Basal-like carcinomas have recently been identified in gene expression profiling studies as a subtype of invasive breast cancer. These lesions are estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative (triple negative), and typically express basal cytokeratins, epidermal growth factor receptor (EGFR), and/or c-kit. As poorly differentiated invasive ductal carcinomas, they presumably have a ductal carcinoma in situ (DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency and even the existence of a DCIS lesion with an immunophenotype analogous to that of invasive basal-like carcinomas have not been previously evaluated. We studied 66 cases of high nuclear grade DCIS using antibodies to ER, PR, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple negative phenotype, and to determine the relationship between the triple negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal-like carcinomas. Four cases (6%) exhibited the triple negative phenotype; the remaining cases showed other combinations of ER, PR, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both were expressed by all four triple negative lesions, but by only 21 of 51 (42%) nontriple negative cases (P ¼ 0.04). We conclude that a small proportion of high-grade ductal carcinomas in situ exhibit an ER-negative/PR-negative/ HER2-negative (triple negative) phenotype, and these lesions more commonly show expression of basal cytokeratins and/or EGFR than nontriple negative high-grade DCIS. Given that invasive breast cancers typically share immunophenotypic features with the ductal carcinoma in situ from which they arise, our findings raise the possibility that the triple-negative, basal cytokeratin and/or EGFR-positive DCIS lesions we identified represent a precursor lesion to invasive basal-like carcinomas. Keywords: breast cancer; basal-like carcinoma; ductal carcinoma in situ Recent gene expression profiling studies have identified a subtype of breast cancer known as basal-like carcinomas. [1][2][3][4] These lesions constitute about 15% of invasive breast cancers, are characterized by lack of expression of estrogen receptor (ER) and progesterone receptor (PR), and absence of HER2 protein overexpression (the so-called 'triple negative' phenotype), and have a poor prognosis. [5][6][7][8] Basal-like carcinomas typically exhibit expression of one or more of the basal cytokeratins (such as CK5/6, CK14, and CK17), epidermal growth factor receptor (EGFR), and/or c-kit. 5-8 These tumors are often seen in women with BRCA1 mutations, but also occur among sporadic breast cancers. [4][5][6][7]9 In expression array studies, the majority of triple negative invasive breast cancers cluster with basal-like carcinoma. [4][5][6][7]10 Basal-like carcinomas are poorly differentiated invasive ductal carcinomas, 4,5,7 and presumably have a ductal carcinoma in situ (DCIS) precursor with sim...
Abstract. Optical coherence microscopy ͑OCM͒ combines confocal microscopy and optical coherence tomography ͑OCT͒ to improve imaging depth and contrast, enabling cellular imaging in human tissues. We aim to investigate OCM for ex vivo imaging of upper and lower gastrointestinal tract tissues, to establish correlations between OCM imaging and histology, and to provide a baseline for future endoscopic studies. Co-registered OCM and OCT imaging were performed on fresh surgical specimens and endoscopic biopsy specimens, and images were correlated with histology. Imaging was performed at 1.06-m wavelength with Ͻ2-m transverse and Ͻ4-m axial resolution for OCM, and at 14-m transverse and Ͻ3-m axial resolution for OCT. Multiple sites on 75 tissue samples from 39 patients were imaged. OCM enabled cellular imaging of specimens from the upper and lower gastrointestinal tracts over a smaller field of view compared to OCT. Squamous cells and their nuclei, goblet cells in Barrett's esophagus, gastric pits and colonic crypts, and fine structures in adenocarcinomas were visualized. OCT provided complementary information through assessment of tissue architectural features over a larger field of view. OCM may provide a complementary imaging modality to standard OCT approaches for endoscopic microscopy.
cytoplasmic vacuoles. The nuclei were round with clumped chromatin and the nucleoli were very prominent, which is classic for Burkitt's lymphoma (Fig 2). The urine flow cytometry showed an abnormal B-cell population expressing CD10, CD19, and CD79a with no expression of nTdT, similar to the lymphoblasts in the peripheral blood at initial presentation. However, the cells in the urine lost expression of lambda light chains and CD20. It has been shown that roughly 6% of lymphoma cells isolated from body cavities and effusions lose expression of surface light chains. 7 Similarly, prior treatment with rituximab can lead to loss of CD20 expression by lymphoma cells. 8,9 These two phenomena likely account for the loss of light chain and CD20 expression in the urine specimen. The urine flow cytometry and cell morphology were felt to be diagnostic for relapsed Burkitt's lymphoma. The patient received salvage chemotherapy with subsequent symptomatic improvement and normalization of the serum creatinine. However, he ultimately developed progressive renal failure and died. In conclusion, urine flow cytometry can be a useful diagnostic tool when GU involvement by high-grade lymphoma is suspected. This case also illustrates that rapid processing of urine samples can preserve morphology and increase the number of viable cells submitted for analysis with flow cytometry.
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