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ORIGINAL ARTICLE Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 2  |  Page : 271-275
Gastrointestinal stromal tumors: Cytomorphologic spectrum in fine needle aspiration smears


Department of Pathology, Sir Ganga Ram Hospital, Rajinder Nagar, Delhi-110 060, India

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Date of Web Publication12-Jun-2010
 

   Abstract 

Objective: To study the variation in the cytologic features of gastrointestinal stromal tumors (GISTs) at different sites targeted by different modalities. Study design: Cytologic smears of 9 cases of gastrointestinal stromal tumors were reviewed with their histopathologic follow-up. Immuno-cytochemistry was performed where possible. Results: The study includes eight males and one female patient with an age range of 42 to 71 years. There were four classical cases of gastrointestinal stromal tumors that showed tight cellular bundles and fascicles of slender spindle cells with scant cytoplasm. The cytological features of three recurrent and one malignant case included moderately to markedly pleomorphic, plump spindle to ovoid cells with variable chromatin pattern and variable pale blue to vacuolated cytoplasm, present in loose clusters and singly. There was one case with classical gastrointestinal stromal tumor cytology but myxoid stroma. All other cases were confirmed with either CD117 immunostain and/or histopathology. Benign mucosal fragments from stomach or duodenal mucosa were observed in smears obtained by endoscopic ultrasound - fine needle aspiration (EUS FNA). Conclusion: The variability in cytologic features in GIST implies that a diagnosis of gastrointestinal stromal tumor should be rendered on cytology only in conjunction with immune-cytochemistry result of CD117.

Keywords: Endoscopic ultrasound, fine needle aspiration cytology, gastrointestinal stromal tumors

How to cite this article:
Kaur G, Manucha V, Verma K. Gastrointestinal stromal tumors: Cytomorphologic spectrum in fine needle aspiration smears. Indian J Pathol Microbiol 2010;53:271-5

How to cite this URL:
Kaur G, Manucha V, Verma K. Gastrointestinal stromal tumors: Cytomorphologic spectrum in fine needle aspiration smears. Indian J Pathol Microbiol [serial online] 2010 [cited 2019 Nov 14];53:271-5. Available from: http://www.ijpmonline.org/text.asp?2010/53/2/271/64338



   Introduction Top


Gastrointestinal stromal tumors (GIST) are mesenchymal tumors arising in the gastrointestinal tract and occasionally elsewhere in the abdomen. They constitute approximately 1% of gastrointestinal malignancies. [1] The origin of these tumors is thought to be from the interstitial cells of Cajal (ICC) the primitive stem cells that can differentiate into both ICC and smooth muscle cells. [2] For this reason they are now designated as specific c-kit expressing tumors and kit signaling driven mesenchymal tumors. [3] Historically, surgery has been the treatment of choice for these tumors. However the advent of gene product targeted therapy utilizing STI-571 (Imatinib mesylate, Gleevec) has facilitated the medical management of GISTs. [1] A rapid and accurate pre-operative cytological diagnosis of primary, metastatic or un-resectable GIST is therefore important to help the clinician to decide a treatment plan. [2] Moreover, with the advent of endoscopic ultrasound guided fine needle aspiration (EUS guided FNA), cytological material from these tumors can be obtained from almost anywhere in the gastrointestinal tract. Though the cytological features of GIST are well described, it is imperative for the cytologist to be aware of the variation and the spectrum of cytological features of GIST. In this case series, cyto-morphologic spectrum of GIST aspirated from different sites through different modalities is presented and pointers towards preoperative diagnosis are highlighted.


   Materials and Methods Top


Nine cases of GIST diagnosed on FNA over a period of two years (November 2006 to October 2008) were retrieved from the archives of the cytopathology laboratory of our hospital. Age of patients ranged from 42 to 71 years. Eight of the patients were males. Clinically, eight of them presented with vague abdominal complaints and one of them presented with a neck mass. Endoscopic ultrasound guided FNA (EUS FNA) was performed in five cases, while computed tomography guided (CT) per-cutaneous trans-abdominal FNA was done in three cases [Table 1]. FNA in the patient with neck mass was done in the laboratory by the pathologist. Two of the nine cases (cases 3 and 6) were known cases of GIST with suspected recurrence. Clinical details and site of tumors are summarized in [Table 1].

In all the cases, FNA material was smeared on glass slides. Slides wet fixed in 95% alcohol were stained with Papanicolaou stain while air dried smears were stained with May Grunwald Giemsa stain (MGG).

In seven of the nine cases, immune-cytochemistry was performed for CD117 after de-staining the MGG stained slide that had adequate amount of representative material. Pre-diluted antibody utilizing peroxidase anti peroxidase method (PAP, Novacastra,UK) was used.

The cytological diagnosis was given on the basis of cytomorphology and immune-cytochemistry. Histopathology slides after resection of tumor were available in four cases (case 2, 5, 7and 8).


   Results Top


The cytological features in all the nine cases are summarized in [Table 2]. The smears in all the cases were moderately to highly cellular. Smears from cases 1, 2, 5 and 9 were characterized by tight cellular bundles and fascicles made up of slender spindle cells with scant cytoplasm [Figure 1]a. The nuclei had fine chromatin and indistinct nucleoli. Three of them showed positive staining with CD117 and were diagnosed GIST on cytology [Figure 1]b. Immuno-cytochemistry for CD117 could not be performed in case no 5 on the smears and this was reported as spindle cell lesion favoring GIST. Surgical resection of the tumor was carried out in cases 2 and 5 and confirmed as GIST on surgical pathology and further by immune-histochemistry, where the tumors were positive for CD117.

Smears from cases 3, 4 and 6 showed moderately pleomorphic, plump, spindle to ovoid cells that were present in loose clusters and singly. The cytoplasm varied from being scant to moderate in amount and was finely vacuolated in case no. 6. The nuclear chromatin also varied from being fine to coarse with indistinct nucleoli. All the three cases were positive for CD117 and diagnosed as GIST on cytology. A histological diagnosis of GIST involving esophagus and stomach had been rendered in case no. 3 and 6 respectively in another hospital [Table 2]. In case no. 4, CT had shown a tumor in duodenum, however, no tissue confirmation was available. Smears from case no. 8 showed similar features as in cases 3, 4 and 6 except that few markedly pleomorphic cells were seen with 1-2 prominent nucleoli [Figure 2]a. Immuno-cytochemistry was not done and it was diagnosed as a malignant spindle cell tumor on cytology. Histopathology of this case revealed a large tumor measuring 15cm in greatest dimension with areas of necrosis. Microscopy showed spindle cell tumor with 1-2 mitosis per 50 hpf [Figure 2]b. The tumor stained positive for CD117 and a diagnosis of GIST with high risk malignant potential was given. No necrosis or mitotic activity was seen on cytology in smears in this case as well as other three cases in metastatic / recurrent category.

Smears from case no. 7 showed the characteristic tight bundles and fascicles of spindle cells, embedded in a prominent myxoid stroma. [Figure 3] Tumor cells stained negative with CD117. On cytology a spindle cell lesion with myxoid change was diagnosed and a GIST was favored. On histopathology, the tumor had a prominent epithelioid component with myxoid background. The tumor cells were negative for CD117, SMA and S-100 with weak and variable positivity for CD34. A diagnosis of GIST was made based on morphology and negative staining for other markers besides CD117.

No significant differences were observed with relation to cellularity or cytomorphologic features based on the modality used to sample the lesion. However, benign mucosal fragments from stomach or duodenal mucosa were observed in smears obtained by EUS FNA.


   Discussion Top


Gastrointestinal stomal tumors are the most common mesenchymal tumors of the gastrointestinal tract. The name "GIST" was proposed in 1983, but the cell of origin remained unclear until 1998 when interstitial cells of Cajal or their precursors were reported as the cells of origin. [4]

Majority of the GIST occur in the stomach (60% to 70%) and small intestine (25% to 35%) with rare occurrence in colon and rectum (5%), esophagus (2%) and appendix. [5] Though primary GISTs are described in the omentum, mesentry or retro-peritoneum, most GISTs in these sites are metastases from stomach or intestine. [6] A few authors have described the utility as well as limitations of FNA cytology in diagnosis of GIST. [7],[8],[9] In the present case series we highlight the features in nine consecutive cases of GIST that were diagnosed or suspected on cytology and later confirmed by immune-cytochemistry and histopathology.

Presence of cohesive and / tight fascicular bundles made up of slender spindle cells with minimal pleomorphism in appropriate clinical setting should raise suspicion of GIST. The important differential diagnosis of GIST without significant nuclear pleomorphism includes leiomyomas and schwannomas. This is clinically important as the GIST have potential malignant behavior while the latter two pursue a benign course. In this review we did not come across any specific cytological features that would help reach a definitive diagnosis and differentiation from smooth muscle tumors and nerve sheath tumors. In our view, a diagnosis of GIST can only be suspected on cytology and needs confirmation by immunostaining with CD117. This is in agreement with the findings of Tadoka et al.[8] and Kimura et al.[9] but in contrast to Li et al.[7] who reported that GIST could be diagnosed with confidence on cytomorphology alone.

In recurrent, metastatic and malignant GIST the cellular groupings are loose along with presence of single cells in the background. The pleomorphism varies from mild to moderate. Nuclear chromatin can again vary from being fine to coarse with occasional prominent one to two micronucleoli. Malignancy is difficult to predict on cytology alone unless the pleomorphism is as marked as was in Case number 8. However, there could be malignant GISTs with no significant pleomoprhism at all. [10],[11] Mitotic activity, a useful histopathologic marker of high risk behaviour in GIST, is a rare finding in cytology. In none of our cases mitosis could be made out. Other authors have also concluded that the assessment of malignant potential is difficult based on cytomorphology alone and should be best reserved for gross and histological examination of the resected specimen. [2],[7]

One peculiar case in our case series was GIST with prominent myxoid change (Case no. 7). Even though the tumor was negative for CD117, a diagnosis of GIST was suggested in view of cohesive spindle cell fragments seen in more classical cases as described above. On histopathology it was diagnosed as an epithelioid variant of GIST with myxoid stroma. Though epithelioid GIST are known to be more often CD117 negative, myxoid stroma is a rare change. [12] Suster et al.[13] had suggested that GIST with myxoid stroma is a distinct morphologic variant of myogenic gastrointestinal stromal tumor and needs to be differentiated from benign schwannoma of the stomach and gastrointestinal autonomic nerve tumors. The myxoid change observed in these tumors represents a secondary, non specific reaction pattern of the tumor cells to some noxious stimulus or it may be a form of degenerative phenomenon. [13] Other authors have suggested that myxoid epithelioid GISTs are a distinct subtype of GISTs that are closely correlated with the PDGFRA gene mutation and that recognition of such histological characteristics should be helpful for molecular subclassification of GISTs that are important for molecular targeting therapy by imatinib mesylate (STI571) inspite of week or negative expression of CD117 on immune-histochemistry. [14]

Many tumors, as in the present case series, are now being sampled through EUS guided FNA which can often result in presence of glandular cells from gastric or duodenal surface and these fragments should not be confused for tumor cells.

As FNAC is being utilized more often to render diagnosis in palpable and deep seated masses, cytopathologist needs to keep in mind possibility of GIST when encountering tumors with tight clusters made of slender spindle cells and resort to immune-cytochemistry for arriving at a final diagnosis.

 
   References Top

1.Fisher C. Gastrointestinal stromal tumors. In: Pignatelli M, Underwood J, editors. Recent Advances in Histopathology. Vol. 21. London: Royal Society of Medicine Press Ltd; 2005. p. 71-85.  Back to cited text no. 1      
2.Kwon MS, Koh SK, Lee SS, Chung JH, Ahn GH. Fine Needle Aspiration Cytology (FNAC) of Gastrointestinal Stromal Tumor: An Emphasis on Diagnostic Role of FNAC, Cell Block, and Immunohistochemistry. J Korean Med Sci 2002;17:353-9.  Back to cited text no. 2      
3.Miettinen M, Majii M, Lasota J. Pathology and diagnostic criteria of gastrointestinal stromal tumors(GISTs): A review. Eur J Cancer 2002;38:39-51.  Back to cited text no. 3      
4.Kitamura Y. Gastrointestinal stromal tumors: past, present and future. J Gastroenterol 2008;43:499-508.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Sakurai S, Fukasawa T, Chong JM, Tanaka A, Fukayama M. Embryonic form of smooth muscle myosin heavy chain in gastrointestinal stromal tumours and interstitial cells of Cajal Am J Pathol 1999;154:23-8.   Back to cited text no. 5      
6.Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004;22:3813-25.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]  
7.Li SQ, O Leary TJ, Buchner SB, Przygodzki RM, Sobin LH, Erozan YS, et al. Fine Needle Aspiration of Gastrointestinal Stromal Tumors. Acta cytol 2001;45:9-17.  Back to cited text no. 7      
8.Tadaoka Y, Hirokawa M, Nakamura E, Fukuoka K, Monobe Y, Shimizu M, et al. Imprint cytology of gastrointetinal stromal tumor of the jejunum in a patient with von Recklinghausens disease. J Jpn Soc Clin Cytol 1998;37:423-6.  Back to cited text no. 8      
9.Kimura M, Satou T, Hashimoto S, Tabaru Y. Can GIST Be Diagnosed Reliably by Cytology. Acta Cytol 2002;46:1170-1.  Back to cited text no. 9  [PUBMED]    
10.Boggino HE, Fernandez MP, Logrono R. Cytomorphology of gastrointestinal stromal tumour: diagnostic role of aspiration cytology, core biopsy and immunocytochemistry. Diagn Cytopathol 2000;23:156-60.  Back to cited text no. 10      
11.Cheuk W, Lee KC, Chan JK. C-kit immunocytochemical staining in the diagnosis of metastatic gastrointestinal stromal tumor: A report of two cases. Acta Cytol 2000;44:679-85.   Back to cited text no. 11  [PUBMED]    
12.Lee HE, Kim MA, Lee HS, Lee BL, Kim WH. Characteristics of KIT negative gastrointestinal stromal tumors and diagnostic utility of protien kinase C theta immunostaining. J Clin Pathol 2008;61:722-9.  Back to cited text no. 12  [PUBMED]  [FULLTEXT]  
13.Suster D, Sorace D, Moran CA. Gastrointestinal stromal tumors with prominent myxoid matrix. Clinicopathologic, immunohistochemical and ultrastructural study of nine cases of a distinctive morphologic variant of myogenic stromal tumor. Am J Surg Pathol 1995;19:59-70.  Back to cited text no. 13      
14.Sakurai S, Hasegawa T, Sakuma Y, Takazawa Y, Motegi A, Nakajima T, Saito K, Fukayama M, Shimoda T. Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: A subtype of GIST with mutations of platelet derived growth factor receptor alpha gene. Hum Pathol 2004;35:1223-30.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]  

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Correspondence Address:
Varsha Manucha
Department of Pathology, Sir Ganga Ram Hospital, Rajinder Nagar, Delhi-110 060
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.64338

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