CASE PRESENTATION

Dian Fajarwati Pangestu Adi

Departement of Internal Medicine Airlangga School of Medicine-dr.Soetomo Teaching Hospital Surabaya 2009

INTRODUCTION
Immunohistochemically KIT +, mesenchymal neoplasm of the GI tract and abdomen Locations: stomach ( 50%-70%), small bowel (20%- 40%) and <5% in the rectum, esofagus, omentum and mesenterium

Term GIST: Mazur and Clark (1983)

GIST

often discovered incidentally

rare tumors ; incidence of 1020/ 1 million /year ; <1% of all GI tumor

median age: 55-60 years, no predilection for either sex

CASE
Chief complaint :
Vomitus

of coffee ground

material Black stool Early satiety, nausea, abdominal discomfort Decreased appetite Fatigue, pale

History of past illness:

Hospitalized

three times , same

Mrs. F, 48 years old Javanesse Stay in Surabaya Housewife

complaint No traditional medicine and NSAID consumption No icteric No cancer in family

Physical Examination
Alert, weak, GCS 456, BP 110/70 mmHg, pulse 92 x/m, RR 20x/m, axillary temp. 36.8C Anemia (+) Heart & Lung : no abnormality, spider nevi - /H/L: unpalpable, mass in epigastrium to left hypocondrium region 8x8 cm, fixed, not well defined

Edema -/- , eritema palm -/-

Laboratory studies
Hb 5.1 g/dl WBC 9,800/mm3 Plt 820,000/mm3 LED 20/60 Coagulation test no abnormality Urinalysis no abnormality Blood sugar 128 mg/dl Creatinine serum 0.7 mg/dl BUN 10 mg/dl

AST 62 IU/L ALT 35 IU/L total protein 4.8 g/dL albumin 2.42 g/dL globulin 2.4 g/dL potassium 3.47 mmol/L sodium 132 mmol/L chlorida 99.3 mmol/L

ECG : sinus rhytm 90 x/ minutes

Imaging studies

Chest X-ray : No abnormality

Abdominal USG : mass 4x 10 cm trace from gaster, liver was normal ( no nodul/ cyst/abses)

Upper endoscopy

1st Endoscopy (Sept,17, 2008): tumor at the corpus that covered posterior wall, minor and major curvatura. Conclusion suspect gaster carcinoma. 1st Biopsy : erosive gastritis

2nd Endoscopy (Nov,3, 2008): no erosion and esophagus varices. Conclusion : mass in the corpus gaster that caused obstruction (suspected as malignancy) 2nd biopsy : chronic gastritis

Imaging studies

Solid mass in the gaster wall 12.2 x 9.4 cm , unclear border, inhomogen contrast enhancement. No liver enlargement. No nodul/mass/cyst. Spleen/ Pancreas/Ren D/S were normal. No bone destruction. Conclusion : mass in the gaster wall.
FNAB,CT Scan guiding (Nov, 27, 2008) : hypercellular consist of group and spreading of spindle cell nucleus partly plump and lobulated, pleiomorfik , coarse chromatin, and matrix myxoid. Conclusion spindle mesenchymal tumor

Planning Dx :

Initial assessment : Obs.Hematemesis melena Anemia Hypoalbumin S. Gastric tumor

Upper GI X-Ray CEA; Ca 19-9

infus PZ Blood tranfusion Gastric lavage/ 6 hours Lavement/12 hours Inj. Octreotid iv. Inj.proton pump inhibitor iv. albumin infusion

Planning Tx :

Imaging studies
Upper GI X-Ray( Des, 5, 2008) : ground glass appearance at the upper left , minimal gas in the gaster. Filling defect with fungating type and ulcerative type, destroyed mucosal pattern in the corpus until anthrum gaster

Progress Note
No hematemesis melena. Consultation to digestive surgery : Gastric malignancy and Dec, 2, post HM. Planning Dx. Upper GI X-Ray , CEA, 2008 Ca19-9 Dec, 5, 2008
Upper GI : filling defect , fungating & ulcerative type, destroyed mucosal pattern in the corpus until anthrum gaster . CEA 0.8 ng/ml ( < 5 ) ; Ca 19-9 1.2 U/ml ( < 37)

The patient underwent operation. Tumor was unresectable because the tumor adhered at the porta vein and multiple Dec,22, nodul in liver. Jejunostomy was done for enteral feeding 2008 No complaint The patient discharged from the hospital and refused to be treated with chemotheraphy Jan,16, 2009 Advice : controlled to gastrohepatology ,hematologyoncology & surgery clinic

Hystopatology

Imunohistochemistry

Malignant tissue tumor: anaplastic cell proliferation, pleiomorphic round nucleus, hyperchromatic, mitosis >20/10 HPF, trabecular formed, Conclusion: high grade malignancy dd. adenocarcinoma poorly differentiated ; stromal tumor.

Imunohistochemistry : CD 117 positive . Conclusion : Gastrointestinal Stromal Tumor (c.KIT positive).

DISCUSSION

Gastrointestinal Stromal Tumor

Sign and Symptom

non-specific : early satiety, bloating, non specific abdominal pain, gastrointestinal bleeding , fatigue from anemia, or obstruction. Abdominal pain, melena and weight loss most common symptoms Rarely, an abdominal mass is palpable

This patient : hematemesis-melena, weight loss, anemia, palpable mass in the abdomen

Laboratory examination

No laboratory test specifically confirm GIST.

This patient : anemia and hypoalbumin. The tumor markers (CEA and Ca 19-9) were negative

Imaging studies

no standard imaging protocol, all imaging techniques may be used. preoperative diagnosis based on clinical and radiologic data is difficult nonspecific presentation typically grow as bulky, well-defined, endo- or exophytic masses parallel to the bowel lumen stromal origin normally present with the typical signs of submucosal or extrinsic GI lesions on imaging studies overlying mucosa can be normal or show signs of necrosis or ulceration.

Imaging studies

Endoscopic examination :smooth protrusion of the bowel wall, lined with mucosa, some cases show signs of bleeding and ulceration Full layer biopsy true histopathologic Dx. GIST: 27-50% by endoscopic biopsy The results : gastric tumor and the biopsy revealed erosive and chronic gastritis

Barium series detect GIST sufficient size filling defect : sharply demarcated and is elevated compared with surrounding mucosa overlying mucosa is smooth unless ulceration the information is limited because of striking image Upper GI : mass in the corpus to anthrum gaster , fungating & ulcerative type with destroyed mucosal pattern

Imaging studies

USG studies : well-defined or polylobulated solid masses. Cystic changes,necrosis, or calcifications. image quality is often degraded by intervening bowel gas USG studies : mass 4x10 cm and no abnormality in the other structures

CT Scan : important in the diagnosis and staging of GIST Detect multiple tumors and provide evidence of metastatic spread less aggressive GIST : < 5 cm, well-defined, round or oval, exophytic masses and homogeneous enhancement Aggressive GIST : irregular and lobulated margins, >10 cm, central necrosis, ulceration, and heterogeneous contrast enhancement CT Scan : solid mass 12.2 x 9.4 cm in the gastric wall , irregular, heterogenous contrast enhancement , no metastatic to adjacent organs.

Biopsy
GIST tend to fall into three categories of morphology epitheloid, spindle cell, or mixed The diagnosis of GIST relies on histopatology and imunohistochemistry CD 117 is generally positive

FNAB with CT scan guiding: spindle mesenchymal tumor Biopsy durante op : adenocarcinoma dd. Stromal tumor Imunohistochemistry: CD 117 positive

Risk Classification in GIST

Kim, 2005

Mass 12.2x 9.4 cm , mitosis > 20/10 HPF high risk

Therapy
Surgical : definitive therapy 1. Complete resection : recurrent < 2. Incomplete resection : locally advanced or metastatic disease Medical : 1. conventional radiotherapy and chemotherapy are ineffective 2. Imatinib mesylate is recommended as adjuvant therapy

This patient underwent operation : tumor was unresectable, planning for receive Imatinib mesylate but the patient refused

Prognosis

1-YSR metastatic disease: 70% 2-YSR metastatic disease : 47% 5-YSR Post Resection : 30-65% Median Survival Time with Imatinib: > 36 months Recurrence Rate 40-52%

This patient was classified in to high risk GIST, metastatic disease and unresectable tumor. The prognosis was poor.

Summary
We have reported a patient with Gastrointestinal stromal tumor with liver metastases The diagnosis of GIST based on histopathology and imunohistochemistry examination The patient underwent operation but the tumor was unresectable. Jejunostomy was done for enteral feeding The patient was classified in to high risk GIST the prognosis was poor

THANK YOU

Kim,2005

Kim,2005

Rubin,2007

Rubin,2007

Rubin,2007

Rubin,2007

Chemical structure of Imatinib mesylate

Rubin,2007

Rubin,2007

Rubin,2007

Rubin,2007

Rubin,2007

Rubin,2007

Miettinen,2006

Miettinen, 2006

Immunohistochemical differential diagnosis of the most important mesenchymal tumor of the GI tract

Miettinen, 2003

Miettinen, 2003

Demetri, 2004

Normal and Mutated KIT and the Action of Imatinib

Demetri, 2004