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Biomedical subjects

G C Cockerham

Publications and source records attributed to G C Cockerham.

8 recordsLinked to original sources

Melkersson-Rosenthal syndrome: new clinicopathologic findings in 4 cases.

OBJECTIVE: To define the clinicopathologic features of eyelid involvement in Melkersson-Rosenthal syndrome (MRS). METHODS: Four patients with eyelid edema consistent with MRS were evaluated clinically, including diagnostic imaging in 2 patients. Eyelid tissue from these patients was examined by light microscopy and immunohistochemistry. Polymerase chain reaction for herpes simplex virus was performed in 1 case. RESULTS: The 3 men and 1 woman ranged in age from 33 to 74 years. All patients had insidious, painless, nonpitting eyelid edema. Three patients had unilateral edema; one had bilateral, asymmetric involvement. Ipsilateral lip edema was present in 1 case. Computed tomography demonstrated periorbital heterogeneous thickening that corresponded to the microscopic finding of scattered granulomas. All 4 patients demonstrated epithelioid granulomas inside and adjacent to dilated lymphatic vessels. Polymerase chain reaction testing was negative for herpes simplex virus. CONCLUSIONS: Isolated eyelid swelling that mimics thyroid-associated ophthalmopathy may occur in MRS. Computed tomography may be useful in the diagnosis. Biopsy should be performed in all cases of unexplained nonpitting eyelid edema. In the eyelid, MRS is characterized histopathologically by a granulomatous lymphangitis, a finding that seems to be unique to this condition.

Adult↗

Primary graft failure : a clinicopathologic and molecular analysis.

OBJECTIVE: Primary graft failure (PGF) corneal tissues were analyzed for herpes simplex virus (HSV) and varicella-zoster virus (VZV). DESIGN: Retrospective, noncomparative case series. MATERIALS: Formalin-fixed, paraffin-embedded tissue of 21 donor corneas and 14 recipient corneas of PGF cases, as well as 10 control corneas. METHODS: Clinical, histologic, immunohistochemical, polymerase chain reaction (PCR), and, in selected cases, transmission electron microscopic characteristics were studied. MAIN OUTCOME MEASURES: Evidence of HSV or VZV in donor tissues. RESULTS: Median patient age was 65 years, and median donor age was 48 years. Donor cornea parameters, including endothelial cell counts, death-to-preservation time, and time in storage, were generally within accepted standards. Stromal edema was found in all 21 donor corneas with PGF. Eighteen donor corneas demonstrated severely reduced or absent endothelium and mild to moderate lymphocytic infiltration without necrosis. Three donor corneas (14%) had necrotizing stromal keratitis (NSK) with keratic precipitates. Positive immunohistochemical staining of keratocytes for HSV was present in two of two donor corneas with NSK and was negative in 18 other donor corneas. Polymerase chain reaction analysis revealed the DNA of HSV type 1 (HSV1) in all donor corneas with NSK and in four donor corneas without NSK (33%). Recipient corneal tissue was negative for HSV1 DNA in three patients with NSK and positive in two of the four other PCR-positive patients. Transmission electron microscopy analysis showed viral particles in two donor corneas with NSK. Polymerase chain reaction analysis revealed no evidence of HSV type 2 or VZV in any cornea. All control corneas were negative for viral DNA. Sixteen corneas remained clear and two had failed after regraft for PGF, with a median follow-up of 3.6 years. CONCLUSIONS: Herpes simplex virus type 1 DNA was present in 33% of patients of PGF. Herpetic stromal keratitis was found in some failed corneas; the lack of HSV in the paired recipient suggests importation within the donor cornea. The overall prognosis for regrafting after PGF is good.

Adult↗

Re-evaluation of "reactive lymphoid hyperplasia of the uvea": an immunohistochemical and molecular analysis of 10 cases.

OBJECTIVE: Cases of uveal lymphoid proliferation previously classified as reactive lymphoid hyperplasia (RLH) were studied to correlate pathologic features with clinical outcome. DESIGN: Retrospective case series. PARTICIPANTS: Ten cases of RLH of the uvea on file at the Armed Forces Institute of Pathology with sufficient formalin-fixed, paraffin-embedded tissue for analysis. METHODS: Clinical, histologic, immunohistochemical, and molecular (polymerase chain reaction [PCR]) characteristics of uveal lymphoid proliferations were studied. MAIN OUTCOME MEASURES: Morphologic, immunohistochemical, and PCR characteristics of study cases. RESULTS: Patient age ranged from 40 to 73 years at time of enucleation, with a mean age of 55 years. Retinal detachment was noted clinically in nine patients and glaucoma in eight. All patients were treated with enucleation, and three received radiotherapy. Histologically, two cases were interpreted as RLH and eight were well-differentiated small-cell lymphoma (WDSCL). Systemic lymphoid infiltrate developed in two patients, but there were no deaths with a mean follow-up of 9.9 years. Mature lymphocytes were noted in the iris and angle structures; the atypical cells of uveal lymphoma were found in the choroid and ciliary body. Eight cases were monoclonal by B-cell and T-cell markers and/or immunoglobulin light chain restriction. Amplifiable DNA was present in 6 of 10 cases by PCR. Three cases monoclonal by cell markers were also monoclonal by PCR, but two cases monoclonal by cell markers could not be confirmed by PCR. Lymphoid follicles with germinal centers were found in two cases of RLH and five cases of WDSCL. Nine specimens demonstrated extraocular lymphoid involvement of the episclera and orbit; most appeared more benign morphologically than the choroidal infiltrates. Extraocular infiltrates of WDSCL were monoclonal by immunohistochemistry in five cases, polyclonal in one case, and indeterminate in two cases. CONCLUSIONS: Most cases (8 of 10) previously described as RLH were low-grade B-cell lymphomas histologically and by immunohistochemistry. PCR results agreed with histologic diagnosis in four of six cases. Open-angle glaucoma was common and related mostly to lymphocytic infiltration of the angle structures. Extraocular involvement is common but may not be representative of the choroidal lesion. Prognosis is excellent in low-grade uveal lymphoid neoplasia.

Adult↗

Retrocorneal membrane with myofibroblasts after perforating injury: an immunohistochemical and ultrastructural study of 11 cases.

PURPOSE: Retrocorneal membranes (RCMs) are sometimes present after perforating corneal injury, including failed corneal grafts. This study was performed to understand the origin and cellular composition of these RCMs. METHODS: Eleven cases of fibrous RCM associated with perforating injury and ulceration were studied by light and electron microscopy. Monoclonal antibodies against vimentin, actin, and alpha-smooth muscle actin (SMA) were used for immunohistochemical analysis. RESULTS: Retrocorneal membranes varied in thickness, extent, and cellularity. There was invariably a direct connection between RCM and wound scar through a gap in Descemet's membrane. Eight RCM and three scars of perforating wounds showed actin- or SMA-positive, vimentin-positive, spindle-shaped cells consistent with myofibroblasts. Electron microscopy showed fibroblasts and myofibroblasts in RCM. Descemet's membrane was often wrinkled in proximity to RCM with myofibroblasts. CONCLUSIONS: The scar tissue in corneal wounds is an apparent source of RCM components after perforating corneal injury, extending through gaps in Descemet's membrane. Contractile myofibroblasts are present in some RCMs and may be responsible for wrinkling of Descemet's membrane.

Actins↗

Herpes simplex virus in primary graft failure.

OBJECTIVE: To determine the frequency of herpes simplex virus type 1 (HSV-1) in primary corneal graft failures. METHODS: The clinical data submitted about all cases of corneal graft failure on file at the Armed Forces Institute of Pathology, Washington, DC, from the last 25 years (1970-1995) were evaluated. Cases that met the definition of primary graft failure were examined microscopically and analyzed using polymerase chain reaction (PCR) for the DNA of HSV-1. RESULTS: Three (2.8%) of the 106 cases of graft failure were primary graft failures. The DNA from 2 of the 3 corneal buttons was amplifiable by PCR analysis and results of the PCR analysis and Southern blotting were positive for HSV-1. None of the results of the PCR analysis and Southern blotting of the corneal buttons from the 3 graft failures occurring later than 30 days were positive for HSV-1. Results of the PCR analysis and Southern blotting indicated that 2 of 3 corneal buttons in the control group of clinically suspected herpetic keratitis were positive for HSV-1. The cornea from the first case of primary graft failure showed acute inflammation with stromal necrosis. The cornea in the second case had loss of endothelium without inflammation. CONCLUSIONS: The finding of DNA from HSV-1 in corneal buttons from 2 cases of primary graft failure supports similar observations by Cleator et al and suggests that HSV-1 may be pathogenic in some cases of primary graft failure. A larger study is needed to determine if HSV-1 is a causative factor in primary graft failure.

Adult↗

Lymphoproliferative disorders of the ocular adnexa.

Immunodysregulation appears to play a prominent role in the evolution of some lymphomas, as evidenced by the strong associations between congenital and acquired immunodeficiencies and lymphoid neoplasia, and abnormal ratios of helper T cells in lymphoid proliferations. Lympho-proliferative diseases of the ocular adnexa encompass a spectrum of lesions that may present with similar clinical and radiological features. Most primary lymphoid proliferations of the ocular adnexa consist of small lymphocytes of B-cell origin. Employing morphological, immunohistochemical, and molecular genetic criteria, proliferations may be separated into polyclonal and monoclonal categories. Increased insight into the biology and behavior of these tumors tells us that seemingly benign, as well as frankly malignant proliferations, might disseminate to nodal or extranodal sites. The diagnosis of lymphoproliferative disease of any type necessitates a complete workup for systemic lymphoma. Major prognostic criteria for lymphomas are anatomical site, stage, and histological features. Radiotherapy is employed for localized lymphoid proliferations, with chemotherapy recommended for disseminated disease. Long-term follow-up with semiannual examination is recommended. A significant percentage of primary ocular adnexal lymphoid lesions are MALT-type lymphomas, extranodal low-grade B-cell lymphomas usually associated with mucosal tissues or glandular epithelia. The pathogenesis of this lymphoma in orbital soft tissue, which normally is devoid of lymphoid tissue, lymphatic vessels, and epithelium, is unclear. MALT-type lymphomas of the ocular adnexa follow an indolent course, with long periods between relapses, and are responsive to therapy. Dissemination, when it occurs, preferentially affects other extranodal sites.

Combined Modality Therapy↗

The clinical spectrum of schwannomas presenting with visual dysfunction: a clinicopathologic study of three cases.

Schwannomas (neurilemomas) are benign tumors that arise from Schwann cells in the peripheral nervous system. The most commonly involved nerves that cause neuro-ophthalmic manifestations are cranial nerves V and VIII. In this series of three women, schwannomas presented as intraconal masses that mimicked a cavernous hemangioma, a superior orbital mass transgressing the superior orbital fissure, and an expansive frontal lobe mass with clinical symptoms and signs of increased intracranial pressure. Although all three complained of visual blurring, none of our patients presented with Vth or VIIIth cranial nerve dysfunction. Histopathologic studies demonstrated well-circumscribed, encapsulated spindle-cell lesions with classic Antoni A and B patterns. Histopathologic examination is essential to confirm the diagnosis of a schwannoma that may be otherwise clinically confusing. Direct optic nerve compression, globe indentation with induced hyperopia, or increased intracranial pressure with optic nerve compromise may be responsible for visual symptoms. A multidisciplinary approach is often required because of the size and location of schwannomas.

Adult↗