Tumor site immune markers associated with risk for subsequent basal cell carcinomas.

BackgroundBasal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic.ObjectiveThe goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors.Materials and methodsLevels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR.ResultsThe median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors.ConclusionsOur results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors

Long Term Therapy with Lenalidomide in a patient with POEMS Syndrome

Lenalidomide is an effective therapy against malignant plasma cells and a potent agent against proinflammatory and proangiogenic cytokines. The use of lenalidomide in POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein with plasma cells, skin changes) has been reported, but its benefit in long-term use is not well established. A 55-year-old man with POEMS and debilitating polyneuropathy was treated with lenalidomide and dexamethasone followed by maintenance lenalidomide. He remains in haematologic remission and in complete recovery of functional status 3.5 years after diagnosis. This case supports the long-term use of lenalidomide in patients with POEMS syndrome

Long Term Therapy with Lenalidomide in a patient with POEMS Syndrome

Lenalidomide is an effective therapy against malignant plasma cells and a potent agent against proinflammatory and proangiogenic cytokines. The use of lenalidomide in POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein with plasma cells, skin changes) has been reported, but its benefit in long-term use is not well established. A 55-year-old man with POEMS and debilitating polyneuropathy was treated with lenalidomide and dexamethasone followed by maintenance lenalidomide. He remains in haematologic remission and in complete recovery of functional status 3.5 years after diagnosis. This case supports the long-term use of lenalidomide in patients with POEMS syndrome

Nuclear IHC enumeration: A digital phantom to evaluate the performance of automated algorithms in digital pathology.

Automatic and accurate detection of positive and negative nuclei from images of immunostained tissue biopsies is critical to the success of digital pathology. The evaluation of most nuclei detection algorithms relies on manually generated ground truth prepared by pathologists, which is unfortunately time-consuming and suffers from inter-pathologist variability. In this work, we developed a digital immunohistochemistry (IHC) phantom that can be used for evaluating computer algorithms for enumeration of IHC positive cells. Our phantom development consists of two main steps, 1) extraction of the individual as well as nuclei clumps of both positive and negative nuclei from real WSI images, and 2) systematic placement of the extracted nuclei clumps on an image canvas. The resulting images are visually similar to the original tissue images. We created a set of 42 images with different concentrations of positive and negative nuclei. These images were evaluated by four board certified pathologists in the task of estimating the ratio of positive to total number of nuclei. The resulting concordance correlation coefficients (CCC) between the pathologist and the true ratio range from 0.86 to 0.95 (point estimates). The same ratio was also computed by an automated computer algorithm, which yielded a CCC value of 0.99. Reading the phantom data with known ground truth, the human readers show substantial variability and lower average performance than the computer algorithm in terms of CCC. This shows the limitation of using a human reader panel to establish a reference standard for the evaluation of computer algorithms, thereby highlighting the usefulness of the phantom developed in this work. Using our phantom images, we further developed a function that can approximate the true ratio from the area of the positive and negative nuclei, hence avoiding the need to detect individual nuclei. The predicted ratios of 10 held-out images using the function (trained on 32 images) are within ±2.68% of the true ratio. Moreover, we also report the evaluation of a computerized image analysis method on the synthetic tissue dataset

Tumor site immune markers associated with risk for subsequent basal cell carcinomas.

BackgroundBasal cell carcinoma (BCC) tumors are the most common skin cancer and are highly immunogenic.ObjectiveThe goal of this study was to assess how immune-cell related gene expression in an initial BCC tumor biopsy was related to the appearance of subsequent BCC tumors.Materials and methodsLevels of mRNA for CD3ε (a T-cell receptor marker), CD25 (the alpha chain of the interleukin (IL)-2 receptor expressed on activated T-cells and B-cells), CD68 (a marker for monocytes/macrophages), the cell surface glycoprotein intercellular adhesion molecule-1 (ICAM-1), the cytokine interferon-γ (IFN-γ) and the anti-inflammatory cytokine IL-10 were measured in BCC tumor biopsies from 138 patients using real-time PCR.ResultsThe median follow-up was 26.6 months, and 61% of subjects were free of new BCCs two years post-initial biopsy. Patients with low CD3ε CD25, CD68, and ICAM-1 mRNA levels had significantly shorter times before new tumors were detected (p = 0.03, p = 0.02, p = 0.003, and p = 0.08, respectively). Furthermore, older age diminished the association of mRNA levels with the appearance of subsequent tumors.ConclusionsOur results show that levels of CD3ε, CD25, CD68, and ICAM-1 mRNA in BCC biopsies may predict risk for new BCC tumors

Division of synthetic images into 10 subsets.

<p>Here SS_i correspond to the i^th subset. The second row contains the ratio of positive to all nuclei within each SS_i. The third row contains the number of images in each subset.</p

Bland Altman Plots for r_a.

<p>The absolute bias and the variability of the pathologists’ estimates of r_a decreased with the increasing percentage of positive nuclei. This shows that for images with higher concentrations of positive nuclei, pathologists’ estimates deviate from accuracy in ways that are not present in the algorithm’s estimates.</p

The plot shows a function which facilitates the mapping of <i>r</i>_<i>a</i> → <i>r</i>_<i>n</i>.

<p>The horizontal axis corresponds to different values of <i>r</i>_<i>a</i> while the vertical axis represents D, i.e. error. Each individual dot represents the error between <i>r</i>_<i>a</i> and <i>r</i>_<i>n</i> for the training images. The solid line corresponds to the mapping function <i>Ψ</i> which facilitates the mapping of <i>r</i>_<i>a</i> to <i>r</i>_<i>n</i> while the dotted lines represent the confidence interval.</p

Examples of positive and negative objects used in creation of synthetic images.

<p>All objects were cropped from Follicular Lymphoma whole slide images stained for Ki67.</p