DOI: 10.14260/jemds/2014/1921
ORIGINAL ARTICLE
CYTODIAGNOSIS OF GASTROINTESTINAL STROMAL TUMOURS (GISTs) ON
ROMANOWSKY STAINED SMEARS
Priyanka Agrawal1, Subhash Agrawal2, Atul Gupta3, Anurag Gupta4
HOW TO CITE THIS ARTICLE:
Priyanka Agrawal, Subhash Agrawal, Atul Gupta, Anurag Gupta. “Cytodiagnosis of Gastrointestinal Stromal
Tumors (GISTs) on Romanowsky Stained Smears”. Journal of Evolution of Medical and Dental Sciences 2014;
Vol. 3, Issue 04, January 27; Page: 895-901, DOI: 10.14260/jemds/2014/1921
ABSTRACT: This is a retrospective study on 7 cases diagnosed as GISTs on cytology. It includes 5
(71.5%) cases from stomach, of which 3(43%) were forming exogastric mass & 2 (28.5%) were from
colon. Two (28.5%) of 7 cases were reported as spindle cell GISTs (possibly benign). Three (43%)
cases were reported as spindle cell GISTs (possibly malignant). Remaining 2 (28.5%) cases were
reported as epithelioid GISTs (possibly malignant). Histological correlation was possible in both cases
of spindle cell GISTs (possibly benign) and 2 of 3 cases of spindle cell GISTs (possibly malignant).
Diagnosis of epithelioid GISTs was also confirmed on histology. All 6 (86%) cases correlated with
cytological diagnosis. Cytological features were studied on Romanowsky stained smear. This study
illustrates the cytological features and helps the cytopathologist to diagnose these cases. A cytologist
should consider the diagnosis of GISTs; both for spindle cell & epithelioid lesions of abdomen. These
lesions respond very well to imatinib & do not have very poor prognosis as that of deep seated
sarcomas and hepatocellular carcinoma.
KEYWORDS: GIST, Cytodiagnosis.
MeSH terms: Gastrointestinal stromal tumor, Cytodiagnosis.
INTRODUCTION: Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the
gastrointestinal tract arising from interstitial cells of Cajal. GISTs are now defined as cellular, spindle
cell, epithelioid or occasionally pleomorphic mesenchymal tumors of the GIT expressing CD 117 (ckit), a product of c-kit proto-oncogene and CD34 (usually).1 They are most common in stomach (6070%).2 Larger tumors protrude intraluminally or to the serosal side and may have a massive
extragastric component. Pathologic assessment of malignancy is disappointing, even on histology.
Aggressive behavior depends on tumor size, mitotic frequency and coagulation necrosis. NIH
consensus guidelines for defining risk of aggressive behavior in GISTs at any anatomical site are given
in Table – 1. 3Because of the submucosal or intramural location of this tumor, endoscopic biopsy is
often ineffective in making a biopsy diagnosis.[2] Ultrasonography (USG) guided, computed
tomography (CT) guided or endoscopic ultrasonographically (EUS) guided fine needle aspiration
cytology (FNAC) is being increasingly used for the diagnosis of these tumors. 1, 2, 4,5The cytological
features of GIST have been documented and few reports have been supported by
immunocytochemistry (ICC). 1, 2, 4-8
This work was conducted to study the cytomorphological features of cases cytologically
diagnosed as GISTs on Romanowsky stained FNA smears and to identify the problems encountered in
cytological interpretation of these aspirates.
METHODS: It is a retrospective study of cases diagnosed as GIST in a period of 1 year (Nov2008Oct2009) on image guided FNAC smear. All tumors were aspirated under ultrasonographic / CT
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ORIGINAL ARTICLE
guidance. Aspirations were done with a 22-gauge needle and 20 ml syringe using the standard
procedure, and smears were prepared, air-dried and stained with May-Grunwald Giemsa stain.
Cytomorphological features were studied and cytodiagnosis was made, which was correlated with
histology, wherever possible. Study was performed after approval of ethical committee of hospital
which conforms to the norms of the Helsinki declaration on human experimentation (institutional or
regional).
RESULTS: Seven cases of GISTs were studied. Five (71.5%) were from stomach and 2 (28.5%) from
colon. Five (71.5%) patients were male and 2 (28.5%) female, with ages between 34 to 61 years. Two
(28.5%) of 7 cases were reported as spindle cell GISTs (possibly benign). Three (43%) cases were
reported as spindle cell GISTs (possibly malignant). Remaining 2 (28.5%) cases were reported as
epithelioid GISTs (possibly malignant). The age, sex, clinical presentation, radiological findings,
cytodiagnosis & histodiagnosis of cases is given in Table-2.
Cytological features: Smears of cases diagnosed as spindle cell GISTs (possibly benign) were cellular
in hemorrhagic background. Spindle to oval cells with mild pleomorphism were arranged in
fascicular & whorling patterns with collagenous stroma (Figure 1). Palisading was also noticed in 1 of
2 cases (Figure 2). Cytoplasm was moderate with ill-defined boundaries. Nucleus was medium sized,
oval with blunt ends and had fine granular chromatin. Few stripped nuclei were seen in 1 of 2 cases.
Histology of both cases supported the cytodiagnosis (Figure 3).
Smears of cases cytologically reported as spindle cell GISTs (possibly malignant) were cellular
with spindle to oval cells in hemorrhagic background; both loosely clustered & dispersed (Figure 4).
Prominent coagulative necrosis was seen in 1 of 3 cases. Cytoplasm was scant to moderate, with some
vacuolization & ill-defined borders (Figure 4). Few stripped nuclei were seen. Nuclei were of medium
size, oval or cigar-shaped & occasionally spindle or comma shape. Chromatin was granular. Two cases
revealed nuclear features as those of benign spindle GIST, while 1 case revealed moderately
pleomorphic nuclei with high N: C ratio & rare mitotic figures but nuclear membrane was regular
(Figure 5). These cases were labeled possibly malignant on the basis of radiological findings & NIH
guidelines, which states that size of more than 10cm is of high risk. Histology of 2 of 3 cases was
available which supported the cytodiagnosis.
Cytology of epithelioid GISTs (possibly malignant) of exogastric mass of 14 cm diameter
revealed cellular smears with groups of histiocytes (Figure 6). Round to polygonal, occasionally
spindled, medium sized cells with moderate pleomorphism were loosely clustered as well as
dispersed (Figure 7). Cytoplasm was abundant & well-defined. Nucleus was medium sized, round,
with coarse chromatin & moderate pleomorphism. Nucleoli were not seen. Cytological features were
somewhat similar to that of hepatocellular carcinoma but radiological finding was mass arising from
stomach. Thus, epithelioid GIST was the first differential diagnosis; others were hepatocellular
carcinoma, metastatic carcinoma, neuroendocrine tumor & melanoma. Immunocytochemistry could
not be performed, due to unavailability. Histology confirmed the cytodiagnosis.
Epithelioid GISTs (possibly malignant) from colon (16 cm diameter) on cytology revealed
cellular smear in hemorrhagic & necrotic background. Medium sized, mildly pleomorphic,
predominantly oval with occasional spindle cells were loosely clustered or dispersed singly (Figure
8). Cytoplasm was moderate in amount, with ill-defined borders & some vacuolization. Medium sized
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ORIGINAL ARTICLE
oval to comma shaped, mildly pleomorphic nuclei with granular chromatin were noticed (Figure 9).
Occasional intranuclear cytoplasmic inclusions & mitosis were seen. A differential diagnosis was also
suggested which includes epithelioid GIST, hepatocellular carcinoma, metastatic carcinoma,
neuroendocrine tumor & melanoma. Later, histology confirmed the diagnosis of epithelioid GIST.
Problem encountered were:
1. Differentiation between benign and malignant GIST (on cytology),
2. Cytological diagnosis of epithelioid GIST.
DISCUSSION: Patients of GISTs were between 34 to 61 years, a finding similar to Deshpande et al.
71.5% cases were male & 28.5% female, a finding resembling that of Gu et al. Five (71.5%) were from
stomach and 2 (28.5%) from colon, a finding in accordance to Deshpande et al.
Cytological findings of spindle cell GIST (possibly benign & possibly malignant) were similar
to those discussed by Boggino et al, Deshpande et al, Gu et al, Li et al, Dodd et al, Kimura et al and
Kwon et al. As given Deshpande et al & Li et al, differentiation between benign and malignant GIST, on
cytology is very difficult. We also found that, loose cohesive clusters, nuclear pleomorphism, high N: C
ratio, nuclear membrane irregularity, coarse chromatin, necrosis & mitosis favor malignant behavior
but if not present the case cannot be labeled as benign GIST. At this point NIH guidelines are helpful
in many cases, which state that size of more than 10 cm, irrespective of mitotic count, shows
aggressive behavior.
According to Dong et al epithelioid gastrointestinal stromal tumors may cause significant
diagnostic confusion on fine-needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and
melanoma, particularly when metastatic. The diagnosis should be considered in aspirates of the
gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the
predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in
making a definitive diagnosis. Histopathological examination is necessary if ICC is not available. On
cytology, we have given epithelioid GIST, hepatocellular carcinoma, metastatic carcinoma,
neuroendocrine tumor & melanoma as differential diagnosis. Cytological features were similar those
discussed by Dong et al. Differentiation between benign and malignant epithelioid GIST, on cytology
is as difficult as for spindle cell GIST. Here also NIH guidelines are helpful in many cases.
We found groups of histiocytes in cytology of epithelioid GISTs (possibly malignant) of
exogastric mass of 14 cm diameter which is not reported in the literatures referred. Cytological
findings were somewhat similar to that of hepatocellular carcinoma but absence of endothelial cells
and nucleoli, along with radiological finding of the mass arising from stomach favored epithelioid
GIST as first differential diagnosis. Later, the cytodiagnosis was confirmed on histology.
CONCLUSION: Many authors believe that a cytologic diagnosis of GIST should not be made without
ICC. 7,9In centers’ where ICC facilities are not available and where the patient's future management
depends on the cytologic diagnosis, a cytopathologist can suggest the diagnosis of GIST (along with
differential diagnosis in case of epithelioid GIST), can give a suggestion on behavior/aggressiveness of
tumor but neither confirm the diagnosis nor tell its benign or malignant character. Cytology is
basically useful in classifying the tumor as epithelial vs. stromal and spindle vs. epithelioid types of
GIST. [1], [2], [4] Most cytology smears show a relatively benign picture without obvious pleomorphism,
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anaplasia or mitoses even when these are seen on histology. 2Since mitoses form an important
criterion for the diagnosis of malignancy; assessment of malignancy should not be attempted on
smears and is best left to histological examination. 1,2,6,7,8,10
Diagnosis of GIST should be considered by cytologist, both for spindle cell & epithelioid
lesions of abdomen. These lesions respond very well to imatinib & do not have very poor prognosis as
that of deep-seated sarcomas & hepatocellular carcinoma.
REFERENCES:
1. Boggino HE, Fernandez MP, Logrono R.F. Cytomorphology of gastrointestinal stromal tumour:
diagnostic role of aspiration cytology, core biopsy, and immunochemistry. Diagn Cytopathol
2000; 23:156-60.
2. Deshpande A, Munshi MM. Gastrointestinal stromal tumours – report of three cases and review
of literature. J Cytol 2007; 24: 96-100.
3. Fletcher CDM, Berman JJ, Corless C. Diagnosis of gastrointestinal stromal tumors: a consensus
approach. Hum Pathol 2002; 33: 459-465.
4. Dong Q, McKee G, Pitman M, Geisinger K, Tambouret R. Epithelioid variant of gastrointestinal
stromal tumour: diagnosis by fine-needle aspiration. Diagn Cytopathol 2003; 29: 55-60.
5. Gu M, Ghafari S, Nguyen PT, Lin F. Cytologic diagnosis of gastrointestinal stromal tumours of the
stomach by endoscopic ultrasound-guided fine-needle aspiration biopsy: cytomorphologic and
immunohistochemical study of 12 cases. Diagn Cytopathol 2001; 25: 343-50.
6. Li SQ, O'Leary TJ, Buchner SB, et al. Fine needle aspiration of gastrointestinal stromal tumours.
Acta Cytol 2001; 45: 9-17.
7. Cheuk W, Lee KC, Chan JK. c-kit immunocytochemical staining in the cytologic diagnosis of
metastatic gastrointestinal stromal tumour. A report of two cases. Acta Cytol 2000; 44: 679-85.
8. Dodd LG, Nelson RC, Mooney EE, Gottfried M. Fine-needle aspiration of gastrointestinal stromal
tumours. Am J Clin Pathol 1998; 109: 439-43.
9. Kimura M, Satou T, Hashimoto S, Tabaru Y. Can GIST be diagnosed reliably by cytology? Acta
Cytol 2002; 46: 1170-1.
10. Kwon MS, Koh JS, Lee SS, Chung JH, Ahn GH. Fine needle aspiration cytology (FNAC) of
gastrointestinal stromal tumour: an emphasis on diagnostic role of FNAC, cell block, and
immunohistochemistry. J Korean Med Sci 2002;17: 353-9.
SIZE (cm)
(in greatest dimension)
MITOTIC COUNT
(per 50 high power fields)
Very low risk
<2
<5
Low risk
2-5
<5
Intermediate risk
<5
6-10
5-10
<5
GROUP
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High risk
>5
>5
>10
Any mitotic count
Any size
>10
Table-1: NIH consensus guidelines for defining risk of
aggressive behavior in GISTs at any anatomical site. [3]
Case no.
Age/sex
1.
42y/M
2.
34y/M
3.
50y/F
4.
61y/M
5.
46y/M
6.
53y/F
7.
49y/M
Clinical
presentation
Radiology
Cytodiagnosis
7cmx6cmx4cm
GIST, spindle
Abdominal lump
transmural mass, cell (possibly
stomach
benign)
7cmx5cmx5cm
GIST, spindle
Abdominal lump
transmural mass, cell (possibly
stomach
benign)
11cmx7cmx4cm
GIST, spindle
Lump, pain in
mass arising
cell (possibly
abdomen
from stomach,
malignant)
exogastric mass.
12cmx6cmx6cm
GIST, spindle
Lump, pain in
mass arising
cell (possibly
abdomen
from stomach,
malignant)
exogastric mass.
12cmx6cmx5cm
GIST, spindle
mass arising
Abdominal lump
cell (possibly
from colon, areas
malignant)
of necrosis seen.
14cmx11cmx7cm
Epithelioid GIST,
mass arising
Abdominal lump
(possibly
from stomach,
malignant)
exogastric mass.
16cmx12cmx7cm Epithelioid GIST,
Lump, pain in
mass arising
(possibly
abdomen
from colon
malignant)
Table-2: Age, sex, clinical presentation, radiological findings,
cytodiagnosis & histodiagnosis of cases of 7 cases of GISTs
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Histology
GIST, spindle
cell, benign
GIST, spindle
cell, benign
GIST, spindle
cell, malignant
GIST, spindle
cell, malignant
Not available
Epithelioid GIST,
malignant
Epithelioid GIST,
malignant
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Fig. 1: Spindle cells in fascicular & whorling patterns
with collagenous stroma. (MGG, x100)
Fig. 3: Histology of GIST, benign. (H&E, x400)
Fig. 5: Moderately pleomorphic nuclei
with high N: C ratio. (MGG, x400)
Fig. 2: Palisading in GIST. (MGG, x400)
Fig. 4: Scant to moderate cytoplasm, with some
vacuolization & ill-defined borders. (MGG, x400)
Fig. 6: Epithelioid GISTs (possibly malignant)
showing groups of histiocytes. (MGG, x100)
Fig. 7: Epithelioid GISTs (possibly malignant)
showing moderate pleomorphism. (MGG, x400)
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Fig. 8: Epithelioid GISTs (possibly malignant) showing
loosely clustered mildly pleomorphic cells. (MGG, x100)
Fig. 9: Cytoplasm with ill-defined borders
& some vacuolization (MGG, x400)
AUTHORS:
1. Priyanka Agrawal
2. Subhash Agrawal
3. Atul Gupta
4. Anurag Gupta
PARTICULARS OF CONTRIBUTORS:
1. Assistant Professor, Department of Pathology,
S.S. Medical College, Rewa, (M.P.)
2. Assistant
Professor,
Department
of
Anaesthesia, S.S. Medical College, Rewa, (M.P.)
3. Professor & Head, Department of Pathology,
S.N. Medical College, Agra, (U.P.)
4.
Associate Professor, Department of Pathology,
S.N. Medical College, Agra, (U.P.)
NAME ADDRESS EMAIL ID OF THE
CORRESPONDING AUTHOR:
Dr. Subhash Agrawal,
F-11/1, New Doctors Colony,
Arjun Nagar, Rewa (M.P.) – 486001.
E-mail: drsubhash24@gmail.com
Date of Submission: 30/12/2013.
Date of Peer Review: 31/12/2013.
Date of Acceptance: 13/01/2014.
Date of Publishing: 22/01/2014.
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