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Giant cell arteritis (GCA) is the most common type of vasculitis in adults, which is classified as a large/medium vessel vasculitis. It has a predilection for the ophthalmic circulation and extracranial carotid system. Temporal artery biopsy specimens can show the presence of inflammatory multinucleated giant cells. Here, we report just the third case of Mönckeberg sclerosis with multinucleated giant cells affecting the temporal artery and mimicking GCA. This rare finding in the evaluation of a common vasculitis is important for rheumatologists to be aware of and emphasizes close collaboration between clinicians and pathologists. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) and age-related macular degeneration (AMD) are important disorders of aging, but significant challenges remain in diagnosis and therapy. Amyloid-beta (Aβ), found in the brain and a defining feature of AD, has also been observed in the retina in both AD and AMD. While current diagnostic modalities for detecting Aβ in the brain are costly or invasive, Aβ in the retina can be noninvasively and conveniently imaged using modern photonic imaging systems such as optical coherence tomography (OCT). Moreover, since many of these retinal changes occur before degenerative changes can be detected in the brain, ocular amyloid biomarkers could be utilized to detect AD as well as AMD in their earliest stages when therapy may be most effective in halting disease progression. Novel technologies to quantify retinal biomarkers have the potential to facilitate early diagnosis and noninvasive monitoring of disease progression with important therapeutic implications. [ABSTRACT FROM AUTHOR]

Idiopathic orbital inflammation developed in the right orbit of a woman in her mid-thirties, causing tearing, photophobia, diplopia, altered depth perception, proptosis, and pain on eye movements. Computed tomography disclosed a mass involving the intraconal and extraconal nasal right orbit, extending to the orbital apex with anterior displacement of the globe, effacement of the medial rectus muscle, portions of the fat plane, and the superior oblique muscle, and bone destruction with extension of the mass through the orbital floor into the superior maxillary sinus and through the lamina papyracea into the ethmoid sinus. Orbital biopsy disclosed dense fibrous connective tissue with numerous lymphocytes and macrophages. Immunohistochemical stains supported a diagnosis of idiopathic inflammatory pseudotumor involving the orbit and sinus mucosa. Treatment with a prednisone taper and a retrobulbar injection of triamcinolone acetonide have relieved her symptoms and diminished her proptosis. This patient highlights the rare potential of idiopathic orbital inflammation to erode though bone into adjacent cranial structures. [ABSTRACT FROM AUTHOR]

We report a case of adenocarcinoma of the pigmented ciliary epithelium arising in a phthisical eye. A 92-year-old man who initially presented with severe ocular pain had calcification extending from the posterior pole to ciliary body on B-scan ultrasonography to a degree not previously reported. We highlight the importance of screening for intraocular neoplasms in adults with a long-standing phthisical eye. [ABSTRACT FROM AUTHOR]

Abstract: Background: Late-onset Pompe disease (LOPD) is a rare cause of declining proximal muscle strength and respiratory function that can also affect other organ systems. The development of enzyme replacement therapy has made it one of the few inherited muscle disorders with treatment, but clinical response is difficult to assess due to the variable and often slow progression of illness. A better understanding of the disease''s systemic effects can be gleaned through autopsy findings. Purpose: The purpose of this study was to: (1) describe the histological findings observed in LOPD, (2) provide correlations between reported histological and clinical findings, and (3) review the literature on autopsy findings in LOPD. Methods: Histological evaluation of autopsy tissues from a 62-year-old woman with LOPD was conducted. A clinical history was obtained by review of the medical records. The literature was reviewed for previously reported histological and clinical findings in LOPD. Based on this case report and information from prior publications, histological and clinical findings for the disease were correlated. Results: Histologic examination revealed mostly mild vacuolar myopathy typical of glycogen accumulation within skeletal and smooth muscle cells. The most prominent vacuolar myopathy was in quadriceps muscle, which also exhibited chronic myositis with degenerating and regenerating muscle fibers. Transmission electron microscopy disclosed lysosomal glycogen accumulation within skeletal, cardiac, and vascular smooth muscle cells, correlating with published case reports of basilar artery and ascending aortic aneurysms and carotid artery dissection. Organs containing smooth muscle cells (the bladder, intestine, and esophagus) were also affected, explaining reports of symptoms such as urinary incontinence and dysphagia. In addition to glycogen accumulation, there was obvious damage to the contraction apparatus of myofibrils within cardiac and skeletal muscle cells. These histological and ultrastructural findings correlate with the clinical manifestations of LOPD. Conclusions: This study is the first to describe histological findings of LOPD utilizing both traditional paraffin-processed tissues and epoxy resin embedded tissues for high-resolution light microscopy. The findings are similar to those seen in previous studies, but with improved morphological detail and glycogen preservation. This patient exhibited histological involvement of multiple organs, correlating with the clinical features of LOPD. With the advent of definitive therapy for Pompe disease, it is important to be aware of these findings and use them to develop methods for tracking therapeutic response. [Copyright &y& Elsevier]

We report a case of catastrophic antiphospholipid syndrome in a patient following mitral valve replacement. The pathophysiology and management of this rare condition is discussed. [ABSTRACT FROM AUTHOR]

Aim: Adnexal tumors with divergent lines of differentiation are uncommon. Herein, I report a hamartoma of the eyelid with follicular, sebaceous and apocrine differentiation that exhibited prominent melanin pigmentation. Methods: A 63-year-old white woman had a nodule present on her left upper eyelid for 15 years. The nodule had been slowly increasing in size but was unchanged in color. Examination disclosed an 8- × 5-mm nodule of the left upper eyelid, with slight purple discoloration. Results: Biopsy showed a well-circumscribed tumor composed of predominantly apocrine glands but with areas of sebaceous and follicular differentiation. Some areas had prominent light-brown, granular pigment within tumor cells. The pigment had histochemical features of neuromelanin. Immunohistochemistry indicated that the hamartomatous elements had antigenic features of various adnexal structures independent of the histological phenotype. The hamartomatous cells did not react with antibodies to tyrosinase or melanoma antigen recognized by T-cells 1 (MART-1). Conclusions: This case is unique because of its location and prominent melanin pigmentation. Lack of tyrosinase activity in the tumor cells and the periodic acid-Schiff (PAS) positivity of the pigment indicating its similarity to neuromelanin raise the possibility that the melanin in the hamartoma is a non-enzymatically derived oxidation product of a substance intrinsic to the tumor cells. [ABSTRACT FROM AUTHOR]

A 93-year-old woman developed a mass on her right lower eyelid that was present for more than 6 months but underwent rapid expansion during several weeks prior to her ophthalmological evaluation. Examination revealed an approximately 1.8 cm in diameter, fleshy, fungating growth involving more than 60% of the right lower eyelid. Excisional biopsy disclosed a neoplasm arising from the epidermis composed of adjoining basal cell and signet-ring squamous cell carcinoma, without a transition zone. The cells comprising the basal and squamous cell carcinomas were distinct immunophenotypically, with only the basal cell carcinoma reacting with Ber-EP4 and CAM 5.2 antibodies. To our knowledge, this case represents the first example of a collision tumor composed of basal cell and signet-ring squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to document the presence of fibrovascular ingrowth into the Ahmed glaucoma valve (AGV) as a cause of AGV failure in the pediatric population. Design: Retrospective case series. Methods: Retrospective study of six children with histologically documented fibrovascular ingrowth of their AGV, with review of relevant demographic, clinical, and surgical factors. Results: Six patients, two males and four females, with a mean age at AGV placement of 27.5 months (range 1 to 122) were identified with AGV failure, AGV removal, and subsequent histology documenting fibrovascular ingrowth into the valve chamber. Etiology of glaucoma included: trauma, aphakia, angle-closure, aniridia, and infantile. Mean time from AGV implantation to explantation was 23 months (range 6 to 65). Mean intraocular pressure at AGV explantation was 35 mm Hg (range 27 to 48). Conclusions: Fibrovascular ingrowth of both the pediatric and adult size AGV occurs in children and should be considered in the presence of AGV failure. [Copyright &y& Elsevier]

Purpose: Prior research in animal models has shown that macrophages and microglia play an important role in pathogenesis of glaucoma, but the phenotype and distribution of macrophages in human glaucomatous tissue have not been sufficiently characterized.Methods: We analyzed H&E, CD68-, and CD163-immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. The diagnosis of glaucoma was made based on a history of glaucoma as reported in the medical record and histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race.Results: Qualitative analysis of the conventional outflow pathway and the optic nerve revealed that all eyes contained CD163+ cells but a negligible number of CD68+ cells. CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm’s canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In optic nerves of control eyes, CD163+ macrophages were present at low levels and restricted to septa between axon bundles. In glaucomatous optic nerves, the number of CD163+ cells was increased both qualitatively and quantitatively (glaucoma 5.1 ± 0.6 CD163+ cells/mm2, control 2.5 ± 0.3 CD163+ cells/mm2, p < 0.001), with CD163+ cells infiltrating axon bundles in cases of both mild and severe diseases.Conclusions: The increase in CD163+ cell number in eyes with mild and severe glaucoma is the first demonstration of macrophage infiltration in glaucomatous human optic nerves. This finding supports a role for macrophages in glaucoma pathogenesis and progression. [ABSTRACT FROM AUTHOR]

Highlights • Survival among children after UCBT has improved substantially over the past 20years. • Nearly half of the improved survival was related to a decline in aspergillosis. • Voriconazole prophylaxis was associated with lower aspergillosis mortality. • Improved strategies to prevent and treat adenovirus, CMV, and GVHD are needed. Abstract Infections and graft-versus-host disease (GVHD) have historically resulted in high mortality among children undergoing umbilical cord blood transplantation (UCBT). However, recent advances in clinical practice have likely improved outcomes of these patients. We conducted a retrospective cohort study of children (<18years of age) undergoing UCBT at Duke University between January 1, 1995 and December 31, 2014. We compared 2-year all-cause and cause-specific mortality during 3 time periods based on year of transplantation (1995 to 2001, 2002 to 2007, and 2008 to 2014). We used multivariable Cox regression to identify demographic and UCBT characteristics that were associated with all-cause mortality, transplantation-related mortality, and death from invasive aspergillosis after adjustment for time period. During the 20-year study period 824 children underwent UCBT. Two-year all-cause mortality declined from 48% in 1995 to 2001 to 30% in 2008 to 2014 (P =.0002). White race and nonmalignant UCBT indications were associated with lower mortality. Black children tended to have a higher risk of death for which GVHD (18% versus 11%; P =.06) or graft failure (9% versus 3%; P =. 01) were contributory than white children. Comparing 2008 to 2014 with 1995 to 2001, more than half (59%) of the reduced mortality was attributable to a reduction in infectious mortality, with 45% specifically related to reduced mortality from invasive aspergillosis. Antifungal prophylaxis with voriconazole was associated with lower mortality from invasive aspergillosis than low-dose amphotericin B lipid complex (hazard ratio,.09; 95% confidence interval,.01 to.76). With the decline in mortality from invasive aspergillosis, adenovirus and cytomegalovirus have become the most frequentinfectious causes of death in children after UCBT. Advances in clinical practice over the past 20years improved survival of children after UCBT. Reduced mortality from infections, particularly invasive aspergillosis, accounted for the largest improvement in survival and was associated with use of voriconazole for antifungal prophylaxis. [ABSTRACT FROM AUTHOR]

Highlights • The autopsy rate for pediatric stem cell transplant recipients declined >50% from the 1990s. • Infectious diagnoses that may have changed outcome are now less frequent on autopsy. • Overall utility of autopsy remains high; there is 1 unexpected diagnosis for every 7 autopsies. Abstract Autopsy may confirm clinical diagnoses or identify conditions that were not suspected prior to a patient's death. Previous studies evaluating the utility of autopsy in hematopoietic stem cell transplant (HSCT) recipients yielded conflicting results. We conducted a retrospective cohort study of children (<18 years of age) undergoing allogeneic HSCT at Duke University who died of any cause between January 1, 1995, and December 31, 2016. We evaluated associations between patient characteristics and autopsy performance using chi-square or Fisher exact tests. We reviewed autopsy reports to determine the concordance between preautopsy causes of death and pathological diagnoses identified on autopsy. We classified unexpected diagnoses on autopsy using criteria developed by Goldman et al. We evaluated for temporal changes in the autopsy consent rate and the frequency of unexpected diagnoses on autopsy using Cochran-Armitage tests. During the 22-year study period, 475 patients died and had data available on autopsy performance, and 130 (27%) of these patients underwent autopsy. The autopsy consent rate declined over time (P <.0001), with autopsies being performed for 40% of deaths in 1995 to 1999 and 17% of deaths in 2009 to 2016. White patients were more likely to undergo autopsy than nonwhite patients (P =.03). There were no associations between autopsy performance and patient age, sex, HSCT indication, or HSCT donor. Unexpected diagnoses were identified in 31 (24%) autopsies. The proportion of autopsies with an unexpected diagnosis did not change during the study period (P =.45). However, infectious diagnoses that would have led to a change in management were more frequently identified on autopsies in 1995 to 2003 than in 2004 to 2016 (20% versus 0%; P =.001). The autopsy consent rate for pediatric HSCT recipients at our institution has declined substantially over the past several decades. The utility of autopsy in this patient population remains high despite a reduction in the identification of unexpected infections. [ABSTRACT FROM AUTHOR]

Massive retinal gliosis, a nonneoplastic retinal glial proliferation, was first described in detail over 25 years ago, before the era of immunohistochemistry, in a series of 38 cases—to which can be added 30 case reports or small series (no more than 3 cases) subsequently. We analyze a new series of 3 nontumoral intraretinal glioses and 15 cases of tumoral retinal gliosis, not all of which, strictly speaking, were massive. The data from this series are compared with the findings in previously published cases. Included are 2 cases of massive retinal gliosis diagnosed from evisceration specimens. In reviewing all published and current cases, we were able to establish 3 subgroups of retinal tumoral glioses rather than a single “massive” category: focal nodular gliosis, submassive gliosis, and massive gliosis. Among 43 reported cases, including the present series, but excluding the previous large series of 38 cases in which substantial clinical data were omitted, there were 19 men and 24 women. Their mean and median ages were 36.2 years and 36 years, respectively, with a range of 2 to 79 years. All lesions were composed of mitotically quiet, compact spindled fibrous astrocytes devoid of an Alcian blue-positive myxoid matrix. The most common associated ocular conditions were phthisis bulbi and congenital diseases or malformations. Histopathologically, all 3 tumoral categories were accompanied by progressively more extensive fibrous and osseous metaplasia of the pigment epithelium, the latter forming a clinically and diagnostically useful, almost continuous, outer rim of eggshell calcification in the submassive and massive categories that should be detectable with appropriate imaging studies. In decreasing order of frequency, microcysts and macrocysts, vascular sclerosis, exudates, calcospherites, and Rosenthal fibers were observed among the proliferating fibrous astrocytes. Immunohistochemistry was positive for glial fibrillary acidic protein in all cases and nestin in most (an intermediate cytoplasmic filament typically restricted to embryonic and reparative neural tissue). The nonneoplastic nature of all categories of gliosis was confirmed by absent TP53 (tumor suppressor gene) dysregulation, Ki-67 negativity, and intact p16 expression (the protein product of the p16 tumor suppressor gene) in the overwhelming majority of cases. These findings indicate an intrinsic attempt to regulate and maintain a low level of glial cell proliferation that becomes unsuccessful as the disease evolves. The categories of tumoral proliferation appeared to constitute a spectrum. We conclude that focal nodular tumors encompass lesions previously called retinal vasoproliferative lesions, which display the same histopathologic and immunohistochemical findings as 3 major categories of retinal gliosis characterized herein. [ABSTRACT FROM AUTHOR]

Intraocular medulloepithelioma (IO MEPL) is an uncommon embryonal neuroepithelial neoplasm of the eye. These ocular neoplasms have been compared with intracranial medulloepitheliomas or other histologic variants of CNS embryonal tumor with multilayered rosettes (CNS ETMR) due to their morphological mimicry. We performed comprehensive molecular analysis to explore the histogenetic and biologic relationships between 22 IO MEPL and 68 CNS ETMR. Routinely prepared paraffin-embedded samples were assessed for genome-wide methylation profiles using the Illumina Methylation 450k BeadChip array. We identified strong cytogenetic and epigenetic differences between ocular neoplasms and CNS ETMR. None of the IO MEPL cases displayed the ETMR-specific amplification of the C19MC locus. Instead, cytogenetic analysis of the IO MEPL showed numerous copy number aberrations which involved either whole chromosomes or chromosomal arms; recurrent aberrations in these tumors affected chromosomes 1p, 4, 8 and 16p. DNA methylation patterns were also strikingly different between these two tumor entities, suggesting that they do not share common origins and biological behaviors. Comparative cluster analysis of 198 pediatric CNS tumors and 22 IO MEPL revealed a clear demarcation of the CNS ETMR and IO MEPL profiles from other CNS entities. In conclusion, although IO MEPL shares some histopathological features with CNS ETMR, they manifest striking molecular diversity at the cytogenetic and epigenetic levels. Consequently they deserve a separate nosologic designation in future tumor classifications, where CNS MEPL could be designated as a histological variant of CNS ETMR. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare immunohistochemical and genetic overlaps and differences between intraocular medulloepitheliomas and embryonal tumors withmultilayered rosettes of the brain. DESIGN: Retrospective histopathologic, immunohistochemical, and genetic analysis of 20 intraocular medulloepitheliomas. METHODS: (1) Review of clinical data and hematoxylin-eosin-stained sections with (2) immunohistochemical staining of paraffin sections using a polyclonal antibody against the protein LIN28A, and (3) fluorescence in situ hybridization (FISH) testing for the amplification of the genetic locus 19q13.42 involving the C19MC cluster of miRNA. Ten retinoblastomas served as controls and to determine the specificity of these biomarkers for intraocular medulloepitheliomas. RESULTS: Nineteen of the 20 intraocular medulloepitheliomas were either diffusely or focally LIN28A positive (weak, moderate, or strong). The most intense positivity correlated with aggressive behavior such as intraocular tissue invasion or extraocular extension. None of the cases studied by FISH harbored an amplicon for C19MC. The 10 retinoblastomas were LIN28A and C19MC negative. CONCLUSION: LIN28A has a putative role in oncogenesis and is found only in embryonic cells and malignancies. Intraocular medulloepitheliomas and embryonal tumors with multilayered rosettes of the brain both display LIN28A positivity. Only the latter, however, display amplification of the 19q13.42 locus involving C19MC, implying that other causative factors are at play in intraocular medulloepitheliomas. More aggressive tumor behavior within the eye can be partially predicted by LIN28A staining intensity. [ABSTRACT FROM AUTHOR]

The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Here, we found that in two mouse glaucoma models, microglia transitioned to a neurodegenerative phenotype characterized by upregulation of Apoe and Lgals3 (Galectin-3), which were also upregulated in human glaucomatous retinas. Mice with targeted deletion of Apoe in microglia or carrying the human APOE4 allele were protected from retinal ganglion cell (RGC) loss, despite elevated intraocular pressure (IOP). Similarly to Apoe −/− retinal microglia, APOE4 -expressing microglia did not upregulate neurodegeneration-associated genes, including Lgals3 , following IOP elevation. Genetic and pharmacologic targeting of Galectin-3 ameliorated RGC degeneration, and Galectin-3 expression was attenuated in human APOE4 glaucoma samples. These results demonstrate that impaired activation of APOE4 microglia is protective in glaucoma and that the APOE-Galectin-3 signaling can be targeted to treat this blinding disease. [Display omitted] • Microglia switch from a homeostatic to a neurodegenerative phenotype in glaucoma • Apoe and APOE3 induce Galectin-3, a key effector of neurodegenerative microglia • Apoe −/− and APOE4 retinal microglia have a decreased response to neurodegeneration • APOE4 allele protects against retinal ganglion cell (RGC) loss in glaucoma The apolipoprotein E4 (APOE4) allele is associated with an increased risk of Alzheimer disease and a decreased risk of glaucoma, but the underlying mechanisms remain poorly understood. Margeta et al. demonstrate that APOE-Galectin-3 signaling regulates cytotoxic neurodegenerative retinal microglia in glaucoma and that the APOE4 allele attenuates microglial neurodegenerative phenotype and protects neurons in glaucoma. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infection is the major cause of bronchiolitis in young children. The factors that contribute to the increased propensity of RSV-induced distal airway disease compared with other commonly encountered respiratory viruses remain unclear. Here, we identified the RSV-encoded nonstructural 2 (NS2) protein as a viral genetic determinant for initiating RSV-induced distal airway obstruction. Infection of human cartilaginous airway epithelium (HAE) and a hamster model of disease with recombinant respiratory viruses revealed that NS2 promotes shedding of infected epithelial cells, resulting in two consequences of virus infection. First, epithelial cell shedding accelerated the reduction of virus titers, presumably by clearing virus-infected cells from airway mucosa. Second, epithelial cells shedding into the narrow-diameter bronchiolar airway lumens resulted in rapid accumulation of detached, pleomorphic epithelial cells, leading to acute distal airway obstruction. Together, these data indicate that RSV infection of the airway epithelium, via the action of NS2, promotes epithelial cell shedding, which not only accelerates viral clearance but also contributes to acute obstruction of the distal airways. Our results identify RSV NS2 as a contributing factor for the enhanced propensity of RSV to cause severe airway disease in young children and suggest NS2 as a potential therapeutic target for reducing the severity of distal airway disease. [ABSTRACT FROM AUTHOR]

Abstract: Epstein–Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) of the elderly is an aggressive B-cell neoplasm related to age-associated impaired immunity. We report such a case in a 59-year-old woman with a catastrophic disease course. The patient initially presented with fever, fatigue, malaise and weakness over one-week period. Despite empirical treatment with antibiotics and antiviral agents, she subsequently developed multi-organ failure and coagulopathy. Radiographic imaging revealed hepatomegaly, splenomegaly, pleural effusion, and ascites. Her complete blood cell count showed marked leukocytosis, anemia and thrombocytopenia. Morphologic examination of blood smear demonstrated many abnormal plasmacytoid lymphocytes, and flow cytometric analysis detected an intermediate-large mature B-cell population (69%) without detectable surface immunoglobulin. High copy numbers of EBV genome were detected in the blood by PCR. A diagnosis of EBV+ DLBCL, leukemic phase, was made. Despite aggressive treatment and supportive care, the patient succumbed to multi-organ failure one week after initial presentation. Autopsy demonstrated EBV+ DLBCL infiltration in all the organs examined. This case describes an unusual presentation of EBV+ DLBCL and highlights the necessity of pertinent ancillary tests to avoid delay in the diagnosis and treatment. [Copyright &y& Elsevier]

Purpose: To characterize and determine the effect of tamsulosin (Flomax) on the human iris dilator muscle anatomy. Design: Retrospective, case-control study. Participants: This study comprised 51 cadaveric eyes from 27 patients (14 with a history of tamsulosin use and 13 control patients) who underwent autopsy at the Duke University Medical Center, Durham, North Carolina. Methods: Patients'' records were reviewed, and age, medical, surgical, and ocular history; gender; medications; and duration and dosage of tamsulosin were recorded. Specimens were sectioned through the pupillary axis in the horizontal meridian and reviewed by light microscopy. A morphometric analysis was performed to measure the maximum and minimum iris dilator muscle thickness and the iris stromal thickness (micrometers) at 6 points in each eye. All microscopic evaluations and measurements were performed by the same masked observer. Main Outcome Measures: To determine whether there is a significant difference in the iris dilator muscle or stromal thickness in those patients receiving tamsulosin treatment compared with age-matched controls. Results: The mean iris dilator muscle thickness in the tamsulosin-treated group (6.53±1.99 μm) was significantly thinner compared with that of the control group (8.50±1.61 μm) (P=0.006). There was no difference in iris stromal thickness between the 2 groups (P=0.268). There was no direct relationship between duration of tamsulosin use and iris dilator muscle or stromal thickness. Statistical significance was maintained when the iris dilator muscle thickness was compared between the groups using history of diabetes and cataract extraction as separate variables. No difference was noted when comparing the iris stromal thickness using diabetes as a separate variable. However, stromal thickness was significantly different between the groups in pseudophakic eyes (P=0.005). Conclusions: According to histologic examination of cadaver eyes, patients receiving tamsulosin treatment exhibited decreased iris dilator muscle thickness compared with control patients. There was no difference noted in the iris stromal thickness within the groups. We believe this finding may shed light on the pathophysiology of intraoperative floppy iris syndrome. Further studies need to be performed to assess the significance of this histologic finding. Financial Disclosure(s): No author has a financial or proprietary interest in any material or method mentioned. [Copyright &y& Elsevier]

Purpose: To describe the histologic findings of full-thickness corneas from penetrating keratoplasty (PK) in 10 patients with a prior history of Descemet stripping with endothelial keratoplasty. Design: Retrospective review of the histopathology of 10 PK specimens. Methods: We reviewed histologic sections stained with hematoxylin and eosin, periodic acid-Schiff, and colloidal iron stains from 10 PK specimens, which had been trisected and submitted in their entirety. Clinical data were abstracted from the medical record. Results: The interface between host and graft in most cases was barely perceptible with minimal changes in the degree of tissue eosinophilia, a subtle increase in keratocyte cellularity focally, or the presence of melanin granules within keratocytes. Residual host Descemet membrane (DM) was found in 8 of the 10 cases, most often at the edges of the graft. In no case did the presence of DM appear to hinder graft adhesion. Conclusion: The adhesion of Descemet stripping with endothelial keratoplasty grafts is not associated with significant scarring or keratocyte proliferation. Contrary to previous assumptions, retained DM did not appear to hinder graft adhesion, raising the possibility that removal of DM may be unnecessary for endothelial transplantation. [Copyright &y& Elsevier]

We report a case of Candida glabrata endophthalmitis following penetrating keratoplasty in a 57-year-old man. The infection was thought to be treated successfully with intravitreal amphotericin B but flared 7 months later following cataract extraction and eventually required explantation of the intraocular lens and therapeutic keratoplasty. The literature regarding this rare infection is reviewed. Candida glabrata, an uncommon ocular pathogen, is being reported with increasing frequency and with a notable predilection for post-keratoplasty eyes. In the 10 reported cases, there is 100% concordance between host and donor tissue cultures. In half the cases, there was a latent period of several months. These infections can be difficult to treat because C glabrata is often resistant to the antifungal agents commonly used to treat Candida albicans. [Copyright &y& Elsevier]

This study investigated stromal changes in expression of tenascin and vasculogenesis in lymphoma. Documenting the dynamic nature of the stromal changes in lymphoma in relation to response to therapy is helpful in planning new therapies directed at these targets. Two hundred and sixty one samples from 111 patients with varying types of non-Hodgkin's lymphoma were reviewed and examined using immunohistochemistry techniques. Samples were stained for factor VIII – related antigen for microvessel density (MVD) analysis and anti-tenascin antibody for qualitative assessment of the stromal expression. Multiple samples from the same patient were taken at the same point in time to assess whether stromal changes were limited to sites of disease. Multiple samples were examined over the course of a patient's illness to assess whether the stromal changes were modulated according to disease activity. There was a significant increase in tenascin expression and MVD in the sites of disease compared with uninvolved sites ( p = 0.01 and p [ABSTRACT FROM AUTHOR]

Collagen-rich crystalloids, also referred to as collagenous crystalloids, are uncommon findings in benign salivary gland tumors with myoepithelial differentiation and in cutaneous neoplasms. Herein, we report the presence of collagen-rich crystalloids in the scarred, vascularized cornea of a 56-year-old woman. The patient underwent penetrating keratoplasty, and microscopic examination of hematoxylin-eosin-stained sections disclosed large aggregates of refractile material within the corneal stroma. The deposits were partially birefringent when viewed with polarized light and composed of radially arranged columns (long rectangles) with rounded to pointed tips. The deposits had tinctorial properties of collagen using Masson trichrome and the van Gieson method for collagen, and they stained with Alcian blue, pH 2.5, and Verhoeff elastic stain. They did not stain with Gomori methenamine silver, Snook reticulin stain, or tyrosine using the Baker modification of the Millon reaction. This is the first report, to our knowledge, of collagen-rich crystalloids in the cornea. Their presence in the cornea indicates that these structures may occur in the absence of neoplasia. [ABSTRACT FROM AUTHOR]

Purpose. To evaluate the chicken cornea as a model for coneal wound healing research. Methods. We conducted studies on normal chicken corneas and on corneas following mechanical debridement and photorefractive keratectomy (PRK). Results. The chicken cornea possesses six distinct layers that resemble the layers of the human cornea, including a substantial Bowman's layer measuring 5.2 ± 0.3 μm thick. Reepithelialization time was 44.8 ±1.1 hours with a sliding rate of 75.3 ± 3.2 μm/hour following mechanical debridement and 54.4 ± 2.8 hours with a sliding rate of 63.3 ±3.2 μm/hour for PRK-treated corneas, Biomicroscopic haze post-PRK peaked at 4-6 weeks and regressed until 20 weeks post-PRK. Histologic and clinical observations of wound healing strongly paralleled that noted in humans. Conclusion. The chicken cornea's morphology and wound healing response render it a useful model for corneal wound healing investigations. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that during cisplatin-induced acute renal failure, there is a significant reduction in proximal tubule fatty acid oxidation. We now report on the effects of peroxisome proliferator-activated receptor-α (PPARα) ligand Wy-14643 (WY) on the abnormalities of medium chain fatty acid oxidation and pyruvate dehydrogenase complex (PDC) activity in kidney tissue of cisplatin-treated mice. Cisplatin causes a significant reduction in mRNA levels and enzyme activity of mitochondrial medium chain acyl-CoA dehydrogenase (MCAD). PPARα ligand WY ameliorated cisplatin-induced acute renal failure and prevented cisplatin-induced reduction of mRNA levels and enzyme activity of MCAD. In contrast, in cisplatin-treated PPARα null mice, WY did not protect kidney function and did not reverse cisplatin-induced decreased expression of MCAD. Cisplatin inhibited renal PDC activity before the development of acute tubular necrosis, and PDC inhibition was reversed by pretreatment with PPARα agonist WY. Cisplatin also induced increased mRNA and protein levels of pyruvate dehydrogenase kinase-4 (PDK4), and PPARα ligand WY prevented cisplatininduced increased expression of PDK4 protein levels in wild-type mice. We conclude that PPARα agonists have therapeutic potential for cisplatin-induced acute renal failure. Use of PPARα ligands prevents acute tubular necrosis by ameliorating cisplatin-induced inhibition of two distinct metabolic processes, MCAD-mediated fatty acid oxidation and PDC activity. [ABSTRACT FROM AUTHOR]

A case of a 64-year-old man with bilateral diffuse uveal melanocytic proliferation is presented. Bilateral diffuse uveal melanocytic proliferation is a rare paraneoplastic disorder where an underlying malignancy causes bilateral blindness by uveal thickening, serous retinal detachment, and rapid cataract formation. The ocular symptoms and signs herald the onset of this disease, which leads to death in most cases within about 1 year. Including the present case, our literature review reveals that a total of 28 cases of bilateral diffuse uveal melanocytic proliferation have now been reported. Several different malignancies have been associated with bilateral diffuse uveal melanocytic proliferation, but ovarian carcinoma in women and lung and suspected pancreatic carcinoma in men are the most common. Our case is the first to be proven at autopsy to be associated with pancreatic carcinoma. The underlying mechanism remains to be identified, as numerous endogenous factors may regulate the proliferation of uveal melanocytes. Consideration of this entity during clinical examination may lead to an earlier diagnosis of malignancy and an improved prognosis. [Copyright &y& Elsevier]

Full-thickness dermal biopsies were performed in healthy volunteers to establish the range of angiogenic responses in wound healing in a normal population. Four-millimeter punch biopsies were made in the forearms of 15 healthy volunteers. Each wound was evaluated microscopically 4-5 times per week for 2 weeks. A semiquantitative wound scoring system to evaluate the neovasculature at the wound periphery was investigated. A vascular score was calculated for each wound at each observation. Two independent observers analyzed the microscopic wound images using the scoring system. At the end of the 14-day period, repeat biopsies were performed on some of the volunteers, and the granulation tissue was stained with anti-CD31. The Kaplan-Meier method was used to estimate the distribution of the time to reach predetermined target average vascular scores. A mixed-effects regression model indicated that time, age, and observer were predictors for the average vascular score outcome. The pattern and time course for wound neovascularization was highly reproducible in this group of healthy volunteers, and the assay was feasible and well tolerated. This wound angiogenesis model may be useful for monitoring the effects of antiangiogenic agents on normal wound neovascularization. [ABSTRACT FROM AUTHOR]

Focuses on interlaboratory variation in results from immunohistochemical assessment of estrogen receptor (ER) status. Need to analyze steroid hormone receptors in the pathologic examination of breast carcinoma specimens; Description of immunohistochemical method used for ER quanitfication and Cell Analysis System quantification method.