Giant liver hemangioma in patient with ileal gastrointestinal stromal tumor/Veliki hemangiom jetre kod pacijenta sa gastrointestinalnim stromalnim tumorom ileuma.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. The term GIST defines a unique group of mesenchymal neoplasms that are distinct from true smooth muscle and neural tumors .
GISTs represent more than 80% of all mesenchymal tumors found in the gastrointestinal tract, though they account only for approximately 3% of all gastrointestinal malignancies [2, 3]. It has now been well established that GISTs arise from the interstitial cells of Cajal, which are specialized pacemaker cells located around the myenteric plexus of the gut wall, particularly in the stomach and small intestine .
The clinical manifestations of GISTs depend on the location and size of the tumors and are often nonspecific [5, 6]. Although the literature suggests that most GISTs are symptomatic, tumors might be incidentally found at examinations performed for other indications. Case reports that can be found in the literature describing symptomatic GISTs generally represent patients with larger tumors that were symptomatic.
We present the case of a small intestinal GIST in a 40-year-old man with associated giant liver tumor, exclusively presented with fever. These data can be important for efficient diagnosis and therapy of unusual and asymptomatic cases of this neoplasm.
A 40-year-old man was referred to our hospital with a 15-day history of fullness, fever (body temperature max 38 C degree) and discomfort in the right lower abdomen. No significant past medical history (one year before operation of left testicular hydrocele) was recorded.
On examination, the patient had a small spherical, painless, fluctuant mass of intestine palpable in the right lower abdomen. Hepatomegaly was diagnosed (2 cm below the right costal angle) with splenomegaly (1 cm below the left costal angle) and without ascites. There was a tumor in the skin of right abdomen measuring about 2 cm and a tumor in the skin of left arm measuring about 1 cm. Those tumors were strongly suspected to be neurofibromatosis but the definitive diagnosis was not investigated.
The patient had an elevated white blood cells count (WBC) (11.5 Rch 10*9/l), mild anemia (Hgb 113.1 cl g/l, MCV 84 fl), and mild thrombocytosis (568 ch 10*9/l). Signs of inflammation were positive: erythrocyte sedimentation rate (ESR) 109, fibrinogen 6.9 g/l, C-reactive protein 249 mg/l, and procalcitonin was increased 0.622 ng/ml. Necrosis of hepatocytes was present (aspartate aminotransferase/AST/ 99 IU/l, alanine aminotransferase/ALT/ 235 IU/l, gama GT 114 IU/l, alkaline phospathase 141 U/l). Iron (Fe) level was decreased to 2.6 umol/l, Ferritin amount was increased to 782 ug/l. Blood proteins were normal but albumin was decreased to 30 g/l, and globulin was increased to 49 g/l. All other laboratory data, including tumor markers (alpha-fetoprotein (AFP), cancer antigen (CA) 19-9 and carcinoembryonic antigen (CEA)), immunology and virusology findings were within normal limits. Hemoculture was positive (Staphylococcus sp., coagulase neg. sensitive to ceftriaxsone and other cephalosporin and aminoglygosides), and uroculture was negative.
Ultrasound scan showed hepatomegaly (measuring 190 mm in the right lobe) and splenomegaly (measuring 160 mm). A tumor was found in the right lobe of liver, not well-defined, hyper echoic in periphery and hypo and anechoic in the center, measuring 120x100x80 mm. Another small tumor adjacent to giant mass was hyper echoic, measuring 12x10 mm, ultrasound characteristics of liver hemangioma (Figure 1).
Computed tomography (CT) scan showed the mass in the liver with not well--defined margins, hyper signal intensity, and central area of necrosis (measuring 137x102x113 mm) in VII and VIII segment of the liver. Two hyper signal intensity tumors close to mass were found in the liver. CT scan revealed few lymphatic nodules in hilus of the liver, measuring about 12 mm each.
Magnetic resonance imaging (MRI) showed solid multi centric tumor clearly defined (measuring 117x80x117 mm), low signal intensity on T1--weighted images, and high signal intensity on T2--weighted images. Another small tumor was found with the same characteristic close to the biggest one, measuring 16x13 mm. The radiologist described the change to be like an infected parasite cyst, infected hemangioma or primary tumor in the liver.
In Clinical Center Serbia in Belgrade, the radiologist performed new contrast MRI and liver tumor was described as giant hemangioma. The surgeons opted for the exploratory laparotomy because the symptoms were persistent. After right subcostal and partial left subcostal laparotomy, a moving rough nodous tumor was found in the intestines. On intraoperative examination, frozen sections revealed mesenchymal cell tumor with unknown malignant potential. The complete excision of tumor was done as well as the resection of the local peritoneum and the further 40 mm of ileum with termino-terminal ileal anastomosis (TTA).
On gross examination, the excised intramural tumor node measured 48x38x35 mm in diameters, with predominant extramural growth. The tumor appeared somehow protuberant in luminal surface, with intact mucosa, and covered with hyperaemic and rough serosis. The cut surface of the tumor showed dark red color, with well-defined borders to adjacent tissue. Histopathologically, the tumor was of obvious mesenchymal origin; it was composed of proliferating spindle and epithelioid cells with a loose interlacing bundle pattern.
Tumor cells were primitive, ovoid-to-spindle or elongated in shape, dominantly with eosinophilic cytoplasm and ovoid or elongated nuclei, but without pronounced hyperchromasia and edema, partly with hypocellular areas. Pathological examination revealed generally low to moderate cellularity, low mitotic index of 1/50 high-power fields (HPF), low nuclear anaplasia and absence of necrosis.
Immunohistochemically, the tumor showed diffuse strong cytoplasmic immunoexpresion of c-KIT (CD117 antigen), but it was negative for CD34 antigen (myeloid stem cell antigen), alpha subunit of smooth muscle actin (SMA), desmin and S-100 protein. The tumor was diagnosed as a low risk intestinal GIST and presented to multidisciplinary team as a tumor with low malignant potential and low metastatic risk.
Postoperatively, the patient was treated by transfusion of deplasmatized erythrocytes and with antibiotics according to antibiogram. So far, the patient is well and there are no signs of relapse.
The multidisciplinary team of the Clinical Centre Serbia claimed that the tumor and local peritoneum was radically excided, concluding that the tumor was in T2 stage. The check-up MRI examination was without local recidivism, but the giant mass in the liver appeared abscessing or centrally necrotizing and/or hemorrhagic, suggesting giant necrotic hemangioma. Although the surgical resection of the tumor was proposed, the decision was made to follow-up the patient because of a high risk of surgical treatment.
According to literature data, this is one of a few described cases with fever and abscess in the tumor of the liver as the first manifestations of the GIST of intestine.
Gastrointestinal stromal tumors are usually solitary tumors. Approximately 60% of GISTs arise in the stomach, then in the small intestine (25-35%) and the colon and rectum (5-10%) [1,7]. True smooth muscle tumors tend to be predominantly in the esophagus. In rare cases, they develop outside of the gastrointestinal tract and have been reported in the mesentery, omentum, or retroperitoneum [1,7].
Gastrointestinal stromal tumors are generally found in adults over 40 years of age (their age ranging from 40 to 80 years), with average age of 60 years at presentation and a slightly male predominance. Similarly to the case reported hereby, GISTs are rarely seen in patients younger than 40 years; however, several cases have been reported in pediatric population .
Although some families with hereditary GISTs have been described, most cases are sporadic. The National Comprehensive Cancer Network (NCCN) Task Force Report 2007 reported GIST incidence to be approximately 14.5 per million people per year or at least 4,500-6,000 new cases per year in the United States .
More than 90% of GISTs result from gain-of-function mutations of the c-KIT/KIT proto-oncogene . KIT encodes for the transmembrane KIT receptor tyrosine kinase. Approximately 10% of GISTs result from mutations in the KIT-related kinase gene, platelet derived growth factor receptor alpha (PDGFRA) . A small percentage of GISTs are wild type, and some may also be part of familial syndromes such as von Recklinghausen neurofibromatosis (NF1) and the Carney triad (GIST, paraganglioma, and pulmonary chordoma) . Patients with neurofibromatosis type 1 (NF1) have an increased prevalence of GISTs. Classically, patients with NF1 have multiple small intestinal GISTs . A Swedish study reports a 500-fold increased incidence of GISTs in patients with NF1 .
More than 90% of GISTs stain positively for cKIT/CD117, (the current immunohistochemical marker of choice), which correlates with our immunohistochemical analysis. Suspected GIST tumors in which CD117 immunostaining is negative should be considered for molecular analysis for KIT or PDGFRA mutations in specialized laboratories .
Contrast-enhanced CT is the radiologic modality of choice for evaluating primary tumors and metastasis, as well as for assessing the efficacy of treatment and follow-up. Typically, the tumor appears as a well-circumscribed, hyper dense-enhancing mass closely associated with the stomach or small intestine growing in an extra luminal manner. The tumor often demonstrates a heterogeneous pattern secondary to underlying necrosis or intratumoral hemorrhage .
On MRI solid portions of tumors typically show low signal intensity on T1-weighted images, intermediate to high signal intensity on T2weighted images. According to literature data, the marked high signal seen on T2-weighted MRI should be considered as a feature strongly indicating diagnosis of GIST .
The liver is the most common site of metastasis, both at the time of presentation and during relapse. It is seen in 49-65% of the cases . Different authors have described various appearances of liver metastasis. However, lesions appear similar to the primary mass in many cases. They are usually multiple, involve both lobes, and appear to be heterogeneous with peripheral enhancement.
Surgery remains the modality of choice for primary, localized, and resectable GIST. Specific tyrosine kinase inhibitors (TKIs), i.e. imatinib mesylate and, more recently, sunitinib malate have proven to be dramatically effective for unresectable, metastatic, and recurrent disease and have been approved by the United States Food Drug Administration for the abovementioned indications. Traditional cancer treatment modalities such as chemotherapy and radiotherapy have been found ineffective when treating GIST [17, 18].
As even several small GISTs have been shown to have metastatic potential, all GISTs are currently regarded as malignant unless proven otherwise. Tumor size and mitotic index are the two most important prognostic factors used for risk stratification of GIST . Tumor smaller than 5 cm and less of 5 mitoses per 50 high power fields, as it was the case in our patient, have low risk for metastasis .
The National Comprehensive Cancer Network Soft Tissue Sarcoma Group 2007 has recommended standard guidelines for the follow-up of patients with GISTs. Those with a complete resection of the tumor should be observed with a history and physical examination every 3-6 months for 5 years and then annually, along with abdominal/pelvic CTs every 3-6 months for 3-5 years and then annually. High-risk patients should be started on imatinib, and more trials are underway to address the issue.
Patients with incomplete resection, persistent gross disease (R2 resection), and metastatic disease should undergo physical examination, and abdominal/pelvic CT every 3-6 months. Less aggressive surveillance is acceptable for GISTs smaller than 2 cm and is up to the discretion of the managing physician . Our patient should be followed up in recommended time every 3-6 months.
Small intestine GIST tumor with liver abscess presentation was described in few articles [20-24]. Clinical presentation of bacteriemia and liver abscess associated with GIST which became infected was described. Streptococcus milleri was detected as an indicator of possible underlying gastrointestinal neoplasm . In a recent article, abscess liver nodules were negative for c-KIT and CD 34. The authors considered the possibility of liver metastasis into abscesses and, therefore, they administered imatinib mesylate to the patient .
On the other hand, mimicking cavernous liver angioma, as it was the case in our patient, associated with giant gastric GIST was described in one article .
According to literature, this is one of a few described cases in which fever and abscess in the tumor of the liver was the first manifestation of the gastrointestinal stromal tumors of intestine. The case report presents a gastrointestinal stromal tumor in a middle-aged patient with unique clinical features, so it could be very important in raising awareness of its timely detection in patients with atypical clinical symptoms and associated diseases that hinder its diagnosis.
Abbreviations CT --computed tomography GISTs --gastrointestinal stromal tumors c-KIT --CD117 antigen NF1 --neurofibromatosis type 1 MRI --magnetic resonance imaging PDGFRA --platelet derived growth factor receptor alpha
Rad je primljen 27. XI 2013.
Recenziran 10. XII 2013.
Prihvacen za stampu 18. XII 2013.
Written consent was obtained from the patient for publication of this case report.
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Vasilije ANTIC (1), Marjan MICEV (2), Danijela BASKIC (3) and Violeta MLADENOVIC (1)
Clinical Center Kragujevac, Kragujevac, Srbija, Department of Internal Medicine (1)
Clinical Center Serbia, Beograd, Srbija, Institute for Pathology (2)
Clinical Center Kragujevac, Kragujevac, Srbija, Center for Cadiology (3)
Corresponding Author: Asist. dr Vasilije Antic, Klinicki centar Kragujevac, 34000 Kragujevac, Svetozara Markovica 69, E-mail: firstname.lastname@example.org
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|Title Annotation:||Case report/Prikazi slucaja|
|Author:||Antic, Vasilije; Micev, Marjan; Baskic, Danijela; Mladenovic, Violeta|
|Article Type:||Case study|
|Date:||Jan 1, 2014|
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