Ganglioneuroma of the pancreas in a 4-year-old girl

Abstract

Ganglioneuroma (GN) is the uncommon, benign representative of the peripheral neuroblastic tumours (PNTs), which arise from primitive sympathetic ganglion cells. PNTs comprise one of the most common groups of neoplastic diseases in infants and children, but its occurrence in the pancreas is rare. We report a 4-year-old girl with GN of the pancreas requiring pancreaticoduodenectomy as a definitive therapy and with a great outcome, and we review the published literature.

Background

Peripheral neuroblastic tumours (PNTs), which include neuroblastoma (NB), ganglioneuroblastoma (GNB) and ganglioneuroma (GN), are derived from immature sympathetic neuroblasts and are found in the locations of embryonic migrating neural crest cells, such as adrenal medulla and structures of the sympathetic nervous system in the thorax, abdomen and pelvis.¹ PNTs are the most common solid tumours in children; however, their occurrence within the pancreas is rare. We report the case of a 4-year-old girl with pancreatic GN who underwent pancreaticoduodenectomy (PD) with curative intent. This is the first case report of a pancreatic GN in the paediatric population based on our literature search.

Case presentation

A 4-year-old girl was found to have an incidental, low-attenuation, 2.5×2.5×3.3 cm pancreatic head mass on abdominal CT after a motor vehicle accident. The mass did not enhance between the arterial and venous phases. Lymphadenopathy or extrapancreatic extension was not found (figure 1). Preoperative laboratory data did not reveal elevated liver function tests, pancreatic enzymes, α-fetoprotein, CA 125 or CA 19-9. She was asymptomatic; however, due to the nature of the mass, inability to rule out malignancy, and its difficult location to perform percutaneous biopsy, surgical resection was recommended to the guardians, who agreed.

Figure 1.

CT scan of the pancreatic tumour. CT scan of the abdomen revealed low-attenuation mass in the head of the pancreas, 2.5×2.5×3.3 cm in size (yellow arrow).

Treatment

Laparotomy revealed no evidence of metastatic or peritoneal disease. After Kocher's mobilisation of the duodenum, a hard pancreatic head tumour was palpated without signs of invasion to surrounding structures. The tumour was extremely adherent to the posterior pancreatic head, which precluded enucleation with clear borders. The decision was made to proceed with PD. The patient underwent a pylorus-preserving PD and feeding jejunostomy catheter placement. The pancreas was transected with electrocautery at the level of superior mesenteric vein, and the specimen was removed without violating the tumour. Large retroperitoneal lymph nodes were identified and removed. A Child's operative reconstruction was then performed, which included retrocolic pancreatic-jejunostomy using the invagination technique with pledgeted 5-0 Prolene sutures, hepatico-jejunostomy with 5-0 PDS sutures and antecolic gastro-jejunostomy with a single layer of 4-0 PDS interrupted sutures, without placement of stents.

Gross evaluation of the specimen showed an intrapancreatic, pale tan-white, well-circumscribed rubbery mas measuring 3.5×3.0×3.0 cm (figure 2A). The mass abutted the pancreatic duct but did not invade past the parenchyma. Microscopic examination of the mass showed that it was composed of sheets, cords and islands of fibrocollagen with numerous peripheral nerve fragments (figure 2B). All these structures were uniform, bland and without interruption. In isolated areas, there were small clusters of ganglion cells with mild variation in morphology with some having less cytoplasm and appearing to be less well differentiated but most were mature with abundant basophilic cytoplasm (figure 2C). The pathological findings were consistent with GN. Resection margins were free of tumour and lymph nodes and bone marrow, bone scintigraphy and MIBG scan were negative for metastasis.

Figure 2.

Pathology of ganglioneuroma of the pancreas. (A) Operative specimen that is composed of a 21.0 cm long×2.5 cm in diameter portion of small bowel, attached 5.0×4.0×3.0 cm portion of pancreas and an attached 6.6×2.3×1.8 cm gallbladder. (B) Microscopic examination of the mass shows bland uniform sheets, cords, islands of fibrocollagen and numerous peripheral nerve fragments (haematoxylin and eosin stain, 100× magnification). (C) Clusters of mature ganglion cells with abundant basophilic cytoplasm and eccentric nuclei with prominent nucleoli (haematoxylin and eosin stain, 200× magnification).

Outcome and follow-up

She has been doing well without findings of recurrence for 3 years after surgery. She does not have diarrhoea or any other gastrointestinal symptoms. Her nutrition has been excellent, and her growth has been within the normal range. She tolerates a regular diet with no glucose intolerance, takes no medication and does not require enzymatic replacement or insulin.

Discussion

PNTs are classified according to the balance between neural-type cells and Schwann-type cells into one of three types: NB, GNB or GN.² The biologically favourable tumours have a potential of involution/spontaneous regression or tumour maturation with or without chemotherapy and/or radiation therapy. In contrast, the biologically unfavourable tumours progress aggressively and often are fatal despite intensive treatment.¹

NB is the most undifferentiated and aggressive tumour among PNTs. Over 80% of children diagnosed with NB during infancy survive 5 years following diagnosis. In contrast, for children diagnosed with NB at age 1 year or older, the 5-year relative survival was reported to be about 45%.³ While patients with localised NB have excellent outcome with surgical excision of the tumour alone, a high-risk group of patients seem to require treatment with multiagent chemotherapy, surgery and radiotherapy, followed by consolidation with high-dose chemotherapy and peripheral blood stem cell rescue.⁴

GN is the rare and benign tumour among PNTs, which occur prevalently in childhood like the other PNTs.⁵ GN is predominantly composed of Schwannian cells studded with maturing or fully mature ganglion cells.^6–8 This tumour is more common in older children (5–7 years of age), while the other more aggressive PNTs tend to occur in younger patients. The prognosis of GN is favourable even when complete tumour removal is not possible. Surgical intervention is still indicated for GN, due to potential local tumour progression and malignant transformation.⁵

Even though PNTs are a relatively common tumour in the paediatric population, the occurrence in the pancreas is extremely rare. To the best of our knowledge, there are only 9 cases of pancreatic PNTs reported in the English literature from 1990 to 2015^9–15 (5 cases of NB and 3 cases of GN including our paediatric presented case). A case report of an 8-week-old female infant with disseminated ganlioneuromatosis involving the pancreas was not included.¹⁶ These reported cases are summarised in table 1.

Table 1.

Reported cases of PNTs

Author and year	Age	Sex	Type of tumour and size	Operation/other treatment	Presentation and brief description
Hoeffel et al,10 1991	4 years	M	NB	DP/adjuvant chemoradiation	Tumour extended into mesocolon, but no lymph node involvement. Received adjuvant chemoradiation, disease free for 7 years.
Christein et al,14 2002	28 years	F	GN	CP	History of adrenal NB.
Kumar et al,11 2010	7 days	M	Poorly diff. NB, 4 cm	DP	Prenatally diagnosed on CT. Disease free at 1 year.
Muller et al,12 2012	8 months	M	NB	PD/NAC	Abdominal mass, elevated urine catecholamine level. Disease free until the report.
Muller et al,12 2012	21 months	F	NB	PD with positive margin/AC	Opsomyoclonic syndrome, obstructive jaundice. Complete response at 3 years
Kargl et al,9 2012	3 weeks	M	Poorly diff. NB, 5 cm	DP	Abdominal pain, diagnosed on US. MIBG with good uptake on the lesion without metastasis. Disease free at 1 year.
Galgano et al,15 2015	21 months	F	NB with unfavourable histology, 3.6 cm	Unresectable/chemotherapy	Ataxia, opsoclonus–myoclonus syndrome/responded to chemotherapy
Poves et al,13 2009	33 years	F	GN	Uncinectomy	Epigastric discomfort and diarrhoea/diagnostic FNA was inconclusive.
Presented case	4 years	F	GN, 3.5 cm	PD	Incidentaloma on CT after MVC. Chyle leak after surgery.

AC, adjuvant chemotherapy; CP, central pancreatectomy; DP, distal pancreatectomy; FNA, fine-needle aspiration; GN, ganglioneuromas; MVC, motor vehicle collision; NAC, neo-adjuvant chemotherapy; NB, neuroblastoma; PNTs, pancreatic neuroblastoma tumors; PD, pancreaticoduodenectomy; US, ultrasonography.

The loss of pancreatic exocrine and endocrine function after pancreatic resection remains a concern for paediatric patients. There are no large studies that address pancreatic function after pancreatic resection in children. Sugito et al¹⁷ reported in their case series two 10-year-old patients who underwent PD for pancreatic tumours who developed mild increase of HbA1c levels but remained normal range, and a softer consistency of stool for 3 years, but returned to normal eventually. Growth disorders were not observed after more than 7 years of follow-up.

In conclusion, GN is an extremely rare and benign tumour that can also present as a pancreatic mass. Surgical resection should be cautiously considered as a treatment option of GN, considering its possible complications depending on the tumour presentation and location. Considering GN potential malignancy transformation, we recommend surgical resection when the preoperative diagnosis is inconclusive and surgical risk factors are acceptable. After pancreatic resection and recovery, surgeons should be vigilant of possible development of pancreatic insufficiency and assess long-term nutritional status.

Learning points.

• Pancreatic neuroblastic tumours in children are rare; only nine cases have been reported, including the present case.

• Surgical resection, including pancreaticoduodenectomy (PD) based on tumour location, should be considered for paediatric patients with pancreatic neuroblastic tumours.

• Patient follow-up including nutritional assessment is important in children after PD.