Retroperitoneal Malignant Solitary Fibrous Tumor of the Small Pelvis Causing Recurrent Hypoglycemia by Secretion of Insulin-like Growth Factor 2

Article (PDF Available)inEuropean Urology 55(3):739-42 · November 2008with55 Reads
DOI: 10.1016/j.eururo.2008.09.050 · Source: PubMed
Abstract
A 28-yr-old man presented with recurrent reduced consciousness, generalized seizures of unknown etiology, recurrent hypoglycemia, psychomotor retardation, and grade 2 ectasia of the left kidney. Abdominal computed tomography (CT) and positron emission tomography (PET) scans demonstrated a well-circumscribed suprapubic pelvic mass, measuring 18 x 15 x 11 cm, with involvement of para-aortic lymph nodes and dilatation of the left ureter suggestive of an extragonadal testicular tumor. We excised the tumor by laparotomy, and it was confirmed to be a solitary fibrous tumor (SFT). After surgery and R0 tumor resection, the patient had no further evidence of hypoglycemia or of recurrence.
Case Study of the Month
Retroperitoneal Malignant Solitary Fibrous Tumor of the Small
Pelvis Causing Recurrent Hypoglycemia by Secretion of
Insulin-like Growth Factor 2
Sigrid Wagner
a,
*
, Francesco Greco
a
, Amir Hamza
a
, Rashid M. Hoda
a
,
Hans Ju¨ rgen Holzhausen
b
, Paolo Fornara
a
a
Department of Urology and Kidney Transplantation, Martin Luther University, Ernst Grube Str. 40, 06120 Halle, Saale, Germany
b
Institute of Pathology, Martin Luther University, Ernst Grube Str. 40, 06120 Halle, Saale, Germany
1. Case report
A 28-yr-old patient suffered left flank pain, with
grade 2 ectasia of the left kidney. The presumptive
diagnosis of an extragonadal testicular tumor was
established after a radiologic examination (abdom-
inal computed tomography [CT] and positron emis-
sion tomography [PET] scan) (Fig. 1).
Because the testicular tumor markers were
negative, we performed a biopsy of the retroper-
itoneal mass, which was suggestive of a mesen-
chymal tumor. Immunohistochemical studies were
strongly positive for vimentin; positive for factor 8
expression in capillary vessels but negative in tumor
cells; positive for clone MIB-1 in only 2–3% of cells;
and negative for calretinin, CD21, CD34, S100,
epithelial membrane antigen (EMA), desmin,
smooth muscle actin (SMA), myogenin, pancytoker-
atin, and CD117. The patient had episodes of severe
hypoglycemia caused by insulin-like growth factors
(IGFs) produced by this tumor.
Because of the presumptive diagnosis of a
hemangiopericytoma after biopsy of the retroper-
itoneal mass, our initial therapeutic approach was
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Article info
Article history:
Accepted September 23, 2008
Published online ahead of
print on October 1, 2008
Keywords:
Solitary fibrous tumor
Hypoglycemia
Doege-Potter syndrome
Abstract
A 28-yr-old man presented with recurrent reduced consciousness, gen-
eralized seizures of unknown etiology, recurrent hypoglycemia, psycho-
motor retardation, and grade 2 ectasia of the left kidney. Abdominal
computed tomography (CT) and positron emission tomography (PET)
scans demonstrated a well-circumscribed suprapubic pelvic mass, mea-
suring 18 15 11 cm, with involvement of para-aortic lymph nodes
and dilatation of the left ureter suggestive of an extragonadal testicular
tumor.
We excised the tumor by laparotomy, and it was confirmed to be
a solitary fibrous tumor (SFT). After surgery and R0 tumor resection,
the patient had no further evidence of hypoglycemia or of recurrence.
# 2008 Published by Elsevier B.V. on behalf of European Association of Urology.
* Corresponding author. Department of Urology and Kidney Transplantation, Martin Luther
University, Ernst Grube Str. 40, 06120 Halle, Saale, Germany.
E-mail address: sigrid.wagner@medizin.uni-halle.de (S. Wagner).
EURURO-2771; No of Pages 4
Please cite this article in press as: Wagner S, et al. Retroperitoneal Malignant Solitary Fibrous Tumor of the Small Pelvis Causing
Recurrent Hypoglycemia by Secretion of Insulin-like Growth Factor 2, Eur Urol (2008), doi:10.1016/j.eururo.2008.09.050
0302-2838/$ see back matter # 2008 Published by Elsevier B.V. on behalf of European Association of Urology. doi:10.1016/j.eururo.2008.09.050
an intravenous infusion of two cycles of bevacizu-
mab (Avastin: Genentech, San Francisco, CA, USA).
After treatment, there was no evidence of any
reduction in the tumor mass, so we performed a
surgical resection (Fig. 2).
The definitive histologic report described a 1660 g
tumor, measuring 18 15 11 cm, with a homo-
genous cut surface and relatively homogenous
white, red, and brown markings (Figs. 3 and 4), well
encapsulated without evidence of invasion of
Fig. 1 Scan showing retroperitoneal mass with a radiologic diagnosis of hemangiopericytoma.
Fig. 2 Intraoperative photo shows pelvic mass in situ with
compression of the transverse colon and left ureter.
Fig. 3 Gross photograph of excised mass measuring 18 T
15 T 11 cm and 1660 g. The tumor was well encapsulated
without evidence of invasion of surrounding structures.
Fig. 4 Cut surface of the tumor.
european urology xxx (2008) xxx–xxx2
EURURO-2771; No of Pages 4
Please cite this article in press as: Wagner S, et al. Retroperitoneal Malignant Solitary Fibrous Tumor of the Small Pelvis Causing
Recurrent Hypoglycemia by Secretion of Insulin-like Growth Factor 2, Eur Urol (2008), doi:10.1016/j.eururo.2008.09.050
surrounding structures. The pathologist diagnosed
the tumor as a malignant solitary fibrous tumor
(SFT) with R0 resection. Immunohistochemistry
demonstrated diffuse membranous expression of
CD99, cytoplasmatic expression of Bcl2, and expres-
sion of CD34 but no expression of EMA, CD31,
HMB45, desmin, or SMA (Fig. 5).
2. Discussion
Malignant SFTs, described in the literature as the
Doege-Potter syndrome, are often associated with
hypoglycemia [1]. SFTs are rare tumors with a 12–
13% rate of malignancy. Hypoglycemia is seen in
<5% of cases. The associated tumors are large, with
a high mitotic rate. The hypoglycemia is related to
IGF 2 (IGF2) produced by the tumor [2,3]. The
downstream oncogenic pathways of IGF2, however,
are not clear. SFT cells secrete IGF2 and proliferate in
serum-free medium, consistent with an IGF2/insu-
lin receptor (IR) autocrine loop. The etiologic
relevance of IGF2 is supported by expression of IR
A (IRA), the isoform with high affinity for IGF2, in all
SFTs.
IR activation plays an oncogenic role in SFTs [3].
The most frequently described locations for these
tumors are the pleura, lung, pancreas, intestine,
greater omentum, and uterus [4–8]. The differential
diagnosis for SFT includes hemangiopericytoma,
gastrointestinal stromal tumors (GIST), malignant
mesothelioma, synovial sarcoma, leiomyomatous
tumors, and granulosa-cell tumors.
Immunohistochemical studies revealed reactivity
for CD34, CD99, and Bcl2 but no staining for desmin,
EMA, HMB45, SMA, S100, or CD31, thus confirming
the diagnosis of SFT. After surgical resection of the
tumor, high-molecular-weight IGF2 was not
detected in the serum, and the hypoglycemia
resolved. Immunohistochemically, IGF2 was loca-
lized to the Golgi area of the tumor cells. These
findings suggest that hypoglycemia in this patient
was caused by the overexpression of IGF2 by the SFT
cells. Although SFT is typically associated with a
favorable prognosis, a close follow-up is recom-
mended because of limited information on its long-
term behavior.
Conflicts of interest: The authors have nothing to disclose.
Fig. 5 (a) Immunohistologic evidence of a diffuse membrane expression of CD99, and (b) cytoplasmatic expression of Bcl2.
CD34 expression was focally positive.
EU-ACME question
Please visit www.eu-acme.org/europeanurology
to answer the below EU-ACME question on-line
(the EU-ACME credits will then be attributed
automatically).
Question:
What were the reasons for hypoglycemia in
this patient?
A.
Paraneoplastic syndrome.
B. High levels of circulated insulin-like growth
factor 2 (IGF2).
C. High mitotic rate of spindle cells.
D. Expression of CD34 by tumor cells.
european urology xxx (2008) xxx–xxx 3
EURURO-2771; No of Pages 4
Please cite this article in press as: Wagner S, et al. Retroperitoneal Malignant Solitary Fibrous Tumor of the Small Pelvis Causing
Recurrent Hypoglycemia by Secretion of Insulin-like Growth Factor 2, Eur Urol (2008), doi:10.1016/j.eururo.2008.09.050
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european urology xxx (2008) xxx–xxx4
EURURO-2771; No of Pages 4
Please cite this article in press as: Wagner S, et al. Retroperitoneal Malignant Solitary Fibrous Tumor of the Small Pelvis Causing
Recurrent Hypoglycemia by Secretion of Insulin-like Growth Factor 2, Eur Urol (2008), doi:10.1016/j.eururo.2008.09.050
    • "We reviewed case reports of NICTH associated with paraneoplastic production of IGF-2 from 2008 to 2012 (Table 3) [17-38]. On our review of literature, we identified 22 published reports of NICTH with elevated IGF-2 levels causing hypoglycemia. "
    [Show abstract] [Hide abstract] ABSTRACT: Background Hypoglycemic episodes are infrequent in individuals without a history of diabetes mellitus or bariatric surgery. When hypoglycemia does occur in such individuals, an uncommon but important diagnosis to consider is non-islet cell tumor hypoglycemia (NICTH). We report a case of NICTH associated with paraneoplastic insulin-like growth factor-2 (IGF-2) production and review current relevant medical literature. Case presentation A 60 year old male with no relevant past medical history was referred to the endocrinology clinic with 18 month history of episodic hypoglycemic symptoms and, on one occasion was noted to have a fingerstick glucose of 36 mg/dL while having symptoms of hypoglycemia. Basic laboratory evaluation was unrevealing. Further evaluation however showed an elevated serum IGF-2 level at 2215 ng/mL (reference range 411–1248 ng/mL). Imaging demonstrated a large right suprarenal mass. A right nephrectomy with resection of the mass demonstrated a malignant solitary fibrous tumor. Post resection, the patient’s IGF-2 levels normalized and hypoglycemic symptoms resolved. Conclusion Due to the structural and biochemical homology between IGF-2 and insulin, elevated levels of IGF-2 can result in hypoglycemia. A posttranslational precursor to IGF-2 known as “big IGF” also possesses biologic activity. Review of recent reported cases of NICTH identified widespread anatomic locations and varied pathologic diagnoses of tumors associated with paraneoplastic production of IGF-2 causing hypoglycemia. Definitive management of hypoglycemia associated with paraneoplastic production of IGF-2 consists of resection of the tumor responsible for IGF-2 production. Accumulating literature provides a firm basis for routine IGF-2 laboratory evaluation in patients presenting with spontaneous hypoglycemia with no readily apparent cause.
    Full-text · Article · Jun 2014
    • "SFT is an uncommon neoplasm of mesenchymal origin that was first recognized by Klemperer and Rabin as a distinctive pleural lesion in 1931 [8]. Over the last 10 years, at least 106 extrapleural SFTs have been reported, located in the meninges, orbit, upper respiratory tract, salivary glands, thyroid, peritoneum, liver, retroperitoneum, adrenal gland, kidney, spermatic cord, urinary bladder and prostate spinal cord, periosteum, and soft tissue mainly in the head and neck12345679101112131415. About 10%–36% of intrathoracic SFTs are histologically or clinically malignant while malignant SFTs have been described in 11%–33% of cases at other locations [2, 3]. "
    [Show abstract] [Hide abstract] ABSTRACT: Solitary fibrous tumour (SFT) is a rare oncological entity that most often arises in the pleura. Over the past 10 years, the tumour has been described at numerous extrapleural locations. We present the case of a 42-year-old female Caucasian patient with an extrapleural SFT located at the anterior thoracic wall for 22 years, with atypical histological characteristics and clinical features of malignancy. Management consisted of a wide surgical resection, plastic reconstruction, and postoperative radiotherapy. Although extrapleural SFT usually behaves as a benign soft tissue tumour, it can also present with a more aggressive local behavior, including locoregional recurrence or metastasis. In that case, a multidisciplinary approach is required for accurate diagnosis and proper management.
    Full-text · Article · Jun 2010
    • "SFTs are uncommon spindle-cell neoplasms, usually arising from the pleura. Extrapleural/extrathoracic SFTs have been increasingly described in various locations, including the genitourinary tract [1,2]. Fewer than 20 cases of SFT of the prostate, reported as single cases and one series of 13 cases seen on either needle biopsies or transurethral resections (TURs), have beenFig. 1 – Endorectal coil magnetic resonance image demonstrating a large solid mass arising from the prostate. "
    [Show abstract] [Hide abstract] ABSTRACT: The clinical and radical prostatectomy features of a case of solitary fibrous tumour (SFT) of the prostate identified on needle biopsy are presented. The main differential diagnoses are discussed. SFTs involving the prostate are relatively uncommon, with only isolated cases reported in the literature. Owing to their relative rarity and lack of long-term follow-up, the clinical behaviour of prostatic SFTs is difficult to predict. Complete resection of the tumour is currently the single main prognostic factor.
    Full-text · Article · Mar 2009
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