A 63 year old woman with white matter lesions and pachymeningeal inflammation.

We describe the case of a 63-year-old woman with CNS Rosai-Dorfman disease, presenting with diffuse dural infiltration, mimicking idiopathic hypertrophic pachymeningitis, and right vertebral artery dissection. Her symptoms included a progressive 11-month history of vertigo, gait ataxia, and right thalamic stroke. A diagnosis of CNS Rosai-Dorfman disease was made following open dural biopsy, and later confirmed on autopsy studies. The autopsy demonstrated widespread dural infiltration by inflammatory cells, principally large histiocytes, many of which exhibited emperipolesis, a characteristic finding in Rosai-Dorfman disease. A second pathological finding on autopsy was the presence of multiple demyelinating plaques (with preservation of axons), located in the corpus callosum, periventricular white matter, and multiple brainstem segments. These were consistent with a diagnosis of multiple sclerosis. This case description serves to remind clinicians that CNS Rosai-Dorfman disease­although uncommon­may present as a focal, dural-based, hemispheric mass lesion, or as diffuse pachymeningeal inflammation. Our case was also unusual due to the co-existence of CNS Rosai-Dorfman disease, multiple sclerosis, and polycythemia vera (all rare diseases) in a single patient. Although the overlap of disorders may have been co-incidental, one could raise the question whether all three disorders were triggered by the same underlying dysimmune state.

Postmortem vascular pathology in PHACES syndrome: a case report.

This case describes the clinical course and autopsy findings of a 5-year-old girl with PHACES syndrome. While the etiopathogenesis of this condition is not yet understood, the pathological changes documented support the concept that the primary defect in PHACES syndrome is an arteriopathy.

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 10 (KLK10) in colorectal cancer.

The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 10 (KLK10) by immunohistochemistry in CRC, to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK10 expression was evaluated by immunohistochemistry and a combined expression score was calculated for each case based on intensity and percentage of positivity. A statistically significant positive association was observed between KLK10 and tumor stage and liver metastases (p = 0.015 and p = 0.035, respectively). Paradoxically, a negative association was observed between KLK10 and tumor grade (p = 0.009). Kaplan-Meier survival curves and univariate analysis showed that both KLK10 expression and stage had statistically significant correlations with disease-free survival (DFS) (p = 0.030 and p < 0.001, respectively) and overall survival (p = 0.010 and p = 0.001, respectively). Cox multivariate analysis showed that both KLK10 expression and stage were independent predictors of unfavorable DFS (p = 0.057 and p = 0.001, respectively) and overall survival (p = 0.009 and p = 0.001, respectively). In conclusion, KLK10 immunostaining is an independent prognostic marker in patients with CRC.

Evaluation and prognostic significance of human tissue kallikrein-related peptidase 6 (KLK6) in colorectal cancer.

The prognosis of patients with colorectal cancer (CRC) is assessed through conventional clinicopathological parameters, which are not always accurate. Members of the human kallikrein-related peptidases gene family represent potential cancer biomarkers. The aim of this study was to investigate the expression of human tissue kallikrein-related peptidase 6 (KLK6) by immunohistochemistry in CRC to correlate this expression with various histopathological and clinical variables, and to evaluate its significance as a predictor of disease outcome. KLK6 expression was evaluated by immunohistochemistry and an expression score was calculated for each case. In CRC, KLK6 expression was decreased compared to normal colonic mucosa. A statistically significant, positive association was observed between KLK6 and tumor stage (p=0.036), lymph node metastases (p=0.030), and liver metastases (p=0.025). Univariate analysis showed that KLK6 expression and stage had statistically significant correlation with disease-free survival (p=0.045 and p<0.001, respectively) and overall survival (p=0.027 and p<0.001, respectively). Cox multivariate analysis showed that KLK6 expression was an independent predictor of unfavorable overall survival (p=0.041). Kaplan-Meier survival curves showed that KLK6-positive patients have statistically significant lower disease-free and overall survival. In conclusion, KLK6 immunostaining is an independent prognostic marker in patients with CRC.

Ancillary testing in lung cancer diagnosis.

The pathologic diagnosis of lung cancer historically has relied primarily on morphologic features of tumors in histologic sections. With the emergence of new targeted therapies, the pathologist is called upon increasingly to provide not only accurate typing of lung cancers, but also to provide prognostic and predictive information, based on a growing number of ancillary tests, that may have significant impact on patient management. This review provides an overview of ancillary tests currently used in the pathologic diagnosis of lung cancer, with a focus on immunohistochemistry and molecular diagnostics.

Microvascular density as an independent predictor of clinical outcome in renal cell carcinoma: an automated image analysis study.

Tumor microvascular density (MVD) has been shown to correlate with the aggressiveness of several cancers. With the introduction of targeted anti-angiogenic therapy, assessment of MVD has the potential not only as a prognostic but also as a therapeutic marker. The significance of tumor vascularity in clear cell renal cell carcinoma (ccRCC) has been debated, with studies showing contradictory results. Previous studies were limited by manual quantification of MVD within a small area of tumor. Since then, the validity of this method has been questioned. To avoid the inaccuracies of manual quantification, we employed a computerized image analysis, which allowed assessment of large areas of tumor and adjacent normal tissue. The latter was used as an internal reference for normalization. MVD and vascular endothelial growth factor (VEGF) were assessed in 57 cases of ccRCC. Sections were immunostained for CD34 and VEGF. Areas of ccRCC and normal kidney medulla were analyzed within scanned images using software that counted CD34-positive vessels and measured the intensity of VEGF staining. We obtained unadjusted values from tumoral areas and calculated adjusted values as tumor/normal ratios. Unadjusted MVD had no association with clinical outcome. However, similarly to tumor stage, higher adjusted MVD was associated with shorter disease-free survival (log-rank P=0.037, Cox P=0.02). This was significant in univariate and multivariate analyses. MVD did not correlate with tumor stage, pointing to its independent prognostic value. As expected due to the known molecular abnormalities in ccRCC, most tumors showed higher VEGF expression than normal tissue. Higher adjusted VEGF was associated with high tumor grade (P=0.049). The finding of increased MVD as an independent marker of tumor aggressiveness may prove useful in the development of new tests for prognostic and therapeutic guidance. Digital techniques can provide more accurate assessment of immunomarkers and may reveal less obvious associations.

Assessment of the prognostic significance of endoglin (CD105) in clear cell renal cell carcinoma using automated image analysis.

The behavior of clear cell renal cell carcinoma can be difficult to predict. Angiogenesis has proven to be a useful prognostic indicator in different malignancies. Endoglin (CD105) is a new marker of angiogenesis found to have prognostic utility in various tumors. Here, we provide the first automated digital assessment of intratumoral microvascular density in clear cell renal cell carcinoma using endoglin and CD31 and assess their utility as predictors of clinical outcome. Both endoglin and CD31 expression showed association with advanced tumor stage (P = .025 and P = .011, respectively). There was a significant correlation between CD31 and tumor grade (P = .034). Kaplan-Meier survival curves showed that patients with higher endoglin expression had significantly shorter progression-free survival (P = .010). Patients with higher CD31 expression tended to have a worse prognosis, although this was not statistically significant (P = .082). In univariate analysis using endoglin as a continuous variable, increased endoglin was strongly associated with reduced survival (hazard ratio, 1.74; 95% CI, 1.39-2.18; P = <.001). CD31 also correlated with poor outcomes (hazard ratio, 1.52; 95% CI, 1.24-1.86; P = .001). There was no correlation between CD31 and endoglin expression (r = -0.090, P = .541). Receiver operating characteristic analysis showed the area under the curve to be 0.749 for endoglin and 0.550 for CD31. In conclusion, increased endoglin and CD31 expression are associated with a higher tumor stage and decreased progression-free survival. Our automated approach overcomes many limitations of manual quantification. Advances in digital assessment of immunohistochemical markers can be helpful in standardizing the evaluation of tumor biomarkers.

Comparison of the incidence of opacification of Hydroview hydrogel intraocular lenses with the ophthalmic viscosurgical device used during surgery.

PURPOSE: To determine the effect of intraoperative ophthalmic viscosurgical devices (OVDs) on late opacification of the Hydroview hydrogel intraocular lens (IOL) (Bausch & Lomb Surgical). SETTING: Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada. METHODS: A retrospective study of 949 cases of Hydroview IOL implantations from February 1998 to September 2000 was conducted. Of the 949 implantations, 462 were performed by 1 surgeon (J.H.S.) using Viscoat (sodium chondroitin sulfate 4.0%-sodium hyaluronate 3.0%) and 487 were performed by a second surgeon (W.A.N.) using Biolon (sodium hyaluronate 1.0%). Surgical techniques were identical with the exception of surgeon OVD preference. The number of IOLs opacifying and requiring explantation was determined in each group. RESULTS: Seventy-one Hydroview IOLs had surface calcification deposits that presented a mean of 39 months postoperatively. Twenty-two IOLs opacified sufficiently to warrant a recommendation of IOL explantation; 20 IOLs were explanted, and 2 surgeries were cancelled due to death or disability. In all cases of opacification, Viscoat had been used intraoperatively. This represented a 15.4% incidence of opacification in the Viscoat group, with 31.0% cases severe enough to warrant a recommendation of explantation. CONCLUSION: The results suggest that the intraoperative use of Viscoat has a facilitating role in the development of late calcification and opacification of the Hydroview IOL.