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Tall cell carcinoma with reverse polarity is a rare subtype of breast carcinoma with solid and papillary growth and nuclear features reminiscent of those of the tall cell variant of papillary thyroid carcinoma. These tumors harbor recurrent IDH2 R172 hotspot mutations or TET2 mutations, co-occurring with mutations in PI3K pathway genes. Diagnosis of tall cell carcinomas with reverse polarity is challenging in view of their rarity and the range of differential diagnosis. We sought to determine the sensitivity and specificity of IDH2 R172 immunohistochemistry for the detection of IDH2 R172 hotspot mutations in this entity. We evaluated 14 tall cell carcinomas with reverse polarity (ten excision and five core needle biopsy specimens), 13 intraductal papillomas, 16 solid papillary carcinomas, and 5 encapsulated papillary carcinomas by Sanger sequencing of the IDH2 R172 hotspot locus and of exons 9 and 20 of PIK3CA, and by immunohistochemistry using monoclonal antibodies (11C8B1) to the IDH2 R172S mutation. The 14 tall cell carcinomas with reverse polarity studied harbored IDH2 R172 hotspot mutations, which co-occurred with PIK3CA hotspot mutations in 50% of cases. None of the other papillary neoplasms analyzed displayed IDH2 R172 mutations, however PIK3CA hotspot mutations were detected in 54% of intraductal papillomas, 6% of solid papillary carcinomas, and 20% of encapsulated papillary carcinomas tested. Immunohistochemical analysis with anti-IDH2 R172S antibodies (11C8B1) detected IDH2 R172 mutated protein in 93% (14/15) of tall cell carcinomas with reverse polarity samples including excision (n = 9/10) and core needle biopsy specimens (n = 5), whereas the remaining papillary neoplasms (n = 34) were negative. Our findings demonstrate that immunohistochemical analysis of IDH2 R172 is highly sensitive and specific for the detection of IDH2 R172 hotspot mutations, and likely suitable as a diagnostic tool in the evaluation of excision and core needle biopsy material of tall cell carcinomas with reverse polarity.

Objectives: To compare the performance of campus-based students with that of distance students during the first 2 years of a doctor of pharmacy program to evaluate parity between the pathways., Methods: Twelve cases were created for each year of the program along with performance criteria. The cases were converted into computer-based simulations for programmatic assessment at the end of the 2002-2003 and 2003-2004 school years. All first-professional year (P1) and second-professional year (P2) students participated in the assessments. Overall class means were calculated and used to compare student performances between campus and distance education pathways., Results: Overall scores for the 2003 P1 class were 56.4% for the campus-based students and 62.4% for the distance students, (p = 0.002); overall scores for the 2003 P2 class were 48.8% and 55.5%, respectively (p < 0.0001). The 2004 overall scores for P1 campus and distance students were 59.0% and 65.7%, respectively, (p = 0.001); and for 2004 P2 scores the results were 51.8% and 56.5%, respectively (p = 0.049)., Conclusions: Students receiving their pharmacy education via a distance pathway scored higher on performance-based assessments compared with students receiving their pharmacy education via the traditional campus-based pathway. This indicates that distance students are receiving at least an equivalent curricular experience in the P1 and P2 years compared to that received by campus-based students.

The immunohistochemistry (IHC) performance of 4 anti-HER-2/neu antibodies was compared with fluorescent in situ hybridization (FISH) analysis of HER-2/neu gene expression in breast cancer patients considered for Herceptin (Trastuzumab) therapy. Interobserver variability in IHC interpretation was measured. Formalin-fixed tissue was received from 24 provincial hospital laboratories. The following anti-Her-2 antibodies were used: DAKO A0485 (polyclonal), Novacastra CB11 (monoclonal), Zymed TAB250 (monoclonal), and DAKO HercepTest (polyclonal). Additional sections were analyzed by FISH (Vysis). Three pathologists blinded to FISH results independently interpreted invasive tumor cell membranous staining on a scale of 0 to +3. The HER-2/neu gene was considered amplified when the FISH signal ratio of HER-2/CEP-17 was > or =2.0. Blocks from all hospitals and of all ages were suitable for IHC and FISH analysis. No interlaboratory analysis variability was noted. The interobserver agreement (kappa) for stain intensity for each antibody was good for 0 and +3 but poor for +1 and +2. Reasonable concordance between IHC and FISH was found with three of the four antibodies. TAB250 was the most sensitive antibody. For the three pathologists, the IHC sensitivities and specificities compared with FISH using 0/+1 as negative and +2/+3 as positive were as follows: A0485, 63-84/95-98; CB11, 63-66/97-98; TAB-250, 82-100/94-95; HercepTest, 59-77/91-93. The positive and negative predictive values varied by stain intensity. Stain scores of 0 and +3 were highly predictive of gene status. Stain scores of +1 and +2 were not sufficiently predictive to classify cases as amplified versus nonamplified. IHC is a reasonable first test to assess HER-2/neu status in patients with breast cancer. For most cases, DAKO A0485, TAB250, and HercepTest adequately predicted gene status. In cases with stain intensity of +1 or +2, the interobserver agreement is poor, and the predictive value is unsatisfactory for clinical use. Additional testing, preferably with FISH, is recommended.

The newly identified mycoplasma, Mycoplasma pentrans shows remarkable pathobiologic properties: it adheres to cell surfaces, deeply penetrates into the cell, strongly hemadsorbs human red blood cells, and cytadsorbs human CD4+ lymphocytes and monocytes. These in vitro biologic activities of mycoplasmas have been previously shown to be associated with pathogenic virulence in vivo. Both adhesion and invasion clearly involve the organism's unique tip-like structure. Invading mycoplasmas often have their tip-like structure deeply buried in the cytoplasm of infected mammalian cells. Extensive invasion of the mycoplasma into the cytoplasm may kill the cells. The same pathobiologic processes of adhesion and invasion using the specialized tip-like structure are found on the epithelium in the patient's urogenital tract infected by M. penetrans. Both in vitro and in vivo findings suggest a possible pathogenic role of this newly discovered human mycoplasma and call for careful evaluation of its role in human diseases.

This paper describes an unusual malignant mixed tumor of the bronchus arising in a 71-yr-old male and provides evidence of an epithelial-myoepithelial origin based on the findings on light microscopy and immunohistochemistry. The neoplasm contained elements of recognizable benign tumor resembling salivary gland-type pleomorphic adenoma, adenosquamous carcinoma, and a spindle-cell sarcomatous component. Immunohistochemical stains showed the characteristic relationship between epithelial and myoepithelial cells in the benign component of the neoplasm. In addition, the spindle cells stained for myoepithelial markers (S-100 protein and actin) but were also positive for keratin (AE1/AE3). The relationship of this neoplasm to classical carcinosarcoma and the recently described adenosquamous carcinoma with amyloid-like stroma is discussed.