Calretinin Staining in Anorectal Line Biopsies Accurately Distinguished Hirschsprung Disease in a Retrospective Study.

INTRODUCTION: The absence of submucosal ganglion cells does not reliably distinguish Hirschsprung disease from non Hirschsprung disease in anorectal line biopsies. Calretinin staining might be helpful in these biopsies. To determine its value, we analyzed calretinin positive mucosal neurites in anorectal line biopsies. METHODS: Two pediatric pathologists, without access to patient data, evaluated calretinin positive mucosal neurites in anorectal line junctional mucosa in archival rectal biopsies contributed by 17 institutions. A separate investigator compiled patient information and sent data for statistical analysis. RESULTS: Biopsies with anorectal junctional mucosa from 115 patients were evaluated for calretinin positive mucosal neurites. 20/20 Hirschsprung disease biopsies were negative. 87/88 non Hirschsprung disease biopsies and 7/7 post pullthrough Hirschsprung disease neorectal biopsies were positive. Statistical analysis of the 108 non pullthrough biopsies yielded an accuracy of 99.1% (sensitivity 100%, specificity 98.9%). Age range was preterm to 16 years. Biopsy size was less than 1 mm to over 1 cm. CONCLUSIONS: Absence of calretinin positive mucosal neurites at the anorectal line was highly accurate in distinguishing Hirschsprung disease from non Hirschsprung disease cases in this blinded retrospective study. Calretinin staining is useful for interpreting biopsies from the physiologic hypoganglionic zone up to the anorectal line.

A patient with atypical presentation of chronic hepatosteatosis harboring a novel variant in the CPT1A gene.

Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare disorder of hepatic long-chain fatty acid oxidation. Most patients with CPT1A deficiency present with hypoketotic hypoglycemia and hepatic encephalopathy. We describe an atypical case of an 8-year-old male with CPT1A deficiency presenting with chronic liver steatosis and cirrhosis. He also had a history of developmental delay, autism spectrum disorder, and mild dysmorphic features of unknown cause. His newborn screening test suggested CPT1A deficiency, but confirmatory biochemical testing was not conclusive. The patient never experienced a metabolic crisis. At age six, hepatomegaly was detected. Further investigations showed transaminitis, hepatosteatosis and cirrhosis. Repeat acylcarnitine profile and total/free carnitine were consistent with CPT1A deficiency. The CPTI enzyme activity was 18% of normal on fibroblast enzyme assay. A novel homozygous variant in the CPT1A gene, c.1394G > A (p.Gly465Glu) was identified from whole-exome sequencing. To our knowledge, the patient is the first reported individual with CPT1A deficiency and chronic liver steatosis and fibrosis. Developmental delay and autistic spectrum disorder are not typical features of CPT1A deficiency, given that the patient never experienced any metabolic decompensation.

Intracardiac Fungal Mass in a Term Neonate.

Systemic fungal infections pose insidious challenges in neonatal intensive care settings. We present the case of a 9-day-old male term neonate admitted for polymicrobial sepsis and hepatic dysfunction who later developed candidemia superinfection. Despite broad antifungal therapy, the fungemia was complicated by progressive growth of a fungus ball in the right ventricular outflow tract that threatened cardiac function. Surgical excision of the mass was undertaken by right atriotomy and histologic examination confirmed Candida albicans.

Durable response of intracranial cellular hemangioma to bevacizumab and temozolomide.

Cellular hemangioma is a subtype of hemangioma that is associated with cellular immaturity and the potential for recurrence. Intracranial location of these lesions is extremely rare, and definitive treatment often requires radical neurosurgical resection. The authors report a case of a 12-year-old boy with a subtemporal cellular hemangioma. He underwent gross-total resection of the tumor, but within 1.5 months the tumor recurred, necessitating a second resection. Because of its proximity to vascular structures, only subtotal resection was possible. Repeat MRI 1 month after the second surgery showed significant tumor recurrence. Given the tumor's demonstrated capacity for recurrence and its proximity to the vein of Labbé and sigmoid sinus, further resection was not indicated. In an effort to limit radiation therapy for this young patient, treatment with bevacizumab and temozolomide was chosen and achieved a complete response that has proven durable for 36 months after cessation of therapy. This is the first report of the successful use of chemotherapy to treat an intracranial hemangioma, a rare condition with limited therapeutic options.

Topically applied imiquimod inhibits vascular tumor growth in vivo.

Vascular tumors occur in approximately 10% of all infants and may be associated with significant morbidity. Available therapies for vascular tumors, such as systemic corticosteroids, vincristine, and interferon-alpha, may cause toxicity, limiting their use to complicated cases. Using a mouse hemangioendothelioma model, we investigated the efficacy and mechanism of action of imiquimod, a topically applied inducer of cytokines. Application of imiquimod cream, whether initiated at the time of cell inoculation or when tumors became visible, significantly decreased tumor growth and increased animal survival in comparison with control mice. Imiquimod-treated tumors showed decreased tumor cell proliferation, increased tumor apoptosis, and increased expression of tissue inhibitor of matrix metalloproteinase-1 with decreased activity of matrix metalloproteinase-9. The demonstration that local application of imiquimod inhibits vascular tumor enlargement in the mouse vascular tumor model suggests a novel, less toxic means of treating infantile hemangioendotheliomas and perhaps other cutaneous vascular tumors.