Metachromatic leukodystrophy associated with choledochal cysts and gallbladder papillomatosis

Metachromatic Leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease caused by the deficiency of the enzyme arylsulfatase A which is responsible for the desulfation of cerebroside sulfate, a myelin glycolipid. Accumulation of these sulfatides in the macrophages of various tissues causes a wide spectrum of presentations including central and peripheral nervous system dysfunction and gallbladder abnormalities. We report a case of a 6-year old girl with infantile Metachromatic Leukodystrophy who was found to have elevated liver enzymes, biliary markers and total and direct bilirubin during work-up for unexplained high-grade fever. Imaging showed dilated intra and extra hepatic biliary tree, markedly expanded CBD by dense content and multiple variable sized filling defects with narrowing in between. The dense content was confirmed to be mucosal papillomatosis with hyperplastic epithelium. To the authors' knowledge, obstructive extra-hepatic biliary tree polypoid masses and cystic dilation with metachromatic leukodystrophy have not previously been reported. Keywords: Metachromatic leukodystrophy, Gallbladder papillomatosis, Choledochal cyst

Human Papillomavirus Is Rare and Does Not Correlate with p16^INK4A Expression in Non-Small-Cell Lung Cancer in a Jordanian Subpopulation

Background and Objectives: Human papillomavirus (HPV) was previously investigated in lung cancer with wide inter-geographic discrepancies. p16INK4a has been used as a surrogate for detecting high-risk HPV (HR-HPV) in some cancer types. This study assessed the evidence of HPV in non-small-cell lung cancer (NSCLC) among Jordanian patients, investigated the expression of p16INK4a, and evaluated its prognostic value and association with HPV status. Materials and Methods: The archived samples of 100 patients were used. HPV DNA detection was performed by real-time polymerase chain reaction (RT-PCR). p16INK4a expression was assessed by immunohistochemistry (IHC). The Eighth American Joint Committee on Cancer protocol (AJCC) of head and neck cancer criteria were applied to evaluate p16INK4a positivity considering a moderate/strong nuclear/cytoplasmic expression intensity with a distribution in ≥75% of cells as positive. Results: HPV DNA was detected in 5% of NSCLC cases. Three positive cases showed HR-HPV subtypes (16, 18, 52), and two cases showed the probable HR-HPV 26 subtype. p16INK4a expression was positive in 20 (20%) NSCLC cases. None of the HPV-positive tumors were positive for p16INK4a expression. A statistically significant association was identified between p16INK4a expression and the pathological stage (p = 0.029) but not with other variables. No survival impact of p16INK4a expression was detected in NSCLC cases as a group; however, it showed a statistically significant association with overall survival (OS) in squamous cell carcinoma (SqCC) cases (p = 0.033). Conclusions: This is the first study to assess HPV and p16INK4a expression in a Jordanian population. HPV positivity is rare in NSCLC among a Jordanian subpopulation. P16 INK4a reliability as a surrogate marker for HPV infection in lung cancer must be revisited