Clinicopathologic Correlation of Lens Epithelial Metaplasia and Late Intraocular Lens Dislocation After Repair of Retinal Detachment.

IMPORTANCE: In-the-bag intraocular lens dislocation is an uncommon but serious complication of cataract surgery in patients with previous repair of retinal detachment. The causative mechanism is currently unknown. We report histologic findings from a retrospective case series from 1993 to 2010 and suggest a possible mechanism to explain this association. OBSERVATIONS: Clinical characteristics of 8 patients presenting with in-the-bag intraocular lens dislocation after repair of retinal detachment were evaluated. Explanted capsular bags from 3 of these patients were compared with pathologic changes of crystalline lenses associated with retinal detachment. Histologic examination of the explanted capsular bags revealed a paucicellular membrane that covered the concertina-like folded surface of the lens capsule. The lens capsule was devoid of epithelial cell nuclei and showed excessive thickening with the presence of spindle-shaped cells, such as fibroblasts. Collagen fibers were noted in the extracellular matrix. CONCLUSIONS AND RELEVANCE: Previous studies of crystalline lens pathologic findings associated with retinal detachment have shown changes in the epithelium with migration and subsequent metaplasia of epithelial cells, resulting in excessive thickening of the anterior capsule with a layer of fibrous tissue. In this retrospective series, similar histologic findings were seen, suggesting that zonular dehiscence and lens dislocation may result from progressive capsular contraction secondary to retinal detachment-induced lens epithelial metaplasia.

Identification of carcinoma cells in peripheral blood samples of patients with advanced breast carcinoma using RT-PCR amplification of CK7 and MUC1.

We have undertaken a pilot study to attempt to identify circulating carcinoma cells in a series of patients with advanced breast carcinoma, using reverse transcription-polymerase chain reaction (RT-PCR) to amplify mRNA of epithelial specific antigens. Using this method to amplify mRNA of MUC1 and cytokeratin 7 (CK7) the sensitivity of the technique was demonstrated by means of diluted concentrations of "spiked MCF7" cells in whole blood, showing a detection limit of 1 in 10(6) (CK7) and 1 in 10(5) (MUC1). Positive results were obtained from the peripheral blood of all nine female patients with advanced breast cancer for CK7 and eight of the nine patients for MUC1. CK7 was however detected in five of 11 healthy controls (eight females, three males) and MUC1 in one of the 11 controls. None of the control group were positive for both CK7 and MUC1, in contrast to eight of the nine patients with advanced breast carcinoma who were positive for both markers. The RT-PCR method thus appears sufficiently sensitive to identify circulating tumour cells in peripheral blood samples from patients with advanced breast carcinoma. However a high proportion of false-positive results was seen in the control population. More extensive investigation is required before the technique is likely to be of benefit clinically.

Pathological changes in the vitreoretinal junction 1: epiretinal membrane formation.

PURPOSE/BACKGROUND: Epiretinal membrane (ERM) formation is a common change resulting in disturbance of macular vision and predisposing to rhegmatogenous retinal detachment. Current treatment strategies rely chiefly on surgical removal of the membranes from the surface of the retina, allowing the retina to remodel and reattach. Improved knowledge of the pathological process behind the formation of these membranes, particularly knowledge of the cell types involved in their formation, is likely to increase our understanding of the way this group of diseases behave and to improve treatment. METHODS: We reviewed the histological findings of 109 surgically removed specimens and correlated these to age-related changes seen in a 32 cadaver eyes studied after corneal harvesting. The samples were studied using light microscopy and immunocytochemistry. RESULTS: In all cases of idiopathic ERMs, including cellophane maculopathy, macular hole, and vitreomacular traction syndrome, laminocytes were the exclusive cell type present. In cases of macular pucker associated with retinal tears, the membranes contain variable cohesive groups of retinal pigment epithelial (RPE) cells in addition to laminocytes. In cases of proliferative diabetic retinopathy, membranes consist almost entirely of capillaries and hyaline stromal tissue, with or without haemosiderin pigment and RPE cells and in which laminocytes and ILM were not identified. In cadaver eyes PVD was seen in 17/32 (53%) of cases, and the vitreous was attached in 14/32 (43.7%) and in one case no vitreous was present. Isolated laminocytes were present on the retinal surface in 12/18 cases with detached vitreous and in 1/14 cases with attached vitreous. In all cases laminocytes were scanty and confined to the optic nerve head, macular or subjacent macular retina. Immunohistochemistry findings indicate that laminocytes are positive for glial fibrillary acidic protein (GFAP), cytokeratin marker AE1/AE3, type II collagen, and type IV collagen. In some cases novel basement membrane formation was seen. There was a tendency for increased positivity of GFAP and AE1/AE3 with increased cellularity, and where novel basement membrane formation was present. CONCLUSION: Laminocytes are the fundamental cell type in idiopathic ERMs. These cells are frequently found in small and dispersed numbers in eyes containing a PVD. The presence of retinal pigment cells invariable indicates proliferative retinopathy and is only seen in association with a retinal detachment or tear. Diabetic membranes are composed of neovascular stromal tissue, which is most likely to be a response to retinal hypoxia.

Clinicopathological changes at the vitreoretinal junction: posterior vitreous detachment.

Separation of the vitreous and posterior hyaloid membrane (PHM) or posterior vitreous detachment (PVD) typically occurs between the ages of 45 and 65 years in the general population, but may occur earlier in myopic or otherwise predisposed individuals. Age-related synergetic changes occurring within the cortical and central gel must be distinguished from the PHM, which envelopes it. This study reports on the correlation between 'true' PVD seen clinically by the physician using dynamic examination, high-power slit-lamp biomicroscopy, and oblique illumination with some of its histological, immunohistochemical, and ultrastructural features post-mortem. The presence of the Weiss ring does not necessarily indicate total clean separation of PHM, nor does its absence confirm that the PHM remains attached, since it may be destroyed during the process of separation. Immediately prior to PVD with the vitreous gel attached, the PHM must, by definition, form part of the inner limiting membrane. The detached PHM frequently exhibits basement membrane (BM) and its indigenous laminocytes stain focally for GFAP and type IV collagen. The PHM is distinct from and much thicker than the BM of Müller cells alone and the factors that initiate or limit separation of the PHM require greater study, particularly the role of laminocyte proliferation and migration.

A rationale for membrane peeling in the repair of stage 4 macular holes.

AIM: To examine the histological and immunocytochemical characteristics of epiretinal membranes (ERM) associated with stage 4 macular holes (MH) so as to establish a vitreoretinal rationale for surgery in stage 4 MH. METHOD: Consecutive patients with stage 4 MH undergoing vitrectomy and membrane peeling were recruited. Preoperatively, the eyes were examined for ERM formation over the macula and completeness of posterior hyaloid membrane (PHM) separation from the retina. ERM peel specimens obtained during surgery were sent for histological and immunocytochemical studies and were compared with the PHM specimens taken from a previous post-mortem study of eyes with physiological posterior vitreous detachment but without macular holes. RESULT: A total of 13 patients with stage 4 MH fulfilled the inclusion criteria and were recruited. Preoperatively, all eyes had an ERM over the macula and incomplete separation of the PHM seen as a defect in the PHM on specular biomicroscopy. Histologically, the ERM specimens had very similar morphological characteristics to PHM, consisting of an eosinophilic membrane of varying thickness with scattered spindle-shaped cells. The membranes stained positively for type IV collagen while the cells were glial fibrillary acidic protein positive. Postoperatively, successful closure of MH was achieved in all cases. CONCLUSION: Stage 4 MH is characterised by incomplete separation of the PHM from the retina with remnants overlying the macula manifesting as ERM. Removal of the ERM is required during vitrectomy in order to relieve the tangential forces involved in the development of MH.

Primary synovial sarcoma of the pleura: beware of misdiagnosis.

Primary synovial sarcoma of the pleura is an uncommon entity in the present medical literature. However, the paucity of documented cases may be due to misdiagnoses as a malignant mesothelioma in the past. Early diagnosis with new molecular techniques may improve the outcome of this tumour, which is believed to have a grave prognosis at present.

Intraocular surgery for optic nerve disorders.

This article discusses two current indications for intraocular surgery for optic nerve conditions. The first topic is macular detachment in association with congenital optic disc pit, and includes a review of the theories of pathogenesis and management options including our own experience of treatment with vitrectomy and gas tamponade. In addition, the histopathological findings of a new case of optic disc pit with serous macular detachment are presented, adding to the rare examples previously reported. The second subject is a radial optic neurotomy, a recently advocated treatment for central retinal vein occlusion, which, despite its controversial nature, is gaining in popularity.

hnRNP B1 expression in benign and malignant lung disease.

Evidence is accumulating to suggest that hnRNP B1 expression may be a useful tool in the early diagnosis of lung cancer. This study examined the immunohistochemical expression of hnRNP B1 in archived sections of resected lung cancers and compared the patterns of expression with those seen in similar archived sections of non-neoplastic lung. Particular attention was paid to the expression of hnRNP B1 in the benign bronchial cells in both cases, to establish if overexpression of this protein in respiratory epithelial cells is specific for malignancy. Nineteen cases of different types of non-small cell carcinoma were examined (eight squamous cell, six adenocarcinomas, two carcinosarcomas, two undifferentiated large cell carcinomas, and one mucoepidermoid carcinoma) and compared with sections from 16 open lung biopsies (three cases of cryptogenic fibrosing alveolitis, two cases of sarcoidosis, two cases of organizing pneumonia, and one case each of tuberculosis, extrinsic allergic alveolitis, non-specific interstitial pneumonitis, pneumocystis pneumonia, aspergilloma, respiratory bronchiolitis-interstitial lung disease, mineral dust disease, Sjögren's syndrome and systemic sclerosis vascular variant). All the tumours showed positive staining, with the vast majority, 16/19 (84%), showing strong diffuse nuclear staining. The background cells of these cases showed positive staining in alveolar macrophages, lymph node germinal centres, bronchial mucous glands, and bronchial epithelial cells. No significant difference was seen in the percentage of positive bronchial epithelial cells in bronchi adjacent to the tumour compared with the resection margins. In the benign lung cases, positive bronchial epithelial cells were seen in a small percentage, 3/16 (18%), of cases, but the majority of cases showed no or very focal staining. The levels of expression between benign epithelial cells of malignant cases, compared with benign, showed a significant difference when the staining was assessed in percentage of positive nuclei (p = 0.001, Fisher's exact test). The results confirm that hnRNP B1 is widely expressed in a range of lung carcinomas; that expression is seen in benign bronchial epithelial cells and inflammatory cells; and that expression in background bronchial epithelial cells appears to be higher in malignant than in benign lung disease. It is feasible that this biomarker may be of use in the detection of early lung cancer, provided that levels of expression can be accurately quantified.

Hyperconvolution of the inner limiting membrane in vitreomaculopathies.

BACKGROUND: This study investigates the similarities and differences between epiretinal membranes in four clinically distinct types of vitreomaculopathy. We propose a hypothesis on the origin of the predominant cell type and its potential role in causing these conditions. METHODS: Epiretinal membranes (ERMs) surgically removed from a prospective, consecutive series of vitrectomies for macular pucker associated with an untreated peripheral horseshoe tear (MP), cellophane maculopathy (CM), stage 4 macular hole (MH) and vitreomacular traction syndrome (VMT) were examined by light microscopy and by immunocytochemistry (ICC) using antibodies marking type IV collagen, type II collagen, glial fibrillary acidic protein (GFAP), and low- and high-molecular-weight cytokeratin (MNF116). These specimens were compared with post-mortem control eyes with and without physiological posterior vitreous detachment (PVD). Light microscopy was carried out on 5-microm-thick sections cut from formalin-fixed, paraffin-embedded tissue blocks. Appropriate autoclave or enzyme pre-digestion steps were deployed to retrieve antigens for ICC. No patient had undergone previous vitreoretinal surgery or peripheral retinopexy. RESULTS: From a series of 38 patients, (13 CM, 8 MP, 16 MH and 1 VMT) a total of 20 specimens contained sufficient tissue for histology and immunocytochemistry. All specimens contained portions of inner limiting membrane (ILM) coated by GFAP-positive cells. Specimens from patients with MP and CM exhibited hyperconvolution of the ILM, which was not found in the specimens from patients with MH or VMT or in the control eyes. Hyperconvolution was associated with increased glial cell density, GFAP staining intensity and duplication of ILM basement membrane. Three cases of ERMs from the MP group contained, in addition, cytokeratin-positive cells. In the control group; post-mortem eyes with PVDs showed patchy staining of the posterior hyaloid membrane for GFAP and type 4 collagen. Post-mortem eyes with attached gel showed weak positivity of the ILM for type 4 collagen, and a monolayer of GFAP-positive cells lined the vitreous aspect of the ILM. CONCLUSIONS: These results indicate that glial cells are fundamentally important in the formation of ERMs found in this group of vitreomaculopathies. The hyperconvolution and duplication of the ILM in CM and MP were striking and distinctive features and suggest a mechanism by which these membranes exert tractional forces on the retina. Post-mortem control eyes contained a similar (but more dispersed) population of GFAP-positive cells in the region of the ILM, suggesting the primary aetiology for CM and MP may originate within the ILM. ERMs from MP cases may, in addition, contain cytokeratin-positive cells, of probable RPE origin.

Clinical, histological and ultrastructural studies of the posterior hyaloid membrane.

AIMS: To investigate the histological, immunohistochemical and ultrastructural features of the posterior hyaloid membrane (PHM) in its naturally separated state in patients without previous surgery and slit-lamp documentation of antemortem posterior vitreous detachment (PVD). METHODS: A prospective study was commenced in 1992 to recruit patients with physiological PVD from an unselected group of general medical inpatients and ascertain the prevalence of PVD. Postmortem specimens subsequently available were studied to analyse the clinicopathological correlation and processed using standard techniques for histology, immunohistochemistry and electron microscopy. RESULTS: Eighty-five patients were examined with ages ranging from 68 to 98 yrs (mean 83.4 yrs). The posterior hyaloid membrane had clearly separated from the retina in 66% of eyes. Twenty-nine eyes from 15 patients were subsequently studied pathologically. The posterior hyaloid membrane exhibited a uniform cellular component, most densely populated around the Weiss' ring. The cells were characterised by oval or round nuclei, indistinct cytoplasm and were only seen within, or abutting, the weakly eosinophilic posterior hyaloid membrane. The posterior aspect of the posterior hyaloid membrane showed a convoluted appearance staining lightly with haematoxylin and eosin. The detached posterior hyaloid membrane exhibited focal positivity for GFAP and type IV collagen. Electron microscopy demonstrates both fibres and basement membrane associated with the cellular component including hemi-desmosome attachment plaques between the cells and basement membrane. CONCLUSIONS: This study illustrates some of the structural differences between the posterior hyaloid membrane and the cortical vitreous gel it envelopes and demonstrates the presence of cells intimately associated with the posterior hyaloid membrane in its naturally separated state. We propose the cellular population integral to the PHM to be designated as laminocytes in order to emphasise their type IV collagen/basement membrane association and planar array within the membrane which separates at posterior vitreous detachment.