Adult-Onset Nesidioblastosis: A Challenging Diagnosis Revealed by Endoscopic Ultrasonography

Introduction

Nesidioblastosis, first described by Laidlaw in 1938, is a rare disease characterized histologically by a normal structure of the Langerhans islets, but with cells exhibiting hypertrophy and/or hyperplasia and enlarged and hyperchromatic nuclei [1]. According to the available literature, nesidioblastosis most probably accounts for only 1% to 5% of all cases of hyperinsulinemic hypoglycemia in adults, whereas insulinoma remains the most common cause [1,2]. Confirmation of the diagnosis requires fulfillment of the major histopathologic criteria. The presented case report provides valuable insight into the diagnostic challenge of distinguishing between an undetected insulinoma and nesidioblastosis. Considering the rarity of this diagnosis in adult patients and the limited number of published cases, we believe that this case report is a meaningful contribution to the existing literature.

Case Report

DIAGNOSTIC TESTS:

Initially, we focused on confirming endogenous hyperinsulinemia. In November 2021, we attempted to perform a standardized 72-hour fasting test, which is considered positive if the following criteria are met: plasma glucose level 2.4 mmol/L or lower, immunoreactive insulin level of 3 μU/mL or higher, and C-peptide level of 0.6 ng/mL or higher [4]. The fasting test was terminated at a glucose level of 2.4 mmol/L, due to severe symptoms of hypoglycemia. The C-peptide level was 2.07 Ug/L and the insulin concentration reached 3.8 mU/L. Complete laboratory results of our patient are presented in Table 1.

Based on the laboratory findings, insulinoma was considered a potential cause of the patient’s symptoms. To confirm or exclude this diagnosis, we pursued multiple diagnostic pathways. Initially, a gastroenterologist recommended endoscopic ultrasonography, which revealed an area of echogenic inconsistency measuring 8.2×6.8 mm in the body and tail of the pancreas; however, the findings were not characteristic of an insulinoma. A fine-needle aspiration biopsy was performed during the procedure. Histopathologic examination of the limited material did not confirm the presence of malignant cells, neuroendocrine tissue, or co-expression of synaptophysin, insulin, or CD56.

Due to the nonspecific findings on endoscopic ultrasonography and limited information obtained from the histopathologic examination, we proceeded with additional objective imaging modalities, including computed tomography (CT) and 68Gallium DOTA-D-Phe1-Tyr3-Octreotide imaging to reliably exclude insulinoma, including potential distant metastases. Simultaneously, we scheduled pancreas-focused magnetic resonance imaging (MRI) to characterize the heterogeneous area in the pancreatic tail and body more precisely. However, none of these imaging modalities revealed any suspicious focal lesions throughout the entire body. The complete diagnostic timeline is illustrated in Table 2.

Based on the patient’s symptoms and the results of prior laboratory tests and imaging studies, we considered nesidioblastosis a diagnosis by exclusion. A consulting hepatopancreatobiliary surgeon recommended laparoscopic resection of a small portion of the pancreatic tail to obtain a more representative tissue sample directly from the heterogeneous area. During the procedure, performed in January 2023, intraoperative ultrasonography was used to reliably rule out the presence of any focal lesions within the pancreas.

The histopathologic examination of the obtained sample revealed an increased number of Langerhans islets with abnormalities in shape and size. In addition, the sample demonstrated an increased number of b cells with enlarged hyperchromatic nuclei or prominent nucleoli (Figure 1A, 1B). The exocrine portion of the pancreas showed no pathological alterations. According to the examining pathologist, the specimen fulfilled the major criteria and several minor criteria for the diagnosis of nesidioblastosis. However, due to the substantial rarity of this diagnosis, the sample was sent for an expert second opinion at a more experienced institution. The second histopathologic examination successfully confirmed the diagnosis of nesidioblastosis in our patient.

SURGICAL INTERVENTION:

In February 2023, a standard laparoscopic distal pancreatosplenectomy was performed. Due to an intraoperative finding suggestive of a pancreatic fistula in the splenic hilum, splenectomy was required as part of the procedure, followed by empiric antibiotic therapy (Figure 2). Approximately 70% of the entire pancreatic tissue was successfully removed during the operation.

FOLLOW-UP:

Distal pancreatectomy was well tolerated, with no postoperative complications. Because a substantial portion of the pancreas had been removed, lifelong pancreatic enzyme replacement therapy was indicated to ensure adequate digestion and nutrient absorption. The patient returned for postoperative evaluation approximately 6 months after surgery. Plasma glucose levels had fully stabilized, ranging from 3.5 to 6.9 mmol/L, with no further episodes of hypoglycemia. A diabetologist recommended a balanced diet with minimized intake of simple carbohydrates with a high glycemic index, along with weight reduction. Following these lifestyle modifications, the patient’s hypoglycemic symptoms completely resolved. She successfully returned to her daily activities without significant physical limitations. She has not experienced hypoglycemic symptoms or exocrine/endocrine pancreatic insufficiency since the surgery.

Discussion

LIMITATIONS:

This case report reflects our unique experience with adult-onset nesidioblastosis in a single patient and therefore cannot be generalized to a broader population. The patient’s data were assessed retrospectively, resulting in certain information being incomplete or previously considered irrelevant during the course of care.

Conclusions

Nesidioblastosis is a rare cause of hyperinsulinemic hypoglycemia in adults and should be considered in the differential diagnosis of patients with persistent hypoglycemia without focal lesions on imaging modalities. Endoscopic ultrasonography has proven to be a valuable tool for detecting heterogeneous pancreatic tissue and should be incorporated in cases of diagnostic uncertainty. The presented case of a young female patient who underwent distal pancreatectomy demonstrates that this procedure is a well-tolerated option that can effectively control clinical symptoms without inducing exocrine or endocrine insufficiency. In our patient, distal pancreatectomy alone resulted in complete symptom eradication and stable plasma glucose levels without the need for additional therapy.