Severe Neonatal Cholestasis in Cerebrotendinous Xanthomatosis: Genetics, Immunostaining, Mass Spectrometry.

OBJECTIVES: Cerebrotendinous xanthomatosis (CTX) is caused by defects in sterol 27-hydroxylase (CYP27A1, encoded by CYP27A1), a key enzyme in the bile acid synthesis pathway. CTX usually presents as neurologic disease in adults or older children. The rare reports of CTX manifest as neonatal cholestasis assess the cholestasis as transient, with patient survival. Our experience differs. METHODS: Homozygous or compound heterozygous CYP27A1 mutations were detected in 8 neonatal cholestasis patients by whole exome sequencing, panel sequencing, or Sanger sequencing. Their clinical and biochemical data were retrospectively reviewed. Immunostaining for CYP27A1 was conducted in liver of 4 patients. Mass spectrometry was used to analyze patients' urine samples. RESULTS: All 8 infants had severe cholestasis. Five died from, or were transplanted for, liver failure; 3 cleared their jaundice eventually. Marking for CYP27A1 was weak or absent in 3 of the 4 patient specimens. Mass spectrometry of urine revealed a predominance of sulfated and doubly conjugated (sulfated-glucuronidated) bile alcohols. No patient harbored a putatively pathogenic mutation in genes other than CYP27A1 that have been implicated in cholestatic liver disease. CONCLUSIONS: CTX manifest as neonatal cholestasis has a bile acid profile different from CTX manifest in later life, and thus may be overlooked. Immunostaining, mass spectrometry of urine, and genetic studies can support one another in making the diagnosis. A substantial proportion of CTX patients with severe neonatal cholestasis may die or need liver transplantation. CTX manifest in infancy as severe cholestasis warrants further investigation of biochemical diagnostic criteria and best management.

Microcystic/reticular schwannoma of the pancreas: a potential diagnostic pitfall.

Schwannomas occurring in the pancreatic head are rare benign non-recurring mesenchymal neoplasms and are reported to show classic morphologic features. Herein we report a case of a 62 year old male presenting with a 5 cm mass in the pancreatic head encasing the portal vein and the truncus coeliacus. Preoperative fine needle aspiration revealed malignant tumour cells consistent with a moderately differentiated adenocarcinoma. A Whipple surgery was performed after palliative chemotherapy. Histological evaluation revealed a multinodular unencapsulated tumour with focal infiltration into pancreas parenchyma and a striking microcystic/reticular growth pattern. Anastomosing and intersecting strands of spindle cells with eosinophilic cytoplasm set in a myxoid partly collagenous stroma were observed. The tumour cell nuclei were round oval and tapered and showed inconspicuous small nucleoli. Degenerative nuclear atypia was seen. Mitotic activity was sparse (1/50 HPF). Pleomorphism or necrosis was absent. The tumour cells showed strong nuclear and cytoplasmic positivity for S-100 protein, and focal positivity for glial fibrillary acidic protein. The diagnosis of a microcystic/reticular schwannoma was made. The awareness of and, to some extent, the knowledge about this rare tumour are needed to achieve the correct diagnosis and to avoid confusion, especially with malignant pancreatic neoplasms.