An Unusual Presentation of Ganglioneuromatosis of Gallbladder in Absence of MEN Type 2b

Abstract

Purpose: Neuronal hyperplasia or ganglioneuromatosis are very rare tumors which may present as components of multiple endocrine neoplasia type 2b (MEN2b). They may evolve from differentiating neuroblastoma or originate as a primary ganglioneuroma. Ganglioneuromas are usually incidental findings. As far as we know, this is a second case report in a literature presenting as an incidental ganglioneuromatosis of gallbladder after elective cholecystectomy for cholelithiasis. Case report: A 36 year old Hispanic female with history of hypothyroidism due to subtotal thyroidectomy for multinodular goiter and cyst was referred to gastroenterology clinic for a symptomatic elevation of liver enzymes. Patient denied history of sweating, palpitation, hypertension, alcohol intake or intravenous drug use. She had marfanoid features on physical examination. Labs revealed ALT 303, AST 167, ALP 224, GGT 103 and TSH 122.22. Antinuclear antibody, anti smooth muscle antibody, sprue serology, iron studies, ceruloplasmin and alpha 1 antitrypsin were unremarkable. Hepatitis serology was negative for Hepatitis A antibody, Hepatitis C antibody and hepatitis B surface antigen. Liver biopsy was also unremarkable. Ultrasound of the abdomen revealed gallstones in gallbladder. Patient subsequently had laparoscopic cholecystectomy and pathology report of the gallbladder specimen showed diffuse subepithelial spindle cell proliferation with rare ganglion cells in the lamina propria. Immunohistochemical stains revealed that spindle cells are positive for S100 and ganglion cells were positive for synaptophysin. The spindle cell proliferation was also present in the cystic duct margin. The staining pattern supported the diagnosis of ganglioneuroma of the gallbladder wall. Patient is being followed up in GI clinic intermittently. Discussion: Ganglioneuromas are asymptomatic regardless of their size, however, may present with abdominal pain, dyspepsia, dyspnea, cough and abdominal mass. Some may be hormonally active and hypertension, diarrhea, flushing and virilization may occur from catecholamine, vasoactive intestinal peptide or androgenic hormone secretion. Tests that can be done if ganglioneuroma is suspected include; CT scan and MRI. Blood and urine testing can also be done for hormonally active tumor. However, the definitive diagnosis is made by tissue biopsy. Treatment is surgical resection of the tumor and prognosis after resection seems to be excellent. Conclusion: Even though Ganglionueromas are benign they may present as a part of MEN type 2b with potentially lethal endocrine neoplasm. Every attempt should be made to look for MEN type 2b with incidental findings of ganglioneuromatosis.