Endocr Pathol DOI 10.1007/s12022-014-9350-7
Gastrointestinal Stromal Tumor of the Adrenal Gland: A Case Report and Review of the Literature Hussam Abou Al-Shaar & Shrouq Solimanie & Ayman Azzam & Tarek Amin & Ahmed Abu-Zaid
# Springer Science+Business Media New York 2014
Abstract Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract. The occurrence of these neoplasms ectopically outside the GI tract is extremely uncommon. Only one case of primary adrenal GIST has been reported in the literature. In this account, we report a second case of primary adrenal GIST in a 34-year-old male who presented with a 5-week history of gradually progressive left flank pain and early satiety. Whole-body positron emission tomography (PET)/computed tomography (CT) scan showed a 14×11 cm hypermetabolic 18fluorodeoxyglucose (FDG)-avid mass lesion involving the left adrenal gland and dorsal part of the left hemi-diaphragm. Biopsy of the lesion revealed tumor cells that are immunoreactive to CD-117 and CD-34 and negative to CD-31, S-100, cytokeratin, desmin, and vimentin, features characteristic of GIST. The patient was given imatinib, which drastically decreased his complaints with almost complete resolution of the tumor on his last follow-up radiographic images. Primary left adrenal GIST is an extremely rare neoplasm and can be confused with GISTs arising from the greater curvature of the stomach. Imatinib therapy is optimal in the management of these tumors.
Keywords Gastrointestinal stromal tumor . Extra-gastrointestinal stromal tumor . Adrenal gland . ?Greater curvature . Stomach . Imatinib H. Abou Al-Shaar : S. Solimanie : A. Abu-Zaid (*) College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia e-mail: [email protected] A. Azzam : T. Amin Oncology Center, King Faisal Specialist Hospital and Research, Riyadh, Saudi Arabia A. Azzam Faculty of Medicine, Alexandria University, Alexandria, Egypt
Introduction Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal, specialized cells in the autonomic nervous system of the intestine [1, 2]. These tumors account for the majority of gastrointestinal (GI) mesenchymal neoplasms [1, 3]. GISTs commonly affect adults with an equal male-tofemale distribution [4, 5]. Extra-gastrointestinal primary GISTs (EGISTs) rarely occur [6, 7]. To the best of our knowledge, the English medical literature describes only two patients with gastric GISTs presenting with left adrenal mass and a single patient with primary adrenal GIST [6, 7]. Herein, we report the second ever primary EGIST arising from the adrenal gland. In addition, a literature review on GISTs is presented.
Case Report A 39-year-old otherwise healthy male patient was referred from a primary care hospital for further evaluation and management of a left adrenal mass. Patient had a 5-week history of gradually progressive left flank pain and early satiety. Patient denied any history of trauma and systemic review was unremarkable. Physical examination was notable for a moderately enlarged and tender mass involving the left flank region. All laboratory tests including complete blood count, renal, bone, hepatic, coagulation, and tumor profiles were normal. Whole-body positron emission tomography (PET)/computed tomography (CT) scan showed a 14×11 cm hypermetabolic 18fluorodeoxyglucose (FDG)-avid mass lesion involving the left adrenal gland and dorsal part of the left hemidiaphragm (Fig. 1). There was no evidence of distant metastasis. In consideration of a neoplastic lesion, an ultrasound-guided core-needle biopsy was recommended. Histopathological
Endocr Pathol Fig. 1 Whole-body positron emission tomography (PET)/ computed tomography (CT) scan. The scan showed a 14×11 cm hypermetabolic 18 fluorodeoxyglucose (FDG)avid mass lesion involving the left adrenal gland and dorsal part of the left hemi-diaphragm
analysis showed a spindle-cell neoplasm (Fig. 2a). Immunohistochemical analysis showed positive immunoreactivity to CD-117 (Fig. 2b) and CD-34 (Fig. 2c) and negative immunoreactivity to CD-31, S-100, cytokeratin, desmin, and vimentin. The final pathological diagnosis was consistent with primary GIST of the left adrenal gland. Surgical resection was advised; however, patient refused. Subsequently, patient was offered imatinib (a tyrosine-kinase inhibitor). Following therapy, a 3-month follow-up PET/CT scan showed almost complete resolution of the metabolic activity of the known left adrenal mass lesion (Fig. 3). Moreover, patient reported markedly reduced left flank symptoms.
Discussion GISTs are considered the most common mesenchymal neoplasms of the GI tract constituting 5 and ≤10 cm and no more than 5 mitoses per 50 HPFs [24, 36]. However, some authors deny the efficiency of these factors for EGISTs [38, 39]. Metastasis of GISTs to lymph nodes and skin is extremely rare. The most common sites of metastasis include, in a descending order of frequency, liver, peritoneum, lung, pleura, bones, and soft tissues [12]. Radiation and chemotherapy are generally ineffective with these tumors [3, 4, 9]. Surgical excision for localized resectable primary tumors, according to surgical oncology protocols, is considered the mainstay treatment for GISTs [8]. The resection should be carried out meticulously in order to avoid the risk of tumor rupture [4]. The resection should be complete with safe margins, due to high risk of recurrence [3, 13]. Owing to the extreme unlikelihood of lymph node involvement, lymph node dissection is not routinely required [4]. The role of imatinib mesylate has revolutionized the management of GISTs, especially with unresectable tumors. It has been proven that imatinib can tremendously decrease tumor size and recurrence rate [4, 9, 12, 13, 40]. The drug is generally safe and well tolerated, yet some side effects have been reported including, diarrhea, edema, skin rashes, and myalgia [8]. Moreover, resistance to the drug has also been recorded [7, 8, 40, 41]. It is estimated that 10 % of patients will develop resistance to imatinib mesylate within 3–6 months of therapy and 40–50 % will develop resistance within 24 months of therapy [40]. Those patients may benefit and respond well to sunitinib (a new tyrosine-kinase inhibitor) [42]. Our patient responded to imatinib therapy with a drastic decrease of his symptoms and almost complete resolution of the tumor on radiographic imaging.
Conclusion EGIST arising primarily from the left adrenal gland is extremely rare. The proximity of the left adrenal gland to the greater curvature can mislead the physician to reach accurate diagnosis. Radiological investigations and immunohistochemical staining of the biopsied lesion are essential to delineate the tumor and aid in reaching the diagnosis. Imatinib therapy for GISTs and EGISTs shows promising results in the management of these neoplasms with complete resolution of both symptoms and tumor as seen in our patient.
Conflict of Interest The authors declare no conflict of interest regarding the production of this article. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.
References 1. Laurini JA, and Carter JE. Gastrointestinal stromal tumors: a review of the literature. Arch Pathol Lab Med, 2010. 134(1): p. 134–141. 2. Miettinen M, and Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med, 2006. 130(10): p. 1466–1478. 3. Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet, 2009. 373(9669): p. 1097–1104. 4. Rammohan A, Sathyanesan J, Rajendran K, et al. A gist of gastrointestinal stromal tumors: A review. World J Gastrointest Oncol, 2013. 5(6): p. 102–112. 5. Sandrasegaran K, Rajesh A, Rydberg J, Rushing DA, Akisik FM, and Henley JD. Gastrointestinal stromal tumors: clinical, radiologic, and pathologic features. AJR Am J Roentgenol, 2005. 184(3): p. 803–811. 6. Chung SD, Chueh JS, and Yu HJ. Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors. World J Gastroenterol, 2012. 18(1): p. 96–98. 7. Sereg M, Buzogány I, Gonda G, et al. Gastrointestinal stromal tumor presenting as a hormonally inactive adrenal mass. Endocrine, 2011. 39(1): p. 1–5. 8. Asija AP, Mejia AV, Prestipino A, and Pillai MV. Gastrointestinal Stromal Tumors: A Review. Am J Ther, 2013. In press. 9. Patil DT, and Rubin BP. Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Pathol Lab Med, 2011. 135(10): p. 1298–1310. 10. Demetri GD, von Mehren M, Antonescu CR, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw, 2010. 8 Suppl 2:S141; quiz S42-44 11. Chandramohan K, Agarwal M, Gurjar G, et al. Gastrointestinal stromal tumour in Meckel’s diverticulum. World J Surg Oncol, 2007. 5: p. 50. 12. Bano S, Puri SK, Upreti L, Chaudhary V, Sant HK, and Gondal R. Gastrointestinal stromal tumors (GISTs): an imaging perspective. Jpn J Radiol, 2012. 30(2): p. 105–115. 13. Tan CB, Zhi W, Shahzad G, and Mustacchia P. Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol, 2012. 2012: p. 595968. 14. Laperouse P, Raines D, Diamond K, et al. Gastrointestinal stromal tumors: a case report and review of the literature. J La State Med Soc, 2008. 160(3): p. 128–133; quiz 134. 15. Reichardt P, Hogendoorn PC, Tamborini E, et al. Gastrointestinal stromal tumors I: pathology, pathobiology, primary therapy, and surgical issues. Semin Oncol. 2009. 36(4): p. 290–301. 16. Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol, 2005. 23(23): p. 5357–5364. 17. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol, 2004. 22(18): p. 3813–3825. 18. Miranda C, Nucifora M, Molinari F, et al. KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin Cancer Res, 2012. 18(6): p. 1769–1776. 19. Barnett CM, Corless CL, Heinrich MC. Gastrointestinal stromal tumors: molecular markers and genetic subtypes. Hematol Oncol Clin North Am, 2013. 27(5): p. 871–888. 20. Künstlinger H, Huss S, Merkelbach-Bruse S, et al. Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotypephenotype correlation and validation of a high-resolution melting assay for mutational testing. Am J Surg Pathol. 2013. 37(11): p. 1648–1659. 21. Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic,
Endocr Pathol
22.
23.
24.
25.
26.
27.
28.
29. 30.
immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol, 2006. 30(4): p. 477–489. Martín J, Poveda A, Llombart-Bosch A, et al. Deletions affecting codons 557–558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol, 2005. 23(25): p. 6190–6198. Lasota J, Dansonka-Mieszkowska A, Sobin LH, Miettinen M. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest, 2004. 84(7): p. 874–883. Miettinen M, Sobin LH, and Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol, 2005. 29(1): p. 52–68. Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer, 2006. 42(8): p. 1093–1103. Blanke CD, Rankin C, Demetri GD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol, 2008. 26(4): p. 626–632. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet, 2004. 364(9440): p. 1127–1134. Heinrich MC, Owzar K, Corless CL, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol, 2008. 26(33): p. 5360–5367. Ulusan S, and Koc Z. Radiologic findings in malignant gastrointestinal stromal tumors. Diagn Interv Radiol, 2009. 15(2): p. 121–126. Kim HC, Lee JM, Kim KW, et al. Gastrointestinal stromal tumors of the stomach: CT findings and prediction of malignancy. AJR, 2004. 183(4): p. 893–898.
31. Burkill GJ, Badran M, Al-Muderis O, et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology, 2003. 226(2): p. 527–532. 32. Nishida T, Kumano S, Sugiura T, et al. Multidetector CT of high risk patients with occult gastro intestinal stromal tumors. AJR, 2003. 180(1): p. 185–189. 33. Kim HC, Lee JM, Kim SH, et al. Primary gastrointestinal stromal tumors in the omentum and mesentery: CT findings and pathologic correlations. AJR, 2004. 182(6): p. 1463–1467. 34. Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol, 2004.183(6): p. 1619–1628. 35. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol, 2002. 33(5): p. 459–465. 36. Miettinen M, and Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol, 2006. 23(2): p. 70–83. 37. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res, 2001. 61: p. 8118–8121. 38. Showalter SL, Lloyd JM, Glassman DT, and Berger AC. Extragastrointestinal stromal tumor of the pancreas: case report and a review of the literature. Arch Surg, 2008. 143(3): p. 305–308. 39. Zhang W, Peng Z, and Xu L. Extragastrointestinal stromal tumor arising in the rectovaginal septum: report of an unusual case with literature review. Gynecol Oncol, 2009. 113(3): p. 399–401. 40. Gramza AW, Corless CL, and Heinrich MC. Resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumors. Clinical Cancer Research, 2009. 15(24): p. 7510–7518. 41. Wang WL, Conley A, Reynoso D, et al. Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor. Cancer Chemother Pharmacol, 2011. 67 (Suppl 1):S15–S24. 42. Rubin BP, Heinrich MC, and Corless CL. Gastrointestinal stromal tumour. Lancet, 2007. 369(9574): p. 1731–1741.
Gastrointestinal Stromal Tumor of the Adrenal Gland: A Case Report and Review of the Literature Hussam Abou Al-Shaar & Shrouq Solimanie & Ayman Azzam & Tarek Amin & Ahmed Abu-Zaid
# Springer Science+Business Media New York 2014
Abstract Gastrointestinal stromal tumors (GISTs) are rare neoplasms of the gastrointestinal (GI) tract. The occurrence of these neoplasms ectopically outside the GI tract is extremely uncommon. Only one case of primary adrenal GIST has been reported in the literature. In this account, we report a second case of primary adrenal GIST in a 34-year-old male who presented with a 5-week history of gradually progressive left flank pain and early satiety. Whole-body positron emission tomography (PET)/computed tomography (CT) scan showed a 14×11 cm hypermetabolic 18fluorodeoxyglucose (FDG)-avid mass lesion involving the left adrenal gland and dorsal part of the left hemi-diaphragm. Biopsy of the lesion revealed tumor cells that are immunoreactive to CD-117 and CD-34 and negative to CD-31, S-100, cytokeratin, desmin, and vimentin, features characteristic of GIST. The patient was given imatinib, which drastically decreased his complaints with almost complete resolution of the tumor on his last follow-up radiographic images. Primary left adrenal GIST is an extremely rare neoplasm and can be confused with GISTs arising from the greater curvature of the stomach. Imatinib therapy is optimal in the management of these tumors.
Keywords Gastrointestinal stromal tumor . Extra-gastrointestinal stromal tumor . Adrenal gland . ?Greater curvature . Stomach . Imatinib H. Abou Al-Shaar : S. Solimanie : A. Abu-Zaid (*) College of Medicine, Alfaisal University, P.O. Box 50927, Riyadh 11533, Saudi Arabia e-mail: [email protected] A. Azzam : T. Amin Oncology Center, King Faisal Specialist Hospital and Research, Riyadh, Saudi Arabia A. Azzam Faculty of Medicine, Alexandria University, Alexandria, Egypt
Introduction Gastrointestinal stromal tumors (GISTs) arise from the interstitial cells of Cajal, specialized cells in the autonomic nervous system of the intestine [1, 2]. These tumors account for the majority of gastrointestinal (GI) mesenchymal neoplasms [1, 3]. GISTs commonly affect adults with an equal male-tofemale distribution [4, 5]. Extra-gastrointestinal primary GISTs (EGISTs) rarely occur [6, 7]. To the best of our knowledge, the English medical literature describes only two patients with gastric GISTs presenting with left adrenal mass and a single patient with primary adrenal GIST [6, 7]. Herein, we report the second ever primary EGIST arising from the adrenal gland. In addition, a literature review on GISTs is presented.
Case Report A 39-year-old otherwise healthy male patient was referred from a primary care hospital for further evaluation and management of a left adrenal mass. Patient had a 5-week history of gradually progressive left flank pain and early satiety. Patient denied any history of trauma and systemic review was unremarkable. Physical examination was notable for a moderately enlarged and tender mass involving the left flank region. All laboratory tests including complete blood count, renal, bone, hepatic, coagulation, and tumor profiles were normal. Whole-body positron emission tomography (PET)/computed tomography (CT) scan showed a 14×11 cm hypermetabolic 18fluorodeoxyglucose (FDG)-avid mass lesion involving the left adrenal gland and dorsal part of the left hemidiaphragm (Fig. 1). There was no evidence of distant metastasis. In consideration of a neoplastic lesion, an ultrasound-guided core-needle biopsy was recommended. Histopathological
Endocr Pathol Fig. 1 Whole-body positron emission tomography (PET)/ computed tomography (CT) scan. The scan showed a 14×11 cm hypermetabolic 18 fluorodeoxyglucose (FDG)avid mass lesion involving the left adrenal gland and dorsal part of the left hemi-diaphragm
analysis showed a spindle-cell neoplasm (Fig. 2a). Immunohistochemical analysis showed positive immunoreactivity to CD-117 (Fig. 2b) and CD-34 (Fig. 2c) and negative immunoreactivity to CD-31, S-100, cytokeratin, desmin, and vimentin. The final pathological diagnosis was consistent with primary GIST of the left adrenal gland. Surgical resection was advised; however, patient refused. Subsequently, patient was offered imatinib (a tyrosine-kinase inhibitor). Following therapy, a 3-month follow-up PET/CT scan showed almost complete resolution of the metabolic activity of the known left adrenal mass lesion (Fig. 3). Moreover, patient reported markedly reduced left flank symptoms.
Discussion GISTs are considered the most common mesenchymal neoplasms of the GI tract constituting 5 and ≤10 cm and no more than 5 mitoses per 50 HPFs [24, 36]. However, some authors deny the efficiency of these factors for EGISTs [38, 39]. Metastasis of GISTs to lymph nodes and skin is extremely rare. The most common sites of metastasis include, in a descending order of frequency, liver, peritoneum, lung, pleura, bones, and soft tissues [12]. Radiation and chemotherapy are generally ineffective with these tumors [3, 4, 9]. Surgical excision for localized resectable primary tumors, according to surgical oncology protocols, is considered the mainstay treatment for GISTs [8]. The resection should be carried out meticulously in order to avoid the risk of tumor rupture [4]. The resection should be complete with safe margins, due to high risk of recurrence [3, 13]. Owing to the extreme unlikelihood of lymph node involvement, lymph node dissection is not routinely required [4]. The role of imatinib mesylate has revolutionized the management of GISTs, especially with unresectable tumors. It has been proven that imatinib can tremendously decrease tumor size and recurrence rate [4, 9, 12, 13, 40]. The drug is generally safe and well tolerated, yet some side effects have been reported including, diarrhea, edema, skin rashes, and myalgia [8]. Moreover, resistance to the drug has also been recorded [7, 8, 40, 41]. It is estimated that 10 % of patients will develop resistance to imatinib mesylate within 3–6 months of therapy and 40–50 % will develop resistance within 24 months of therapy [40]. Those patients may benefit and respond well to sunitinib (a new tyrosine-kinase inhibitor) [42]. Our patient responded to imatinib therapy with a drastic decrease of his symptoms and almost complete resolution of the tumor on radiographic imaging.
Conclusion EGIST arising primarily from the left adrenal gland is extremely rare. The proximity of the left adrenal gland to the greater curvature can mislead the physician to reach accurate diagnosis. Radiological investigations and immunohistochemical staining of the biopsied lesion are essential to delineate the tumor and aid in reaching the diagnosis. Imatinib therapy for GISTs and EGISTs shows promising results in the management of these neoplasms with complete resolution of both symptoms and tumor as seen in our patient.
Conflict of Interest The authors declare no conflict of interest regarding the production of this article. The authors have no personal financial or institutional interest in any of the drugs, materials, or devices described in this article.
References 1. Laurini JA, and Carter JE. Gastrointestinal stromal tumors: a review of the literature. Arch Pathol Lab Med, 2010. 134(1): p. 134–141. 2. Miettinen M, and Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med, 2006. 130(10): p. 1466–1478. 3. Dematteo RP, Ballman KV, Antonescu CR, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet, 2009. 373(9669): p. 1097–1104. 4. Rammohan A, Sathyanesan J, Rajendran K, et al. A gist of gastrointestinal stromal tumors: A review. World J Gastrointest Oncol, 2013. 5(6): p. 102–112. 5. Sandrasegaran K, Rajesh A, Rydberg J, Rushing DA, Akisik FM, and Henley JD. Gastrointestinal stromal tumors: clinical, radiologic, and pathologic features. AJR Am J Roentgenol, 2005. 184(3): p. 803–811. 6. Chung SD, Chueh JS, and Yu HJ. Laparoscopic resection of gastric gastrointestinal stromal tumors presenting as left adrenal tumors. World J Gastroenterol, 2012. 18(1): p. 96–98. 7. Sereg M, Buzogány I, Gonda G, et al. Gastrointestinal stromal tumor presenting as a hormonally inactive adrenal mass. Endocrine, 2011. 39(1): p. 1–5. 8. Asija AP, Mejia AV, Prestipino A, and Pillai MV. Gastrointestinal Stromal Tumors: A Review. Am J Ther, 2013. In press. 9. Patil DT, and Rubin BP. Gastrointestinal stromal tumor: advances in diagnosis and management. Arch Pathol Lab Med, 2011. 135(10): p. 1298–1310. 10. Demetri GD, von Mehren M, Antonescu CR, et al. NCCN Task Force report: update on the management of patients with gastrointestinal stromal tumors. J Natl Compr Canc Netw, 2010. 8 Suppl 2:S141; quiz S42-44 11. Chandramohan K, Agarwal M, Gurjar G, et al. Gastrointestinal stromal tumour in Meckel’s diverticulum. World J Surg Oncol, 2007. 5: p. 50. 12. Bano S, Puri SK, Upreti L, Chaudhary V, Sant HK, and Gondal R. Gastrointestinal stromal tumors (GISTs): an imaging perspective. Jpn J Radiol, 2012. 30(2): p. 105–115. 13. Tan CB, Zhi W, Shahzad G, and Mustacchia P. Gastrointestinal stromal tumors: a review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol, 2012. 2012: p. 595968. 14. Laperouse P, Raines D, Diamond K, et al. Gastrointestinal stromal tumors: a case report and review of the literature. J La State Med Soc, 2008. 160(3): p. 128–133; quiz 134. 15. Reichardt P, Hogendoorn PC, Tamborini E, et al. Gastrointestinal stromal tumors I: pathology, pathobiology, primary therapy, and surgical issues. Semin Oncol. 2009. 36(4): p. 290–301. 16. Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol, 2005. 23(23): p. 5357–5364. 17. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol, 2004. 22(18): p. 3813–3825. 18. Miranda C, Nucifora M, Molinari F, et al. KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin Cancer Res, 2012. 18(6): p. 1769–1776. 19. Barnett CM, Corless CL, Heinrich MC. Gastrointestinal stromal tumors: molecular markers and genetic subtypes. Hematol Oncol Clin North Am, 2013. 27(5): p. 871–888. 20. Künstlinger H, Huss S, Merkelbach-Bruse S, et al. Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotypephenotype correlation and validation of a high-resolution melting assay for mutational testing. Am J Surg Pathol. 2013. 37(11): p. 1648–1659. 21. Miettinen M, Makhlouf H, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic,
Endocr Pathol
22.
23.
24.
25.
26.
27.
28.
29. 30.
immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol, 2006. 30(4): p. 477–489. Martín J, Poveda A, Llombart-Bosch A, et al. Deletions affecting codons 557–558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors: a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol, 2005. 23(25): p. 6190–6198. Lasota J, Dansonka-Mieszkowska A, Sobin LH, Miettinen M. A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest, 2004. 84(7): p. 874–883. Miettinen M, Sobin LH, and Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol, 2005. 29(1): p. 52–68. Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer, 2006. 42(8): p. 1093–1103. Blanke CD, Rankin C, Demetri GD, et al. Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol, 2008. 26(4): p. 626–632. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet, 2004. 364(9440): p. 1127–1134. Heinrich MC, Owzar K, Corless CL, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol, 2008. 26(33): p. 5360–5367. Ulusan S, and Koc Z. Radiologic findings in malignant gastrointestinal stromal tumors. Diagn Interv Radiol, 2009. 15(2): p. 121–126. Kim HC, Lee JM, Kim KW, et al. Gastrointestinal stromal tumors of the stomach: CT findings and prediction of malignancy. AJR, 2004. 183(4): p. 893–898.
31. Burkill GJ, Badran M, Al-Muderis O, et al. Malignant gastrointestinal stromal tumor: distribution, imaging features, and pattern of metastatic spread. Radiology, 2003. 226(2): p. 527–532. 32. Nishida T, Kumano S, Sugiura T, et al. Multidetector CT of high risk patients with occult gastro intestinal stromal tumors. AJR, 2003. 180(1): p. 185–189. 33. Kim HC, Lee JM, Kim SH, et al. Primary gastrointestinal stromal tumors in the omentum and mesentery: CT findings and pathologic correlations. AJR, 2004. 182(6): p. 1463–1467. 34. Choi H, Charnsangavej C, de Castro Faria S, et al. CT evaluation of the response of gastrointestinal stromal tumors after imatinib mesylate treatment: a quantitative analysis correlated with FDG PET findings. AJR Am J Roentgenol, 2004.183(6): p. 1619–1628. 35. Fletcher CD, Berman JJ, Corless C, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol, 2002. 33(5): p. 459–465. 36. Miettinen M, and Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol, 2006. 23(2): p. 70–83. 37. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res, 2001. 61: p. 8118–8121. 38. Showalter SL, Lloyd JM, Glassman DT, and Berger AC. Extragastrointestinal stromal tumor of the pancreas: case report and a review of the literature. Arch Surg, 2008. 143(3): p. 305–308. 39. Zhang W, Peng Z, and Xu L. Extragastrointestinal stromal tumor arising in the rectovaginal septum: report of an unusual case with literature review. Gynecol Oncol, 2009. 113(3): p. 399–401. 40. Gramza AW, Corless CL, and Heinrich MC. Resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumors. Clinical Cancer Research, 2009. 15(24): p. 7510–7518. 41. Wang WL, Conley A, Reynoso D, et al. Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor. Cancer Chemother Pharmacol, 2011. 67 (Suppl 1):S15–S24. 42. Rubin BP, Heinrich MC, and Corless CL. Gastrointestinal stromal tumour. Lancet, 2007. 369(9574): p. 1731–1741.
