Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber-Purkinje cell synapses

The cannabinoid CB₁ receptor localizes to the glutamatergic parallel fiber (PF) terminals of the cerebellar granule cells and participates in synaptic plasticity, motor control and learning that are impaired in CB₁ receptor knockout (CB ₁-KO) mice. However, whether ultrastructural changes at the PF-Purkinje cell (PC) synapses occur in CB ₁-KO remains unknown. We studied this in the vermis of the spinocerebellar lobule V and the vestibulocerebellar lobule X of CB ₁-KO and wild-type (CB ₁-WT) mice by electron microscopy. Lobule V, but not lobule X, of CB ₁-KO had significantly less and longer synapses than in CB ₁-WT. PF terminals were significantly larger in both lobules of CB ₁-KO with no changes in PC dendritic spines. The PF terminals in lobule V of CB ₁-KO contained less synaptic vesicles and lower vesicle density; by contrast, vesicle density in lobule X of CB ₁-KO remained unchangeable relative to CB ₁-WT. There were as many vesicles in lobule V of CB ₁-KO as in CB ₁-WT, but their distribution decreased drastically at 300 nm of the active zone. In lobule X of CB ₁-KO, less vesicles were found within 150 nm from the presynaptic membrane; however, no vesicles were at 450–600 nm of the active zone. A significant higher amount of synaptic vesicles close to the active zone in lobule V and X of CB ₁-KO was observed. In conclusion, the absence of CB₁ receptors strikingly and distinctively impacts on the ultrastructural architecture of the PF-PC synapses located in cerebellar lobules that differ in vulnerability to damage and motor functions.     

Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas

Wnt/beta-catenin signaling is frequently activated in cancer cells by stabilizing mutations of beta-catenin or loss-of-function mutations of the APC tumor suppressor gene. We have analysed the role of beta-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age. Sequence analysis of the beta-catenin NH2-terminal domain in 18 epithelial and mixed HBs revealed missense mutations in the GSK3beta phosphorylation motif or interstitial deletions in 12 tumors (67%). In the remaining cases, no truncating mutation of APC could be evidenced. Immunohistochemical analysis of beta-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear beta-catenin immunostaining in undifferentiated cells. Membranous beta-catenin localization was preserved only in fetal-type tumoral hepatocytes and was associated with E-cadherin expression. Moreover, we show that beta-catenin is aberrantly overexpressed in a large spectrum of tumor components, including hepatocyte-like cells at various differentiation stages and heterologous elements such as squamous, osteoid and chrondroid tissues, and in occasional other mesenchymally-derived cells. These data strongly suggest that activation of beta-catenin signaling is an obligatory step in HB pathogenesis, and raise the possibility that it interferes with developmental signals that specify different tissue types at early stages of hepatic differentiation.     

Occipital condyle syndrome secondary to bone metastases from rectal cancer

Skull-base metastases are very unfrequent. Occipital condyle syndrome (OCS) is usually underdiagnosed. Until now few cases have been reported in the literature. We present a 71-year-old woman with metastatic rectum adenocarcinoma, with right occipital headache and ipsilateral hypoglossal palsy, diagnosed by computed tomography and magnetic resonance imaging of OCS due to a skull-base metastasis and treated with radiation therapy.     

Lichen sclerosus et atrophicus in a surgical scar treated with fractional laser

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory disease of unknown cause that typically affects the genital area (1). It has been reported in post-traumatic areas as a result of Koebner phenomenon. LSA responds poorly to treatment making it a therapeutic challenge (2). Laser therapy has been described for LSA with variable results (3,4).     

Multiple adult xanthogranuloma

Juvenile xanthogranuloma is an infrequent, benign, normolipemic, non-Langerhans cell histiocytosis, which primarily affects young children. Clinically, it is characterized by the appearance of one or several brownish-yellow papulonodular lesions on the upper body, especially on the head and neck. Xanthogranulomas are less frequent in adults, and generally present as solitary lesions. The diagnosis of multiple xanthogranulomas in adults is exceptional. We describe the case of a female patient diagnosed with this rare disease.