|Year : 2018 | Volume
| Issue : 2 | Page : 140-142
Discordant Primary Resistance to Imatinib Mesylate in the Same Individual and Splenic Involvement in Recurring Gastric Gastrointestinal Stromal Tumors: Assessment by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography
Preeti Fargose, Sandip Basu
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe; Homi Bhabha National Institute, Mumbai, Maharashtra, India
|Date of Web Publication||15-Mar-2018|
Dr. Sandip Basu
Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Jerbai Wadia Road, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Discordant primary resistance and response of the metastatic lesions in the same individual coupled with splenic involvement in gastrointestinal stromal tumors (GISTs) are relatively uncommon. We herein report such a case of recurring GIST of the stomach that presented with the involvement of spleen with 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) imaging documentation. Ultrasonography-guided fine needle aspiration cytology from the splenic and paravesical lesions demonstrated metastatic spindle cell tumor consistent with diagnosis of metastasis from GIST of the stomach. The splenic and the paravesical lesions appeared resistant to the conventional 400 mg of imatinib mesylate, while most other abdominopelvic metastatic lesions demonstrated good metabolic response on FDG-PET/CT, with the noteworthy findings of interlesional heterogeneity of the metastatic lesions in terms of differential primary response in the same individual.
Keywords: 18F-fluorodeoxyglucose-positron emission tomography/computed tomography, gastrointestinal stromal tumors, imatinib mesylate, splenic metastasis
|How to cite this article:|
Fargose P, Basu S. Discordant Primary Resistance to Imatinib Mesylate in the Same Individual and Splenic Involvement in Recurring Gastric Gastrointestinal Stromal Tumors: Assessment by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography. Indian J Nucl Med 2018;33:140-2
|How to cite this URL:|
Fargose P, Basu S. Discordant Primary Resistance to Imatinib Mesylate in the Same Individual and Splenic Involvement in Recurring Gastric Gastrointestinal Stromal Tumors: Assessment by Fluorodeoxyglucose-Positron Emission Tomography/Computed Tomography. Indian J Nucl Med [serial online] 2018 [cited 2022 Jan 20];33:140-2. Available from: https://www.ijnm.in/text.asp?2018/33/2/140/227497
| Introduction|| |
Molecularly targeted therapy, with imatinib mesylate, is beneficial in unresectable and advanced metastatic gastrointestinal stromal tumors (GISTs), as well as an adjuvant therapy after the resection of primary GISTs. The tumors have a highly variable clinical course, and recurrent disease sometimes develops despite curative treatment. The common metastatic sites are liver (65%), omentum, and peritoneum, and other reported metastatic sites include lungs, pleura, retroperitoneum, bone, and subcutaneous tissues. Reports of discordant response to metastasis to the spleen exist,, though relatively uncommon. Herein, we document such a case of recurring GIST of the stomach with 18 F-fluorodeoxyglucose positron emission tomography-computed tomography (18 F-FDG PET-CT) imaging documentation.
| Case Report|| |
A 55-year-old male patient diagnosed with gastric GIST and on molecularly targeted therapy with imatinib mesylate 400 mg daily was referred for 18 F-FDG PET-CT whole-body disease survey. There was a history of discontinuation of imatinib by himsel for 1 year with CT abdomen finding of increasing size of a mass lesion (5.7 cm × 11.6 cm × 7.6 cm) along the larger portion of greater curvature of stomach, extending anteromedially in close approximation to the liver and anterolaterally along lateral abdominal wall, following which wedge resection of the stomach was undertaken. Peroperatively, tumor was observed to infiltrate left lobe of the liver and greater omentum with histopathology was consistent with residual malignant GIST (histological response to prior imatinib was noted in 12% of tumor area) with omental deposits (spindle cell and epithelioid morphology). On immunohistochemistry, it was CD117 and CD34 positive with Mib-1-labeling index being 25%–30%. Mutational analysis on the primary tumor showed mutation in 31-bp heterozygous deletion spanning intron 10 and exon 11. Exons 9, 13, and 17 were of wild type. Thus, the lesions were positive for exon 11 KIT mutation. Thereafter, he was in disease-free state on regular follow-up for almost 2½ years.
Subsequently, he presented with CT-documented multiple heterogenous mass lesions in the left infradiaphragmaic, perisplenic region, along serosal surface of small bowel abutting anterosuperior surface of the urinary bladder, posterior surface of bladder abutting the rectum, peritoneum, and anterior abdominal wall with perisplenic fluid collection and was restarted on imatinib 400 mg daily. A follow-up CT showed resolution of peritoneal deposits and reduction in perisplenic collection of fluid, but there was an increase in size of surface splenic deposit to 41 mm and left pleural effusion, the cytology of pleural fluid being negative for malignancy. In view of overall good response to imatinib therapy at most sites, he was on the same dose with observation every 3 months. The recent ultrasonography (USG) of the abdomen and pelvis showed multiple hypoechoic lesions with central necrotic area in the spleen, largest measuring 4.2 cm × 4.3 cm and another ill-defined hypoechoic lesion in the pelvis on the right side, anterior to the urinary bladder. He was referred for FDG-PET/CT evaluation, which demonstrated multiple well-defined FDG avid lesions with central necrotic area in spleen, largest measuring approximately 4.4 cm × 4.6 cm maximum standardized uptake value (SUVmax) 10.61, and FDG avid ill-defined mass lesion on the right paravesical region with SUVmax 13.36 [Figure 1] and [Figure 2]. USG-guided fine needle aspiration cytology from these above-mentioned lesions showed metastatic spindle cell tumor consistent with diagnosis of metastatic GIST. The dose of imatinib was increased to 800 mg daily, to which he was noncompliant, hence started on sunitinib 37.5 mg daily, to which he showed disease progression, and was started on pazopanib. The last FDG-PET/CT showed stable disease since the start of pazopanib.
|Figure 1: Whole-body fluorodeoxyglucose positron emission tomography-computed tomography three-plane view. Multiple well-defined fluorodeoxyglucose avid splenic lesions with central necrosis are evident in [Figure 1] and [Figure 2] (largest measuring approximately 4.4 cm × 4.6 cm; maximum standardized uptake value – 10.61)|
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|Figure 2: Whole-body transaxial view of computed tomography and fused positron emission tomography-computed tomography transaxial images. Multiple well-defined fluorodeoxyglucose avid splenic lesions with central necrosis are evident in [Figure 1] and [Figure 2]; lower panel showing fluorodeoxyglucose avid ill-defined mass lesion also noted in the right paravesical region (maximum standardized uptake value – 13.36)|
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| Discussion|| |
GISTs comprise 0.1%–0.3% of all gastrointestinal tumors, with immunohistochemical defining features of CD117 and CD34 positivity. Tumor size and mitotic rate form key parameters in risk stratification schemes of GIST: tumors <2 cm and mitotic rate of <5/50 are equated with lower risk of recurrence; imatinib is recommended to high-risk patients (size >5 cm and mitotic rate >5/50) for 3 years for a better recurrence-free survival. Abdominal CT has been considered the imaging method of choice for staging and treatment monitoring of GISTs, but recently, the use of FDG PET-CT has been advocated as a noninvasive diagnostic tool in the management, particularly for early therapeutic response and whole-body assessment to imatinib mesylate treatment.,, The current definitive treatment of GIST is complete surgical resection. Imatinib mesylate, an oral tyrosine kinase inhibitor of KIT (85% associated with c-KIT mutations) and platelet-derived growth factor receptor alpha mutations (except for D842V), is now considered standard adjuvant therapy for tumors considered at high risk for recurrence and also indicated in neoadjuvant setting for locally advanced, unresectable tumors.,, With this agent and its congeners sunitinib and regorafenib (used in case of resistance to imatinib), survival and outcomes have vastly improved.,,
Reports of metastasis of GIST to the spleen are relatively uncommon. A review of peer-review literature yielded two reports of splenic metastasis. In the described report by Kim et al., splenic metastasis was reported in conjunction with that in the liver, greater omentum, and mesentery from a gastric primary. Kang et al. reported an unresectable gastric GIST at diagnosis that had invaded pancreas and spleen but was responsive to neoadjuvant imatinib mesylate (dose of 400 mg daily), which allowed surgical excision of residual disease. Our report had similarity from the point that it was also from gastric primary and had multiple sites of involvement, though the splenic lesions appeared resistant to the conventional dose (400 mg) of imatinib, while other abdominopelvic lesions showed good metabolic response on FDG-PET/CT.
| Conclusion|| |
The learning points from the presented case are as follows: (a) the noteworthy finding in the present case was that in the same individual, interlesional heterogeneity between metastatic lesions is possible and this could lead to differential response to administered therapy; (b) metastasis to the unusual sites from solid tumors is often encountered in clinical practice; herein, uncommon splenic metastasis from GIST is presented with FDG-PET/CT documentation.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]