Autoimmune hepatitis type-2 and Epstein-Barr virus infection in a toddler: art of facts or an artifact?

Epstein-Barr virus (EBV) can cause frequently asymptomatic (or anicteric) and self-limited hepatitis, while occasionally may result in considerable cholestatic hepatitis. Herein, we describe the case of a previously healthy toddler (26 month old girl) with prolonged cholestasis, elevated serum transaminases, EBV serology compatible with recent EBV infection and positive anti liver kidney microsomal antibody type 1 which is characteristic of new-onset autoimmune hepatitis type 2. Liver biopsy was also typical of autoimmune hepatitis as attested by the presence of portal inflammation with predominant T-lymphocytes and plasma cells and interface hepatitis. Persistent EBV-related hepatitis was excluded by the absence of viral inclusions and steatosis on liver specimens and negative liver EBV-PCR. In conclusion, our case strongly suggests that in children with prolonged cholestatic hepatitis, positive EBV serology cannot exclude the presence of other causes of liver disease. In this context, autoimmune hepatitis should be considered as an alternate diagnosis, particularly when there is specific liver-related autoantibody detection. In such conditions, liver biopsy seems mandatory in an attempt to achieve a correct and timely diagnosis of a potentially catastrophic disease as autoimmune hepatitis. Although some cases of autoimmune hepatitis type 1 following EBV infection have been reported in adults, to the best of our knowledge, the present case of autoimmune hepatitis type 2 after EBV infection represents the first case in children ever reported in the English literature.

Cystic mesenchymal hamartoma arising in intrathoracic heterotopic liver: a case report.

Intrathoracic heterotopic liver tissue is an exceedingly rare clinical entity. In most patients, it is associated with other congenital defects, including cardiac anomalies, congenital diaphragmatic hernia, pectus excavatum, and intralobar pulmonary sequestration. Although heterotopic liver could potentially lead to the same benign liver diseases that can affect the mother liver, the association of heterotopic liver tissue with tumors in childhood is extremely rare. We describe a unique case of cystic mesenchymal hamartoma arising from an intrathoracic heterotopic liver that was found incidentally during a diaphragmatic eventration repair. Association of ectopic liver tissue with mesenchymal hamartoma has not previously been reported in the literature.

Immunohistochemical expression of cell cycle/apoptosis regulators and epidermal growth factor receptor in pediatric intracranial ependymomas.

Intracranial ependymomas are the third most common primary brain tumor in children. We set out to investigate the expression of p-53, p-27, bcl-2, and epidermal growth factor receptor in 13 pediatric infratentorial ependymomas, in correlation with Ki-67/ MIB-1 proliferation index and prognosis. The median progression-free survival was 37.5 months, and the 5-year overall survival was 50%. There was a statistically significant higher expression of Ki-67 and p-53 index in anaplastic tumors. There was also a higher expression of p-27, bcl-2, and epidermal growth factor receptor in anaplastic tumors, but the difference was not statistical significant. No significant correlation was found between overall survival and level of expression of Ki-67, p-53, p-27, bcl-2, and epidermal growth factor receptor. Epidermal growth factor receptor detection in a considerable number of ependymomas probably reflects its role in the neoplastic transformation and can serve as a therapeutic target.

Expression of epidermal growth factor receptor and HER-2 in pediatric embryonal brain tumors.

BACKGROUND/AIMS: Medulloblastomas (MBs), atypical teratoid rhabdoid tumors (AT/RTs) and central nervous system primitive neuroectodermal tumors (PNETs) are aggressive embryonal brain neoplasms in children with overlapping histological features but with different pathogenetic pathways. We set out to evaluate the role of epidermal growth factor receptor (EGFR), HER-2, Ki-67 and p53 in embryonal tumors. MATERIAL AND METHODS: We retrospectively evaluated 36 children with embryonic tumors (27 MBs, 7 AT/RTs and 2 supratentorial PNETs). The immunohistochemical expression of EGFR and HER-2 was correlated to histology, expression of the Ki-67/MIB-1 proliferative index, p53 tumor suppressor oncoprotein and prognosis. RESULTS: High expression of Ki-67 was observed in all MBs being particularly increased (> 50%) in 8 cases, while p53 protein was detected in 25/27 MBs showing a high expression in 16 cases. EGFR and HER-2 expression was observed in 10/27 and 17/27 MBs, respectively. High Ki-67/MIB-1 and p53 expression was revealed in all AT/RTs and PNETs, while EGFR and HER-2 were detected in 3/7 and 6/7 AT/RTs, respectively. The 5-year progression-free survival and overall survival were 55.5 and 69.2%, respectively. In MBs, the univariate analysis revealed that the Ki-67 index and male gender were both at a significant level related to the survival of the patient. In multivariate analysis, the Ki-67 index was the only independent predictive variable. CONCLUSIONS: The Ki-67 index was identified as a factor with independent prognostic power. EGFR and HER-2 expression is variable in embryonal tumors. HER-2 expression, in a considerable number of MBs and AT/RTs, suggests that HER-2 may be implicated in their pathogenesis representing a potential target for novel therapies.

Hepatitis C treatment concomitant to chemotherapy as "salvage" therapy in children with hematologic malignancies.

In patients with malignancies, chronic hepatitis C reactivation or severe flare is uncommon and antiviral treatment is deferred mainly due to underlying bone marrow and immune suppression. We report the use of antiviral treatment concomitantly to chemotherapy in 3 children with hematologic malignancies, chronic hepatitis C, and significant liver dysfunction.

Histological and immunohistochemical study of granuloma annulare and subcutaneous granuloma annulare in children.

BACKGROUND: The aim of this study was to investigate the histological and immunohistochemical features of granuloma annulare (GA) in comparison to deep granuloma annulare (DGA) and granulomatous dermatoses (GDs). METHODS: Our material comprised 13 GA, 8 DGA and 1 atypical granuloma annulare (AGA) in a child with primary immunodeficiency, 10 cases of nonspecific GDs and 1 case of sarcoidosis with cutaneous involvement. The immunohistochemical streptavidin-biotin-Horseradish peroxidase (HRP) analysis was performed on paraffin sections for the detection of CD68/KP-1, CD68/anti-human CD68 clone PGM1 (PGM1), lysozyme, S-100 protein, CD1a, CD3, CD20/L-26, CD4 and CD8. RESULTS: All 13 GA were characterized by typical palisading and interstitial granulomas. In 6 cases, the lesion extended to the subcutaneous fat, while a considerable perivascular lymphocytic infiltrate without any signs of vasculitis was observed in 10 cases. The DGA were located to the deep dermis and subcutaneous fat, showing palisading granulomas with central necrobiosis. Immunohistochemistry revealed a broad intense expression of CD68/PGM1 in the histiocytic population in all cases, a constant but fainter detection of CD68/KP-1 and a variable one of lysozyme. T-cell markers (CD3, CD4 and CD8) were mainly detected in the perivascular lymphocytic infiltrate of GA and DGA, with CD4+ T lymphocytes predominating over CD8+ in GA and DGA, while CD8+ T lymphocytes was the predominant population in AGA. CONCLUSIONS: CD68/PGM1 is a sensitive and reliable histiocytic marker in confirming the histiocytic nature of equivocal GA and DGA, but the histiocytic immunoprofile is of no particular usefulness in differentiating GA from other GD.