, and mitotic count are

considered independent prognostic factors for GISTs

[15,16] and tumors that measure ≥5 cm in size are asso-

ciated with an unfavorable prognosis. The anatomic site

of origin of a GIST is associated strongly with its clinical

behavior. The patients who have tumors arising in the

rectum or small intestine have the worst prognosis as

compared to the patients who have esophageal and gas-

tric neoplasms [16]. Likewise, GISTs that exhibit ≥5

mitoses per 50 HPF or ≥2 mitotic figures per 10 HPF are

associated with an unfavorable prognosis regardless of

their site of origin [15,17].

In a series of 200 GISTs, median survival was 66

months for complete resection compared with 22 months

for incomplete resection or unresectable disease [18].

Spontaneous tumor rupture, or rupture during surgery,

increases the risk of peritoneal recurrence and is an ad-

verse prognostic factor. Overall 5-year survival rates for

primary resected disease are in the order of 50% - 55%.

A. K. Tiwari et al. / Open Journal of Gastroenterology 3 (2013) 267-271

270

Most recurrences occurs within the first 2 years of re-

section necessitating the regular follow up of these pa-

tients.

A high risk patient should have a CT scan every 3 - 4

months for 3 years, then every 6 months to 5 years. For

low risk, a CT scan every 6 months for 5 years is ac-

ceptable [14].

GISTs of the jejunum and ileum treated surgically

have been shown to have a 39% tumor related mortality,

which was twice that of gastric GISTs [19].

Our case had mesenteric stromal tumor near duodeno-

jejunal junction, mitoses were >10 per 50 HPF and total

tumor diameter was 17 cm. The localization was unfa-

vorable but bad prognostic signs such as liver or lymph

node metastases were not seen.

Gene expression patterns in GISTs are assessed by

DNA microarray techniques. The technique revealed that

the gene FLJ10261 responsible for encoding the DOG1

protein is specifically expressed in GISTs, irrespective of

KIT or PDGFRA mutation status. However, its function

is not well understood, although it seems to be fairly

specific to GIST and rarely being expressed in other soft

tissue tumors. In future it may play a pivotal role in di-

agnosis of GISTs, especially in PDGFR mutants failing

to express the KIT antigen [20].

5. CONCLUSION

GIST occurrence is not restricted to bowel but can in-

volve unusual sites also and involvement of mesentery

near dudeno-jejunal junction is very rare. The mainstay

of treatment remains surgical resection with adequate

margin. In cases where tumor has malignant potential

based on high mitotic figures on histopathology adjuvent

treatment with tyrosine kinase may prevent or delay re-

lapse. DNA microarray technique may play a vital role in

identifying the gene encoding DOG1 protein in mutants

that does not express KIT antigen and thus may help in

its diagnosis.

6. AUTHOR’S CONTRIBUTIONS

All authors have contributed to patient management,

writing the case report, reviewing and have given the

final approval for publishing the manuscript.

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