Faculty Bibliography

The ketogenic diet, a diet high in fat and extremely low in carbohydrates, has recently gained momentum and is increasingly employed by patients in order to lose weight. We report a case of an otherwise healthy 47-year-old male who developed seizures and hypoglycemia shortly after initiating this diet. Biochemical testing confirmed hyperinsulinemic hypoglycemia and a subsequent abdomen MRI showed a pancreatic mass. The tumor was ultimately excised with pathology confirming an insulinoma. It was felt that his abrupt decrease in carbohydrate consumption led to the rapid unmasking of this tumor.

The pathogenesis of uterine leiomyosarcomas (LMS) is poorly understood. It is unknown if these tumors arise de-novo or from pre-existing leiomyomata (LM) or atypical leiomyomata. In this study, we evaluated morphologic heterogeneity within uterine LMS to identify possible precursor lesions. We reviewed 11 cases of total hysterectomy in which the final diagnosis was LMS. All slides from the grossly recognized tumor were evaluated for the degree of atypia and mitotic counts within the leiomyosarcomas. The slides with the lowest and highest mitotic count were stained with monoclonal antibody to p53, MIB-1 and ER/PR. The number of cells stained was subjectively assessed to nearest 5%, with 1% for rare positive cells. Morphologically benign tumor areas were identified in 5 of the 11 tumors. These areas showed <5 mitoses/10 HPF, with 1+ atypia in 4 cases and 1-2+ atypia in 1 case. No necrosis was seen by definition. Immunostains could be done in 4 of these 5 cases. These morphologically benign areas showed a p53 expression of 1% in each of the 4 cases, with low MIB-1 (5 to 15%) and high ER/PR expression (ER: 50-100%, PR: 10-100%). Morphologically malignant areas had 13 to 31 mitoses/10 HPF, 2+ to 3+ atypia, p53 expression of 70% to 100%, MIB-1 expression of 40% to 100%, ER expression of 1 to 100% and PR expression of 1 to 100%. The benign and malignant areas merged in all cases. Morphologic and immunohistochemical spectrum of changes from benign to malignant is seen in 50% of LMS. This raises the possibility of progression of some leiomyomata to LMS

CDX-2 is a homeobox gene, which encodes a transcription factor that plays a vital role in the development and differentiation of intestinal epithelial cells. Recent studies showed that CDX-2 protein expression by immunohistochemistry (IHC) has a high predictive value for confirming the diagnosis of colorectal adenocarcinoma (ACA). The differentiation of primary pulmonary ACA from metastatic colorectal ACA can be extremely challenging on fine-needle aspiration (FNA). The results of immunostains for TTF-1, CK 7, and CK 20 may be controversial in the differential diagnosis. In this study, we evaluated the clinical utility of CDX-2 in lung FNA specimens. Cell blocks from 41 primary lung and 20 colorectal ACAs metastatic to the lungs were retrieved. Cell block sections were immunostained with a CDX-2 monoclonal antibody. Sensitivity and specificity of CDX-2 for colorectal ACA was 75 and 100%, respectively. All five cases negative for CDX-2 were moderately to poorly differentiated colorectal ACAs. Our study confirms that CDX-2 is a highly useful immunohistochemical marker for the differentiation of primary pulmonary ACA from colorectal ACA metastatic to the lungs in FNA specimens. Of diagnostic importance is the loss of CDX-2 immunoreactivity in poorly differentiated colorectal ACAs. Diagn. Cytopathol. 2006;34:191-195. (c) 2006 Wiley-Liss, Inc