Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood. bipolar disorder ͉ circadian rhythms ͉ dopamine

Membranous basal cell adenoma (MBCA) is a rare benign salivary gland neoplasm. It is difficult to diagnose MBCA based on fine-needle aspiration (FNA) cytology due to rare reporting of its FNA cytology and overlapping of its FNA cytologic features with some benign and malignant entities. We present a case of MBCA in a 67-year-old female that was originally misinterpreted as adenoid cystic carcinoma (ACC) on FNA cytology. The FNA smears showed numerous uniform small basaloid epithelial cells with round or oval nuclei and inconspicuous nucleoli, and scant cytoplasm. The basaloid cells surround acellular, dense, homogenous material or are surrounded by acellular or paucicellular dense homogeneous material possibly containing bland spindle cells. The basaloid cells are present in variably sized three-dimensional clusters, acini, or sheets with variable cohesion. The dense homogenous material surrounded by basaloid cells may be interconnected. High power magnification reveals the homogeneous material to have a fibrillar texture. The edges of dense homogenous materials were well-demarcated. We describe the diagnostic pitfalls of FNA for MBCA, particularly versus ACC, basal cell adenoma, cellular pleomorphic adenoma, myoepithelioma, basal cell adenocarcinoma, and basaloid squamous cell carcinoma in hope of improving clinical management and patient treatment.

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Malignant melanoma has a variety of morphologic patterns and can metastasize and mimic any type of neoplastic process creating significant diagnostic difficulty. When metastasis to the gastrointestinal system is identified, it is most commonly associated with widely metastatic disease. We report a rare case of isolated gallbladder intramucosal metastatic melanoma with features mimicking lymphoepithelial carcinoma in an adult patient who presented with cholecystitis. Additionally, we report the imaging and morphologic features and discuss the importance of these findings along with a clear clinical history and immunohistochemical profile to make a definitive diagnosis.