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- Case Report -
Extragastrointestinal stromal tumor presenting as a scrotal
mass: an unusual case
Seok-Ho Kang1, Myung-Joon
Kim1, Min-Gu Park1, Hong-Seok
Park1, Du-Geon Moon1, Deuk-Jae
Sung2, Hyun-Chul Kim3, Yang-Seok
Chae3, Jun Cheon1, Je-Jong
Kim1
1Department of Urology,
2Department of Radiology, 3Department of Pathology, Korea University School of Medicine, Seoul 136-705, Korea
Abstract
Aim: We describe an unusual case of extragastrointestinal stromal tumor (EGIST) presenting as a scrotal mass. A
71-year-old man presented with a gradually enlarging scrotal mass with a 20-year duration. Physical examination
revealed a huge (as large as volleyball), round, nontender mass occupying the whole scrotum, which was resected
completely. Clinical and radiological findings did not comply with any other primary site disease. Under histological
examination, the tumor showed a spindle cell pattern with low cellularity, absence of necrotic and mitotic features.
Immunohistochemical anlaysis revealed the tumor reactive for CD117 and CD34, while negative for smooth muscle
actin, desmin and S-100 protein. To our knowledge, this is the first reported case of an EGIST involving the
scrotum. (Asian J Androl 2007 Mar; 9: 275_279)
Keywords: extragastrointestinal stromal tumor; scrotum; immunohistochemistry
Correspondence to: Dr Je-Jong Kim, Department of Urology, Korea University Hospital, Seoul 136-705, Korea.
Tel: +82-2-920-5367 Fax: +82-2-928-7864
E-mail: jjkim98@korea.ac.kr
Received 2006-06-15 Accepted 2006-08-28
DOI: 10.1111/j.1745-7262.2007.00235.x
1 Introduction
Gastrointestinal stromal tumors (GIST) are the most
common mesenchymal tumors that arise from the wall
of the gastrointestinal tract expressing CD117 and/or
CD34 [1]. Similar tumors in the soft tissue of the
abdomen are called extragastrointestinal stromal tumors
(EGIST). We report a case of a huge left scrotal mass in
a 71-year-old man, which was treated with complete
surgical resection. Histological assessment showed a spindle
cell neoplasm, which was positive for CD117 and CD34
on immunohistochemical analysis, consistent with an
EGIST. To our knowledge, there has been no report of
a primary GIST in the scrotum.
2 Case report
A 71-year-old man was admitted to our department
because of a huge scrotal mass, which had enlarged
gradually over a 20-year period. Physical examination
revealed a huge, round, nontender mass, approximate to
the size of a volleyball, occupying the whole left
scrotum and several tortuous engorged blood vessels on the
distended scrotal wall (Figure 1). Laboratory findings
showed the level of serum tumor markers, including
alpha-fetoprotein, human chorionic gonadotropin and
lactic acid dehydrogenase, were within the normal range.
Scrotal ultrasonography showed a huge, heteroechogenic
lesion in the left scrotum, but there was no abnormal
finding in both testis and epididymis (Figure 2).
Preoperative magnetic resonance imaging revealed a
12 × 15 × 18 cm-sized, well demarcated mass in the left
scrotum. The mass showed a slightly high signal intensity
on both the T1 and T2 weighted images (Figure 3).
Multiple flow void with intense enhancement indicated
vasculature within the mass. There was a non-enhancing central
portion of the mass that was considered necrotic, with a
high signal intensity on the T2 weighted image and low
signal intensity on the T1 weighted image. Both testes were
normal and showed good separation from the mass. There
was no evidence of lymph node enlargement or ascites.
Computed tomography scans of the chest, abdomen and
pelvis failed to reveal other mass lesions.
The patient underwent a complete gross excision of
the mass with a vertical left scrotal incision extending to
the left lower inguinal area. At surgery, there were many
engorged blood vessels to the mass and we ligated all of
these during excision. The mass displaced the left testis
to the upper lateral scrotum but the left testis and
epididymis appeared normal. After excising and trimming
the remnant scrotal wall for cosmetic purposes we orchiopexied the left testis.
Grossly, the surgical specimen consisted of an
ovoid, whitish-gray, firm lobulated mass, measuring
19.5 × 12.5 × 12 cm and weighing 1.8 kg. It was
encapsulated well and cut sections showed yellowish fibrotic
lobulated tissue with focal calcification. A 2.5 × 1.5 cm
cystic change, not necrotic, was noted in the central
portion of the mass. Microscopically, the tissue was
composed of a densely packed spindle cell proliferation.
The cells were predominantly arranged in short,
interweaving fascicles with multifocal hyalinization and
calcification. Individual cells showed oval, uniform
nuclei without any mitosis per 50 high power field and clear
cytoplasm. The Ki-67 labeling index was also less than
5%. Immunohistochemical stains demonstrated strong
positivity for both c-kit (CD117) and CD34. However,
the stains were negative for smooth muscle actin, desmin,
or the S-100 protein (Figure 4). After an uneventful
postoperative course, the patient was discharged 7 days
after surgery. There was no recurrence of the tumor
during the 7-month follow-up examination.
3 Discussion
Gastrointestinal stromal tumors are nonepithelial
neoplasm that usually arise in the muscular layer of the
digestive tract, particularly in the stomach and small
intestine. Stromal tumors that arise outside the
gastrointestinal tract are extremely rare and these lesions are
known as EGIST. EGIST are generally considered
similar to their gastrointestinal counterpart histologically and
immunohistochemically. However, because of their rarity, the clinicopathological features of the EGIST are
not well documented.
Reith et al. [2] reported 48 cases of EGIST. In their
study, 40 tumors arose within the abdominal cavity, where
they involved the omentum or mesentery. The
remaining 8 tumors were located in the retroperitoneum. Other
unusual sites of reported occurrence include the bladder
[3], the inguinal hernia sac [4], and the vagina [5]. In a
previously reported case of EGIST, Froehner
et al. [6] showed that GIST might involve the scrotum by direct
extension from the abdominal wall. Our patient presented
with a huge left scrotal mass, which caused difficulty in
identification of left testes. Clinical and radiological
findings did not identify any other primary site of disease nor
obvious direct extension from the hernia sac. Moreover,
the patient did not present any abdominal pain, or change
in bowel or urinary habits.
The diagnosis of GIST and their extragastrointestinal
variants are now specifically diagnosed by the
demonstration of a specific marker profile with expression of
CD 117 and CD34 [7]. It was found that most GIST expressed KIT, a receptor tyrosin kinase encoded by
protooncogene c-kit. In normal gastrointestinal wall, KIT
is expressed by interstitial cells of Cajal (ICC), which are
a pacemaker for autonomous gastrointestinal movement.
Because both GIST and ICC are double-positive for KIT
and CD34, and because familial and multiple GIST
appear to develop from diffuse hyperplasia of ICC, GIST
are considered to originate from ICC [8]. It has also
been found that approximately 90% of sporadic GIST
have somatic gain-of-function mutations of the
c-kit gene, and that patients with familial and multiple GIST
have germline gain-of-function mutations of the
c-kit gene [1]. These facts strongly suggested that the
c-kit gene mutations are a cause of GIST. Approximately half of
the sporadic GIST without c-kit gene mutations have
been demonstrated to have gain-of-function mutations
in platelet-derived growth factor receptor-α
(PDGFRA) gene that encodes another receptor tyrosine kinase [9,
10]. Because KIT is immunohistochemically negative in
a minority of GIST, especially in PDGFRA gene
mutation-harboring GIST, mutational analyses of
c-kit and PDGFRA genes might be required to diagnose such GIST
with certainty [8]. Histologically, GIST generally shows
one of three patterns: spindle cell, epitheloid or mixed.
The spindle cell pattern, as present in the current case, is
the most common type, accounting for 70% of reported
cases [7].
There is growing evidence that despite the fact that
virtually all stromal tumors express the c-kit receptor,
they display various site-specific differences. Most
importantly, the behavior of stromal tumors differs by
location, and there seems to be a general trend for
increasingly aggressive behavior as one proceeds distally
along the gastrointestinal tract [11, 12]. For example,
the minority of GIST located in the stomach have a good
prognosis, whereas those in the small intestine have a
significantly worse prognosis.
Predicting the prognosis of EGIST is not easy, but
EGIST are usually presumed to have a more aggressive
course resembling small intestinal tumors from the
viewpoint of location. The National Institute of Health
consensus conference has proposed a risk classification of
GIST based on tumor size and histopathological mitotic
count [7]. If the tumor is less than 5 cm and the mitotic
count is below 5 per 50 high power field (HPF), the risk
of malignancy is considered to be low. Ando
et al. [13] report that the presence of mitotic cells and the Ki-67
labeling index are significant predictive factors for
malignant GIST. Recently, Reith et al. [2] assess the
histopathologic prognostic factors of EGIST. In their report,
cellularity, mitotic activity (> 2 per 50 HPF), and
necrosis are associated with statistically significant increases
in the risk for an adverse outcome. Overall, 5% of
patients who had none or one of the above three risk
factors developed adverse outcomes (metastasis and/or death
from a complication of their tumor), compared with 92%
of patients who had two or three risk factors. In the
present case, there were no risk factors (low cellularity,
absent mitosis per 50 HPF without nuclear pleomorphism
and absent necrosis), suggesting good prognosis. The
Ki-67 labeling index also showed less than 5%. Besides,
the risk of malignancy might be low based on his scrotal
mass, which had enlarged gradually over a 20-year period.
The current definitive treatment for GIST is
complete surgical resection. Lymphadenectomy is not
necessary, because lymph-node metastasis of GIST is
very rare [14]. Conventional chemotherapy and
radiation therapy have been reported to be ineffective in the
treatment of GIST. Imatinib (a tyrosine kinase inhibitor)
has been confirmed to be an effective treatment against
metastatic and unresectalbe GIST [15]. In the treatment
of EGIST, complete surgical resection is recommended;
however, the role of imatinib is unclear. In our case,
complete surgical resection of the tumor was performed
successfully. Imatinib was not used because no
primary site was found, except scrotal mass on clinical and
radiologic evaluation, nor any adverse prognostic factor
detected on histological examination. There was no
recurrence of the tumor during the 7-month follow-up
examination, but close follow up is be required because
of the huge tumor size. The 7-month follow-up is too
short to completely rule out an extrascrotal primary tumor,
especially given the slow growth of this tumor.
In summary, the current case emphasizes the
possibility that this rare tumor can involve the scrotum as a
primary site. Further studies will be necessary to clarify
the management and biologic behavior of these unique
tumors.
References
1 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.
2 Reith JD, Goldblum JR, Lyles RH, Weiss SW.
Extragastro-intestinal (soft tissue) stromal tumors: an analysis of 48 cases
with emphasis on histologic predictors of outcome. Mod Pathol
2000; 13: 577_85.
3 Krokowski M, Jocham D, Choi H, Feller AC, Horny HP.
Malignant extragastrointestinal stromal tumor of bladder. J
Urol 2003; 169: 1790_1.
4 Goyal A, Mansel RE, Goyal S. Gastrointestinal stromal
tumour in an inguinal hernia sac: an unusual presentation. Postgrad
Med J 2003; 79: 707_8.
5 Weppler EH, Gaertner EM. Malignant extragastrointestinal
stromal tumor presenting as a vaginal mass: report of an
unusual case with literature review. Int J Gynecol Cancer 2005;
15: 1169_72.
6 Froehner M, Ockert D, Aust DE, Wirth MP, Saeger HD.
Gastrointestinal stromal tumor presenting as a scrotal mass.
Int J Urol 2004; 11: 445_7.
7 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.
8 Hirota S, Isozaki K. Pathology of gastrointestinal stromal
tumors. Pathol Int 2006; 56: 1_9.
9 Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen
CJ, Joseph N, et al. PDGFRA activating mutations in
gastrointestinal stromal tumors. Science 2003; 299: 708_10.
10 Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K,
Shinomura Y, et al. Gain-of-function mutations of
platelet-derived growth factor receptor alpha gene in gastrointestinal
stromal tumors. Gastroenterology 2003; 125:660-7.
11 Brainard JA, Goldblum JR. Stromal tumors of the jejunum and
ileum: a clinicopathologic study of 39 cases. Am J Surg Pathol
1997; 21: 407_16.
12 Goldblum JR, Appelman HD. Stromal tumors of the duodenum:
a hstologic and immunohistochemical study of 20 cases. Am J
Surg Pathol 1995; 19: 71_80.
13 Ando N, Goto H, Niwa Y, Hirooka Y, Ohmiya N, Nagasaka T,
et al. The diagnosis of GI stromal tumors with EUS-guided
fine needle aspiration with immunohistochemical analysis.
Gastrointest Endosc 2002; 55: 37_43.
14 Bray JY, Bonvalot S, Casali P, Choi H, Debiac-Richter M,
DeiTos AP, et al. Consensus meeting for the management of
gastrointestinal stromal tumors. Report of the GIST
consensus conference of 20-21 March 2004, under the auspices of
ESMO. Ann Oncol 2005; 16: 566_78.
15 Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC,
Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase
inhibitor STI571 in a patient with a metastatic gastrointestinal
stromal tumor. N Engl J Med 2001; 344: 1052_6. |