Histologic transformation of EGFR mutant lung adenocarcinoma without exposure to EGFR inhibition.

Resistance to EGFR kinase inhibitors appears to be invariable in the treatment of non-small cell lung cancer. Several mechanisms have been described. Here, we report the first case of histologic transformation of EGFR mutant lung adenocarcinoma without prior exposure to EGFR inhibition.

Defining early mycosis fungoides: validation of a diagnostic algorithm proposed by the International Society for Cutaneous Lymphomas.

BACKGROUND: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma and is often difficult to diagnose. Early-stage disease is particularly challenging and requires clinical and histopathologic correlation to make an accurate diagnosis. In order to facilitate the diagnosis of early MF, an algorithm has been proposed by the International Society for Cutaneous Lymphomas (ISCL) whereby clinical and histopathologic characteristics as well as immunohistochemistry and T-cell receptor gene rearrangement studies may be applied to suspected cases of MF. The diagnostic utility of this algorithm has not yet been validated. We sought to determine the validity of the proposed algorithm via an investigator-blinded, retrospective, case-control study. METHODS: A total of 34 cases were randomly selected from the database of a clinic for cutaneous T-cell lymphomas and included patients with MF and patients with clinicopathologic mimics. The proposed diagnostic algorithm was systematically applied to the entire cohort. Each case was assigned a composite score based on the parameters in the proposed algorithm. RESULTS: Among the 24 cases of MF, 21 cases achieved four or more points through application of the algorithm. Among the 10 cases of MF mimics, only four achieved four or more points. This difference was significant (Fisher's exact test, p = 0.009). The sensitivity of the 4-point threshold for a diagnosis of MF was 87.5% and the specificity was 60%. CONCLUSIONS: The diagnostic algorithm proposed by the ISCL is a statistically valid method for defining cases of early MF and distinguishing these cases from other benign dermatoses. However, the clinical utility of the algorithm may be limited by its low specificity. Further refinement of the algorithm may improve its accuracy.

Intestinal edema: effect of enteral feeding on motility and gene expression.

OBJECTIVE: Edema formation, inflammation, and ileus in the intestine are commonly seen in conditions like gastroschisis, inflammatory bowel disease, and cirrhosis. We hypothesized that early enteral feeding would improve intestinal transit. We also wanted to study the impact of early enteral feeding on global gene expression in the intestine. DESIGN: Rats were divided into Sham or Edema +/- immediate enteral nutrition (IEN). At 12 h, small intestinal transit via FITC-Dextran and tissue water were measured. Ileum was harvested for total RNA to analyze gene expression using cDNA microarray with validation using real-time PCR. Data are expressed as mean +/- SEM, n = 4-6 and (*), (**) = P < 0.05 versus all groups using ANOVA. RESULTS: IEN markedly improved intestinal transit with minimal genetic alterations in Edema animals. Major alterations in gene expression were detected in primary, cellular and macromolecular metabolic activities. Edema also altered more genes involved with the regulation of the actin cytoskeleton. CONCLUSIONS: Intestinal edema results in impaired small intestinal transit and globally increased gene expression. Early enteral nutrition improves edema-induced impaired transit and minimizes gene transcriptional activity.

Fine needle aspiration biopsy and immunostaining findings in an aggressive inflammatory myofibroblastic tumor of the lung: a case report.

BACKGROUND: Inflammatory myofibroblastic tumors (IMTs) can vary from benign pseudosarcomatous tumors to low grade sarcomas. To date, fine needle aspiration (FNA) findings of lung IMTs, especially in the aggressive form, have not been fully described. Here we present FNA biopsy findings in conjunction with immunohistochemical studies in a case of primary and recurrent pulmonary IMT. CASE: A 22-year-old man first presented with a left lung mass and 4.5 years later with a recurrent mass. Preoperative computed tomography-guided FNA was performed on both tumors. FNA cytologic smears of both specimens consisted of scant, distorted spindle cells suggestive of a spindle cell lesion but were insufficient for further classification. Needle core biopsies as well as touch imprints were performed during the FNA procedures. The imprints revealed abundant, well-preserved spindle cells with mild to moderate atypia and intermixed lymphocytes and plasma cells. The spindle cells in both specimens were immunoreactive for vimentin and smooth muscle actin and were negative for pancytokeratin, desmin, CD34 and c-kit. Thirty percent of the tumor cells were positive for p53. The findings were compatible with those of IMT. Histologic examination of the surgically resected initial and recurrent masses confirmed the diagnosis of lMT. CONCLUSION: The cytologic findings of pulmonary IMT in FNA specimens are suggestive of, although not specific for, IMT. Immunohistochemical studies can assist in the diagnosis by excluding other spindle cell lesions. Cytologic atypia and p53 immunoreactivity may be indicators of aggressive IMTs.

8-Hydroxyguanosine repair is defective in some microsatellite stable colorectal cancer cells.

Mutator phenotypes are involved in the carcinogenesis of some cancers, e.g., defects in mismatch repair produce a mutator phenotype that drives carcinogenesis and causes microsatellite instability in hereditary nonpolyposis colon cancers and some sporadic colorectal cancers (CRC). Less understood, however, is the potential role of mutator phenotypes in microsatellite stable (MSS) CRC carcinogenesis. A novel transversion mutator phenotype was reported recently in an MSS CRC cell line. We hypothesized that 8-hydroxyguanosine could be involved and found elevations in 5 of 15 (33%) MSS CRC cell lines analyzed. Repair of an adenine*8-hydroxyguanosine mispair was functionally defective in the same five cell lines. The human MutY homologue transcript and MutY homologue protein levels were also decreased. These findings may reflect a MSS mutator phenotype contributing to the development of CRC.

Aspergillus Mural Vegetation Identified by Transesophageal Echocardiography.

We report a case of Aspergillus sp. mural or nonvalvular endocarditis, which was diagnosed by transesophageal echocardiography (TEE) as a vegetation attached to the anterolateral papillary muscle of the left ventricle. Mural endocarditis is often missed by transthoracic echocardiography (TTE) as was the case with this patient. TEE easily identified the vegetation.