IGF-II-Secreting Pelvic Tumor Presenting with Neuropsychiatric Symptoms

JSCR 2013; 12(4 pages) doi:10.1093/jscr/rjt116

Case Report

IGF-II-secreting pelvic tumor presenting with neuropsychiatric symptoms

Divya Dahiya1,*, Sanjay Bhadada2, Uma Nahar3, Mandeep Garg4, Lileswar Kaman1 and Arunanshu Behera1

1Department of Surgery, PGIMER, Chandigarh, India, 2Department of Endocrinology, PGIMER, Chandigarh, India, 3Department of Histopathology, PGIMER, Chandigarh, India and 4Department of Radiodiagnosis, PGIMER, Chandigarh, India

*Correspondence address. Department of Surgery, PGIMER, Chandigarh 160012, India. E-mail: dahiyadivya30@ gmail.com

Received 16 October 2013; accepted 18 November 2013

A 48-year-male presented with a gradually increasing lump in the abdomen, which was con- ﬁrmed on investigations as a pelvic tumor. He developed frequent episodes of hypoglycemia and neuropsychiatric symptoms while awaiting surgery. During episodes of hypoglycemia, his serum C-peptide and insulin levels were negligible and the insulin-like growth factor (IGF)-II to IGF-I ratio was .10. He successfully underwent an en bloc excision of the tumor. Histopathology revealed a solitary ﬁbrous tumor.

INTRODUCTION rectum without any mucosal irregularity. His initial basic laboratory investigations which included hemogram, coagulo- Hypoglycemia associated with non-islet cell tumor (NICT) is gram, blood sugar, serum sodium, potassium, chloride, one of the manifestations of paraneoplastic syndrome. The calcium, renal and liver function tests and urine analysis were most common NICTs causing hypoglycemia are mesenchy- within normal range. CECT abdomen (Figs 1 and 2) revealed mal tumors. Frequently implicated mesenchymal tumors that a20Â 15 Â 7 cm heterogenous well-defined lobulated mass cause hypoglycemia are solitary fibrous tumor (SFT), fibrosar- with calcification and areas of necrosis in the pre-sacral region coma, leiomyosarcoma, mesothelioma and hemangiopericy- and was extending superiorly up to the lower border of L3. tom [1]. High-molecular-weight insulin-like growth factor-II It was indenting into the bladder anteriorly and rectum posteri- (Big-IGF-II) secretion plays an important role in causation orly, also abutting pelvic vessels but maintaining fat planes of hypoglycemia [2]. Herein we present the patient with with all these structures. This mass was causing bilateral neuroglycopenic symptoms due to IGF-II-secreting SFT. hydroureteronephrosis. During his hospital stay while awaiting surgery he dis- played a widely fluctuating behavior, slurring of speech, CASE REPORT double vision, episodes of aggression and confusion, followed A 48-year-male patient presented with awareness of gradually by lucid interval. There was no relation with food and this first increasing lower abdominal lump and abdominal discomfort episode was self-limiting. He did not give history of any such for 8 months. There was no history of anorexia and weight behavior prior to his visit to the hospital. Fundus examination loss. He was a non-smoker and non-alcoholic. His general was normal. CT brain did not reveal any abnormality. physical examination was unremarkable with no clinical evi- Psychiatrist made a diagnosis of delirium of unknown origin dence of hepatic disease and adrenal or pituitary insufficiency. and started benzodiazipines for him. After 2 days, he again On abdominal examination, about 8 Â 10 cm non-tender, underwent a similar episode which was also associated with hard, well-defined intra-abdominal lump was present in hypo- hemiparesis. His blood sugar during this episode was 31 mg% gastrium, which was extending into right iliac fossa, right and he responded symptomatically and biochemically after re- lumbar and umbilical region for which the lower margin was ceiving 50 ml 50% dextrose infusion, thus fulfilling the cri- not palpable. The lump was bimanually palpable on rectal teria for diagnosing organic hypoglycemia (Whipple’s triad). examination. It was causing intra-luminal projection within History of diabetes, intake of hypoglycemic or steroids was

Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. # The Author 2013. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by-nc/3.0/), which permits non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected]. Page 2 of 4 D. Dahiya et al.

Figure 1: Axial section of contrast-enhanced CT of the abdomen reveals a large heterogeneously enhancing mass with a small hyperenhancing component (asterisk). Foci of calciﬁcation are noted within the lesion (white arrow). A few hypoenhancing areas are also seen within the lesion, which might repre- sent necrosis or scar formation. Incidentally, a ureteric calculus is seen on the right side (black arrow). Dilated ureter (u) is noted on the left side due to com- pression by the mass lower down. Note that the fat planes with the bowel and the retroperitoneal vessels are maintained.

Figure 3: Intra-operative picture: a 20 Â 13 cm solid well-encapsulated tumor was present in the pelvic cavity posterior to urinary bladder.

ruled out. During his next episode of hypoglycemia (blood sugar 30 mg%); C-peptide was 0.709 (1.1–4.4) ng/ml, serum insulin was ,0.200 (2.6–24.9) mU/ml and ketones were 0.2 mmol/l. The concentration of IGF II was in the normal range, 623 (288–736) ng/ml, while IGF I was reduced, 56.1 (94–252) ng/ml. But the ratio of IGF II–I was 11.105 (refer- ence range is ,10.00), which was highly suggestive of IGF II-secreting NICT. Thyroid function tests, serum cortisol were within the normal range. He was maintained on 10% dextrose infusion and subsequently was taken up for laparotomy. There was no visceral, peritoneal or lymphatic metastasis. There was a 20 Â 13 cm solid well-encapsulated vascular tumor present in the pelvic cavity posterior to urinary bladder, which was extending above and anterior to the right common iliac vessels. An en bloc excision of the tumor was performed (Figs 3 and 4). Cut section of tumor was nodular with areas of necrosis, calciﬁcation and hemorrhage. Histopathology diagnosis was consistent with SFT with short interlacing spindle cells in short fascicles and with thick intervening collagen (Fig. 5). There was no evidence of mitosis. There were areas of ische- mic necrosis and osseous metaplasia. Immunostaining for CD Figure 2: Contrast-enhanced sagittal reformatted CT section of the abdomen 34 was strongly positive (Fig. 6). depicts a large enhancing mass posterior to the urinary bladder and anterior to The patient had an uneventful postoperative recovery. the lower lumbar vertebrae and sacrum. The lesion is heterogeneously enhancing with a small hyperenhancing component (asterisk). Foci of calciﬁcation He did not have any episode of hypoglycemia during are noted within the lesion (white arrow). Note that the fat planes with the his hospital stay after surgery and subsequently at home bowel and the urinary bladder are maintained. after discharge. He received radiotherapy to tumor bed Case study of a neuropsychiatric patient with IGF-II secreting pelvic tumor Page 3 of 4

DISCUSSION Non-islet cell tumor-induced hypoglycemia (NICTH) is a rare paraneoplastic syndrome and is caused by the overproduction of incompletely processed IGF-II. Hypoglycemia can also be caused by autoantibodies against insulin or insulin receptors, substantial tumor infiltration of liver and adrenal glands, or by excessive utilization of glucose by a large tumor itself. However, the major cause of hypoglycemia is inhibition of gluconeogenesis and increase glucose utilization in skeletal muscles due to Big-IGF-II. It was first described for hepatocellular carcinoma (HCC) in 1929 [3]. It can occur both in benign as well as in malignant tumors. It has been chiefly reported in solid tumors of mesenchymal or epithelial origin, but it has also been reported in Figure 4: Tumor after en bloc excision. tumors of hematopoietic (myeloma, lymphoma) or neuroen- docrine (carcinoid, malignant pheochromocytoma) origin, hemangiopericytomas and colorectal carcinomas [4]. Tumors causing NICTH are either very large or metastatic. NICTH suppresses insulin secretion, lipolysis and ketogen- esis, leading to low serum concentration of C-peptide, growth hormone (GH) and beta-hydroxy butyrate [4]. Diagnosis is confirmed by blood sugar estimation ,50 mg%, low or negligible serum C-peptide, insulin and GH, low serum IGF-I, normal or elevated levels of IGF-II [5]. The IGF-II to IGF-I molar ratio .10 is highly suggestive of IGF-II-secreting tumor [6]. Clinical presentation in NICTH may vary from subtle symptoms of hypoglycemia (anxiety, palpitation, sweating, numb- ness) to severe neuroglycopenic (abnormal mentation, impaired judgement, fatigue, personality changes, confusion, amnesia, delirium, double vision, slurred speech, paralysis, hemipar- Figure 5: Microphotograph showing short interlacing spindle cells in short esis, seizures, amnesia) symptoms [4, 5, 7]. In addition, they fascicles with intervening thick collagen (H&E Â 200). may present with acromegaloid features [4, 8]. The patient in our study developed neuropsychiatric symptoms secondary to IGF-II-secreting abdominal SFT without any clinical evidence of acromegaly. Curative treatment is complete excision of tumor, which leads to complete reversibility of metabolic alterations caused by IGF-II. If removal of tumor is not a possibility then allevi- ation of hypoglycemia is a challenge. Various options like debulking of tumor, directed chemotherapy, selective tumor embolization, radiotherapy or medical treatment with diazox- ide, steroids, octreotide or GHs individually or in combination can be tried to improve the symptoms of hypoglycemia [7]. NICT is one of the major causes of hypoglycemia, which develops as a result of excessive production of Big-IGF II. In a patient with mesenchymal tumor with neuropsychiatric symptoms, NICTH should be considered after ruling out intra- cerebral vascular events and brain metastasis. Tumor resection can lead to complete resolution of symptoms. Figure 6: Microphotograph showing a strong CD 34 positivity in the tumor cells (IHC Â 200). postoperatively as an adjuvant treatment. He is doing well CONFLICT OF INTEREST STATEMENT on follow-up after 6 months without recurrence of tumor and hypoglycemia. There is no conflict of interest between authors. Page 4 of 4 D. Dahiya et al.

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