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Year : 2015  |  Volume : 58  |  Issue : 3  |  Page : 410-412
Is histopathology informative for further characterization of DOTANOC-proven islet cell lesions in infancy?

1 Department of Pathology, G. B. Pant Hospital, New Delhi, India
2 Department of Paediatric Surgery, Lady Hardinge Medical College, New Delhi, India

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Date of Web Publication14-Aug-2015

How to cite this article:
Gupta RK, Saran RK, Debnath PR, Chadha R. Is histopathology informative for further characterization of DOTANOC-proven islet cell lesions in infancy?. Indian J Pathol Microbiol 2015;58:410-2

How to cite this URL:
Gupta RK, Saran RK, Debnath PR, Chadha R. Is histopathology informative for further characterization of DOTANOC-proven islet cell lesions in infancy?. Indian J Pathol Microbiol [serial online] 2015 [cited 2022 Jan 22];58:410-2. Available from: https://www.ijpmonline.org/text.asp?2015/58/3/410/162939


Nesidioblastosis occurs due to islet cell hyperplasia and also known as persistent hyperinsulinemic hypoglycemia of infancy (PHHI). [1] It is frequently seen in the infancy and childhood but also reported in the adults, particularly in postoperative patients with bariatric surgery. Fewer than 25 cases of congenital hyperinsulinism have been reported in the Indian pediatric literature. [2] An association of nesidioblastosis with Beckwith Weidmann syndrome, cystic fibrosis, chronic pancreatitis and endocrine neoplasms is described. Many specific genes such as SUR1, Kir6.2, GCK, and GLUD1 are described in the pathogenesis of nesidioblastosis in the recent years. Focal and diffuse forms of nesidioblastosis have been reported. In neonates, focal type of PHHI accounts for 40% of the cases, and the rest are of the diffuse form. Genetic analysis has shown a different molecular basis for the two forms of the disease. [3] The focal form is associated with loss of heterozygosity for paternally inherited mutations in the Katp geneswhile in diffuse variant homozygous recessive or compound heterozygote mutations in the ABCC8 and KCNJ11 genes occur. Nesidioblastosis may or may not present as anatomical lesion causing difficulty in the radiological interpretation. Partial/total pancreatectomy is the treatment of choice, in case of failed medical treatment/compliance and or patient resistant to drugs.

A female neonate was brought to the Pediatric Intensive Care Unit of our hospital at 36 h of life with the chief complaints of decreased oral acceptance, lethargy and seizures. Although the baby was full term having 2.8 kg weight but was delivered by emergency caesarian due to fetal distress. The blood glucose levels of the child were persistently low requiring a continuous glucose infusion rate of up to 14 mg/kg/min. Serum fasting insulin level was done and found to be elevated (19.7μIU/ml). However, serum acetone levels (1.20 mg/dl) were within normal range. She was further subjected to radiotracer study by "68 Ga-DOTANOC scan" that showed a focal area of increased radiotracer uptake in the body of pancreas [Figure 1]. Diazoxide was started to bring down insulin levels, however, oral medication failed to control levels and partial pancreatectomy was planned. The patient was operated with a clinical diagnosis of insulinoma. Intraoperatively, a suspected nodule of 1.5 cm diameter was found in the body of pancreas near uncinate process. We received a specimen of partial pancreatectomy measuring 4 cm × 3 cm, grossly which showed a small pale yellow nodule of size 1.2 cm. On histopathology, marked islet cell hyperplasia was discernible in the nodular area. Each nodule of hyperplastic islets were separated by thin fibro-vascular septa. The cells were monomorphic with mild variation in nuclear size, mild nuclear enlargement, salt and pepper chromatin and a moderate amount of eosinophilic cytoplasm, arranged in nests with frequent ductulo-insular complex formation. Numerous peliosis like ectatic blood vessels were present. Adjacent normal compressed pancreatic parenchyma was also noted. The immunohistochemical stain for synaptophysin, chromogranin-A and insulin highlighted these areas [Figure 2]. A final diagnosis of nesidioblastosis of focal type was made.
Figure 1: 68 Ga-DOTANOC whole body positron emission tomography-computerised tomography scan showing focal area of increased radiotracer uptake in the body of pancreas

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Figure 2: Photomicrographs showing histomorphological and immunohistochemical features of nesidioblastosis, (a) showing islet cells arranged in nesting pattern with ductulo-insular complex, the cells are having 'salt and pepper' chromatin and eosinophilic cytoplasm which is characteristic of endocrine tumors (×200). Immunohistochemistry showing diffuse cytoplasmic positivity for (b) insulin, (c) synaptophysin and (d) chromogranin-A (each ×200). Arrow in A; highlighting "ductulo-insular complex" and in c; 'peliosis like vascular space'

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Post-operatively baby had labile blood sugar levels for which she was kept on alternate insulin and glucose infusion along with diazoxide and steroid for 2 weeks. Presently, baby is off the medication and maintaining almost normal glucose level with gaining of weight exclusively through breast feed for the last 3 months. Initially, child had few short episodes of seizure but currently she is healthy and attaining normal developmental milestones.

Insulinoma was considered as the main clinical diagnosis, as rare case reports exist. Insulinoma usually presents as mass lesion on imaging. Histologically, these show the absence of both ductulo-insular complexes and peliosis-like blood vessels along with usual features of a neuroendocrine tumour/carcinoid having immunopositivity for insulin. [4]

Hence, nesidioblastosis needs to be differentiated from insulinoma in the infants and in the adults presenting with persistent hyperinsulinemic hypoglycemic conditions. A confirmatory diagnosis is difficult to ascertain by routine investigations. DOTANOC scan is very sensitive and specific to differentiate between focal and diffuse PHHI with an accuracy of 96% in diagnosing focal or diffuse disease. [5] Histopathology can further characterize in DOTANOC proved cases of islet cell lesions in infancy to insulinoma or focal form of nesidioblastosis, particularly in localized tracer uptake. This was found to be very useful in this case.

   References Top

Glaser B, Landau H, Smilovici A, Nesher R. Persistent hyperinsulinaemic hypoglycaemia of infancy: Long-term treatment with the somatostatin analogue Sandostatin. Clin Endocrinol (Oxf) 1989;31:71-80.  Back to cited text no. 1
Prashanth GP, Kurbet SB. Comment on persistent hyperinsulinemic hypoglycemia of infancy. J Indian Assoc Pediatr Surg 2013;18:92.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
James C, Kapoor RR, Ismail D, Hussain K. The genetic basis of congenital hyperinsulinism. J Med Genet 2009;46:289-99.  Back to cited text no. 3
Jain M, Singh S, Madan NK, Choudhury SR. Diffuse nesidioblastosis of the pancreas in a neonate with seizures. Indian J Pathol Microbiol 2011;54:864-6.  Back to cited text no. 4
[PUBMED]  Medknow Journal  
Arun S, Rai Mittal B, Shukla J, Bhattacharya A, Kumar P. Diffuse nesidioblastosis diagnosed on a Ga-68 DOTATATE positron emission tomography/computerized tomography. Indian J Nucl Med 2013;28:163-4.  Back to cited text no. 5
[PUBMED]  Medknow Journal  

Correspondence Address:
Dr. Ravindra Kumar Saran
Depatment of Pathology, G. B. Pant Hospital, New Delhi - 110 002
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.162939

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