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MINI SYMPOSIUM: STROMAL TUMOR
Year : 2013  |  Volume : 50  |  Issue : 1  |  Page : 41-45
 

Primary extragastrointestinal stromal tumors: A clinicopathological and immunohistochemical study-A tertiary care center experience


1 Department of Pathology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh 517 507, India
2 Department of Surgical Oncology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh 517 507, India
3 Department of Surgical Gastroenterology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh 517 507, India

Date of Web Publication20-May-2013

Correspondence Address:
R Patnayak
Department of Pathology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh 517 507
India
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Source of Support: Patnayak R,Jena A,Parthasarathy S,Durgaprasad P,Reddy MK,Chowhan AK,Rukhamangadha N,Phannendra BV.., Conflict of Interest: None


DOI: 10.4103/0019-509X.112298

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 » Abstract 

Background: Extra gastrointestinal stromal tumors (EGIST) are uncommon compared to their gastrointestinal counterparts. EGISTs involve omentum, mesentery, retroperitoneum, pancreas, and pelvis. Materials and Methods: Ten EGISTs were analyzed in this study from January 1995 to November 2011. They were analyzed with respect to clinical features, imageological, histopathological, and immunohistochemical findings. The immunohistochemical stains used were Smooth muscle actin (SMA), Desmin, S-100 protein, CD34 and CD-117. Results: There was slight female preponderance with wide age range. Four of the tumors were in retroperitoneum, three in mesentery, and two in omentum and one in pelvis. Histopathologically majority were spindle cell tumors. Immunohistochemically CD117 was consistently positive followed by CD34. Smooth muscle actin was positive in eight cases, S-100 protein and desmin were positive in two cases each. Conclusion: EGISTs are rare and should be considered in the differential diagnosis of the mesenchymal tumors and immunohistochemistry helps to confirm the diagnosis. Further study with better follow-up is desired to characterize these uncommon tumors.


Keywords: CD34, CD117, extra gastrointestinal stromal tumors, mesentery, omentum, retroperitoneum


How to cite this article:
Patnayak R, Jena A, Parthasarathy S, Prasad P D, Reddy M K, Chowhan A K, Rukamangadha N, Phaneendra B V. Primary extragastrointestinal stromal tumors: A clinicopathological and immunohistochemical study-A tertiary care center experience. Indian J Cancer 2013;50:41-5

How to cite this URL:
Patnayak R, Jena A, Parthasarathy S, Prasad P D, Reddy M K, Chowhan A K, Rukamangadha N, Phaneendra B V. Primary extragastrointestinal stromal tumors: A clinicopathological and immunohistochemical study-A tertiary care center experience. Indian J Cancer [serial online] 2013 [cited 2020 Jun 5];50:41-5. Available from: http://www.indianjcancer.com/text.asp?2013/50/1/41/112298



 » Introduction Top


Mesenchymal tumors originating from the wall of the gastrointestinal tract have contributed to fascinating literature worldwide regarding their controversial histogenesis. Most common mesenchymal tumor arising in the gastrointestinal tract is gastrointestinal stromal tumor (GIST). [1],[2],[3],[4],[5],[6],[7] Apart from gastrointestinal tract, GISTs that involve omentum, mesentery and retroperitoneum are commonly known as extra gastrointestinal stromal tumors (EGISTs). According to Armed Forces Institute of Pathology, EGISTs are rather uncommon compared to their gastro-intestinal counterpart. [8],[9],[10],[11],[12],[13],[14] Though there are many studies regarding various aspects of GISTs, yet primary EGISTs literature are limited. [14],[15],[16],[17],[18],[19],[20],[21],[22] Majority of GISTs show somatic mutation of CD117. [15],[16],[17] In EGISTs the immunohistochemical findings are similar to that of GISTs. [19] In the present study, we present the clinicopathological and immunohistochemical analysis of 10 EGISTs.


 » Materials and Methods Top


In this study from January 1995 to November 2011, all cases of GISTs diagnosed histopathologically were retrieved from the archives of Department of pathology. Clinical data and follow-up information were obtained from the medical records. Tumors originating from the gastrointestinal tract (GIT) were excluded. Hematoxylin and eosin stained slides were reviewed in each case. Immunohistochemistry was performed on formalin fixed, paraffin embedded sections using the super sensitive polymer Horse radish peroxidase method. Appropriates controls were included. After application of prediluted antibodies, immunoreactivity was visualized using 3,3-di-amino benzidine tetrachloride as chromogen. The immunohistochemical stains used were Smooth muscle actin (SMA), Desmin, S-100 protein, CD34 and CD-117. All these markers were from Biogenex. Tumors were considered immunoreactive if more than 10% of the tumor cells stained for the antigen. [19]


 » Results Top


Out of the total 62 cases of mesenchymal tumors, 52 were of gastrointestinal origin. So, the study comprised of ten cases located extragastrointestinally. There were six females and four males in the study group. Age range was wide (23-71 years) with a mean age of 50.6 year. Location wise four of the tumors were in retroperitoneum, three in mesentery, two in omentum and one in pelvis. Data collected from the medical records show that preoperative investigations such as endoscopy, computerized tomography (CT) scans and even intraoperative finding could not suggest possible gastrointestinal origin in these tumors. The case of pelvic EGIST also did not show any evidence of uterine origin [Figure 1]. All these patients were symptomatic with pain abdomen being the commonest presentation. Gross examination revealed cystic degeneration in almost all the cases [Figure 2]. Size of the tumors was variable. Barring two mesenteric tumors, all the tumors were more than 10 cm in size. Histopathologically majority were exhibiting spindle cell morphology [Figure 3] with exception of two retroperitoneal tumors which showed the dual morphology of spindle and epithelioid cells. Mitotic activity was variable. Necrosis was observed in six cases [Table 1].
Table 1: Extragastrointestinal stromal tumors: Clinicopathological features

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Figure 1: Computerized tomography scan of pelvic GIST: Well defined soft tissue mass lesion measuring 10 × 9 cm2 in the pelvis

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Figure 2: Gross appearance of EGIST of mesentery

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Figure 3: Microphotograph showing criss-cross arrangement of spindle cells (H and E ×20)

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Immunohistochemically CD117 was positive in all the cases [Figure 4] followed by CD34 in eight (80%). Smooth muscle actin was positive in eight (80%), S-100 protein and desmin were positive in two cases (20%) each [Table 2].
Figure 4: Microphotograph showing diffuse staining for immunohistochemical marker CD117 (IHC ×40).

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Table 2: Immunohistochemical features of primary extragastrointestinal stromal tumors

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Follow-up data were available in only six cases. Two retroperitoneal tumors were treated with imatinib mesylate after the diagnosis of EGIST, but unfortunately these patients discontinued the treatment due to poor financial conditions. These two patients presented with recurrence at the end of one year. The case of pelvic EGIST also discontinued the treatment and was disease free for 18 months after which she was lost for follow-up. Other two cases were quite recent and had follow-up of only two months. One case of omental EGIST succumbed to illness in the postoperative period.


 » Discussion Top


GISTs are mesenchymal tumors, originating primarily from interstitial cells of Cajal or related stem cell-like precursors, the majority of which are c-KIT (CD117) positive. [16],[17],[18]

They occur most frequently in the stomach followed by jejunum and ileum, colon, rectum and esophagus. [23] Primary EGISTs are exceedingly rare. They usually present as enlarging masses of variable duration in adults. Majority are located in the omentum or mesentery, other locations are retroperitoneum, pelvis, pancreas, etc. [8],[9],[10] In our study of 10 cases majority were located in the retroperitoneum. These tumors tend to be large, most measure more than 10 cm at the time of detection. [19] Gross appearance of EGISTs varies from firm, fleshy gray-red masses to cystic ones. They lack the whorled appearance of the conventional smooth muscle tumors. Cystic change is seen in majority, associated with extensive hemorrhage or necrosis. In our study group except two mesenteric tumors all others were more than 10 cm in size and exhibited cystic changes. Microscopically EGISTs exhibit epithelioid, spindle cell pattern or combination of both patterns. In our study group two retroperitoneal tumors showed admixture of both spindle and epithelioid pattern. Sometimes tumors with epithelioid pattern show prominent vacuolation giving signet ring like appearance whereas tumors with spindled cell pattern resemble smooth muscle tumors. The cells of EGISTs usually have a short, fusiform shape arranged in short ill-defined fascicles. Immunohistochemical characteristics of EGISTs are similar to GISTs, the majority of both having mutually exclusive gain-of-function KIT/ platelet-derived growth factor receptor-alpha (PDGFRA) mutations. [7],[19] Another recent marker, DOG1 (discovered on GIST-1), is expressed in GISTs irrespective of KIT or PDGFRA mutation status. [23] However, we have not done markers like PDGFRA or DOG-1 in these cases. Along with CD117, CD 34 is also expressed by majority of the EGISTs. [19] Our findings were similar.

The literature regarding primary EGISTs are sparse ,as majority are case reports. [9],[10],[14],[21],[22] Reith et al. in one of the largest study described EGISTs in patients with a mean age of 58 years with female preponderance. [18] Compared to this, the mean age of patients in our study is slightly lower at 50.6 with slight female preponderance. The chief complaint of our patients was pain abdomen. Majority of EGIST in our study group were in retroperitoneum in contrast to Reith et al where intra-abdominal EGISTs constituted a majority. The large size of tumors and the cystic change as described by Reith et al. are also noted in our cases. In our study we have also encountered mostly spindle celled EGISTs and immunohistochemistry showed high percentage of CD117 and CD34 positivity. Other markers like SMA, desmin and S-100 protein also showed higher percentage of positivity in our study compared to Reith et al. [19] Majority of our patients discontinued treatment due to poor financial condition .With the limited follow up available in six cases ranging from 2 to 18 months , two patients presented with recurrence at the end of 12 months.

Miettinen et al, are of the opinion that the occurrence of CD117-positive tumors outside the gastrointestinal tract advocates against an origin of EGISTs exclusively from the interstitial cells of Cajal. [20] But Goh et al, suggested that most, if not all, cases of EGISTs are likely to represent mural GISTs with extensive extramural growth with eventual loss of contact with the muscle layer of the gut. [21] However none of our cases exhibited the connection with the GIT histopathologically. The intraoperative findings also did not suggest otherwise.

EGISTs which are more likely to metastasize have high cellularity, mitotic figures more than 2 per 50 high power fields and any amount of coagulative necrosis. [19] According to Miettinen et al, omental lesions are associated with a better prognosis compared to mesenteric lesions. [20]

The main differential histopathological diagnoses which were considered in EGISTs were fibromatosis, smooth muscle tumors, neural tumors and malignant fibrous histiocytomas (MFH). The distinction from fibromatosis is made mainly based on histopathology findings. In fibromatosis cellularity is low and it is composed of spindle cells within a collagenous stroma. Necrosis and mitotic activity is not seen in fibromatosis. Smooth muscle tumors and neural tumors are differentiated from EGISTs on the basis of both morphology and immunohistochemistry. All these tumors are negative for CD117. [22] Similarly MFH usually exhibits typical histological features of fibrohistiocytic tumor with pleomorphism.

Nearly half of EGISTs patients develop metastases or die of their tumors. Because of this reason, these tumors should be considered as highly aggressive and treated like high grade intraabdominal sarcoma. [19]

EGISTs are rare and should be considered in the differential diagnosis of the mesenchymal tumors and immunohistochemistry helps to confirm the diagnosis. In our country, poor financial status of patients put a hindrance in the beneficial effects of targeted therapy. Further study with better follow-up is definitely required to characterize these uncommon tumors.

 
 » References Top

1.Miettinen M, Hala M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the jejunum and ileum. A clinicopathological, immunohistochemical and molecular genetics study of 906 cases before imatinib with long term follow up. Am J Surg Pathol 2006;30:477-89.  Back to cited text no. 1
    
2.Miettinen M, Lasota J, Sobin LH. Gastrointestinal stromal tumors of the stomach in children and growing adults. A clinicopathological, immunohistochemical and molecular genetics study of 44 cases with long term follow up and review of literature. Am J Surg Pathol 2005;29:1373-81.  Back to cited text no. 2
    
3.Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Esophageal stromal tumors - A clinicopathological, immunohistochemical and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol 2000;24:211-22.  Back to cited text no. 3
    
4.Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach - A clinicopathological, immunohistochemical and molecular genetic study of 1765 cases with long term follow up. Am J Surg Pathol 2005;29:52-98.  Back to cited text no. 4
    
5.Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Gastrointestinal stromal tumors and leiomyosarcomas in the colon. A clinicopathological, immunohisto-chemical and molecular genetic study of 44 cases. Am J Surg Pathol 2000;24:1339-92.  Back to cited text no. 5
    
6.Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J. Gastrointestinal stromal tumors, intramural leiomyomas and leiomyosarcomas in the rectum and anus - A clinicopathological, immunohistochemical and molecular genetic study of 144 cases. Am J Surg Pathol 2001;25:1121-33.  Back to cited text no. 6
    
7.van der Zwan SM, DeMatteo RP. Gastrointestinal stromal tumor: 5 years later. Cancer 2005;104:1781-8.  Back to cited text no. 7
    
8.Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ. Prognosis of gastrointestinal smooth -muscle (stromal) tumors. Am J Surg Pathol 1999;23:82-7.  Back to cited text no. 8
    
9.Harindhanavudhi T, Tanawuttiwat T, Pyle J, Silva R. Extra-gastrointestinal stromal tumor presenting as hemorrhagic pancreatic cyst diagnosed by EUS-FNA. JOP 2009;10:189-91.  Back to cited text no. 9
    
10.Jindal G, Rastogi R, Kachhawa S, Meena GL. CT findings of primary extra-intestinal gastrointestinal stromal tumor of greater omentum with extensive peritoneal and bilateral ovarian metastases. Indian J Cancer 2011;48:135-7.  Back to cited text no. 10
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11.Jain A, Dubashi B, Mangaladevi, Chandra SS, Halanaik D. Mesentric gastrointestinal stromal tumor with bone metastases. Indian J Cancer 2011;48:383-4.  Back to cited text no. 11
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12.Miettinen M, Lasota J. Gastrointestinal stromal tumors -definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 2001;438:1-12.  Back to cited text no. 12
    
13.De Mates RP, Lewis JJ, Lewing D, Mudon SS, Woodrnff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: Recurrence patterns and prognostic factors for survival. Annal Surg 2000;231:51-8.  Back to cited text no. 13
    
14.Gowrishankar S. Epithelioid omental extragastrointestinal stromal tumor: Report of a case. Indian J Pathol Microbiol 2011;54:618-9.  Back to cited text no. 14
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15.Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Hum Pathol 2002;33:459-65.  Back to cited text no. 15
    
16.Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998;152:1259-69.  Back to cited text no. 16
    
17.Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-80.  Back to cited text no. 17
    
18.Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): Definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol 2003;54:3-24.  Back to cited text no. 18
    
19.Reith J, Goldblum JR, Weiss SW. Extragastrointestinal (soft tissue) stromal tumors: An analysis of 48 cases with emphasis on histologic predictors of outcome. Mod Pathol 2000;13:577-85.  Back to cited text no. 19
    
20.Miettinen M, Monihan JM, Sarlomo-Rikala M, Kovatich AJ, Carr NJ, Emory TS, et al. Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: Clinicopathologic and immunohistochemical study of 26 cases. Am J Surg Pathol 1999;23:1109-18.  Back to cited text no. 20
    
21.Goh BK, Chow PK, Kesavan SM, Yap WM, Chung YF, Wong WK. A single-institution experience with eight CD117-positive primary extragastrointestinal stromal tumors: Critical appraisal and a comparison with their gastrointestinal counterparts. J Gastrointest Surg 2009;13:1094-8.  Back to cited text no. 21
    
22.Gupta N, Mittal S, Lal N, Misra R, Kumar L, Bhalla S. A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis to the cervix uteri. World J Surg Oncol 2007;5:137.  Back to cited text no. 22
    
23.West R, Corless C, Chen X, Rubin B, Subramanian S, Montgomery K, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004;165:107-13.  Back to cited text no. 23
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]

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